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Patients with peritoneal metastasis (PM) of colorectal cancer (CRC) have poorer overall survival outcomes than those without PM. Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and mediate CRC progression and PM. It is imperative to identify and develop novel therapeutic targets for PM-CRC driven by CAFs. Using lipidomics, we reveal that the abundance of phosphatidylcholine (PC) with unsaturated acyl chains was increased in clinical PM-CRC specimens. Additionally, we found that CAFs were present at a higher relative abundance in primary PM-CRC tumors and that membrane fluidity in CRC cells was increased after incubation with CAF-conditioned medium (CM) through three independent methods: lipidomics, fluorescence recovery after photobleaching (FRAP), and generalized polarization. Then, we found that increased membrane fluidity can enhance glucose uptake and metabolism, as supported by real-time bioenergetics analysis and U more...

Background The current risk stratification system defined by clinicopathological features does not identify the risk of recurrence in early-stage (stage I-II) colorectal cancer (CRC) with sufficient accuracy. We aimed to investigate whether DNA methylation could serve as a novel biomarker for predicting prognosis in early-stage CRC patients. Methods We analyzed the genome-wide methylation status of CpG loci using Infinium MethylationEPIC array run on primary tumor tissues and normal mucosa of early-stage CRC patients to identify potential methylation markers for prognosis. The machine-learning approach was applied to construct a DNA methylation–based prognostic classifier for early-stage CRC (MePEC) using the 4 gene methylation markers FAT3, KAZN, TLE4, and DUSP3. The prognostic value of the classifier was evaluated in 2 independent cohorts (n = 438 and 359, respectively). Results The comprehensive analysis identified an epigenetic subtype with high risk of recurrence based on a group of CpG loci in the CpG-depleted region. In multivariable analysis, the MePEC classifier was independently and statistically significantly associated with time to recurrence in validation cohort 1 (hazard ratio = 2.35, 95% confidence interval = 1.47 to 3.76, P Conclusions We demonstrated the prognostic statistical significance of a DNA methylation profile in the CpG-depleted region, which may serve as a valuable source for tumor biomarkers. MePEC could identify an epigenetic subtype with high risk of recurrence and improve the prognostic accuracy of current clinical variables in early-stage CRC. more...

The metal additive manufacturing (AM) industry is actively developing instruments and strategies to enable higher productivity, optimal build quality, and controllable as-built microstructure. One of the beam controlling techniques, laser oscillation has shown potential in all these aspects in laser welding; however, few attempts have been made to understand the underling physics of the oscillating keyholes/melt pools which are the prerequisites for the these strategies to become a useful tool for laser-based AM processes. To address this gap, we utilized a synchrotron-based X-ray operando technique to image the dynamic keyhole oscillation in Ti-6Al-4V using a miniature laser powder bed fusion setup. We found good agreement between the experimental observations and simulations performed with a validated Lattice Boltzmann multi-physics model. The study revealed the continuous and periodic fluctuations in the characteristic keyhole parameters that are unique to the oscillating laser beam processing and responsible for the chevron pattern formation at solidification. Despite the intrinsic longer-range fluctuation, the oscillating technique displayed potential for reducing keyhole instability, mitigating porosity formation, and altering surface topology. The results provide important insights about the dynamics of the oscillating keyholes which are valuable guidelines for the future development and application of this technique. more...

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-related death in the world. More comprehensive studies of key molecular alterations in CRC progression were urgent. DNA methylation promotes tumor progression. However, the mechanism of the ANKRD13 gene methylation that drives colorectal cancer evolution remains largely unknown. This was the first study focused on the role of ANKRD13 and the hypermethylated mechanisms in colorectal cancer. Methods: Chi-Square tests were utilized to the comparison of the baseline characteristics of patients with hypomethylation ANKRD13B and hypermethylated ANKRD13B. Kaplan-Meier analysis were used to estimate the difference of overall survival between the two groups patients. The methylation level of ANKRD13B was quantified by qMSP in colorectal cancer, normal colon epitheliums and colorectal adenoma tissues. CRISPR/dCas9-DNMT3A and CRISPR/dCas9-TET1-CD methylation editing tools were applied to enable targeted and specific CpG methylation at the CpG loci near stop codon of ANKRD13B. Transwell-migrated assay, wound scratch assay and colony formation assay were preformed to ascertain the abilities of viability, migration and invasion in the editing CRC cell lines. The methylated RNA immunoprecipitation (MeRIP) assays, chromatin immunoprecipitation (ChIP) assays and 5-AZA treatment assays were performed combined with qPCR to quantify the m6A levels of ANKRD13B mRNA following hypermethylated-editing. Results: Here, we identified a novel oncogenic gene, ANKRD13B, encoding ankyrin repeat domain 13B. This gene was frequently hypermethylated in CpG islands surrounding the stop codon region of colorectal cancer. This hypermethylation was associated with poor clinical outcomes in patients diagnosed with colorectal cancer. Compared with normal tissue (4.2%), this type of epigenetic alteration upregulated ANKRD13B expression in both adenoma (73.0%) and adenoma cancer tissues (83.3%) (P< 0.0001), and it also promoted colorectal cancer cell growth, invasion, and migration. Demethylation treatment can reduce the ANKRD13B expression and the growth, migration, and invasion of the cancer cell. Moreover, we found that the aberrant ANKRD13B methylated surrounding the stop codon, and it can promote RNA N6-methyladenosine methylation modification, suggesting that aberrant DNA 5mC methylation promotes ANKRD13B expression and tumor progression in an RNA m6A-dependent manner. Conclusions: In summary, our findings illustrated that ANKRD13B is an oncogenic gene of colorectal cancer that is commonly methylated and overexpressed in colorectal cancer whose function in the pathogenesis of colorectal cancer depends on RNA m6A-dependent manner. Aberrant DNA 5mC methylation promotes ANKRD13B expression and tumor progression in an RNA m6A-dependent Manner. Key words: ANKRD13B, DNA methylation, Epigenetic regulation, Colorectal cancer Citation Format: JingRong Weng, JinXin Lin, YuMo Xie, GuanNan Tang, LiangLiang Bai, JinHua Chen, ZengHong Huang, ZhuoKai Zhuang, ShaoYong Peng, Heng Wang, GaoPo Xu, Yu Zhang, XiaoXia Liu, MeiJin Huang, YanXin Luo, XiaoLin Wang, Huichuan Yu. RNA m6A methylation relay the oncogenic flow from DNA methylationto gene expression of ANKRD13B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6006. more...

A novel 4H-SiC multizone collector vertical insulated-gate bipolar transistor (MZC-IGBT) with an alternate P+/P−/P+ multizone structure in the collector region is proposed and investigated by numerical simulations in this article. Comparing with conventional 4H-SiC IGBTs, lower potential barrier regions are formed in the proposed MZC-IGBT at the interface between the N field-stop buffer and the collector region, modifying the carrier extraction effect to a proper level and resulting in a superior tradeoff between the static and dynamic performances. The proposed device consumes less energy in a wide frequency range. The numerical simulation reveals that the average dissipation power of the optimized 4H-SiC MZC-IGBT can be decreased by 63.1% at a high frequency of 20 kHz and even 2.26% at a low frequency of 500 Hz, which makes the proposed device much more suitable for high-frequency applications. more...

Additional file 1. Table S1. Primer and Probe Sequences. Table S2. The mean methylation of NTRKs promoter in CRC samples and matched normal mucosae in FHCRC cohort. Table S3. Univariate Cox analysis of probes targeting NTRKs gene in TCGA-COADREAD cohort. Table S4. Sensitivity analysis excluding patients with CIMP-positive status. Table S5. Sensitivity analysis excluding patients with MSI. Table S6. Sensitivity analysis excluding patients with BRAF mutation. Table S7. Sensitivity analysis excluding patients with KRAS mutation. more...

Purpose: Intratumoral heterogeneity emerges from accumulating genetic and epigenetic changes during tumorigenesis, which may contribute to therapeutic failure and drug resistance. We aimed to develop a tool that can evaluate the intratumoral epigenetic heterogeneity using the DNA methylation profiles from bulk tumors. Methods: Ggenomic DNA of three laser micro-dissected tumor regions, including digestive tract surface (DTS), central bulk (CB), and invasive margin (IM), was extracted from formalin-fixed paraffin-embedded (FFPE) sections of 98 colorectal cancer patients. The genome-wide methylation profiles were generated with methylation array. The most variable methylated probes were selected to construct a DNA methylation-based heterogeneity (MeHEG) estimation tool that can deconvolve the proportion of each reference tumor region with the support vector machine model-based method. A PCR-based assay for quantitative analysis of DNA methylation (QASM) was developed to specifically determine the methylation status of each CpG in MeHEG assay at single-base resolution to realize fast evaluation of epigenetic heterogeneity. Results: In the discovery set with 79 patients, the differentially methylated CpGs among the three tumor regions were found. The 7 most representative CpGs were identified by random forest analysis and subsequently selected to develop the MeHEG algorithm. We validated its performance of deconvolution of tumor regions in an independent cohort with 19 patients. In addition, we showed the significant association of MeHEG-based epigenetic heterogeneity with the genomic heterogeneity in mutation and copy number variation in our in-house and TCGA cohorts. Finally, we found that the patients with higher MeHEG score had worse disease-free and overall survival outcomes. Conclusion: By constructing a 7-loci panel with a machine learning approach and QASM assay to facilitate its use in a PCR manner, we developed a valuable method to evaluate the intratumoral epigenetic heterogeneity. The MeHEG algorithm provides innovative insights into the intratumoral heterogeneity from the epigenetic perspective that may add valuable sources to current knowledge about tumor heterogeneity. Citation Format: Yumo Xie, Yu Zhang, Guannan Tang, Xiaolin Wang, Meijin Huang, Yanxin Luo, Huichuan Yu. Spatial deconvolution from bulk DNA methylation profiles determines intratumoral epigenetic heterogeneity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6079. more...

Solidification or hot cracks are commonly observed defects in a number of metal alloys and may lead to deterioration of additively manufactured parts quality. In this study, ultra-high-speed x-ray radiography experiments enable the observation and characterization of bundles of hot-cracks that form in monobloc AA6061 substrate. The crack bundles are related to meltpool characteristics and pore formation. Crack propagation rate is also presented for the case of a crack that initiates from a pore. Two types of relevant pore formation are also described, namely keyhole porosity and crack-remelting porosity. The results of this study are expected to facilitate the validation of theoretical and numerical models of solidification cracking. more...

Effects of ZnO and NiO on structural, morphological, magnetic properties and microwave absorption behavior of glass-ceramic tiles derived from iron ore tailings (IOTs) were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), magnetization measurements, fourier transform infrared spectroscopy (FTIR) and complex permittivity and permeability measurements. Gradual replacement of NiO by ZnO was found to lower crystallinity of the glass-ceramic and reduce average grain size of the only crystalline phase indexed as spinel Ni–Zn ferrite. Ni 2+ ion oscillations at different coordination environments inside glass network led to several notable dielectric losses in 3.8–15 GHz. Ferromagnetic resonance frequency is positively correlated with the amount of Ni 2+ . These Ni-related effects enhanced the maximum microwave attenuation of the glass-ceramic to reach −34.35 dB with its frequency being tunable in 6.70–11.20 GHz. more...

A novel 4H-SiC trench metal–oxide–semiconductor field-effect transistor (MOSFET) with an L-shaped gate (LSG) is proposed and studied via numerical simulations in this letter. Adoption of an additional LSG region that surrounds the bottom corner of the trench allows the peak electric field in the SiO2 dielectric to be significantly relieved by charge compensation, and the device breakdown voltage can be greatly enhanced without causing significant degradation of the output characteristics. In high-voltage blocking states, the electric field at the bottom corner of the trench is weakened, which leads to improved device performance. The peak electric field value in the SiO2 dielectric decreases by 32.3% when compared with that of a conventional 4H-SiC trench MOSFET, while the breakdown voltage increases by 80.4%. more...

A novel technique for improving SiO 2 /4H-SiC interface properties by over-oxidation the nanoscale heavily nitrogen-doped 4H-SiC epitaxial layer is proposed in this paper. The potential of such method for device application was demonstrated by fabricating and testing Al/SiO 2 /4H-SiC metal–oxide–semiconductor (MOS) capacitors. The results indicate that this process could strongly reduce the density of interface traps (D it ) without degrading the oxide insulating properties. The D it extracted using C-V measurements show the lower D it of about $6 \times 10 ^ { 11 } \mathrm { cm } ^ { - 2 } \bullet \mathrm { e } \mathrm { V } ^ { - 1 }$ at the energy of 0.3 eV below the conduction band, which is comparable with that of conventional NO-annealed process. Finally, secondary ion mass spectroscopy (SIMS) and x-ray photoelectron spectroscopy (XPS) results show that nitrogen atoms, initially introduced by the nanoscale heavily nitrogen-doped epi-layer, have been successfully incorporated at the interface of SiO 2 /4H-SiC. These results show that the proposed technique is an alternative nitridation technique and can be used to improve the interface properties of the SiO 2 /4H-SiC. more...

Water-soluble silver nanoparticles stabilized by poly(amic acid) salt (Ag–PAAS) were synthesized by a one-pot method and were characterized by using UV-vis absorption, transmission electron microscopy, powder X-ray diffraction, and ζ potential measurements. The Ag–PAAS catalyzed selective hydration of nitriles to amides in water allowed for not only highly efficient quasi-homogeneous catalytic reactions under mild conditions, but also an easy recovery and reuse of the catalyst attributed to the pH response of the PAAS. more...

The conformal nature of in situ polymerization of adhesive dopamine molecules permits the strong underwater adhesion between polydopamine (PDA) nanomembranes and the target substrates. However, the adhesive interaction between the postdeposit PDA nanomembranes and other macrobodies is strongly influenced by the texture of PDA nanomembranes. Here we report the texture-dependent adhesion of PDA nanomembranes both in air and aqueous environments. Despite the nanometer-scale roughness of PDA nanomembranes, interfacial adhesion between PDA nanomembranes and elastomeric bodies are the strong function of the root-mean-square roughness of PDA nanomembranes, root-mean-square gradient of PDA nanomembranes, and the elasticity of the bulk materials. Reduced adhesion due to increased texture is intensified in hydrated conditions, possibly hinting that the conventional explanation of the negative effect of water to adhesion from a molecular level needs to be revisited. These findings can inform the role of adhesive interaction in conformal coatings and provide an explanation for the differential adhesion observed in freestanding PDA nanomembranes. more...

In this study, multiple shapes like spherical, ellipsoidal, disk-like, and rod-like inorganic/organic hybrid particles are fabricated using droplet-based microfluidics. Instead of photo-polymerization, which is commonly used in previously reported studies, the diversity in particle configuration is realized via the fast hydrolysis of an organometallic compound. In comparison to inorganic/organic hybrid particles fabricated by directly incorporating inorganic components in the dispersed phase before droplet formation, our hybrid particles are synthesized in situ because the inorganic component is one of the hydrolysis products, which avoids the agglomeration or precipitation of inorganic components and thus ensures particle homogeneity. In this study, we demonstrate a new strategy by using hybrid particle containing poly (lactide-co-glycolide) (PLGA) and TiO2 as a model material, among which TiO2 is obtained from the hydrolysis of n-butyl titanate (TBT). The convoluted surface texture of PLGA/TiO2 particles can be attributed to either the interfacial instabilities of droplets induced by n-butanol as the other hydrolysis product, or the elastic-driven wrinkling of the solid film generated on PLGA/TBT droplet surfaces through TBT hydrolysis. Moreover, due to the presence of hyper-dispersed n-butanol caused by localized TBT hydrolysis in the PLGA matrix, a porous internal structure can be formed in the PLGA/TiO2 particle. We believe this strategy is versatile to fabricate numerous types of inorganic/organic hybrid particles, among which partial or all components can be synthesized through the quick hydrolysis of organometallic compounds. more...

Three different kinds of modified starch (MS) were prepared as fillers to assess the compatibility between them and poly(lactic acid) (PLA) resin. The blends were prepared by incorporating 15 wt% of the MS into PLA using a twin-screw extruder. Through morphology analysis, it can be seen that the dispersion state of MS granules was greatly different. Investigations of thermal behavior indicated that the addition of MS decreased thermal properties which found expression in the decrease of melting temperature and vicat softening temperature (VST). But thermal stability of PLA/maleic anhydride grafted starch (MA-g-ST) was slightly higher than those of other blends. PLA/MA-g-ST blend exhibited the highest notched impact strength, elongation at break, and tensile strength, which means MA-g-ST was suitable as a filler improving the toughness of PLA. It was also proved that biodegradability rate of blends increased dramatically and reached up to 1.80, 1.89, 1.44 g day−1 after 60 days, respectively. POLYM. COMPOS., 2011. © 2011 Society of Plastics Engineers more...

In this paper, we report one-step fabrication of poly(lactide-co-glycolic acid)/titanium oxide (PLGA/TiO2) hybrid microspheres with tunable surface texture via droplet-based microfluidics. Surface texture of microspheres can be continuously tuned by changing the mass ratio between titanium tetraisopropoxide (TTIP) and PLGA in the dispersed phase. The fast hydrolysis of TTIP on the droplet surface can generate a thin shell membrane, resulting in a wrinkled surface after extraction of organic solvent. In vitro drug release monitoring of tanshinone IIA-loaded PLGA/TiO2 hybrid microsphere reveals that surface texture can affect the drug release rate to a large extent without sacrificing the drug encapsulation efficiency. Our finding might benefit the sustained drug delivery where variable drug release rate and high drug encapsulation efficiency are both required. more...

A junction termination method adopting heavily doped p-well rings with a shallow trench for each ring, named as a trench multiple floating limiting rings (TMFLRs), is analyzed and fabricated without any additional process in 4H-SiC junction barrier Schottky diode. A breakdown voltage of 6.7 kV is achieved using TMFLRs structure on an epitaxial layer with thickness of 50 $\mu \text{m}$ , while the breakdown voltage of the conventional planar FLRs structure with the same termination area is only 5.7 kV. The experimental result has demonstrated that the TMFLRs termination structure yields about 90% of the parallel plane breakdown voltage. In addition, the simulation results show that the TMFLRs make the bulk peak electric field ( $E_{p,\text {bulk}})$ reduce and move away from the device surface, successfully making the interface peak electric field ( $E_{p,\text {interface}})$ decrease by about 30% compared with a conventional planar FLRs structure when same reverse voltages applied. more...