Genome-wide DNA methylation and transcriptomic patterns of precancerous gastric cardia lesions.

BACKGROUND: Intestinal metaplasia (IM) and intraepithelial neoplasia (IEN) are considered precursors of gastric cardia cancer (GCC). Here, we investigated the histopathologic and molecular profiles of precancerous gastric cardia lesions (PGCLs) and biomarkers for risk stratification of gastric cardia IM. METHODS: We conducted a hospital-based evaluation (n = 4578) for PGCL profiles in high-incidence and non-high-incidence regions for GCC in China. We next performed 850K methylation arrays (n = 42) and RNA-seq (n = 44) in tissues with PGCLs. We then examined the protein expression of candidate biomarker using immunohistochemistry. RESULTS: Of the 4578 participants, 791 were diagnosed with PGCLs (600 IM, 62 IM with IEN, and 129 IEN). We found that individuals from high-incidence regions (26.7%) were more likely to develop PGCLs than those from non-high-incidence areas (13.5%). DNA methylation and gene expression alterations, indicated by differentially methylated probes (DMPs) and differentially expressed genes (DEGs), exhibited a progressive increase from type I IM (DMP = 210, DEG = 24), type II IM (DMP = 3402, DEG = 129), to type III IM (DMP = 3735, DEG = 328), peaking in IEN (DMP = 47 373, DEG = 2278). Three DEGs with aberrant promoter methylation were identified, shared exclusively by type III IM and IEN. Of these DEGs, we found that OLFM4 expression appears in IMs and increases remarkably in IENs (P < .001). CONCLUSIONS: We highlight that type III IM and IEN share similar epigenetic and transcriptional features in gastric cardia and propose biomarkers with potential utility in risk prediction.

Aberrant DNA methylation and expression of EYA4 in gastric cardia intestinal metaplasia.

Background: Intestinal metaplasia (IM) of the gastric cardia is an important premalignant lesion. However, there is limited information concerning its epidemiological and molecular features. Herein, we aimed to provide an overview of the epidemiological data for gastric cardiac IM and evaluate the role of EYA transcriptional coactivator and phosphatase 4 (EYA4) as an epigenetic biomarker for gastric cardiac IM. Methods: The study was conducted in the context of the gastric cardiac precancerous lesion program in southern China, which included 718 non-cancer participants, who undertook endoscopic biopsy and pathological examination in three endoscopy centers, between November 2018 and November 2021. Pyrosequencing and immunohistochemistry were performed to examine the DNA methylation status and protein expression level of EYA4. Results: Gastric cardiac IM presented in 14.1% (101/718) of participants and was more common among older (>50 years; 22.0% [95% CI: 17.8-26.8]) than younger participants (≤50 years; 6.7% [95% CI: 4.5-9.9]; P < 0.001). IM was more common in male participants (16.9% [95% CI: 13.2-21.3] vs. 11.3% [95% CI: 8.3-15.1]; P = 0.04). Pyrosequencing revealed that IM tissues exhibited significantly higher DNA methylation levels in EYA4 gene than normal tissues (P = 0.016). Further, the protein expression level of EYA4 was reduced in IM and absent in intraepithelial neoplasia tissues compared to normal tissues (P < 0.001). Conclusions: Detection rates of gastric cardiac IM increase with age and are higher in men. Our findings highlight the important role of promoter hypermethylation and downregulation of EYA4 in gastric cardiac IM development.

Esophageal Squamous Cancer from 4NQO-Induced Mice Model: CNV Alterations.

Squamous esophageal carcinoma is a common pathological type of esophageal carcinoma around the world. The prognosis of esophageal carcinoma is usually poor and diagnosed at late stages. Recently, research suggested that genomic instability occurred in esophageal cells during the development of esophageal squamous cell carcinoma (ESCC). Identifying prognostic and specific genomic characteristics, especially at the early hyperplasia stage, is critical. Mice were given 4-nitroquinoline 1-oxide (4NQO) with drinking water to induce esophageal cancer. The immortalized human esophageal epithelial cell line (NE2) was also treated with 4NQO. We performed histologic analyses, immunofluorescence, and immunohistochemical staining to detect DNA damage at different time points. Whole-exome sequencing was accomplished on the esophagus tissues at different pathological stages to detect single-nucleotide variants and copy number variation (CNV) in the genome. Our findings indicate that all mice were tumor-forming, and a series of changes from simple hyperplasia (ESSH) to intraepithelial neoplasia (IEN) to esophageal squamous cell carcinoma (ESCC) was seen at different times. The expression of γ-H2AX increased from ESSH to ESCC. In addition, mutations of the Muc4 gene were detected throughout the pathological stages. Furthermore, CNV burden appeared in the esophageal tissues from the beginning of ESSH and accumulated more in cancer with the deepening of the lesions. This study demonstrates that mutations caused by the early appearance of DNA damage may appear in the early stage of malignant tissue before the emergence of atypia. The detection of CNV and mutations of the Muc4 gene may be used as an ultra-early screening indicator for esophageal cancer.

Potential Chemotherapeutic Effect of Selenium for Improved Canceration of Esophageal Cancer.

Esophageal squamous cell carcinoma is the most common type of esophageal cancer and accounts for 5% of malignant tumor deaths. Recent research suggests that chronic inflammation and DNA damage may drive the onset of esophageal squamous cell carcinoma, implying that lowering chronic inflammation and DNA damage compounds may provide chemo-prevention. According to epidemiological and experimental evidence, selenium is linked to a lower risk of several malignancies, including esophageal squamous cell carcinoma. However, its exact mechanism is still unclear. In the present study, we used cell lines and a 4-NQO mice model to explore the anti-cancer mechanism of four types of selenium. Our findings indicated that selenium inhibited the proliferation, colony formation, and ROS level of ESCC cell lines in a time-dependent manner. Intriguingly, selenium treatment impeded 4-NQO-induced high-grade intraepithelial neoplasia and reduced the number of positive inflammatory cells by preserving DNA from oxidative damage. In addition, selenium significantly decreased the expression of Ki-67 and induced apoptosis. This study demonstrates that selenium has a significant chemo-preventive effect on ESCC by reducing high-grade dysplasia to low-grade dysplasia. For the first time, selenium was shown to slow down the progression of esophageal cancer by lowering inflammation and oxidative DNA damage.

Two-dimensional magneto-photoconductivity in non-van der Waals manganese selenide.

Deficient intrinsic species and suppressed Curie temperatures (Tc) in two-dimensional (2D) magnets are major barriers for future spintronic applications. As an alternative, delaminating non-van der Waals (vdW) magnets can offset these shortcomings and involve robust bandgaps to explore 2D magneto-photoconductivity at ambient temperature. Herein, non-vdW α-MnSe2 is first delaminated as quasi-2D nanosheets for the study of emerging semiconductor, ferromagnetism and magneto-photoconductivity behaviors. Abundant nonstoichiometric surfaces induce the renormalization of the band structure and open a bandgap of 1.2 eV. The structural optimization strengthens ferromagnetic super-exchange interactions between the nearest-neighbor Mn2+, which enables us to achieve a high Tc of 320 K well above room temperature. The critical fitting of magnetization and transport measurements both verify that it is of quasi-2D nature. The above observations are evidenced by multiple microscopic and macroscopic characterization tools, in line with the prediction of first-principles calculations. Profiting from the negative magnetoresistance effect, the self-powered infrared magneto-photoconductivity performance including a responsivity of 330.4 mA W-1 and a millisecond-level response speed are further demonstrated. Such merits stem from the synergistic modulation of magnetic and light fields on photogenerated carriers. This provides a new strategy to manipulate both charge and spin in 2D non-vdW systems and displays their alluring prospects in magneto-photodetection.

Recent Progress of Fluxgate Magnetic Sensors: Basic Research and Application.

Fluxgate magnetic sensors are especially important in detecting weak magnetic fields. The mechanism of a fluxgate magnetic sensor is based on Faraday's law of electromagnetic induction. The structure of a fluxgate magnetic sensor mainly consists of excitation windings, core and sensing windings, similar to the structure of a transformer. To date, they have been applied to many fields such as geophysics and astro-observations, wearable electronic devices and non-destructive testing. In this review, we report the recent progress in both the basic research and applications of fluxgate magnetic sensors, especially in the past two years. Regarding the basic research, we focus on the progress in lowering the noise, better calibration methods and increasing the sensitivity. Concerning applications, we introduce recent work about fluxgate magnetometers on spacecraft, unmanned aerial vehicles, wearable electronic devices and defect detection in coiled tubing. Based on the above work, we hope that we can have a clearer prospect about the future research direction of fluxgate magnetic sensor.

Influence of Annealing on the Damping Behavior of Ni-Cu-Mn-Ga Ferromagnetic Shape Memory Alloys.

Damping materials have attracted much attention for wide potential applications in the industry. Previous research shows that annealing treatment is an effective and costless way of improving the functional properties of conventional shape memory alloys. However, there are few investigations concerning the annealing effect of the ambient-temperature damping behavior. In this paper, we present the influence of annealing treatment on the martensitic transformation and damping behaviors of Ni 55 - x Cu x Mn 25 Ga 20 (x = 0, 2, 4, 6) alloys within the ambient-temperature range. With increasing annealing time, the martensitic transformation temperature and the temperature span of martensitic transformation decrease. Moreover, annealing treatment greatly enhances the twin boundary damping peak of martensite. The X-ray diffraction (XRD) measurement demonstrates that annealing can improve the degree of L2 1 atomic order, which relieves the pinning effects for the twin boundary motion and thus leads to the enhancement of the twin boundary damping of these alloys.

Ferromagnetic Resonance Biosensor for Homogeneous and Volumetric Detection of DNA.

The ability to detect and analyze the state of magnetic labels with high sensitivity is of crucial importance for developing magnetic biosensors. In this work, we demonstrate, for the first time, a ferromagnetic resonance (FMR) based homogeneous and volumetric biosensor for magnetic label detection. Two different isothermal amplification methods, i.e., rolling circle amplification (RCA) and loop-mediated isothermal amplification (LAMP), are adopted and combined with a standard electron paramagnetic resonance (EPR) spectrometer for FMR biosensing. For the RCA-based FMR biosensor, binding of RCA products of a synthetic Vibrio cholerae target DNA sequence gives rise to the formation of aggregates of magnetic nanoparticles. Immobilization of nanoparticles within the aggregates leads to a decrease of the net anisotropy of the system and a concomitant increase of the resonance field. A limit of detection of 1 pM is obtained with a linear detection range between 7.8 and 250 pM. For the LAMP-based sensing, a synthetic Zika virus target oligonucleotide is amplified and detected in 20% serum samples. Immobilization of magnetic nanoparticles is induced by their coprecipitation with Mg2P2O7 (a byproduct of LAMP) and provides a detection sensitivity of 100 aM. The fast measurement, high sensitivity, and miniaturization potential of the proposed FMR biosensing technology makes it a promising candidate for designing future point-of-care devices.

Simulation study on exchange interaction and unique magnetization near ferromagnetic morphotropic phase boundary.

Extensive efforts have been made in searching enhanced functionalities near the so-called morphotropic phase boundaries (MPBs) in both ferroelectric and ferromagnetic materials. Due to the exchange anti-symmetry of the wave function of fermions, it is widely recognized that the exchange interaction plays a critical role in ferromagnetism. As a quantum effect, the exchange interaction is magnitudes larger than electric interaction, leading to a fundamental difference between ferroelectricity and ferromagnetism. In this paper, we establish an energetic model capturing the interplay among the anisotropy energy, magnetostatic energy and the exchange energy to investigate systematically the effects of the exchange energy on the behavior of the ferromagnetic MPB. For the first time, it is found that the exchange energy can narrow the width of MPB region in the composition temperature phase diagram for ferromagnetic MPB systems. As temperature increases, MPB region becomes wider because of the weakening of the exchange interaction. Our simulation results suggest that the exchange energy play a critical role on the unique behavior of ferromagnetic MPB, which is in contrast different from that of ferroelectric MPB.

Monte Carlo simulation of magnetic domain structure and magnetic properties near the morphotropic phase boundary.

The morphotropic phase boundary (MPB), which is the boundary separating a tetragonal phase from a rhombohedral phase by varying the composition or mechanical pressure in ferroelectrics, has been studied extensively for decades because it can lead to strong enhancement of piezoelectricity. Recently, a parallel ferromagnetic MPB was experimentally reported in the TbCo2-DyCo2 ferromagnetic system and this discovery proposes a new way to develop potential materials with giant magnetostriction. However, the role of magnetic domain switching and spin reorientation near the MPB region is still unclear. For the first time, we combine micromagnetic theory with Monte Carlo simulation to investigate the evolution of magnetic domain structures and the corresponding magnetization properties near the MPB region. It is demonstrated that the magnetic domain structure and the corresponding magnetization properties are determined by the interplay among anisotropy energy, magnetostatic energy and exchange energy. If the anisotropy energy barrier is large compared with the magnetostatic energy barrier and the exchange energy barrier, the MPB region is a T and R mixed structure and magnetic domain switching is the dominant mechanism. If the anisotropy energy barrier is small, the MPB region will also contain M phases and spin reorientation is the dominant mechanism. Our work could provide a guide for the design of advanced ferromagnetic materials with enhanced magnetostriction.

Combination of sacral neuromodulation and tolterodine for treatment of idiopathic overactive bladder in women: a clinical trial.

PURPOSE: To evaluate the efficacy of intermittent percutaneous needle sacral nerve stimulation (IPN-SNS) in women with idiopathic overactive bladder (IOAB) treated with tolterodine. MATERIALS AND METHODS: A total of 240 female patients diagnosed with IOAB were randomized to receive tolterodine only treatment (group 1, n = 120) or tolterodine combined with IPN-SNS (group 2, n = 120). Each group included 120 participants, who were divided into subgroups depending on whether they had dry OAB (urinary frequency and urgency) or wet OAB (urinary frequency and urgency with urgency incontinence). In the treatment group, patients received percutaneous IPN-SNS plus tolterodine (2 mg once daily), while in the control group, only tolterodine (2 mg once daily) was administered for 3 months. The voiding diary and urodynamic parameters were monitored, and patients' psychological depression and anxiety scores were recorded before and after treatment. RESULTS: There were significantly greater improvements in the conditions of first desire to void (FDV), max­imum cystometric capacity (MCC), and daily average volumes, as well as the daily single maximum voided volumes in group 2 (P = .001) than in group 1. In addition, there were significantly greater decreases in self-rating depression scale (SDS) and self-rating anxiety scale (SAS) scores in group 2 compared with group 1 (P < .001). CONCLUSION: Combined treatment with tolterodine plus IPN-SNS can not only improve the symptoms of voiding dysfunction but can also reduce the concomitant depression and anxiety in women with IOAB, there­by improving patients' quality of life.