Mathematical modeling the gene mechanism of colorectal cancer and the effect of radiation exposure.

Cancer is the result of continuous accumulation of gene mutations in normal cells. The number of mutations is different in different types of cancer and even in different patients with the same type of cancer. Therefore, studying all possible numbers of gene mutations in malignant cells is of great value for the understanding of tumorigenesis and the treatment of cancer. To this end, we applied a stochastic mathematical model considering the clonal expansion of any premalignant cells with different mutations to analyze the number of gene mutations in colorectal cancer. The age-specific colorectal cancer incidence rates from the Surveillance, Epidemiology and End Results (SEER) registry in the United States and the Life Span Study (LSS) in Nagasaki and Hiroshima, Japan are chosen to test the reasonableness of the model. Our fitting results indicate that the transformation from normal cells to malignant cells may undergo two to five driver mutations for colorectal cancer patients without radiation-exposed environment, two to four driver mutations for colorectal cancer patients with low level radiation-exposure, and two to three driver mutations for colorectal cancer patients with high level radiation-exposure. Furthermore, the net growth rate of the mutated cells with radiation-exposure was is higher than that of the mutated cells without radiation-exposure for the models with two to five driver mutations. These results suggest that radiation environment may affect the clonal expansion of cells and significantly affect the development of tumors.

Mathematical modeling the order of driver gene mutations in colorectal cancer.

Tumor heterogeneity is a large obstacle for cancer study and treatment. Different cancer patients may involve different combinations of gene mutations or the distinct regulatory pathways for inducing the progression of tumor. Investigating the pathways of gene mutations which can cause the formation of tumor can provide a basis for the personalized treatment of cancer. Studies suggested that KRAS, APC and TP53 are the most significant driver genes for colorectal cancer. However, it is still an open issue regarding the detailed mutation order of these genes in the development of colorectal cancer. For this purpose, we analyze the mathematical model considering all orders of mutations in oncogene, KRAS and tumor suppressor genes, APC and TP53, and fit it on data describing the incidence rates of colorectal cancer at different age from the Surveillance Epidemiology and End Results registry in the United States for the year 1973-2013. The specific orders that can induce the development of colorectal cancer are identified by the model fitting. The fitting results indicate that the mutation orders with KRAS → APC → TP53, APC → TP53 → KRAS and APC → KRAS → TP53 explain the age-specific risk of colorectal cancer with very well. Furthermore, eleven pathways of gene mutations can be accepted for the mutation order of genes with KRAS → APC → TP53, APC → TP53 → KRAS and APC → KRAS → TP53, and the alternation of APC acts as the initiating or promoting event in the colorectal cancer. The estimated mutation rates of cells in the different pathways demonstrate that genetic instability must exist in colorectal cancer with alterations of genes, KRAS, APC and TP53.

Transcriptome Sequencing and Metabolome Analysis Reveals the Molecular Mechanism of Drought Stress in Millet.

As one of the oldest agricultural crops in China, millet (Panicum miliaceum) has powerful drought tolerance. In this study, transcriptome and metabolome analyses of 'Hequ Red millet' (HQ) and 'Yanshu No.10' (YS10) millet after 6 h of drought stress were performed. Transcriptome characteristics of drought stress in HQ and YS10 were characterized by Pacbio full-length transcriptome sequencing. The pathway analysis of the differentially expressed genes (DEGs) showed that the highly enriched categories were related to starch and sucrose metabolism, pyruvate metabolism, metabolic pathways, and the biosynthesis of secondary metabolites when the two millet varieties were subjected to drought stress. Under drought stress, 245 genes related to energy metabolism were found to show significant changes between the two strains. Further analysis showed that 219 genes related to plant hormone signal transduction also participated in the drought response. In addition, numerous genes involved in anthocyanin metabolism and photosynthesis were confirmed to be related to drought stress, and these genes showed significant differential expression and played an important role in anthocyanin metabolism and photosynthesis. Moreover, we identified 496 transcription factors related to drought stress, which came from 10 different transcription factor families, such as bHLH, C3H, MYB, and WRKY. Further analysis showed that many key genes related to energy metabolism, such as citrate synthase, isocitrate dehydrogenase, and ATP synthase, showed significant upregulation, and most of the structural genes involved in anthocyanin biosynthesis also showed significant upregulation in both strains. Most genes related to plant hormone signal transduction showed upregulated expression, while many JA and SA signaling pathway-related genes were downregulated. Metabolome analysis was performed on 'Hequ red millet' (HQ) and 'Yanshu 10' (YS10), a total of 2082 differential metabolites (DEMs) were identified. These findings indicate that energy metabolism, anthocyanins, photosynthesis, and plant hormones are closely related to the drought resistance of millet and adapt to adversity by precisely regulating the levels of various molecular pathways.

Research of the Algebraic Multigrid Method for Electron Optical Simulator.

At present, electron optical simulator (EOS) takes a long time to solve linear FEM systems. The algebraic multigrid preconditioned conjugate gradient (AMGPCG) method can improve the efficiency of solving systems. This paper is focused on the implementation of the AMGPCG method in EOS. The aggregation-based scheme, which uses two passes of a pairwise matching algorithm and the K-cyle scheme, is adopted in the aggregation-based algebraic multigrid method. Numerical experiments show the advantages and disadvantages of the AMG algorithm in peak memory and solving efficiency. The AMGPCG is more efficient than the iterative methods used in the past and only needs one coarsening when EOS computes the particle motion trajectory.

Kitchen-waste-derived biochar modified nanocomposites with improved photocatalytic performances for degrading organic contaminants.

Kitchen-waste-derived biochar (KBC) was produced by thermal treatment at 400 °C, and a series of KBC/BiOX (X = Br, Cl) photocatalysts were developed using ultrasonication and solvothermal treatment. The as-prepared photocatalysts were characterized by several tests and investigated by photocatalytic reactions towards methyl orange (MO) and tetracycline (TC). The best photocatalysts, 0.15KBC/BiOBr and 0.15KBC/BiOCl separately achieved complete MO photodegradation in 20 min and 35 min. Further study confirmed that 0.15KBC/BiOBr and 0.15KBC/BiOCl possessed excellent photocatalytic efficiency that was 17.9 and 14.8 times higher than BiOBr and BiOCl, respectively. In addition, 0.15KBC/BiOX showed higher activity removal of TC than pure BiOX in 60 min. Notably, 0.15KBC/BiOX maintained a reproducible high photocatalytic efficiency after five recycles. Estimated band gap energy for 0.15KBC/BiOBr (2.40 eV) and 0.15KBC/BiOCl (3.00 eV) was considerably lower than that of BiOBr (2.73 eV) and BiOCl (3.30 eV), indicating a delocalized state was created when forming electronic pathways on the interface. Besides, visible-light harvesting of photocatalysts got promoted by the modification of KBC. Active species trapping experiments and electron paramagnetic resonance (EPR) tests illustrated that photogenerated holes were the principal active species, while ∙OH was involved in the reaction. The successful synthesis of 0.15KBC/BiOX catalyst provided a new approach on simultaneously degrading organic contaminants in water and disposing of excessive kitchen waste.

Supramolecular Crystal Networks Constructed from Cucurbit[8]uril with Two Naphthyl Groups.

Naphthyl groups are widely used as building blocks for the self-assembly of supramolecular crystal networks. Host-guest complexation of cucurbit[8]uril (Q[8]) with two guests NapA and Nap1 in both aqueous solution and solid state has been fully investigated. Experimental data indicated that double guests resided within the cavity of Q[8], generating highly stable homoternary complexes NapA2@Q[8] and Nap12@Q[8]. Meanwhile, the strong hydrogen-bonding and π···π interaction play critical roles in the formation of 1D supramolecular chain, as well as 2D and 3D networks in solid state.

Diagnosis and laparoscopic excision of accessory cavitated uterine mass in a young woman: A case report.

BACKGROUND: Accessory and cavitated uterine mass (ACUM) is an uncommon form of connate Müllerian anomaly seen in young and nulliparous women, which presents as chronic periodic pelvic pain and severe dysmenorrhea. The entity is often underdiagnosed due to a broad differential diagnosis, including rudimentary uterine horn, true cavitated adenomyosis and degenerating fibroids. CASE SUMMARY: A 22-year-old woman who presented with severe dysmenorrhea and was initially misdiagnosed with cystic adenomyosis. Gynecological examination and ultrasonography were performed. The patient underwent laparoscopic excision of the mass and histopathological examination confirmed the diagnosis. Postoperatively, the patient did well, with no further dysmenorrhea. CONCLUSION: ACUM is difficult to diagnose. A correct diagnosis can be made only after excision and histopathological evaluation. Surgical excision is necessary and can be carried out by laparoscopy.

Two-Dimensional Design Strategy to Construct Smart Fluorescent Probes for the Precise Tracking of Senescence.

The tracking of cellular senescence usually depends on the detection of senescence-associated ß-galactosidase (SA-ß-gal). Previous probes for SA-ß-gal with this purpose only cover a single dimension: the accumulation of this enzyme in lysosomes. However, this is insufficient to determine the destiny of senescence because endogenous ß-gal enriched in lysosomes is not only related to senescence, but also to some other physiological processes. To address this issue, we introduce our fluorescent probes including a second dimension: lysosomal pH, since de-acidification is a unique feature of the lysosomes in senescent cells. With this novel design, our probes achieved excellent discrimination of SA-ß-gal from cancer-associated ß-gal, which enables them to track cellular senescence as well as tissue aging more precisely. Our crystal structures of a model enzyme E. coli ß-gal mutant (E537Q) complexed with each probe further revealed the structural basis for probe recognition.

A theranostic probe of indoleamine 2,3-dioxygenase 1 (IDO1) for small molecule cancer immunotherapy.

Discovering novel small molecules for cancer immunotherapy represents a promising but challenging strategy in future cancer treatment. Herein, we designed the first theranostic fluorescent probes to efficiently detect and inhibit the enzymatic activity of 2,3-dioxygenase 1 (IDO1). Probe 6b is a highly active IDO1 inhibitor (IC50 = 12 nM, Cellular IC50 = 10 nM), which can sensitively and specifically detect endogenous IDO1 in living cells. Furthermore, as a theranostic probe, 6b showed excellent in vivo antitumor efficacy in the CT26 xenograft mouse model as well. Therefore, it can be applied as a valuable chemical tool for better understanding the immunotherapy mechanism of IDO1 and improving the therapeutic efficiency.

First-generation species-selective chemical probes for fluorescence imaging of human senescence-associated ß-galactosidase.

Human senescence-associated ß-galactosidase (SA-ß-gal), the most widely used biomarker of aging, is a valuable tool for assessing the extent of cell 'healthy aging' and potentially predicting the health life span of an individual. Human SA-ß-gal is an endogenous lysosomal enzyme expressed from GLB1, the catalytic domain of which is very different from that of E. coli ß-gal, a bacterial enzyme encoded by lacZ. However, existing chemical probes for this marker still lack the ability to distinguish human SA-ß-gal from ß-gal of other species, such as bacterial ß-gal, which can yield false positive signals. Here, we show a molecular design strategy to construct fluorescent probes with the above ability with the aid of structure-based steric hindrance adjustment catering to different enzyme pockets. The resulting probes normally work as traditional SA-ß-gal probes, but they are unique in their powerful ability to distinguish human SA-ß-gal from E. coli ß-gal, thus achieving species-selective visualization of human SA-ß-gal for the first time. NIR-emitting fluorescent probe KSL11 as their representative further displays excellent species-selective recognition performance in biological systems, which has been herein verified by testing in senescent cells, in lacZ-transfected cells and in E. coli-ß-gal-contaminated tissue sections of mice. Because of our probes, it was also discovered that SA-ß-gal content in mice increased gradually with age and SA-ß-gal accumulated most in the kidneys among the main organs of naturally aging mice, suggesting that the kidneys are the organs with the most severe aging during natural aging.