POU6F1 promotes ferroptosis by increasing lncRNA-CASC2 transcription to regulate SOCS2/SLC7A11 signaling in gastric cancer.

OBJECTIVE: This study investigated the effect and mechanism of POU6F1 and lncRNA-CASC2 on ferroptosis of gastric cancer (GC) cells. METHODS: GC cells treated with erastin and RSL3 were detected for ferroptosis, reactive oxygen species (ROS) level, and cell viability. The expression levels of POU6F1, lncRNA-CASC2, SOCS2, and ferroptosis-related molecules (GPX4 and SLC7A11) were also measured. The regulations among POU6F1, lncRNA-CASC2, FMR1, SOCS2, and SLC7A11 were determined. Subcutaneous tumor models were established, in which the expressions of Ki-67, SOCS2, and GPX4 were detected by immunohistochemistry. RESULTS: GC patients with decreased expressions of POU6F1 and lncRNA-CASC2 had lower survival rate. Overexpression of POU6F1 or lncRNA-CASC2 decreased cell proliferation and GSH levels in GC cells, in addition to increasing total iron, Fe2+, MDA, and ROS levels. POU6F1 directly binds to the lncRNA-CASC2 promoter to promote its transcription. LncRNA-CASC2 can target FMR1 and increase SOCS2 mRNA stability to promote SLC7A11 ubiquitination degradation and activate ferroptosis signaling. Knockdown of SOCS2 inhibited the ferroptosis sensitivity of GC cells and reversed the effects of POU6F1 and lncRNA-CASC2 overexpression on ferroptosis in GC cells. CONCLUSION: Transcription factor POU6F1 binds directly to the lncRNA-CASC2 promoter to promote its expression, while upregulated lncRNA-CASC2 increases SOCS2 stability and expression by targeting FMR1, thereby inhibiting SLC7A11 signaling to promote ferroptosis in GC cells and inhibit GC progression.

Robust structured light 3D measurement method based on polarization-encoded projection patterns.

Fringe projection profilometry (FPP) is widely used in 3D vision measurement because of its high robustness and measurement accuracy. In the case of HDR objects, due to the problem of surface reflectivity, the obtained image will be overexposed. This will cause the sinusoidality of the fringes projected on the surface of the object in the acquired image to be interfered, resulting in a phase error in the calculated wrapped phase. Therefore, a polarization-encoded sinusoidal structured light is proposed to enhance the sinusoidality of the fringe. The phase information contained in the polarized sinusoidal structured light fringe is only related to the polarization state, not to the light intensity. A polarization coding assisted structured light measurement strategy (PASM) is proposed. This method uses polarization coding assisted polarization phase-shifting fringes for phase unwrapping. The angle of the linear polarizer is set to zero in this method, and it does not require rotating the polarizer. It only needs a single exposure to improve the fringe quality and obtain a more stable unwrapping phase. The experimental results show that the obtained polarization fringes have better sinusoidality, and the phase unwrapping can be more accurate. The reconstructed 3D point cloud also does not appear missing and has better accuracy. It is a reliable method for vision measurement of HDR objects.

Critical Contribution of Imbalanced Charge Loss to Performance Deterioration of Si-Based Lithium-Ion Cells during Calendar Aging.

Increasing the energy density of lithium-ion batteries, and thereby reducing costs, is a major target for industry and academic research. One of the best opportunities is to replace the traditional graphite anode with a high-capacity anode material, such as silicon. However, Si-based lithium-ion batteries have been widely reported to suffer from a limited calendar life for automobile applications. Heretofore, there lacks a fundamental understanding of calendar aging for rationally developing mitigation strategies. Both open-circuit voltage and voltage-hold aging protocols were utilized to characterize the aging behavior of Si-based cells. Particularly, a high-precision leakage current measurement was applied to quantitatively measure the rate of parasitic reactions at the electrode/electrolyte interface. The rate of parasitic reactions at the Si anode was found 5 times and 15 times faster than those of LiNi0.8Mn0.1Co0.1O2 and LiFePO4 cathodes, respectively. The imbalanced charge loss from parasitic reactions plays a critical role in exacerbating performance deterioration. In addition, a linear relationship between capacity loss and charge consumption from parasitic reactions provides fundamental support to assess calendar life through voltage-hold tests. These new findings imply that longer calendar life can be achieved by suppressing parasitic reactions at the Si anode to balance charge consumption during calendar aging.

Reversible Iron Oxyfluoride (FeOF)-Graphene Composites as Sustainable Cathodes for High Energy Density Lithium Batteries.

Two large barriers are impeding the wide implementation of electric vehicles, namely driving-range and cost, primarily due to the low specific energy and high cost of mono-valence cathodes used in lithium-ion batteries. Iron is the ideal element for cathode materials considering its abundance, low cost and toxicity. However, the poor reversibility of (de)lithiation and low electronic conductivity prevent iron-based high specific energy multi-valence conversion cathodes from practical applications. In this work, a sustainable FeOF nanocomposite is developed with extraordinary performance. The specific capacity and energy reach 621 mAh g-1 and 1124 Wh kg-1 with more than 100 cycles, which triples the specific capacity, and doubles the specific energy of current mono-valence intercalation LiCoO2 . This is the result of an effective approach, combing the nanostructured FeOF with graphene, realized by making the (de)lithiation reversible by immobilizing FeOF nanoparticles and the discharge products over the graphene surface and providing the interparticle electric conduction. Importantly, it demonstrates that introducing small amount of graphene can create new materials with desired properties, opening a new avenue for altering the (de)lithiation process. Such extraordinary performance represents a significant breakthrough in developing sustainable conversion materials, eventually overcoming the driving range and cost barriers.

Optimal Microstructure of Silicon Monoxide as the Anode for Lithium-Ion Batteries.

Because of its metastable nature, silicon monoxide (SiO) consists of Si nanodomains in an amorphous matrix of SiO2. The microstructure of SiO, including SiO2, Si domains, and interphase (SiOx) between domains, was modified via an annealing treatment in argon gas and thoroughly characterized by in-situ and ex-situ X-ray diffraction, pair distribution function, and electron energy loss spectroscopy. Two microstructure transformation routes were observed during the annealing process: (1) at a temperature of <800 °C, the annealing treatment was found to affect mainly the structural conformation of the amorphous SiO2 matrix and the interphase, while (2) an annealing temperature of >800 °C led to significant Si nanodomain growth. We found that the microstructure has a great impact on the electrochemical performance of SiO. The optimized microstructure of SiO appears to be achieved through annealing treatment at 800 °C or less, which results in interphase (SiOx) reduction without causing significant Si domain growth. This work provides a deep insight into the domain and interphase transformation of SiO upon heat treatment. The improved understanding of the relationship between SiO microstructure and its electrochemical behavior will enable proper design and development of high-energy SiO for lithium-ion batteries.

Long-Cycling Sulfide-Based All-Solid-State Batteries Enabled by Electrochemo-Mechanically Stable Electrodes.

The anode plays a critical role relating to the energy density in all-solid-state lithium batteries (ASLBs). Silicon (Si) and lithium (Li) metal are two of the most attractive anodes because of their ultrahigh theoretical capacities. However, most investigations focus on Li metal, leaving the great potential of Si underrated. This work investigates the stability, processability, and cost of Si anodes in ASLBs and compares them with Li metal. Moreover, single-crystal LiNi0.8 Mn0.1 Co0.1 O2 is stabilized with lithium silicate (Li2 SiOx ) through a scalable sol-gel method. ASLBs with a cell-level energy density of 285 Wh kg-1 are obtained by sandwiching the Si anode, the thin sulfide solid-state electrolyte membrane, and the interface stabilized LiNi0.8 Mn0.1 Co0.1 O2 . The full cell delivers a high capacity of 145 mAh g-1 at C/3 and maintains stability for 1000 cycles. This work inspires commercialization of ASLBs on a large scale with exciting manufacturing lines for large-scale, safe, and economical energy storage.

Editorial for focus on nanophase materials for next-generation lithium-ion batteries and beyond.

Lithium-ion batteries (LIBs) have revolutionized our society in many respects, and we are expecting even more favorable changes in our lifestyles with newer battery technologies. In pursuing such eligible batteries, nanophase materials play some important roles in LIBs and beyond technologies. Stimulated by their beneficial effects of nanophase materials, we initiated this Focus. Excitingly, this Focus collects 13 excellent original research and review articles related to the applications of nanophase materials in various rechargeable batteries, ranging from nanostructured electrode materials, nanoscale interface tailoring, novel separators, computational calculations, and advanced characterizations.

Insights into the Li Diffusion Mechanism in Si/C Composite Anodes for Lithium-Ion Batteries.

Recently, Si/C composite materials have attracted enormous research interest as the most promising candidates for the anodes of next-generation lithium-ion batteries, owing to their high energy density and mechanical buffering property. However, the fundamental mechanism of Li diffusion behavior in various Si/C composite materials remains unclear, with our understanding limited by experimental techniques and continuum modeling methodologies. Herein, the atomic behavior of Li diffusion in the Si/C composite material is studied within the framework of density functional theory. Two representative structural mixing formats, that is, simple mixture mode and core-shell mode, are modeled and compared. We discover that the carbon material increases Li diffusion in silicon from 7.75 × 10-5 to 2.097 × 10-4 cm2/s. The boost is about 50% more obvious in the mixture mode, while the core-shell structure shows more dependence on the atomic structures of the carbon layer. These results offer new insights into Li diffusion behavior in Si/C composites and unlock the enhancing mechanism for Li diffusion in Si/C. This understanding facilitates the modeling of batteries with composite anodes and will guide the corresponding structure designs for robust and high-energy-density batteries.

Analysis of the HNF4A isoform-regulated transcriptome identifies CCL15 as a downstream target in gastric carcinogenesis.

OBJECTIVE: Hepatocyte nuclear factor 4α (HNF4A) has been demonstrated to be an oncogene in gastric cancer (GC). However, the roles of different HNF4A isoforms derived from the 2 different promoters (P1 and P2) and the underlying mechanisms remain obscure. METHODS: The expression and prognostic values of P1- and P2-HNF4A were evaluated in The Cancer Genome Atlas (TCGA) databases and GC tissues. Then, functional assays of P1- and P2-HNF4A were conducted both in vivo and in vitro. High-throughput RNA-seq was employed to profile downstream pathways in P1- and P2-HNF4A-overexpressing GC cells. The expression and gene regulation network of the candidate target genes identified by RNA-seq were characterized based on data mining and functional assays. RESULTS: HNF4A amplification was a key characteristic of GC in TCGA databases, especially for the intestinal type and early stage. Moreover, P1-HNF4A expression was significantly higher in tumor tissues than in adjacent non-tumor tissues (P < 0.05), but no significant differences were found in P2-HNF4A expression (P > 0.05). High P1-HNF4A expression indicated poor prognoses in GC patients (P < 0.01). Furthermore, P1-HNF4A overexpression significantly promoted SGC7901 and BGC823 cell proliferation, invasion and migration in vitro (P < 0.01). Murine xenograft experiments showed that P1-HNF4A overexpression promoted tumor growth (P < 0.05). Mechanistically, RNA-seq showed that the cytokine-cytokine receptor interactions pathway was mostly enriched in P1-HNF4A-overexpressing GC cells. Finally, chemokine (C-C motif) ligand 15 was identified as a direct target of P1-HNF4A in GC tissues. CONCLUSIONS: P1-HNF4A was the main oncogene during GC progression. The cytokine-cytokine receptor interaction pathway played a pivotal role and may be a promising therapeutic target.

Niobium Modification of Au/CeO2 for Enhanced Catalytic Performance over Benzene Combustion.

A novel Au/Nb-CeO2 was obtained by loading Au to Nb-modified CeO2 adopting a thermal decomposition method. The modification effect of Nb on the physicochemical properties and performance of Au/CeO2 for benzene combustion was systematically clarified. The incorporated Nb species are found to be present in the two forms of highly-dispersed state and bulk NbO x into CeO2 lattice in the obtained Au/Nb-CeO2 catalyst. They greatly enlarged the BET surface area, improved the redox property, and strengthened the Au-support interaction. The addition of Nb also promotes catalytic performance of Au/CeO2, especially high-temperature performance: T 90% decreases by ca. 40 °C and Au/Nb-CeO2 exhibits superior stability to Au/CeO2 at 230 °C. The slightly improved Au dispersion and redox properties resulted in the small increase on initial activity of Au/Nb-CeO2, but the large BET surface area and the strong Au-support interaction greatly promoted the high-temperature performance improvement of Au/Nb-CeO2 for benzene combustion reaction.

Discovery of oxyepiberberine as a novel tubulin polymerization inhibitor and an anti-colon cancer agent against LS-1034 cells.

Coptis chinensis Franch. has been extensively used in traditional Chinese medicine. The chemical structure of oxyepiberberine, as an alkaloid isolated from Coptis chinensis Franch., has been previously studied. However, anti-cancer effects and underlying mechanisms of oxyepiberberine need to be explored. This study aimed to investigate the anti-cancer effects and underlying mechanisms of oxyepiberberine on LS-1034 human colon cancer cells. The anti-proliferative effects of six derivatives of oxyepiberberine on colon cancer cells were assessed. Among six derivatives, oxyepiberberine showed the greatest anti-proliferative effect on LS-1034 cells with an IC50 value of 1.36 µM. Oxyepiberberine also induced apoptosis and inhibited migration of LS-1034 cells in a concentration-dependent manner. Importantly, oxyepiberberine was identified as a potent tubulin polymerization inhibitor. The tubulin polymerization inhibitory effects of oxyepiberberine in a concentration-dependent manner with an IC50 value of 1.26 µM were observed. A xenograft mouse model of colon cancer showed that oxyepiberberine could suppress tumor growth without an obvious toxicity. Conclusion Oxyepiberberine was found as a novel tubulin polymerization inhibitor, and it could be a promising agent to treat colon cancer.

Resveratrol inhibits bile acid-induced gastric intestinal metaplasia via the PI3K/AKT/p-FoxO4 signalling pathway.

Gastric intestinal metaplasia (GIM) is the essential pre-malignancy of gastric cancer. Chronic inflammation and bile acid reflux are major contributing factors. As an intestinal development transcription factor, caudal-related homeobox 2 (CDX2) is key in GIM. Resveratrol has potential chemopreventive and anti-tumour effects. The aim of the study is to probe the effect of resveratrol in bile acid-induced GIM. We demonstrated that resveratrol could reduce CDX2 expression in a time- and dose-dependent manner in gastric cell lines. A Cignal Finder 45-Pathway Reporter Array and TranSignal Protein/DNA Array Kit verified that resveratrol could increase Forkhead box O4 (FoxO4) activity and that Chenodeoxycholic acid (CDCA) could reduce FoxO4 activity. Furthermore, bioinformatics analysis showed that FoxO4 could bind to the CDX2 promoter, and these conjectures were supported by chromatin-immunoprecipitation (ChIP) assays. Resveratrol can activate FoxO4 and decrease CDX2 expression by increasing phospho-FoxO4 nucleus trans-location. Resveratrol could increase FoxO4 phosphorylation through the PI3K/AKT pathway. Ectopic FoxO4 expression can up-regulate FoxO4 phosphorylation and suppress CDCA-induced GIM marker expression. Finally, we found a reverse correlation between p-FoxO4 and CDX2 in tissue arrays. This study validates that resveratrol could reduce bile acid-induced GIM through the PI3K/AKT/p-FoxO4 signalling pathway and has a potential reversing effect on GIM, especially that caused by bile acid reflux.

Crack-Free Silicon Monoxide as Anodes for Lithium-Ion Batteries.

The volume expansion of Si and SiO particles was investigated using a single-particle battery assembled with a focused ion beam and scanning electron microscopy (FIB-SEM) system. Single Si and SiO particles were galvanostatically charged and discharged as in real batteries. Microstructural changes of the particles were monitored in situ using FIB-SEM from two different angles. The results revealed that the volume expansion of micrometer size particle SiO was not only much smaller than that of Si, but it also kept its original shape with no sign of cracks. This isotropic mechanical property of a SiO particle can be attributed to its microstructure: nanosized Si domains mixed with SiO2 domains. The nanosized Si domains can mitigate the anisotropic swelling caused by the orientation-dependent lithium-ion insertion; the surrounding SiO2 domains can act as a buffer to further constrain the localized anisotropic swelling.

Mesenchymal epithelial transition factor regulates tumor necrosis factor-related apoptotic induction ligand resistance in hepatocellular carcinoma cells through down-regulation of cyclin B1.

Tumor necrosis factor-related apoptotic induction ligand can induce cell apoptosis in various tumor cells. However, many cancer cells are resistant to tumor necrosis factor-related apoptotic induction ligand. Therefore, overcoming the tumor necrosis factor-related apoptotic induction ligand resistance makes it possible for tumor necrosis factor-related apoptotic induction ligand-based anti-cancer therapies. In this study, we took mesenchymal epithelial transition factor as the research target to study its role in tumor necrosis factor-related apoptotic induction ligand-resistant hepatocellular carcinoma. Mesenchymal epithelial transition factor gene has been proved to be an effective predictor of recurrence after hepatocellular carcinoma resection. The expression of mesenchymal epithelial transition factor and cyclin B1 were measured in tumor necrosis factor-related apoptotic induction ligand-resistant and non-resistant hepatocellular carcinoma tissues. Cyclin B1-knockdown and cyclin B1-overexpression hepatocellular carcinoma cells were treated with tumor necrosis factor-related apoptotic induction ligand; mesenchymal epithelial transition factor knockout, mesenchymal epithelial transition factor re-introduction and cyclin B1 restored in hepatocellular carcinoma cells treated with tumor necrosis factor-related apoptotic induction ligand were established. And MTT, bromodeoxyuridine, flow cytometry and western blotting were performed to evaluate the effect of mesenchymal epithelial transition factor and cyclin B1 on hepatocellular carcinoma cells treated with tumor necrosis factor-related apoptotic induction ligand. In addition, subcutaneous tumor transplantation in nude mice was conducted to access the effect of mesenchymal epithelial transition factor and cyclin B1 on tumor formation in vivo. In conclusion, cyclin B1 enhanced the cell growth and inhibited apoptosis in tumor necrosis factor-related apoptotic induction ligand-resistant hepatocellular carcinoma cells. And mesenchymal epithelial transition factor promoted the cell growth and apoptosis in tumor necrosis factor-related apoptotic induction ligand-resistant hepatocellular carcinoma cells by regulating cyclin B1. Therefore, mesenchymal epithelial transition factor regulates the cyclin B1 to regulate tumor necrosis factor-related apoptotic induction ligand resistance in hepatocellular carcinoma cells. Our results suggest a novel molecular mechanism for regulating tumor necrosis factor-related apoptotic induction ligand resistance, which might be helpful to select drug targets in the treatment of liver cancer.

Protective Effects of Yiqi Xingnao Oral Liquid on Cerebral Ischemia-Reperfusion Injury in Rats and Its Related Mechanisms.

PURPOSE: This study aimed to investigate the effects of different concentrations of Yiqi Xingnao (YQXN) oral liquid on cerebral ischemia/reperfusion (I/R) injury in rats and YQXN's related mechanisms. METHODS: Rats were pretreated with 3 mL/kg, 6 mL/kg, and 12 mL/kg YQXN and Naoxuekang capsule (NXK). Afterwards, cerebral I/R model rats were established by a middle cerebral artery occlusion surgery. Neurological deficits, histopathology, and cerebral infarction volume were used to evaluate the effects of YQXN. Evans blue and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining were utilized to determine the blood-brain barrier permeability and cell apoptosis, respectively. The expression of VEGF and Bcl-2 was analyzed by real-time quantification PCR (RT-qPCR) and western blot. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured using corresponding assay kits. RESULTS: The rats pretreated with YQXN had improved neurological deficits, reduced infarct volume and blood-brain barrier permeability, and ameliorated ischemia-induced morphology change in injured brain tissues. TUNEL staining results showed that different concentrations of YQXN inhibited cell apoptosis of neurocytes in I/R rats. Besides, RT-qPCR and western blot analyses indicated that the expression levels of VEGF and Bcl-2 were significantly upregulated by YQXN compared with the I/R group (P < 0.05). Additionally, rats in the I/R group had lower SOD activity and higher MDA content than those in the sham-operated group, while their levels were recovered by YQXN (P < 0.05). CONCLUSION: YQXN could alleviate cerebral I/R injury by suppressing blood-brain barrier permeability, neuron apoptosis, and oxidative stress, promoting angiogenesis.

TGR5-HNF4α axis contributes to bile acid-induced gastric intestinal metaplasia markers expression.

Intestinal metaplasia (IM) increases the risk of gastric cancer. Our previous results indicated that bile acids (BAs) reflux promotes gastric IM development through kruppel-like factor 4 (KLF4) and caudal-type homeobox 2 (CDX2) activation. However, the underlying mechanisms remain largely elusive. Herein, we verified that secondary BAs responsive G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) was increased significantly in IM specimens. Moreover, TGR5 contributed to deoxycholic acid (DCA)-induced metaplastic phenotype through positively regulating KLF4 and CDX2 at transcriptional level. Then we employed PCR array and identified hepatocyte nuclear factor 4α (HNF4α) as a candidate mediator. Mechanically, DCA treatment could induce HNF4α expression through TGR5 and following ERK1/2 pathway activation. Furthermore, HNF4α mediated the effects of DCA treatment through directly regulating KLF4 and CDX2. Finally, high TGR5 levels were correlated with high HNF4α, KLF4, and CDX2 levels in IM tissues. These findings highlight the TGR5-ERK1/2-HNF4α axis during IM development in patients with BAs reflux, which may help to understand the mechanism underlying IM development and provide prospective strategies for IM treatment.

DKK1 is epigenetically downregulated by promoter methylation and inhibits bile acid-induced gastric intestinal metaplasia.

Dickkopf-related protein 1 (DKK1) is essential to gastric cancer as an inhibitor of Wnt signaling. Gastric intestinal metaplasia (GIM) is an important precancerous lesion of gastric cancer that can be activated by bile acid reflux and chronic inflammation. However, the exact mechanism of DKK1 in bile acid-induced GIM has not been completely elucidated. We aimed to explore the epigenetic alterations and biological functions of DKK1 in the development of GIM. In the present study, bile acid was found to induce the expression of intestinal markers in gastric epithelial cells, whereas DKK1 was downregulated in response to bile acid stimulation. The mRNA and protein expression levels of DKK1 were decreased in GIM tissues as evidenced by qRT-PCR and immunohistochemical staining. Surprisingly, the methylation of the DKK1 promoter increased in GIM tissues, and we discovered 28 differential methylation sites of the DKK1 promoter in GIM tissues. Bile acid was able to induce the partial methylation of the DKK1 promoter, while 5-aza could increase DKK1 expression as well as decrease intestinal markers expression in gastric epithelial cells. In conclusion, the promoter methylation and downregulation of DKK1 might play important roles in the development of GIM, especially bile acid-induced GIM.

Evaluation of MT Family Isoforms as Potential Biomarker for Predicting Progression and Prognosis in Gastric Cancer.

BACKGROUND: Metallothioneins (MTs) family comprises many isoforms, most of which are frequently dysregulated in a wide range of cancers. However, the expression pattern and exact role of each distinct MT family isoform which contributes to tumorigenesis, progression, and drug resistance of gastric cancer (GC) are still unclear. METHODS: Publicly available databases including Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier plotter, SurvExpress, MethHC, cBioportal, and GeneMANIA were accessed to perform an integrated bioinformatic analysis and try to detect fundamental relationships between each MT family member and GC. RESULTS: Bioinformatic data indicated that the mRNA expression of all MT family members was almost lowly expressed in GC compared with normal gastric tissue (P<0.05), and patients with reduced mRNA expression of each individual MT member had inconsistent prognostic value (OS, FP, PPS), which depended on the individual isoform of MT. A negative correlation between the methylation in promoter region of majority of MT members and their mRNA expression was detected from MethHC database (p<0.001). Data downloaded from TCGA revealed that MTs were rarely mutated in GC patients and MT2A was frequently regulated by other three genes (FOS, JUN, SP1) in GC patients. CONCLUSION: MTs were nearly downregulated, and distinct type of MT harbored different prognostic role in GC patients. Methylation in gene promoter region of MTs partially contributed to their reduced expression in GC. Our comprehensive analyses from multiple independent databases may further lead researches to explore MT-targeting reagents or potential diagnostic and prognostic markers for GC patients.

Polymorphic transition and nucleation pathway of barium dititanate (BaTi2O5) during crystallization from undercooled liquid.

The nucleation pathway plays an important role in vitrification, preparation of glass-ceramic composites and synthesis of metastable materials. In this paper, we studied the nucleation pathway of a novel ferroelectric BaTi2O5 (BT2) during crystallization from undercooled liquid by aerodynamic levitation (ADL) containerless processing and structural analysis. An interesting polymorphic transition of BT2 regulated by the undercooling was observed during the crystallization process: the ferroelectric monoclinic phase (γ-BT2) was fabricated at low undercoolings and the paraelectric orthorhombic metastable phase (ß-BT2) was obtained from hypercooled liquid. This polymorphic transition phenomenon corresponds to a non-classical nucleation pathway: metastable ß-BT2 preferentially nucleates from undercooled melt and γ-BT2 is generated from ß phase by solid-state phase transition. The two-step nucleation pathway stems from the structural heredity between the undercooled liquid and crystals. A stronger structural homology exists between the undercooled melt and ß-BT2 than γ-BT2 based on diffraction data and atomic configurations analysis. This structural homology coupled with nucleation barrier calculation was used to elucidate the non-classical nucleation pathway of BT2 crystallization: the similarity of the structural unit (Ti-O polyhedra) between the undercooled liquid and the metastable ß-BT2 reduces the nucleation barrier and contributes to the preferential precipitation of ß-like clusters. This work reveals the formation route of BT2 from cooling melt, which not only benefits the synthesis and application of this novel functional material but also provides a guideline of the crystallization process of titanates from melt at atomic level.

SOX2 interferes with the function of CDX2 in bile acid-induced gastric intestinal metaplasia.

BACKGROUND: Intestinal metaplasia (IM) is a premalignant lesion associated with gastric cancer. Both animal and clinical studies have revealed that bile acid reflux and subsequent chronic inflammation are key causal factors of IM. Previous studies indicated that SOX2, the key transcription factor in gastric differentiation, was downregulated during IM development while CDX2, the pivotal intestine-specific transcription factor was upregulated significantly. However, it remains unclear whether the downregulation of SOX2 promotes gastric IM emergence or is merely a concomitant phenomenon. In addition, the underlying mechanisms of SOX2 downregulation during IM development are unclear. METHODS: Gastric cell lines were treated with deoxycholic acid (DCA) in a dose-dependent manner. The expression of CDX2 and miR-21 in gastric tissue microarray were detected by immunohistochemistry and in situ hybridization. Coimmunoprecipitation and immunofluorescence were performed to ascertain the interaction of SOX2 and CDX2. Luciferase reporter assays were used to detect the transcriptional activity of CDX2, and confirm miR-21 binding to SOX2 3'-UTR. The protein level of SOX2, CDX2 and downstream IM-specific genes were investigated using western blotting. mRNA level of miR-21, SOX2, CDX2 and downstream IM-specific genes were detected by qRT-PCR. RESULTS: Bile acid treatment could suppress SOX2 expression and simultaneously induce expression of CDX2 in gastric cell lines. Furthermore, we demonstrated that SOX2 overexpression could significantly inhibit bile acid- and exogenous CDX2-induced IM-specific gene expression, including KLF4, cadherin 17 and HNF4α expression. In contrast, SOX2 knockdown had the opposite effect. A dual-luciferase reporter assay demonstrated that SOX2 overexpression could significantly suppress CDX2 transcriptional activity in HEK293T cells. CDX2 and SOX2 could form protein complexes in the nucleus. In addition, bile acid induced the expression of miR-21. The inhibition of SOX2 in bile acid-treated gastric cell lines was rescued by miR-21 knockdown. CONCLUSIONS: These findings suggested that SOX2 can interfere with the transcriptional activity of CDX2 in bile acid-induced IM and that miR-21 might play a key role in this process, which shed new lights in the prevention of gastric cancer.