EIF4A3-negatively driven circular RNA ß-catenin (circß-catenin) promotes colorectal cancer progression via miR-197-3p/CTNND1 regulatory axis.

BACKGROUND: Circß-catenin, our first reported circRNA, has been reported to mediate tumorigenesis in various cancers. However, its biological functions and underlying mechanisms in colorectal cancer (CRC) remain unknown. METHODS: The qRT-PCR examination was used to detect the expression of circß-catenin, miR-197-3p, and CTNND1 in cells and human tissues. Western blot was conducted to detect the protein expression levels. The biological function of circß-catenin was verified by MTT, colony formation, wound healing, and transwell assays. The in vivo effects of circß-catenin were verified by nude mice xenograft and metastasis models. The regulatory network of circß-catenin/miR-197-3p/CTNND1 was confirmed via dual-luciferase reporter and RIP assays. RESULTS: In the present study, circß-catenin was found to promote CRC cell proliferation and metastasis in vitro and in vivo. Mechanistically, circß-catenin served as miRNA decoy to directly bind to miR-197-3p, then antagonized the repression of the target gene CTNND1, and eventually promoted the malignant phenotype of CRC. More interestingly, the inverted repeated Alu pairs termed AluJb1/2 and AluY facilitated the biogenesis of circß-catenin, which could be partially reversed by EIF4A3 binding to Alu element AluJb2. CONCLUSIONS: Our findings illustrated a novel mechanism of circß-catenin in modulating CRC tumorigenesis and metastasis, which provides a potential therapeutic target for CRC patients.

LncRNA-NEF suppressed oxaliplatin resistance and epithelial-mesenchymal transition in colorectal cancer through epigenetically inactivating MEK/ERK signaling.

A major cause of oxaliplatin chemoresistance in colorectal cancer (CRC) is acquired epithelial-mesenchymal transition (EMT) in cancer cells, making the cancer cells easy to metastasis and recurrence. LncRNA Neighboring Enhancer of FOXA2 (lncRNA-NEF) has been characterized as a tumor suppressor to mediate cancer metastasis in multiple cancer types. However, whether it mediated the drug resistance remains unknown. In the present study, an oxaliplatin-resistant CRC cell line (SW620R) was established and lncRNA-NEF was obviously down-regulated in this resistant cell line. The further loss and gain-of-function studies demonstrated that this lncRNA suppressed oxaliplatin resistance as well as EMT programme in vitro and inhibited metastasis in vivo. Mechanistically, lncRNA-NEF epigenetically promoted the expression of DOK1 (Downstream of Tyrosine kinase 1), a negative regulator of MEK/ERK signaling, by disrupting DNA methyltransferases (DNMTs)-mediated DNA methylation. DOK1, in turn, induced the inactivation of MEK/ERK signaling, forming the lncRNA-NEF/DOK1/MEK/ERK regulatory axis to mediate oxaliplatin resistance in CRC. Collectively, our work reveals the critical function of lncRNA-NEF in mediating the oxaliplatin chemotherapy resistance in CRC, and provides a promising therapeutic strategy for CRC patients with oxaliplatin resistance.

Preparation and research of PCL/cellulose composites: Cellulose derived from agricultural wastes.

For the rational use of agricultural wastes, bagasse, orange peel and wheat bran were used to fabricate bio-based polymer materials. Cellulose was extracted from the three different agricultural wastes, and poly(ε-caprolactone) (PCL) was used as the matrix material. PCL was mixed with nanocrystalline cellulose (CNC), extracted bagasse cellulose (GC), orange peel cellulose (JC) and wheat bran cellulose (MC) by solution casting. Morphology and structure of the extracted cellulose were studied by Scanning Electron Microscope, Fourier Infrared spectrometer, thermogravimetry and X-ray diffractometer. The influence of GC, JC, MC on the crystallization process and mechanical properties of PCL was investigated by DSC and tensile test. Experimental results show that the addition of CNC, GC, JC, MC increases the crystallization temperature of PCL, accelerates the crystallization process of PCL, and improves the tensile property of PCL.

Linc-ROR drive adriamycin resistance by targeting AP-2α/Wnt/ß-catenin axis in hepatocellular carcinoma.

Adriamycin is widely used as a chemotherapeutic strategy for advanced hepatocellular carcinoma (HCC). However, the clinical response was disappointing because of the acquired drug resistance with long-term usage. Revealing the underlying mechanism could provide promising therapeutics for the drug-resistant patients. The recently identified linc-ROR (long intergenic non-protein-coding RNA, regulator of reprogramming) has been found to be an oncogene in various cancers, and it also demonstrated to mediate drug resistance and metastasis. We thereby wonder whether this lincRNA could mediate adriamycin chemoresistance in HCC. In this study, linc-ROR was found to be upregulated in adriamycin-resistant HCC cells. And its overexpression accelerated epithelial-mesenchymal transition (EMT) program and adriamycin resistance. Conversely, its silence suppressed EMT and made HCC cells sensitize to adriamycin in vitro and in vivo. Further investigation revealed that linc-ROR physically interacted with AP-2α, mediated its stability by a post-translational modification manner, and sequentially activated Wnt/ß-catenin pathway. Furthermore, linc-ROR expression was positively associated with ß-catenin expression in human clinical specimens. Taken together, linc-ROR promoted tumorigenesis and adriamycin resistance in HCC via a linc-ROR/AP-2α/Wnt/ß-catenin axis, which could be developed as a potential therapeutic target for the adriamycin-resistant patients.

MicroRNA-613 Enhances Nasopharyngeal Carcinoma Cell Radiosensitivity via the DNA Methyltransferase 3B/Tissue Inhibitor of Matrix Metalloproteinase-3/Signal Transducer and Activator of Transcription-1/Forkhead Box O-1 Axis.

Nasopharyngeal carcinoma (NPC) is a common malignancy of the nasopharynx, and radioresistant represents the main obstacle in NPC treatment. Malignant transformation of normal cells is driven by genetic and epigenetic changes, which are primarily manifested as changes in miRNA levels and DNA methylation status. microRNA (miR)-613 plays an inhibitory role in several types of cancer. Herein, the current study sought to explore the roles of miR-613 in NPC cell radiosensitivity. miR-613 expression patterns in NPC tissues were detected, and its correlation with clinical indexes was analyzed. NP-69 and C666-1 cell lines were selected for cellular experimentation. Radioresistant cell line C666-1R was obtained by fractionated radiation. Cell viability, survival fraction, and apoptosis were detected by CCK-8, colony formation assay, and flow cytometry. The binding relation between miR-613 and DNMT3B was verified by dual-luciferase and RIP assays. miR-613 was lowly expressed in NPC tissues and cells, with lower expression levels in C666-1R than C666-1, and further correlated with lymph node metastasis, tumor size, and tumor metastasis. miR-613 overexpression reduced C666-1R cell viability and survival fraction and increased apoptosis, while C666-1 cells with silencing miR-613 presented the opposite trends. miR-613 targeted DNMT3B. miR-613 and DNMT3B overexpression led to enhanced C666-1R cell viability and survival fraction and decreased apoptosis. miR-613 reduced TIMP3 methylation and elevated TIMP3 protein level by inhibiting DNMT3B. miR-613 enhanced NPC radiosensitivity by inhibiting the DNMT3B/TIMP3/STAT1/FOXO1 pathway. Collectively, miR-613 inhibited DNMT3B, reduced TIMP3 methylation, and increased TIMP3 protein level, thus inhibiting the STAT1/FOXO1 pathway and enhancing the radiosensitivity of NPC cells.

Icariside II suppressed tumorigenesis by epigenetically regulating the circß-catenin-Wnt/ß-catenin axis in colorectal cancer.

Icariside II, a flavonol glycoside, one of the major components of Traditional Chinese Medicine Herba epimedii. In the present study, we found that Icariside II suppressed the proliferation of CRC by inducing cell cycle arrest and apoptosis in vitro and inhibited tumor growth in vivo. The further mechanism investigation showed that Icariside II suppressed the expression of ß-catenin and led to the functional inactivation of Wnt/ß-catenin signaling. Circß-catenin was considered as a promising candidate for mediating the tumorigenesis and the activation of Wnt/ß-catenin signaling in CRC cells. Furthermore, Icariside II has been proven to suppress the biogenesis of circß-catenin via epigenetically targeting DNA methyltransferases (DNMTs) to decrease global DNA methylation levels in CRC cells. Taken together, our results indicated that Icariside II suppressed tumorigenesis by epigenetically silencing the activation of circß-catenin-Wnt/ß-catenin axis in colorectal cancer. More importantly, the information gained from this study suggest that Icariside II may have great potential to be developed as a therapeutic drug for CRC patients.

An effective strategy for improving charge separation efficiency and photocatalytic degradation performance using a facilely synthesized oxidative TiO2 catalyst.

Titanium dioxide (TiO2) has attracted enormous interest in abundant photocatalytic reactions, but its photocatalytic efficiency is limited by its wide bandgap and the rapid recombination of electron-hole pairs. To overcome the disadvantages of its rapid electron-hole recombination rate, herein, oxidative TiO2 was one-step fabricated using potassium permanganate (KMnO4), exhibiting improved charge separation efficiency and photocatalytic degradation performance towards methyl orange (MO). Remarkably, the first-order photodegradation rate of oxidative TiO2 is 3.68 times higher than that of pristine TiO2 under the irradiation of simulated sunlight and 2.15 times higher under ultraviolet light. This exceptional photocatalytic activity is attributed to the additional oxygen doped into the interstices of the TiO2 lattice, creating impurity states in the bandgap acting as trapping sites, thus facilitating charge separation. This work provides a promising strategy for the insertion of O atoms into the TiO2 lattice and expands the photocatalytic application of the related materials.

Sufentanil Inhibits the Proliferation and Metastasis of Esophageal Cancer by Inhibiting the NF-κB and Snail Signaling Pathways.

Sufentanil is a µ-opioid receptor agonist, widely used in intraoperative and postoperative analgesia of esophageal cancer. This study investigated the effects of sufentanil on the proliferation, invasion, and metastasis of esophageal carcinoma cells and its molecular mechanisms. Human esophageal carcinoma cells CaES-17 and Eca-109 were cultured in vitro. Different concentrations of sufentanil (1 and 10 µmol/L) were added to the experimental group. MTT was used to detect the proliferative activity of esophageal carcinoma cells. The migration ability of esophageal carcinoma cells was measured by the scratch test. Transwell was used to detect the invasive ability of esophageal carcinoma cells. The EMT marker expression was detected by qPCR. Meanwhile, effects of sufentanil on NF-κB and Snail expression and nucleation were evaluated. Establish a subcutaneous xenograft tumor model of nude mice with esophageal carcinoma cells and evaluate the antitumor effect of sufentanil. Sufentanil can inhibit the proliferation, invasion, and migration of CaES-17 and Eca-109 cells and has a dose-dependent relationship. The molecular mechanism showed that sufentanil could upregulate the expression of E-cadherin and inhibit the expression of vimentin. Sufentanil can inhibit the expression of NF-κB and Snail, as well as the nuclear expression of NF-κB and Snail. Xenograft tumor model results showed that sufentanil could inhibit tumor proliferation and NF-κB and Snail expression in tumor tissues of nude mice. Sufentanil inhibits esophageal cancer epithelial-mesenchymal transition (EMT) by acting on NF-κB and Snail signaling pathways to inhibit proliferation and metastasis of esophageal cancer.

Quantifying the contributions of human activities and climate change to vegetation net primary productivity dynamics in China from 2001 to 2016.

Vegetation is an important component of the terrestrial ecosystem, driven by climate change and human activities. Quantifying the relative contributions of climate change and anthropogenic activities to vegetation dynamics are essential to cope with global climate change. In this paper, the relative contributions of anthropogenic activities and climate change to net primary productivity (NPP) in China were analyzed by a two-step methodology based on the residual trend analysis (RESTREND). Firstly, the unaltered natural vegetation only affected by climate change (Vclimate) and the vegetation affected by climate change and human activities (Vclimate+human) were separated by the multi-temporal land use land cover (LULC) data. Secondly, RESTREND was applied to NPP of Vclimate and Vclimate+human, respectively, to calculate contributions of climatic factors and human activities to vegetation growth. Results revealed that NPP exhibited a significant increase with 3.13 g C m-2 yr-1 from 2001 to 2016 in China. Climate change and human activities both made favorable impacts on vegetation growth during the study period. Besides, with the separation of Vclimate and Vclimate+human, contributions of climatic factors to vegetation changes increased from 1.57 to 1.88 g C m-2 yr-1, with the proportion of 60.06%. While contributions of human activities to NPP decreased from 1.56 to 1.25 g C m-2 yr-1, with the proportion of 39.94%. Moreover, the average contributions of precipitation, temperature, solar radiation, and other climatic factors to NPP over the entire country were 0.72, 0.24, 0.61, and 0.31 g C m-2 yr-1. Precipitation played a decisive role in vegetation changes in arid and semi-arid regions, temperature was the dominant factor for alpine vegetation dynamics, and solar radiation was beneficial to vegetation growth in most areas of China.

RNA N6-methyladenosine modification is required for miR-98/MYCN axis-mediated inhibition of neuroblastoma progression.

Neuroblastoma (NB) is one of the most common malignant tumors of the sympathetic nervous system in childhood. NB severely threatens patient's health and life. However, more effective diagnosis and treatment methods are badly needed in clinics all over the world. MYCN is well recognized as a genetic biomarker of high risk and poor outcome in NB. miRNAs are small RNAs and miR-98 involved in the pathogenesis of various cancers. The role and mechanism of miR-98 in NB remains to be investigated. Here we found that miR-98 was decreased in human MYCN-high-expression NB tissues, and its down-regulation was associated with poor prognosis of NB. Over-expression of miR-98 inhibited cell proliferation, migration and invasion of NB cells. The analysis by employing the software of miRanda predicted the possible binding sites of miR-98 in the 3'-UTR of MYCN, and experimental data illustrated that miR-98 directly bound to MYCN 3'-UTR and decreased MYCN expression. Over-expression of MYCN rescued the decreased malignant phenotype caused by over-expression of miR-98 in NB. N6-methyladenosine modification in 3'-UTR of MYCN promoted its interaction with miR-98. The data collectively demonstrated that RNA m6A modification was required for miR-98/MYCN axis-mediated inhibition of neuroblastoma progression, and miR-98 might be novel targets for NB detection and treatment.

Improving glucose metabolism in the auditory cortex delays the aging of auditory function of guinea pig.

The glucose homeostasis is essential for brain function, and energy deficiency is a key feature of brain aging. We investigated whether improving glucose metabolism in the auditory cortex can delay the aging of auditory function of guinea pigs with age-related hearing loss (ARHL) by d-galactose. Auditory function was assessed by auditory brainstem response (ABR), glucose metabolism was detected by micro PET/CT, and the proteome were identified in auditory cortex by two-dimensional electrophoresis and matrix assisted laser desorption/ionization mass spectrometry. Glucose metabolism decreased in the auditory cortex of d-galactose group, and improving glucose metabolism can delay the aging of auditory function by upregulating seven metabolism-related proteins including ATP synthase subunit beta, triosephosphate isomerase, creatine kinase U-type, pyruvate dehydrogenase E1 component subunit beta, alpha-enolase, phosphoglycerate kinase, and tubulin beta-2A chain. These results suggest that the decrease of glucose metabolism in the auditory cortex may be an important role in the aging of auditory function, and improving glucose metabolism in the auditory cortex can delay the aging of auditory function of guinea pig with ARHL induced by d-galactose.

[Effect of Electroacupuncture on Expression of Catechol-O-methyltransferase in the Inferior Colliculus and Auditory Cortex in Age-related Hearing Loss Guinea Pigs].

OBJECTIVE: To observe the expression of catechol-O-methyltransferase (COMT) in inferior colliculus and auditory cortex of guinea pigs with age-related hearing loss(AHL) induced by D-galactose, so as to explore the possible mechanism of electroacupuncture(EA) underlying preventing AHL. METHODS: Thirty 3-month-old guinea pigs were randomly divided into control group, model group and EA group(n=10 in each group), and ten 18-month-old guinea pigs were allocated as elderly group. The AHL model was established by subcutaneous injection of D-galactose. EA was applied to bilateral "Yifeng"(SJ 17) and "Tinggong"(SI 19) for 15 min in the EA group while modeling, once daily for 6 weeks. After treatment, the latency of auditory brainstem response(ABR) Ⅲ wave was measured by a brain-stem evoked potentiometer. The expressions of COMT in the inferior colliculus and auditory cortex were detected by Western blot. RESULTS: Compared with the control group, the latencies of ABR Ⅲ wave were significantly prolonged and the expressions of COMT in the inferior colliculus and auditory cortex were significantly decreased in the model group and the elderly group(P<0.05). After the treatment, the latency of ABR Ⅲ wave was significantly shortened and the expressions of COMT in the inferior colliculus and auditory cortex were significantly increased in the EA group in comparison with the model group (P<0.05). CONCLUSIONS: EA at "Yifeng" (SJ 17) and "Tinggong" (SI 19) can improve the hearing of age-related deafness in guinea pigs, which may contribute to its effect in up-regulating the expression of COMT in the inferior colliculus and auditory cortex.

[Runoff and sediment yielding processes on red soil engineering accumulation containing gravels by a simulated rainfall experiment].

Engineering accumulation formed in production and construction projects is characterized by unique structure and complex material composition. Characteristics of soil erosion on the engineering accumulation significantly differ from those on farmland. An artificially simulated rainfall experiment was carried out to investigate the effects of rainfall intensity on the processes of runoff and sediment yielding on the engineering accumulation of different gravel contents (0%, 10%, 20% and 30%) in red soil regions. Results showed that the initial time of runoff generation decreased with increases in rainfall intensity and gravel content, the decreased amplitudes being about 48.5%-77.9% and 4.2%-34.2%, respectively. The initial time was found to be a power function of rainfall intensity. Both runoff velocity and runoff rate manifested a trend of first rising and then in a steady state with runoff duration. Rainfall intensity was found to be the main factor influencing runoff velocity and runoff rate, whereas the influence of gravel content was not significant. About 10% of gravel content was determined to be a critical value in the influence of gravel content on runoff volume. For the underlying surface of 10% gravel content, the runoff volume was least at rainfall intensity of 1.0 mm · min(-1) and maximum at rainfall intensity of greater than 1.0 mm · min(-1). The runoff volume in- creased 10%-60% with increase in rainfall intensity. Sediment concentration showed a sharp decline in first 6 min and then in a stable state in rest of time. Influence of rainfall intensity on sediment concentration decreased as gravel content increased. Gravels could reduce sediment yield significantly at rainfall intensity of greater than 1.0 mm · min(-1). Sediment yield was found to be a linear function of rainfall intensity and gravel content.

Mechanism and symmetry properties of depolarization in weak scattering of light.

The mechanism and some symmetry properties of depolarization upon weak scattering of light from a class of random media were studied theoretically. Departing from the angular distribution of the degree of polarization, our derivations showed the mechanism that induces the change of polarization can be split into two parts of different nature. One is the vectorial effect that redistributes the original light components, and the other is the interaction effect of the medium that modulates the correlation properties of the incident field. We also showed that there is dependence of the angular distribution on the incident polarization state; i.e., the angular pattern and its symmetry depend on both the orientation and ellipticity of the incident polarization. Random light was analyzed in the space-frequency domain.