Effect of axial stresses on longitudinal guided waves in a fluid-filled pipe.

This paper describes the study of the acoustic field of a fluid-filled pipe subjected to axial stress based on the acoustoelastic theory. The pipe with applied axial stresses can be approximated as a transversely isotropic pipe, and hence, its acoustic fields can be expressed using potential functions. The velocity changes of longitudinal wave modes with applied stresses are analyzed for the pipe filled with oil by an analytical method. It was found that the longitudinal mode velocity changes almost uniformly with the applied stresses. The high speed and low frequency plateaus of longitudinal wave modes are sensitive to stress. The relationship between stress and the velocity change of the guided wave is given. The results indicate that non-destructive testing techniques using longitudinal wave modes have strong potential to identify and monitor the stress levels in pipe structures.

Association study of genetic variation in the autophagy lysosome pathway genes and risk of eight kinds of cancers.

The autophagy lysosome pathway is essential to maintain cell viability and homeostasis in response to many stressful environments, which is reported to play a vital role in cancer development and therapy. However, the association of genetic alterations of this pathway with risk of cancer remains unclear. Based on genome-wide association study data of eight kinds of cancers, we used an adaptive rank truncated product approach to perform a pathway-level and gene-level analysis, and used a logistic model to calculate SNP-level associations to examine whether an altered autophagy lysosome pathway contributes to cancer susceptibility. Among eight kinds of cancers, four of them showed significant statistics in the pathway-level analysis, including breast cancer (p = 0.00705), gastric cancer (p = 0.00880), lung cancer (p = 0.000100) and renal cell carcinoma (p = 0.00190). We also found that some autophagy lysosome genes had signals of association with cancer risk. Our results demonstrated that inherited genetic variants in the overall autophagy lysosome pathway and certain associated genes might contribute to cancer susceptibility, which warrant further evaluation in other independent datasets.

Effects of rTMS Intervention on Functional Neuroimaging Activities in Adolescents with Major Depressive Disorder Measured Using Resting-State fMRI.

Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) is commonly used for the clinical treatment of major depressive disorder (MDD). The neuroimaging biomarkers and mechanisms of rTMS are still not completely understood. This study aimed to explore the functional neuroimaging changes induced by rTMS in adolescents with MDD. A total of ten sessions of rTMS were administrated to the L-DLPFC in thirteen adolescents with MDD once a day for two weeks. All of them were scanned using resting-state functional magnetic resonance imaging at baseline and after rTMS treatment. The regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and the subgenual anterior cingulate cortex (sgACC)-based functional connectivity (FC) were computed as neuroimaging indicators. The correlation between changes in the sgACC-based FC and the improvement in depressive symptoms was also analyzed. After rTMS treatment, ReHo and ALFF were significantly increased in the L-DLPFC, the left medial prefrontal cortex, bilateral medial orbital frontal cortex, and the left ACC. ReHo and ALFF decreased mainly in the left middle occipital gyrus, the right middle cingulate cortex (MCC), bilateral calcarine, the left cuneus, and the left superior occipital gyrus. Furthermore, the FCs between the left sgACC and the L-DLPFC, the right IFGoper, the left MCC, the left precuneus, bilateral post-central gyrus, the left supplementary motor area, and the left superior marginal gyrus were enhanced after rTMS treatment. Moreover, the changes in the left sgACC-left MCC FC were associated with an improvement in depressive symptoms in early improvers. This study showed that rTMS treatment in adolescents with MDD causes changes in brain activities and sgACC-based FC, which may provide basic neural biomarkers for rTMS clinical trials.

HIF-1α-induced histone demethylase JMJD2B contributes to the malignant phenotype of colorectal cancer cells via an epigenetic mechanism.

Hypoxia-inducible factor 1α (HIF-1α) plays a key role in mediating cancer cell malignant characteristics. Recent studies have shown that the histone demethylase JMJD2B is a target of HIF-1α, suggesting that histone methylation may be involved in tumor malignancy during hypoxia. However, little is known about the tumorigenic role of JMJD2B and its association with hypoxia in colorectal cancer (CRC). Furthermore, the downstream target genes and the mechanisms by which JMJD2B regulates its target genes in CRC during hypoxia remain to be clarified. Our results demonstrated that JMJD2B was induced under hypoxia in an HIF-1α-dependent manner in CRC cells. JMJD2B played an important role in CRC cell proliferation, apoptosis, cell cycle arrest and invasion, which could be modulated through upregulation of a subset of hypoxia-inducible genes expression by decreasing trimethylation of histone H3 lysine 9 on their promoters. We also showed that JMJD2B was overexpressed in CRC tissues and positively correlated with expression of the hypoxic marker carbonic anhydrase 9 (CA9), deeper depth of invasion and advanced clinical stages. Therefore, our findings suggest that JMJD2B may serve as a potential therapeutic cancer target.

Interaction of two peptide drugs with biomacromolecules analyzed by molecular docking and multi-spectroscopic methods.

Peptide drugs, which are mainly used for the treatment of AIDS, myeloma, and breast cancer, have evolved rapidly owing to their high efficacy and low side effects. The interaction mechanisms of two peptide drugs with two biological macromolecules (protein and DNA), which are of great significance in disease prevention and drug design, were investigated using molecular docking, fluorescence spectroscopy, circular dichroism (CD) spectroscopy, UV-visible spectroscopy and viscosity measurements. The interaction between a series of common drugs and ovalbumin (OVA) was simulated by molecular docking, and two peptide drugs with the highest energy values, namely atazanavir and carfilzomib, were selected; the binding energy values of these drugs with OVA were -59.20 and -55.93 kcal/mol, respectively. The Kb values of the interaction of the two drugs with OVA/DNA were in the range of 104-107 M-1, and the binding affinity of the drugs was stronger with OVA than with DNA. Hydrogen bonds and van der Waals forces were very important for the binding between drugs and OVA through molecular docking studies, and it was consistent with experimental results (ΔH < 0, ΔH < 0). The synchronous fluorescence spectrum showed that the interaction caused a change to the original structure of OVA, and atazanavir had a greater effect on OVA than carfilzomib. CD spectrum analysis also demonstrated that the conformation of OVA changed slightly. The interaction between atazanavir and DNA was mainly driven by hydrophobic forces (ΔH > 0 and ΔH > 0), whereas the major interaction forces involved in the binding of carfilzomib with DNA were hydrogen bonds and van der Waals forces. DNA melting studies, UV-visible spectroscopy, CD spectroscopy and viscosity measurements established that the interaction between the drugs and DNA was groove binding.

Enhancement of long-lived luminescence in nanophosphors by surface defect passivation.

Herein, we found that surface defects quench persistent luminescence in nanophosphors. Passivation of surface defects by thermal treatment or surface coating can effectively enhance the intensity and prolong the decay time of persistent luminescence. The surface passivated persistent nanophosphors are promising in autofluorescence-free bioimaging and time-gated steganography.

JMJD2B-induced amino acid alterations enhance the survival of colorectal cancer cells under glucose-deprivation via autophagy.

Rationale: Post-translational modifications have emerged as vital players in alterations to tumor metabolism, including amino acid metabolic reprogramming. Jumonji domain-containing protein 2B (JMJD2B) enhances colorectal cancer (CRC) cell survival upon glucose deficiency. In the present study, we hypothesized that JMJD2B affects tumor cell amino acid metabolism in CRC and consequently promotes survival of CRC cells upon glucose deprivation. Methods: Non-target metabolic profiling was used to evaluate the roles of JMJD2B in CRC cell metabolism under glucose starvation. The roles of amino acid alterations induced by JMJD2B on CRC cell survival were determined by cell viability, immunoblotting, and clonogenic assays, and flow cytometry. The underlying mechanisms by which JMJD2B affected CRC cell metabolism were assessed using immunofluorescence staining, chromatin immunoprecipitation assays, electron microscopy in CRC cell lines, and using xenograft models. The correlation between JMJD2B and LC3B expression in human CRC specimens was assessed using immunohistochemistry. Results: Profound metabolic reprogramming was detected in JMJD2B knockdown CRC cells under glucose deficiency, especially those involving amino acid metabolites. Silencing of JMJD2B reduced the levels of certain amino acids that were induced by glucose deficiency. Among these amino acids, asparagine (Asn), phenylalanine (Phe), and histidine (His) promoted CRC cell survival under glucose starvation when JMJD2B was knocked down. Mechanistically, downregulation of JMJD2B inhibited autophagy in CRC cells through epigenetic regulation of microtubule associated protein 1 light chain 3 beta (LC3B), and subsequently decreased intracellular amino acid (Asn, Phe, His) levels under glucose deprivation, thus suppressing the survival of CRC cells. Using a nude mouse xenograft model, we verified that inhibiting JMJD2B could decrease the levels of amino acids (Asn, Phe, His). In addition, the inhibitory effects of JMJD2B-knockdown on tumor growth and amino acids level were rescued by overexpression of LC3B. Furthermore, we observed that the high expression of LC3B was more likely detected in tissuses with high expression of JMJD2B (P < 0.001) in 60 human CRC tissues. Conclusion: These results indicated that JMJD2B sustained the intracellular amino acids derived from autophagy in CRC cells upon glucose deficiency, partly through epigenetic regulation of LC3B, thus driving the malignancy of CRC.

Enterotoxigenic Bacteroides fragilis induces the stemness in colorectal cancer via upregulating histone demethylase JMJD2B.

The enrichment of Enterotoxigenic Bacteroides fragilis (ETBF) has been identified in CRC patients and associated with worse prognosis. Cancer stem cells (CSCs) play essential roles in CRC development. However, whether ETBF is involved in CSCs regulation is unknown. To clarify the role of ETBF in CSCs properties, we performed extreme limited dilution assays (ELDA) in nude mice injected with ETBF-treated or untreated CRC cells subcutaneously, tumor organoids culture in azoxymethane (AOM) mouse model after gavaging with or without ETBF, and cell sphere formation assay after incubating CRC cell lines with or without ETBF. The results indicated that ETBF increased the stemness of CRC cells in vivo and in vitro. Furthermore, ETBF enhanced the expression of core stemness transcription factors Nanog homeobox (NANOG) and sex determining region Y-box 2 (SOX2). Histone H3 Lysine 9 trimethylation (H3K9me3) is critical in regulating CSCs properties. As an epigenetic and transcriptional regulator, JmjC-domain containing histone demethylase 2B (JMJD2B) is essential for embryonic stem cell (ESC) transformation and H3K9me3 demethylation. Mechanistically, ETBF infection significantly upregulated JMJD2B levels in CRC cell lines and nude mice xenograft model. JMJD2B epigenetically upregulated NANOG expression via demethylating its promoter H3K9me3, to mediate ETBF-induced stemness of CRC cells. Subsequently, we found that the Toll-like receptor 4 (TLR4) pathway, activated by ETBF, contributed to the enhanced expression of JMJD2B via nuclear transcription factor nuclear factor of activated T cells 5 (NFAT5). Finally, in human CRC samples, the amount of ETBF positively correlated with nuclear NFAT5, JMJD2B, and NANOG expression levels. In summary, ETBF upregulated JMJD2B levels in a TLR4-NFAT5-dependent pathway, and played an important role in stemness regulation, which promoted colorectal carcinogenesis.

Sirtuin5 contributes to colorectal carcinogenesis by enhancing glutaminolysis in a deglutarylation-dependent manner.

Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in 13C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth. Mechanistically, the direct interaction between SIRT5 and glutamate dehydrogenase 1 (GLUD1) causes deglutarylation and functional activation of GLUD1, a critical regulator of cellular glutaminolysis. Consistently, GLUD1 knockdown diminishes SIRT5-induced proliferation, both in vivo and in vitro. Clinically, overexpression of SIRT5 is significantly correlated with poor prognosis in CRC. Thus, SIRT5 supports the anaplerotic entry of glutamine into the TCA cycle in malignant phenotypes of CRC via activating GLUD1.

Long Noncoding RNA CCAT2 as a Potential Novel Biomarker to Predict the Clinical Outcome of Cancer Patients: A Meta-Analysis.

Background: Colon Cancer-Associated Transcript 2 (CCAT2) has been demonstrated associated with clinical outcomes in various tumors. However, the results from each study were unfortunately insufficient and not completely consistent. Therefore, we conduct a systematic meta-analysis to evaluate the value for a feasible biomarker for metastasis and prognosis. Methods: A meta-analysis was performed using data obtained through a systematic search of PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, Wanfang database and VIP database. The pooled odds ratio (OR) and hazard ratio (HR) with 95% Confidence interval (CI ) using random-effect were used to identify the relationship of CCAT2 with clinical outcome of cancer patients. Subgroup analysis and sensitivity analysis were performed. Results: A total of 867 patients from eight studies were finally included. Patients with high CCAT2 expression underwent an increased risk of lymph node metastasis (LNM) (OR=3.09, 95% CI: 1.53-6.26) and distant metastasis (DM) (OR=7.70, 95% CI: 3.26-18.17). CCAT2 was also significantly correlated with overall survival (OS) (HR=2.19, 95%CI: 1.70-2.82) and progression-free survival (PFS) (HR=2.59, 95% CI: 1.78-3.76). Moderate heterogeneity was observed in meta-analysis for LNM. However, the results remained robust in multiple sensitivity analyses. Conclusions: High expression of CCAT2 was linked with poor clinical outcome. CCAT2 can serve as a potential molecular marker for prognosis in different types of cancers.

Legume consumption and colorectal adenoma risk: a meta-analysis of observational studies.

BACKGROUND: The anticancer effects of legumes have been explored extensively, but evidence from epidemiologic studies on colorectal adenoma is controversial. We performed a meta-analysis to assess these issues. METHODS: A systemic search of several databases was conducted for relevant studies evaluating the relationship between legume intake and adenoma risk, with no language restriction, from January 1, 1966, to April 1, 2013. RESULTS: Three cohort and eleven case control studies with 8,380 cases and a total of 101,856 participants were included in the analysis; the pooled odds ratio (95% confidence interval) for the highest vs. lowest consumption categories was 0.83 (0.75-0.93), with moderate level of heterogeneity (I(2) = 25.9% and P = 0.146) based on a random effects model. A decreased risk of adenoma was also observed in most of our subgroup meta-analyses. CONCLUSIONS: Higher intake of legumes significantly reduced the risk of colorectal adenoma in our meta-analysis. Nevertheless, due to possible confounders and bias, further investigations are warranted to confirm this relationship.