Integrin α6β4 Upregulates Amphiregulin and Epiregulin Through Base Excision Repair-Mediated DNA Demethylation and Promotes Genome-Wide DNA Hypomethylation

Aberrant DNA methylation patterns are a common theme across all cancer types. Specific DNA demethylation of regulatory sequences can result in upregulation of genes that are critical for tumor development and progression. Integrin α6β4 is highly expressed in pancreatic carcinoma and contributes to cancer progression, in part, through the specific DNA demethylation and upregulation of epidermal growth factor receptor (EGFR) ligands amphiregulin (AREG) and epiregulin (EREG). Whole genome bisulfite sequencing (WGBS) revealed that integrin α6β4 signaling promotes an overall hypomethylated state and site specific DNA demethylation of enhancer elements within the proximal promoters of AREG and EREG. Additionally, we find that the base excision repair (BER) pathway is required to maintain expression of AREG and EREG, as blocking DNA repair molecules, TET1 GADD45A, TDG, or PARP-1 decreased gene expression. Likewise, we provide the novel finding that integrin α6β4 confers an enhanced ability on cells to repair DNA lesions and survive insult. Therefore, while many known signaling functions mediated by integrin α6β4 that promote invasive properties have been established, this study demonstrates that integrin α6β4 can dramatically impact the epigenome of cancer cells, direct global DNA methylation levels toward a hypomethylated state, and impact DNA repair and subsequent cell survival

3DSAM-adapter: Holistic Adaptation of SAM from 2D to 3D for Promptable Medical Image Segmentation

Despite that the segment anything model (SAM) achieved impressive results on general-purpose semantic segmentation with strong generalization ability on daily images, its demonstrated performance on medical image segmentation is less precise and not stable, especially when dealing with tumor segmentation tasks that involve objects of small sizes, irregular shapes, and low contrast. Notably, the original SAM architecture is designed for 2D natural images, therefore would not be able to extract the 3D spatial information from volumetric medical data effectively. In this paper, we propose a novel adaptation method for transferring SAM from 2D to 3D for promptable medical image segmentation. Through a holistically designed scheme for architecture modification, we transfer the SAM to support volumetric inputs while retaining the majority of its pre-trained parameters for reuse. The fine-tuning process is conducted in a parameter-efficient manner, wherein most of the pre-trained parameters remain frozen, and only a few lightweight spatial adapters are introduced and tuned. Regardless of the domain gap between natural and medical data and the disparity in the spatial arrangement between 2D and 3D, the transformer trained on natural images can effectively capture the spatial patterns present in volumetric medical images with only lightweight adaptations. We conduct experiments on four open-source tumor segmentation datasets, and with a single click prompt, our model can outperform domain state-of-the-art medical image segmentation models on 3 out of 4 tasks, specifically by 8.25%, 29.87%, and 10.11% for kidney tumor, pancreas tumor, colon cancer segmentation, and achieve similar performance for liver tumor segmentation. We also compare our adaptation method with existing popular adapters, and observed significant performance improvement on most datasets.Comment: 14 pages, 6 figures, 5 table

Kinetic Theory Approach to Modeling of Cellular Repair Mechanisms under Genome Stress

Under acute perturbations from outer environment, a normal cell can trigger cellular self-defense mechanism in response to genome stress. To investigate the kinetics of cellular self-repair process at single cell level further, a model of DNA damage generating and repair is proposed under acute Ion Radiation (IR) by using mathematical framework of kinetic theory of active particles (KTAP). Firstly, we focus on illustrating the profile of Cellular Repair System (CRS) instituted by two sub-populations, each of which is made up of the active particles with different discrete states. Then, we implement the mathematical framework of cellular self-repair mechanism, and illustrate the dynamic processes of Double Strand Breaks (DSBs) and Repair Protein (RP) generating, DSB-protein complexes (DSBCs) synthesizing, and toxins accumulating. Finally, we roughly analyze the capability of cellular self-repair mechanism, cellular activity of transferring DNA damage, and genome stability, especially the different fates of a certain cell before and after the time thresholds of IR perturbations that a cell can tolerate maximally under different IR perturbation circumstances

What has affected the governance effect of the whole population coverage of medical insurance in China in the past decade? Lessons for other countries

ObjectiveThis study aimed to explore the current state of governance of full population coverage of health insurance in China and its influencing factors to provide empirical references for countries with similar social backgrounds as China.MethodsA cross-sectional quantitative study was conducted nationwide between 22 January 2020 and 26 January 2020, with descriptive statistics, analysis of variance, and logistic regression models via SPSS 25.0 to analyze the effectiveness and influencing factors of the governance of full population coverage of health insurance in China.ResultsThe effectiveness of the governance relating to the total population coverage of health insurance was rated as good by 59% of the survey respondents. According to the statistical results, the governance of the public's ability to participate in insurance (OR = 1.516), the degree of information construction in the medical insurance sector (OR = 2.345), the government's governance capacity (OR = 4.284), and completeness of the government's governance tools (OR = 1.370) were all positively correlated (p < 0.05) on the governance effect of the whole population coverage of health insurance.ConclusionsThe governance of Chinese health insurance relating to the total population coverage is effective. To effectively improve the effectiveness of the governance relating to the total population coverage of health insurance, health insurance information construction, governance capacity, and governance tools should be the focus of governance to further improve the accurate expansion of and increase the coverage of health insurance

On Transient Response of Piezoelectric Transducers

In this paper, we report a new model in analysis of spherical thin-shell piezoelectric transducers for transient response, based on Fourier transform and the principle of linear superposition. We show that a circuit-network, a combination of a series of parallel-connected equivalent-circuits, can be used in description of a spherical thin-shell piezoelectric transducer. When excited by a signal with multiple frequency components, each circuit would have a distinctive radiation resistance and a radiation mass, arising from an individual frequency component. Each frequency component would act independently on the electric/mechanic-terminals. A cumulative signal-output from the mechanic/electric-terminals is measured as the overall acoustic/electric output. As a prototype example in testing the new model, we have designed two spherical shin-shell transducers, applied a gated sine electric-signal as the initial excitation, and recorded the experimental information. The transient response and the output signals are calculated based on the new model. The results of calculation are in good agreement with that of experimental observation

The oyster genome reveals stress adaptation and complexity of shell formation

The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa. © 2012 Macmillan Publishers Limited. All rights reserved

Draft genome sequence of the mulberry tree Morus notabilis

Human utilization of the mulberry–silkworm interaction started at least 5,000 years ago and greatly influenced world history through the Silk Road. Complementing the silkworm genome sequence, here we describe the genome of a mulberry species Morus notabilis. In the 330-Mb genome assembly, we identify 128 Mb of repetitive sequences and 29,338 genes, 60.8% of which are supported by transcriptome sequencing. Mulberry gene sequences appear to evolve ~3 times faster than other Rosales, perhaps facilitating the species’ spread worldwide. The mulberry tree is among a few eudicots but several Rosales that have not preserved genome duplications in more than 100 million years; however, a neopolyploid series found in the mulberry tree and several others suggest that new duplications may confer benefits. Five predicted mulberry miRNAs are found in the haemolymph and silk glands of the silkworm, suggesting interactions at molecular levels in the plant–herbivore relationship. The identification and analyses of mulberry genes involved in diversifying selection, resistance and protease inhibitor expressed in the laticifers will accelerate the improvement of mulberry plants

Experimental Investigation and Numerical Simulation of CO2–Brine–Rock Interactions during CO2 Sequestration in a Deep Saline Aquifer

CO2 mineralization is a long-term and secure solution for geological CO2 storage that primarily depends on the CO2–brine–rock interaction during CO2 sequestration in subsurface formations. In this study, lab experiments were conducted to investigate the CO2–brine–rock interaction over short timescales, and numerical simulations were performed to reveal dynamic interactions and equilibrium interactions by applying TOUGHREACT and PHREEQC, respectively. In the experiments, the main ions of HCO3− and Ca2+ were detected in the solution, and calcite dissolution and dawsonite precipitation were observed from SEM images. The simulation results showed that the CO2 dissolution and the solution pH were affected by the temperatures, pressures, types of solutions, and solution concentrations and were further influenced by mineral dissolution and precipitation. The results of the equilibrium simulation showed that the dissolved minerals were albite, anhydrite, calcite, Ca-montmorillonite, illite, K-feldspar, and chlorite, and the precipitated minerals were dolomite, kaolinite, and quartz, which led to HCO3−, K+, and Na+ being the main ions in solutions. The results of the dynamic simulation showed that calcite and dolomite dissolved in the early period, while other minerals began to dissolve or precipitate after 100 years. The dissolved minerals were mainly albite, kaolinite, K-feldspar, and chlorite, and precipitated minerals were Ca-montmorillonite, illite, and quartz. Anhydrite and pyrite did not change during the simulation period, and the main ions were HCO3−, Na+, Ca2+, and Mg2+ in the simulation period. This study provides an effective approach for analyzing the CO2–brine–rock interaction at different stages during CO2 storage, and the results are helpful for understanding the CO2 mineralization processes in deep saline aquifers