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An immune-related gene signature (IRGS) was established to better understand the molecular and immunologic characteristics of microsatellite instable (MSI) and microsatellite stable (MSS) endometrial carcinoma (EC), and provide potential immunotherapy directions for MSS patients. Top 20 immune-related hub genes were screened by weight gene coexpression network analysis (WGCNA), and an IRGS was further established through Cox regression analysis. The molecular and immune characteristics were clarified in IRGS high and low risk groups. Expression and MS status validation of the IRGS were conducted through quantitative real-time Polymerase Chain Reaction (rt-qPCR) and immunohistochemistry (IHC) analysis. The IRGS includes 2 oncogenes (AGTR1 and HTR3C) and 2 tumor suppressor genes (CD3E and SERPIND1). Patients in IRGS high-risk group were more with MSS status, higher tumor grade, later FIGO stage, serous histology and elder ages compared with IRGS low-risk group (P < 0.05). Besides, patients in MSS group were more FIGO stages II–IV (42.7% vs. 26%), serous histology (35.7% vs. 5.3%) and with higher IRGS risk score (1.51 ± 3.11 vs. 1.02 ± 0.67) (P < 0.05) than patients in MSI group. Furthermore, patients in IRGS high-risk group had higher tumor purity, more Macrophages M1 and Macrophages M2 infiltrating, higher proportion of Macrophages M2 and Dendritic cells activated, lower proportion of T cells regulatory (Tregs), lower tumor mutation burden (TMB). Correspondingly, subjects in IRGS low-risk group had higher immunphenoscores than IRGS high-risk group. The relative mRNA level of AGTR1 and HTR3C were gradually increase, while CD3E and SERPIND1 were reversed in rt-qPCR. Through IHC experiments, AGTR1(69.2% vs 30%, P = 0.074) and HTR3C (76.9% vs 30%, P = 0.024) had higher positive staining rates in ECs than non-ECs. While SERPIND1 (84.6% vs 20%, P = 0.003) and CD3E (61.5% vs 40%, P = 0.000) had higher positive staining rates in non-ECs. IRGS is a potential diagnostic and prognostic biomarker for EC. IRGS low risk group might benefit from immune checkpoint inhibitors, while IRGS high risk group deserve other potential immunotherapy. [ABSTRACT FROM AUTHOR]

The unremitting pursuit of high-performance and multifunctional materials has consistently propelled modern industries forward, stimulating research and motivating progress in related fields. In such materials, polybenzoxazine (PBz) aerogel, which combines the virtues of PBz and aerogel, has attracted salient attention recently, emerging as a novel research focus in the realm of advanced materials. In this review, the preparation scheme, microscopic morphology, and fundamental characteristics of PBz aerogels are comprehensively summarized and discussed in anticipation of providing a clear understanding of the correlation between preparation process, structure, and properties. The effective strategies for enhancing the performance of PBz aerogels including composite fabrication and hybridization are highlighted. Moreover, the applications of PBz-based aerogels in various domains such as adsorption (including wastewater treatment, CO 2 capture, and microwave adsorption), thermal insulation, energy storage as well as sensors are covered in detail. Furthermore, several obstacles and potential directions for subsequent research are delineated with a view to surmounting the prevailing constraints and achieving a realization of the shift from experimental exploration to practical applications. [Display omitted] • Polybenzoxazine (PBz) aerogels present a wide-ranging potential for applications as emerging high-performance materials. • Elaborate summaries of preparation routes for PBz aerogels. • The microscopic morphology of PBz aerogels can be modulated through colloid chemistry principles. • Comprehensive introduction of composite and hybrid materials based on PBz aerogels. • Challenges and potential development directions faced by PBz aerogels. [ABSTRACT FROM AUTHOR]

• A boric acid-regulated sol–gel transition strategy is used to achieve modulation of the morphology. • Ethanol is employed as a green solvent for the preparation of boron-doped polybenzoxazine (BPBz) aerogels. • The introduction of boric acid provides multifunctional properties to BPBz aerogels. • The BPBz aerogels exhibit intrinsic and alterable wettability that correlates with their morphologies. Polybenzoxazine aerogels have gained widespread attention in recent years, but the prevalent use of hazardous solvents in the preparation process has severely impeded their further development and promotion for practical applications. Herein, using ethanol as a solvent, a strategy of boric acid-induced microstructure regulation is proposed to construct boron-doped polybenzoxazine (BPBz) aerogels, which provides a feasible approach to overcome the above situation. The introduction of boric acid enhances the backbone strength by forming intermolecular bridged structures between PBz chains and allows the use of ambient pressure drying. The resulting BPBz aerogel demonstrates high stiffness (specific modulus up to 255.97 kN·m·kg−1), low bulk density (0.203 g·cm−3), and low thermal conductivity (0.043 W·m−1·K−1), exhibiting excellent fire resistance when exposed to a 1200 °C flame (the self-extinguishing interval less than 1 s). More interestingly, the aerogel demonstrates intrinsic and tunable wettability that correlates with the morphology. Combining the environmentally friendly preparation strategy and these advantages, BPBz aerogels hold promise for thermal management and fire protection applications in energy-saving construction and other harsh conditions. [ABSTRACT FROM AUTHOR]

Bone loss remains a major health concern for astronauts during space flight. Increased osteoclast activity is one of the main causes of bone loss in astronauts subjected to microgravity conditions. However, the underlying molecular mechanisms remain unclear. Microtubule actin crosslinking factor 1 (MACF1) has been implicated in the regulation of cytoskeletal distribution, cell migration, and cell differentiation. Our previous studies have shown that MACF1 promotes the differentiation of pre-osteoclasts. However, whether MACF1 regulates the migration and cytoskeletal arrangement of pre-osteoclasts under microgravity conditions has not yet been elucidated. In this study, we used a hind-limb unloading (HLU) mouse model and a random positioning machine (RPM) to simulate the effects of microgravity on pre-osteoclasts. In the HLU mouse model, the expression of MACF1 was upregulated in primary pre-osteoclasts of mice, accompanied by enhanced migration in vivo. Moreover, simulated microgravity using the RPM also promoted MACF1 expression and migration of pre-osteoclasts in vitro. Additionally, knockdown of MACF1 disrupted cytoskeletal arrangement (F-actin and microtubules) and further inhibited the migration of pre-osteoclasts via the RhoA/ROCK1 signaling pathway. We further demonstrated that knockdown of MACF1 disrupted the enhanced migration and cytoskeleton arrangement of pre-osteoclasts induced by simulated microgravity. These data demonstrate that MACF1 positively regulates the migration and cytoskeletal organization of pre-osteoclasts under simulated microgravity, suggesting that MACF1 may be a therapeutic target for the treatment of bone loss induced by microgravity. • MACF1 is a microgravity sensitive gene. • Simulated microgravity induced MACF1 expression and migration of pre-osteoclasts. • MACF1 knockdown attenuated the cytoskeleton arrangement of pre-osteoclasts. • MACF1 knockdown inhibited the migration via the RhoA/Rock1 pathway. • MACF1 knockdown prevented the migration and cytoskeleton arrangement of pre-osteoclasts induced by simulated microgravity. [ABSTRACT FROM AUTHOR]

The lightweight ablation materials that have been successfully applied in thermal protection systems (TPS) are the focus of attention owing to the urgent demand for aerospace vehicles to have efficient thermal insulation materials with lightweight, long-term antioxidant, and micro-ablation. However, improving the antioxidant ablation properties in a long-term aerobic atmosphere is still a significant challenge. Herein, a novel strategy to fabricate needle quartz fiber (NQF) reinforced SiO 2 aerogel interpenetrating polybenzoxazine (PBO) aerogel thermal protection composites (NQF/SiO 2 –PBOs) with a binary network structure is proposed. The as-prepared NQF/SiO 2 –PBOs perfectly inherited their porous nanostructure and captivating properties, including lightweight (0.53 g/cm3), high mechanical strengths, and low thermal conductivity of 0.048 W/(m·K) at 25 °C and 0.079 W/(m·K) at 1100 °C. Moreover, the NQF/SiO 2 –PBOs exhibited outstanding high-temperature thermal insulation and long-time antioxidant ablation with low linear and mass ablation rates. The cold surface temperature peaked at approximately 307.2 °C within 1800 s when the hot surface temperature exceeded 1100 °C. The ablation/thermal insulation mechanism was also discussed through the analysis of the microstructure, chemical structure, and crystal structure. This research provides a meaningful reference for the development and exploitation of new advanced lightweight, long-term antioxidant, and micro-ablative thermal protective materials. [ABSTRACT FROM AUTHOR]

Polybenzoxazine (PBO) aerogels were prepared from 4,4′-diamino-diphenylmethane (MDA) benzoxazine monomer by HCl-catalyzed ring-opening polymerization at room temperature after CO2 supercritical drying. This study systematically analyzes the microstructures, thermal insulation properties, compressive properties, and thermal stabilities of the PBO aerogels. The aerogel structure was a cross-linked three-dimensional network with a pore size of 10–140 nm. The conductivity of the aerogels was 0.035–0.057 W/m K under ambient conditions, reducing to 0.009 W/m K at 3 Pa. The compressive strength reached 14.42 MPa under 10% strains, much greater than in SiO2 aerogels of similar density (0.40 g/cm3) reinforced by high-silica glass fiber, which is only 1.30 MPa. Hydrogen bonding interaction was found to be critical for constructing the three-dimensional network structure of the aerogels. This work provides a valuable reference for exploring new structures and expanding the thermal insulation applications of PBO aerogels. [ABSTRACT FROM AUTHOR]

[Display omitted] • The facile preparation of PBz aerogel with excellent thermal insulation performance is realized. • The char yields of PBz aerogel reach 55.00 % at 600 °C. • The obtained PBz aerogel demonstrates a low thermal conductivity of 0.0313 W m−1 K−1 at 25 °C. • The obtained PBz aerogel exhibits super-hydrophobicity and outstanding mechanical properties. Polybenzoxazine (PBz) aerogels with outstanding mechanical properties and thermal insulation have attracted significant attention because of their classification as the most advanced and efficient thermal insulation material. However, the complex and environmentally unfriendly preparation technology has consistently hindered the performance improvement and broad practical applications of PBz aerogels. Herein, we report a facile preparation method of PBz aerogels through an aqueous solution system and ambient pressure drying (APD), thereby overcoming the limitations of the conventional methods. The resulting PBz aerogel exhibits lightweight (0.194 g cm−3), efficient thermal insulation, low thermal conductivity (0.0313 W m−1 K−1), self-extinguishing, super-hydrophobicity (contact angle of 148°), and remarkable mechanical properties. This study proposes a cutting-edge approach to fabricate PBz aerogels, which further amplifies their potential application in the field of thermal insulation. [ABSTRACT FROM AUTHOR]

Background/aim: This study aimed to compare neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) with primary debulking surgery (PDS) followed by chemotherapy in patients with advanced ovarian carcinoma International Federation of Gynecology and Obstetrics (FIGO) stages IIIc and IV.Methods: PubMed, the Cochrane Library, and manual searches were applied to discriminate potentially eligible studies published before June 30, 2016.Results: A total of 12 comparative studies were finally included; 1,372 patients underwent NAC followed by IDS, and 2,680 patients underwent PDS followed by chemotherapy. For overall pooled estimates, significant between-trial differences were found in the optimal debulking rate, grade 3-5 postoperative adverse reactions, and median overall survival (OS), but no difference was found in the median progression-free survival (PFS). Moreover, a significantly higher incidence was identified in major infections, vascular events, and wound complications for patients in the PDS group.Conclusions: This study suggested that NAC followed by IDS could improve the optimal debulking rate and decrease the postoperative adverse reactions for the current studies, but whether it could improve the OS and PFS compared with PDS followed by chemotherapy in patients with ovarian carcinoma FIGO stages IIIc and IV were still needed to be verified by conducting more randomized controlled trials. [ABSTRACT FROM AUTHOR]

Spectraplakins are a family of evolutionarily conserved gigantic proteins and play critical roles in many cytoskeleton-related processes. Microtubule actin crosslinking factor 1 (MACF1) is one of the most versatile spectraplakin with multiple isoforms. As a broadly expressed mammalian spectraplakin, MACF1 is important in maintaining normal functions of many tissues. The loss-of-function studies using knockout mouse models reveal the pivotal roles of MACF1 in embryo development, skin integrity maintenance, neural development, bone formation, and colonic paracellular permeability. Mutation in the human MACF1 gene causes a novel myopathy genetic disease. In addition, abnormal expression of MACF1 is associated with schizophrenia, Parkinson’s disease, cancer and osteoporosis. This demonstrates the crucial roles of MACF1 in physiology and pathology. Here, we review the research advances of MACF1’s roles in specific tissue and in human diseases, providing the perspectives of MACF1 for future studies. [ABSTRACT FROM AUTHOR]

Porous silicon oxycarbide (SiCO) aerogel monoliths were prepared by the sol-gel method using Tetraethylortosilicate/Polydimethylsiloxane as organic-inorganic precursors. The precursor gels were dried by supercritical ethanol fluid and pyrolyzed at 1200 °C in nitrogen atmosphere to form SiCO aerogels. The as-prepared SiCO aerogels are amorphous and present a network microstructure, surface area of 198.04 m 2 /g, average pore diameter of 56 nm, and pore volume of 0.648 cm 3 /g. The thermal conductivity of aerogel monoliths is only 0.027 W/m·K at 25 °C (Hot disk method). The atom ratios of Si, C, O elements in the SiCO aerogels are 30.77%, 14.67%, 54.56% respectively. The network microstructure of the SiCO aerogels are retained until 1100 °C, and the chemical groups and crystal phase structures are kept up until 1200 °C. There is only 1.65% of weight-loss until the same heated at 1200 °C in air, which is one of the highest thermally stable temperatures for SiCO aerogels ever reported. [ABSTRACT FROM AUTHOR]

By using a simple solution chemistry approach with polyvinyprrolidone (PVP) as a capping agent, Mn2W(CN)8 · xH2O microcrystals with unique morphologies including rice-like, rod, octahedron, square platelet, and hollow-core square platelet have been successfully synthesized. The influence of experimental parameters such as reaction temperature, feed ratio of Mn2+ to PVP, reaction time, and reactant concentration on the morphology and size of Mn2W(CN)8 · xH2O microcrystals were systematically investigated. The reaction temperature proved to be a key factor for morphological evolution of the products. It was found that 20, 55, and 85 °C were key points of morphological transformation. A possible growth mechanism of the Mn2W(CN)8 · xH2O microcrystals is proposed. [ABSTRACT FROM AUTHOR]

Objective: To analyze the pregnancy outcomes of patients with cervical lesions treated by cold-knife conization (CKC). Methods: Clinical data of healthy pregnant women and pregnant women who underwent CKC in Dalian Women and Children's Medical Group from March 2010 to December 2019 were retrospectively analyzed. These patients were divided into a CKC group and a control group according to inclusion and exclusion criteria. Statistical methods were used to compare pregnancy and delivery outcomes between the two groups. Results: There were 400 patients in CKC group and control group, with 200 patients in each. There was no significant difference in the mode of delivery, abortion, ectopic pregnancy, in-hospital perinatal management, and cervical cerclage between the CKC group and the control group (P>0.05). The rates of preterm delivery, premature rupture of membranes, cesarean section, and neonatal admission in the CKC group were higher than those in the control group (P<0.05). In the CKC group, the incidence of premature rupture of membranes within six months postoperatively was higher than that after six months (P<0.05). The incidences of preterm delivery and premature rupture of membranes were not completely consistent in different conization ranges (P<0.05). Conclusion: CKC increases the incidence of preterm delivery, premature rupture of membranes, and neonatal adverse outcomes. Conization height can predict the occurrence of preterm delivery. Delaying pregnancy after surgery can reduce the incidence of adverse outcomes during the perinatal period. [ABSTRACT FROM AUTHOR]

The preparation of novel polymer aerogel materials with enhanced flame-retardancy, superior thermal insulation and mechanical strength is of great practical significance in energy-savings and fire-prevention for buildings. Herein, we reported the fiber-reinforced polybenzoxazine (PBO) aerogel composites with flame retardance and thermal insulation, which were prepared under room temperature and atmospheric pressure, and using 4,4′-diaminodiphenlymethane (MDA) benzoxazine monomer as the raw material and oxalic acid (OA) as the catalyst. Several outstanding attributes were achieved in the aerogel composites, such as relatively low thermal conductivity (0.069 W/m·K at 105 Pa, 0.031 W/m·K at 5 Pa), high limiting oxygen index (LOI) up to 32.5, and enhanced mechanical properties. It can be compressed to more than 80% of the deformation without obvious cracks, and shows high compressive modulus and specific modulus (20.69 MPa and 5.05 × 104 N·m/Kg, respectively). All the excellent comprehensive properties mean that fiber-reinforced PBO aerogel composites have broad application prospects in the fields of flame retardancy and thermal insulation. [ABSTRACT FROM AUTHOR]

Osteoclasts are responsible for bone resorption and play essential roles in causing bone diseases such as osteoporosis. Microtubule actin crosslinking factor 1 (MACF1) is a large spectraplakin protein that has been implicated in regulating cytoskeletal distribution, cell migration, cell survival and cell differentiation. However, whether MACF1 regulates the differentiation of osteoclasts has not been elucidated. In this study, we found that the expression of MACF1 was increased in primary bone marrow-derived monocytes (BMMs) of osteoporotic mice and was downregulated during receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis of pre-osteoclast cell lines RAW264.7 cells. RAW264.7 cells were transfected with shMACF1 using a lentiviral vector to study the role of MACF1 in osteoclastogenic differentiation. Knockdown of MACF1 in RAW264.7 cells inhibited the formation of multinucleated osteoclasts and decreased the expression of osteoclast-marker genes (Ctsk , Acp5 , Mmp9 and Oscar) during RANKL-induced osteoclastogenesis. Additionally, knockdown of MACF1 disrupted actin ring formation in osteoclasts and further blocked the bone resorption activity of osteoclasts by reducing the area and depth of pits. Knockdown of MACF1 had no effect on the survival of pre-osteoclasts and mature osteoclasts. We further established that knockdown of MACF1 attenuated the phosphorylation of Akt and GSK3β and inhibited the expression of its downstream target NFATc1. Akt activator rescued the inhibition of osteoclast differentiation by MACF1 knockdown. These data demonstrate that MACF1 positively regulates osteoclast differentiation via the Akt/GSK3β/NFATc1 signalling pathway, suggesting that targeting MACF1 may be a novel therapeutic approach against osteoporosis. • MACF1 knockdown inhibited RANKL-induced osteoclast differentiation and activity. • MACF1 knockdown has no effect on the survival of pre-osteoclasts and mature osteoclasts. • MACF1 knockdown attenuated the phosphorylation of Akt and GSK3β induced by RANKL. • MACF1 knockdown attenuated RANKL-induced osteoclast differentiation by regulating the Akt/GSK3β/NFATc1 signalling pathway. [ABSTRACT FROM AUTHOR]

Polybenzoxazine (PBO) aerogels with low densities and low thermal conductivities are prepared from Bisphenol A (BPA) benzoxazine monomers by ring‐opened polymerisation using HCl as a catalyser at 10 °C. The obtained PBO aerogels have cross‐linked and 3D network structures with the densities ranging from 0.084 to 0.526 g cm−3. The thermal conductivities under different pressures (3–105 Pa, air) and different atmospheres (N2, Ar, and CO2, 105 Pa) are investigated. The thermal conductivities are in the range of 0.0335–0.0652 W m K−1 under ambient pressure and 0.0098–0.0571 W m K−1 at 3 Pa. The thermal transfer mechanism under different gas pressures is analyzed with increasing pressure. Under different atmospheres, the thermal conductivities decrease as the molecular weight of the gas increases. Compared with the traditional organic foam insulating materials of phenolic foam, polyurethane and polystyrene, which have similar apparent densities, PBO aerogels exhibit lower thermal conductivity of 0.0335 W m K−1 than that of traditional organic foam at room temperature. [ABSTRACT FROM AUTHOR]

Polybenzoxazine/Melamine (PBa/MS) double network aerogels were prepared using melamine foam (MS) as the backbone and bisphenol A-type benzoxazine (Ba) as the maxtrix. The effect of Ba concentration in the sol-gel on the performance of the double network aerogel was investigated. During the combustion, the PBa/MS composite aerogel exhibited self-extinguishing performance. Compared with PBa-18%, the contact angle of PBa-18%/MS composite aerogel was 18° higher, and the heat release peak (PHRR) and total smoke production (TSP) of the composite aerogel decreased by 7% and 39%, respectively. These values indicate that MS can significantly reduce the release of heat and smoke from the PBa aerogel, thus improving its flame retardancy. In addition, the composite aerogel formed a denser and more complete carbon layer during combustion, which blocks both heat and mass transfer. Thus, the resulting PBa/MS dual-network composite aerogels obtained in the current work are expected to meet the demands for flame-retardant, hydrophobic thermal insulation materials in many fields. [Display omitted] • Benzoxazine/melamine composite aerogel has a double network structure. • Aerogels was prepared through drying at normal temperature and pressure. • Aerogel owned the properties of flame retardancy, smoke suppression, resilience, heat insulation and hydrophobic properties. • The composite aerogel has good thermal insulation at 200 ℃. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is fast‐growing and highly metastatic with the poorest prognosis among the breast cancer subtypes. Inactivation of glycogen synthase kinase 3 beta (GSK3β) plays a vital role in the aggressiveness of TNBC; however, the underlying mechanism for sustained GSK3β inhibition remains largely unknown. Here, we find that protein phosphatase 1 regulatory inhibitor subunit 14C (PPP1R14C) is upregulated in TNBC and relevant to poor prognosis in patients. Overexpression of PPP1R14C facilitates cell proliferation and the aggressive phenotype of TNBC cells, whereas the depletion of PPP1R14C elicits opposite effects. Moreover, PPP1R14C is phosphorylated and activated by protein kinase C iota (PRKCI) at Thr73. p‐PPP1R14C then represses Ser/Thr protein phosphatase type 1 (PP1) to retain GSK3β phosphorylation at high levels. Furthermore, p‐PPP1R14C recruits E3 ligase, TRIM25, toward the ubiquitylation and degradation of non‐phosphorylated GSK3β. Importantly, the blockade of PPP1R14C phosphorylation inhibits xenograft tumorigenesis and lung metastasis of TNBC cells. These findings provide a novel mechanism for sustained GSK3β inactivation in TNBC and suggest that PPP1R14C might be a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Chitosan aerogels could be applied potentially in thermal insulation for energy-saving buildings, separation/adsorption, and catalysis. However, disadvantages of chitosan aerogels include their hydrophilicity and low insufficient mechanical strength. Here we propose a silica-phase hybriding route to create chitosan/silica hybrid aerogels with a synergistic capability for favourable hydrophobicity and superior mechanical strength, demonstrating an emergent finding (hydrophobicity optimised with the improved mechanical strength). The aerogels exhibit low drying shrinkage (as low as 13.41 %), lightweight (lowest to 0.149 g cm−1), high-efficient thermal insulation (thermal conductivity as low as to 0.024 W m−1 K−1 at room temperature and normal pressure) either under cryogenic (−196 °C) or high-temperature conditions, exceptional fire-retardancy (self-extinguishing in 1.8 s) and environmentally friendly characteristic (initial mineralisation after 10 d). High hydrophobic property (water contact angle up to 142°) of the aerogels were achieved depending upon 1H, 1H, 2H, 2H-perfluorodecyltriethoxysilane of vapor deposition, presenting a discovery concerning substantial improvement of mechanical properties (up to 0.188 MPa at 5 % strain, increased by 25 %). Furthermore, we demonstrate that a plausible mechanism for simultaneous hydrophobic and mechanical enhancement is depending upon the modulation of networking skeletons at the nanoscale. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: HOMER family scaffolding proteins (HOMER1-3) play critical roles in the development and progression of human disease by regulating the assembly of signal transduction complexes in response to extrinsic stimuli. However, the role of HOMER protein in breast cancer remains unclear. Methods: HOMER3 expression was examined by immunohistochemistry in breast cancer patient specimens, and its significance in prognosis was assessed by Kaplan–Meier survival analysis. The effects of HOMER3 in growth factor-induced β-Catenin activation were analyzed by assays such as TOP/FOP flash reporter, tyrosine phosphorylation assay and reciprocal immunoprecipitation (IP) assay. Role of HOMER3 in breast cancer metastasis was determined by cell function assays and mice tumor models. Results: Herein, we find that, among the three HOMER proteins, HOMER3 is selectively overexpressed in the most aggressive triple negative breast cancer (TNBC) subtype, and significantly correlates with earlier tumor metastasis and shorter patient survival. Mechanismly, HOMER3 interacts with both c-Src and β-Catenin, thus providing a scaffolding platform to facilitate c-Src-induced β-Catenin tyrosine phosphorylation under growth factor stimulation. HOMER3 promotes β-Catenin nuclear translocation and activation, and this axis is clinically relevant. HOMER3 promotes and is essential for EGF-induced aggressiveness and metastasis of TNBC cells both in vitro and in vivo. Conclusion: These findings identify a novel role of HOMER3 in the transduction of growth factor-mediated β-Catenin activation and suggest that HOMER3 might be a targetable vulnerability of TNBC. [ABSTRACT FROM AUTHOR]

Cyst(e)ine is a key precursor for the synthesis of glutathione (GSH), which protects cancer cells from oxidative stress. Cyst(e)ine is stored in lysosomes, but its role in redox regulation is unclear. Here, we show that breast cancer cells upregulate major facilitator superfamily domain containing 12 (MFSD12) to increase lysosomal cyst(e)ine storage, which is released by cystinosin (CTNS) to maintain GSH levels and buffer oxidative stress. We find that mTORC1 regulates MFSD12 by directly phosphorylating residue T254, while mTORC1 inhibition enhances lysosome acidification that activates CTNS. This switch modulates lysosomal cyst(e)ine levels in response to oxidative stress, fine-tuning redox homeostasis to enhance cell fitness. MFSD12-T254A mutant inhibits MFSD12 function and suppresses tumor progression. Moreover, MFSD12 overexpression correlates with poor neoadjuvant chemotherapy response and prognosis in breast cancer patients. Our findings reveal the critical role of lysosomal cyst(e)ine storage in adaptive redox homeostasis and suggest that MFSD12 is a potential therapeutic target. [Display omitted] • Lysosomal cyst(e)ine storage and release maintains GSH levels for ROS buffering • MFSD12 is phosphorylated by mTORC1 at T254 to control lysosomal cyst(e)ine storage • MFSD12-T254A mutant acts as a dominant-negative inhibitor of MFSD12 functions • MFSD12 upregulation induces chemoresistance and poor prognosis in breast cancer He et al. report that MFSD12 upregulation in breast cancer increases the lysosomal cyst(e)ine storage, providing a ready source of cyst(e)ine for GSH synthesis, which is regulated by mTORC1 to fine-tune redox homeostasis and enhance cell fitness. [ABSTRACT FROM AUTHOR]

Highly transparent magneto-optical (MO) glasses (heavily xTb-doped SiO 2 -B 2 O 3 -P 2 O 5 -ZnO-ZrO, x = 15, 25, 32, 35, 40 mol%) were prepared by high temperature melting-quenching technique. The optical and magnetooptical properties have been measured at room temperature. The infrared transmission spectra and XRD confirms that [BO 4 ], [BO 3 ], [SiO 4 ], [PO 4 ], [BPO 4 ] units the glass structure without crystallization by accommodating more Tb ions. The typical absorption bands could be observed in the UV–vis transmission spectra ascribing to 5d–4f electronic transition of Tb 3+ and the absorption edges shift to a longer wavelength by increasing the Terbium ions content. The intensity of the emission peaks and decay time which is in the order of milliseconds decreases caused by concentration quenching. The cross-relaxation is responsible for the luminescence gradually disappearing of 5 D 3 . The highest Verdet constant of the prepared glasses at room temperature @632.8 nm is −136.648 rad/T/m and the contribution V/N of each ion Tb is proportional to mole volume. [ABSTRACT FROM AUTHOR]

Polybenzoxazine (PBZ) aerogels are potential thermal insulation and ablative material for thermal protection system in aerospace. However, obtaining the excellent properties of thermal insulation and compression strength remain a formidable challenge at an extreme temperature. Here we proposed a new strategy by optimizing the nanoporous networking structure and pore size distribution to prepare PBZ aerogel (PAs-Fx), which could be self-extinguished in 0.24 s only once departing the outer flame, and the compressive stress of PAs–F10 reached up to 6.62 MPa at the strain of 10%. PAs–F10 presented great advantage in thermal insulation property (although the hot surface existed in the atmosphere at 302.4 °C, the temperature of cold surface remained at only 112.4 °C when heat flow was stable). Even burning the hot surface with 1200 °C outer flames for 30 min, the highest temperature of the cold surface only reached 254 °C at the heat balance state, moreover, the prominent shape-keeping property was confirmed after ultra-high temperature burning. We also found that PAs–F10 has superior compressive strengths which are 5.52 and 9.38 MPa at 10% strain in the conditions of ambient temperatures for 150 and −50 °C, respectively. PAs-Fx could also retain the excellent compression property after treating cryogenically in liquid nitrogen (−196 °C). The work would be a great promise in the application of ablative thermal insulation materials in a great measure in the future. [Display omitted] • The PAs-Fx aerogels behave abundant nanoporous networking structure, good thermal insulation properties, flame retardancy feature. • PAs–F10 behave excellent thermal insulation property in extreme high temperature environment (1200 °C). • This is the first report on the compression properties of PBZ aerogels in extreme environments (150 and −50 °C). • PAs-Fx aerogels could also retain the excellent compression property after treating cryogenically in liquid nitrogen (−196 °C). [ABSTRACT FROM AUTHOR]

[Display omitted] • Polybenzoxazine aerogels with excellent thermal insulation property were fabricated by Lewis acid catalysis. • The self-extinguishing performance of PBz aerogels could be obtained apparently. • The aerogels as-prepared possessed a three-dimensional networking structure in the range of 20–140 nm. Polybenzoxazine aerogel is a new polymer aerogel material developed in recent years, which the ring-opening polymerization of benzoxazine monomer under high temperature or HCl could achieve the formation of cross-linked three-dimensional network structure so that to further reduce the cost of preparation. However, HCl as a catalyst has the disadvantages of easy volatilization and corrosion. Here we introduced Lewis acid as the catalyst for fabricating nanoporous polybenzoxazine aerogels with low density and self-extinguishing properties depending upon the evolution law for the influence of the mixed ratio of Lewis acid and hydrochloric acid (volume ratio) on the corresponding aerogels. The results show that PBz aerogels prepared in the mixed acid environment (with n -hexane as the exchange solvent) have a good three-dimensional nanopore network structure, and the pore size distribution is in the range of 20–140 nm. Additionally, the obvious self-extinguishing performance (even exposing to a flame at 1200 °C), low density and excellent mechanical properties are reflected as well, potentially suggesting the broad application prospects in the field of aerospace. [ABSTRACT FROM AUTHOR]

• PEITC inhibits the invasion and migration of colorectal cancer cells. • PEITC suppresses the EMT of colorectal cancer cells. • PEITC blocks the TGF-β1/Smad signaling pathway and TGF-β1 induced EMT. • PEITC might serve as a novel therapeutic agent with potent anti-cancer effects. Tumor metastasis is the leading cause of death in patients with colorectal cancer (CRC), in which epithelial-mesenchymal transition(EMT) plays a vital role. However, the exact mechanisms of this process remain largely unknown. The aim of the present study was to determine the role of phenethyl isothiocyanate (PEITC) in CRC metastasis by regulating EMT. Wound healing assays and Transwell matrix assays were used to evaluate the potential of PEITC to inhibit CRC cells invasion and migration in vitro. Western blotting, light microscopy and immunofluorescence assays were used to detect the occurrence of EMT. Luciferase activity assay, real time-PCR and western blotting were used to investigate TGF-β1/Smad signaling activity. We observed that PEITC, an isothiocyanate compound from crucifer with chemopreventive potential, inhibited the invasion and migration of CRC cells. Moreover, we showed that PEITC regulated the EMT of CRC cells. Additionally, we demonstrated that PEITC blocked the activation of the TGF-β1/Smad pathway and significantly suppressed TGF-β1-induced EMT. Our results suggested that PEITC plays a crucial role in inhibiting the invasion and migration of CRC cells by regulating TGF-β1-induced EMT. The results of the present study provide a theoretical basis for the use of PEITC to treat CRC. [ABSTRACT FROM AUTHOR]

Silica aerogels with different particle size were prepared by monodispersed silica sol for the first time. The properties of the silica aerogels under normal and high temperature were systematically studied. Among the four different particle size aerogels, the SA-2 sample consisted of 20.31 ± 1.21 nm particles with narrow size distribution had high temperature resistance and low thermal conductivity. Compared with the traditional acid-base two-step prepared silica aerogels, the monodisperse silica aerogels can significantly increase the temperature resistance while maintaining a low thermal conductivity (0.02723 W·m−1·K−1). The sturdy skeleton structure formed by the interconnection of large particles can effectively inhibit the viscous flow between aerogel particles and avoid pore collapse caused by skeleton failure which can maintain a stable structure until 900 °C and retain a relatively complete structure at 1000 °C with only about 35% volume shrinkage after 2 h heat treatment. At 1100 °C, the viscous flow between aerogel particles and pore collapse cannot be effectively suppressed, and the pure silica aerogels can only be used during a short period at 1100 °C. The results will be meaningful for the design of super thermal insulation materials with high temperature resistance and low thermal conductivity. Unlabelled Image • SiO 2 aerogels with high temperature resistance are prepared by controllable particle size monodispersed silica sol. • Thermal conductivity of SiO 2 aerogels is as low as 0.02723 W·m−1·K−1 despite forming large particle structure. • The aerogel large particle skeleton structure can inhibit the viscous flow between aerogel particles. • Pore collapse caused by skeleton failure can be obviously inhibited depending on formed sturdy skeletons. [ABSTRACT FROM AUTHOR]