[Bioinformatic analysis of the relationship between protein phosphatase 2A catalytic subunit alpha (PPP2CA) expression and prognosis and immune infiltration in colorectal cancer patients].

Objective To analyze the relationship between protein phosphatase 2A catalytic subunit alpha (PPP2CA) expression and prognosis and immune infiltration in colorectal cancer (CRC) patients, and further explore the mechanism about the development and progression of CRC. Methods The differences in PPP2CA expression levels between CRC tissues and normal tissues were analyzed using the gene chip database Oncomine and The Tumor Immune Estimation Resource (TIMER) database. The impact of PPP2CA expression levels on the prognosis of CRC patients was analyzed using The University of Alabama at Birmingham Cancer data analysis portal (UALCAN) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. To further understand the role of PPP2CA in CRC, the co-expression network of PPP2CA was constructed using LinkedOmics platform, followed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Besides, the correlation between PPP2CA and immune infiltration was analyzed using TIMER and GEPIA databases. The gene mutation of PPP2CA in colon adenocarcinoma (COAD) were analyzed using c-BioPortal platform. Results PPP2CA was down-regulated in CRC tissues compared with normal tissues, and higher PPP2CA expression indicated better Overall Survival (OS) and Progression-Free Survival (PFS). In COAD, the expression level of PPP2CA was positively correlated with immune infiltrating cells including CD8+ T cells, neutrophils and dendritic cells. However, certain immune cell markers including CD19 and CD38 in B cells, NOS2 in M1 macrophages, Arginase 1 (ARG1) and Mannose Receptor C-Type 1 (MRC1) in M2 macrophages, Human Leukocyte Antigen G (HLA-G) and CD80 in Tumor Associated Macrophage (TAM) and CD14 and Fc Gamma Receptor 3A (FCGR3A) in monocytes, showed a different pattern of PPP2CA-associated immune infiltration. In other words, PPP2CA expression level was significantly associated with B cells, macrophages, monocytes, TAM, Th1 cells, Th2 cells, regulatory T cells, exhausted T cells and neutrophils in both COAD and rectum adenocarcinoma (READ). Conclusion PPP2CA is down-regulated in CRC tissues and closely correlated with immune infiltration.

PPP2CA Inhibition Promotes Ferroptosis Sensitivity Through AMPK/SCD1 Pathway in Colorectal Cancer.

PURPOSE: Colorectal cancer (CRC) is a very common malignancy of the digestive system. Despite a variety of treatments including surgery, chemotherapeutic and targeted drugs, the prognosis for patients with CRC is still unsatisfactory and the mortality remains high. Protein phosphorylation plays an essential role in tumorigenesis and progression and is also crucial for protein to act with proper functions. Ferroptosis is found widely involved in various diseases especially tumors as a newly identified programmed cell death. METHODS: In our study, we aimed at PPP2CA as a prospective target which may play a crucial role in CRC progression. In one hand, knockdown of PPP2CA significantly enhanced the malignant phenotype in HCT116. In the other hand, knockdown of PPP2CA significantly enhanced Erastin-induced ferroptosis as well. RESULTS: Specifically, knockdown of PPP2CA in HCT116 significantly increased the relative level of malondialdehyde (MDA), reactive oxygen species (ROS) and Fe2+, and decreased GSH/GSSG ratio after the treatment of certain concentration of Erastin. Besides, we found that the inhibition of PPP2CA further led to the suppression of SCD1 expression in CRC cells in a AMPK-dependent way. CONCLUSION: Ultimately, we conclude that PPP2CA may regulate Erastin-induced ferroptosis through AMPK/SCD1 signaling pathway.

In situ resource utilization of lunar soil for highly efficient extraterrestrial fuel and oxygen supply.

Building up a lunar settlement is the ultimate aim of lunar exploitation. Yet, limited fuel and oxygen supplies restrict human survival on the Moon. Herein, we demonstrate the in situ resource utilization of lunar soil for extraterrestrial fuel and oxygen production, which may power up our solely natural satellite and supply respiratory gas. Specifically, the lunar soil is loaded with Cu species and employed for electrocatalytic CO2 conversion, demonstrating significant production of methane. In addition, the selected component in lunar soil (i.e. MgSiO3) loaded with Cu can reach a CH4 Faradaic efficiency of 72.05% with a CH4 production rate of 0.8 mL/min at 600 mA/cm2. Simultaneously, an O2 production rate of 2.3 mL/min can be achieved. Furthermore, we demonstrate that our developed process starting from catalyst preparation to electrocatalytic CO2 conversion is so accessible that it can be operated in an unmmaned manner via a robotic system. Such a highly efficient extraterrestrial fuel and oxygen production system is expected to push forward the development of mankind's civilization toward an extraterrestrial settlement.

Quantitative assessment of OCT and OCTA parameters in diabetic retinopathy with and without macular edema: single-center cross-sectional analysis.

Aim: The retinal and choroidal parameters were analyzed to understand the impairment of microcirculation of both retina and choroid in patients with diabetic retinopathy (DR). Methods: Fifty-five treatment-naive non-proliferative diabetic retinopathy (NPDR) patients (75 eyes) with type 2 diabetes mellitus (T2DM), including 28 patients (36 eyes) with diabetic macular edema (DME) and 27 patients (39 eyes) without DME, and 25 healthy subjects (47 eyes) were enrolled in this study. The following parameters of DR patients with and without DME were evaluated: the foveal avascular zone area (FAZ-a), FAZ perimeter (FAZ-p), FAZ circularity index (FAZ-CI), total subfoveal choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI), choriocapillaris flow area percentage, superficial capillary plexus (SCP), and deep capillary plexus (DCP). Results: SCP, DCP, and the percentage of choriocapillaris flow area were significantly different between DR patients with and without DME. The DR patients presented lower LA, CVI, and FAZ-CI compared to those of healthy controls (all p < 0.05). The percentage of choriocapillaris flow area in DR patients with and without DME was significantly lower than that in healthy controls (p < 0.05). SCP and DCP were significantly correlated with FAZ-a and FAZ-p but presented insignificant associations with FAZ-CI. Conclusions: Optical coherence tomography (OCT) and OCT angiography (OCTA) parameters, such as LA, CVI, FAZ-CI, and the percentage of choriocapillaris flow area, were reduced compared to those in controls, indicating that the microcirculations of the retina and choroid in the macular area were impaired in DR patients with DME and without DME.

[Metal-organic framework UiO-67-based enrichment and purification of progesterone residues in milk].

Progesterone functions as an endocrine-disrupting compound. Imitating endogenous hormones disrupt the animals' hormone levels. The potential hazard of progesterone in milk cannot be neglected. Thus, research has focused on establishing an efficient and convenient pretreatment and analytical approach. In this study, a metal-organic framework (MOF) material UiO-67 was prepared, which possessed a large specific surface area and excellent stability. It was employed to enrich and purify trace progesterones in a complex milk matrix as a filler to integrate the solid phase extraction column. An approach based on MOF was developed using ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS). This approach could simultaneously determine seven kinds of progesterone residues in milk. The element spectra of UiO-67 were first measured and analyzed using X-ray photoelectron spectroscopy. The chemical interaction between UiO-67 and progesterone was proved by comparing the changes in binding energy and relative contents of functional groups, and the adsorption efficiency of 1 mg/L and 5 mg/L progesterones by UiO-67 was studied. The adsorption efficiencies of UiO-67 for 1 mg/L and 5 mg/L progesterones were 99.73%-99.95% and 88.87%-99.23%, respectively, according to the results. It proved the efficient adsorption of UiO-67 to progesterones and ensured that subsequent studies went smoothly. Furthermore, key parameters, such as the amount of sorbent, elution solvent type, and pH value, were examined and optimized to obtain optimal extraction recovery of the progesterones. Spiked concentrations of 50 µg/L were employed for extraction optimization. All experiments were performed three times. It also evaluated the matrix effect on mass spectrum signal of the progesterones. The optimized results showed that the seven progesterones could be satisfactorily recovered when the amount of adsorbent was 40 mg, pH value of the sample solution was 5, and elution solution was 5-mL acetone. Additionally, the matrix effect of progesterone in the milk sample was <20%. The matrix effect could be neglected using the aforementioned approach to extract and purify progesterones in milk. Finally, the seven progesterones showed good linearity between 1 and 100 µg/L under the optimized conditions, with linear correlation coefficients values >0.99. The limits of detection (LODs) ranged from 0.06 to 0.30 µg/L, and limits of quantification (LOQs) ranged from 0.19 to 1.0 µg/L, respectively. At various concentration levels of progesterones in milk, the recoveries were 87.10%-105.58%, with relative standard deviations of 2.66%-9.64%. Most importantly, the approach was successfully employed to determine progesterone levels in milk samples, with results in good agreement with the standard SN/T 1980-2007. The proposed approach had the advantages of high sensitivity and satisfactory accuracy compared with the reported pretreatment and detection approaches of progesterone in milk. Satisfactory experimental results can be obtained without the calibration by isotope inner standard. Meanwhile, considering the excellent performance of MOF materials in reducing matrix interference in complex samples, such the application of materials offers a new approach. It can be employed to enrich and detect hazards in a complex matrix in the future.

MiR-182-5p inhibits colon cancer tumorigenesis, angiogenesis, and lymphangiogenesis by directly downregulating VEGF-C.

MicroRNAs (miRNAs) are gene modulators essential for biological processes. However, the precise functions of miRNAs in growth and development of colon cancer are still elusive. To clarify their role, here we analyzed a miRNA microarray of colon cancer. MiR-182-5p was found markedly downregulated in colon cancer tissues and cells, and strongly correlated with pathological stage, differentiation, and lymphatic metastasis. In vitro, miR-182-5p overexpression repressed colon cancer cell proliferation, colony formation, migration, and invasion, and triggered G1 arrest and apoptosis. MiR-182-5p overexpression also downregulated vascular endothelial growth factor (VEGF)-C and inhibited the activity of a luciferase reporter containing the VEGF-C 3'-untranslated region. Moreover, miR-182-5p overexpression in colon cancer cells and human umbilical vein endothelial cells (HUVECs) downregulated VEGF-A as well as VEGF receptor (VEGFR)-2 and VEGFR-3, thereby inhibiting the phosphorylation of ERK and AKT. In vivo, miR-182-5p overexpression strikingly suppressed oncogenicity of SW620 cells as well as angiogenesis and lymphangiogenesis of xenograft tumors in nude mice. These data indicate that miR-182-5p regulates colon cancer tumorigenesis partially through modulating angiogenesis and lymphangiogenesis by targeting VEGF-C, and inhibiting ERK and AKT signaling pathways.

Long noncoding RNA BDNF-AS is a potential biomarker and regulates cancer development in human retinoblastoma.

BACKGROUND: Long non-coding RNAs (lncRNA) have been shown to play important roles in human cancer. We examined expression, prognostic potential and functional roles of lncRNA, brain-derived neurotrophic factor antisense (BDNF-AS) in human retinoblastoma (RB). METHODS: BDNF-AS expression in RB tumors was characterized according to the clinicopathological parameters of patients. BDNF-AS mRNA level was compared between RB tumors and normal retinas, as well as RB cell lines and normal retinal epithelial cells. RB patients' overall survival was compared between those with low and high BDNF-AS tumor expressions. Statistical analysis was performed to examine the independence of BDNF-AS being cancer biomarker in RB. In Y79 and WERI-Rb-1 cells, BDNF-AS was upregulated. It's effect on cancer proliferation, migration and cell-cycle transition were assessed. RESULTS: BDNF-AS is downregulated in RB tumors and cell lines. Low BDNF-AS expression in RB tumors is correlated with patients' advanced clinical stage and tumor differentiation status. Low BDNF-AS expression is associated with shorter overall survival and may be acting as an independent marker in RB. In Y79 and WERI-Rb-1 cells, forced overexpression of BDNF-AS inhibited cancer proliferation and migration. It also induced cell-cycle arrest at G0/G1 phase by downregulating CDC42, Cyclin E and BDNF. CONCLUSION: BDNF-AS is lowly expressed, and may be used as a prognostic biomarker in RB. Upregulating BDNF-AS has inhibitory effect on RB development, probably through the suppression of cell-cycle transition.

Long non-coding RNA H19 suppresses retinoblastoma progression via counteracting miR-17-92 cluster.

Long non-coding RNAs (lncRNAs) are frequently dysregulated and play important roles in many cancers. lncRNA H19 is one of the earliest discovered lncRNAs which has diverse roles in different cancers. However, the expression, roles, and action mechanisms of H19 in retinoblastoma are still largely unknown. In this study, we found that H19 is downregulated in retinoblastoma tissues and cell lines. Gain-of-function and loss-of-function assays showed that H19 inhibits retinoblastoma cell proliferation, induces retinoblastoma cell cycle arrest and cell apoptosis. Mechanistically, we identified seven miR-17-92 cluster binding sites on H19, and found that H19 directly bound to miR-17-92 cluster via these seven binding sites. Through binding to miR-17-92 cluster, H19 relieves the suppressing roles of miR-17-92 cluster on p21. Furthermore, H19 represses STAT3 activation induced by miR-17-92 cluster. Hence, our results revealed that H19 upregulates p21 expression, inhibits STAT3 phosphorylation, and downregulates the expression of STAT3 target genes BCL2, BCL2L1, and BIRC5. In addition, functional assays demonstrated that the mutation of miR-17-92 cluster binding sites on H19 abolished the proliferation inhibiting, cell cycle arrest and cell apoptosis inducing roles of H19 in retinoblastoma. In conclusion, our data suggested that H19 inhibits retinoblastoma progression via counteracting the roles of miR-17-92 cluster, and implied that enhancing the action of H19 may be a promising therapeutic strategy for retinoblastoma.

[Research on Spectrum Matching Method for PbSe Quantum Dots Luminescence Spectrum and Gas Absorption Spectrum].

As typical nano metarials in near infrared waveband, PbSe Quantum Dots have a very large exciton Bohr radius of 46 nm and a small band gap of 0.28 eV at room temperature. PbSe QDs have very unique properties, such as the quantum confined optical property, and which possess high photoluminescence (PL) quantum yield (QY) with size dependent tunable wavelength emissions. By analyzing the luminescence spectrum of PbSe Quantum Dots, a method through adjusting the particle size of PbSe Quantum Dots (QDs) to match gas absorption spectrum was presented in this paper. 4.6 and 6.1 nm PbSe QDs were synthesized and deposited on the GaN chip to fabricate the NIR QDs light sources. The PbSe QDs-UV glue composites thickness was determined to be 48.0 and 671.5 µm for 6.1 and 4.6 nm PbSe QDs. The NIR QDs were used to detect the C2H2 and NH3 gas. The experiments show that the PL spectrum of 4.6 nm NIR QDs can cover the entire absorption spectrum of C2H2 gas (from 1 500 to 1 550 nm) and the PL spectrum of 6.1 nm NIR QDs can cover the entire absorption spectrum of NH3 gas (from 1 900 to 2 060 nm). By changing the quantum size of QDs, the PL peak of the NIR QDS light source can be adjusted to cover the absorption peak of different gases. The matching method presented in this paper is efficient and feasible, which has great application potential in gas detection.

MiR199b suppresses expression of hypoxia-inducible factor 1α (HIF-1α) in prostate cancer cells.

MicroRNAs (miRNAs) are a class of small noncoding RNAs that post-transcriptionally repress expression of target genes via imperfect base-pairing with the 3'-untranslated region (3'-UTR). The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays important roles in physiology and pathology. Constitutive over-expression of HIF-1α is observed in many types of cancers including prostate carcinoma, but the mechanisms underlying this event remain largely unknown. Here we investigated the expression of miR199b and HIF-1α in normal prostate tissue, prostate cancer tissues and prostate carcinoma (PCa) cell lines LNCaP, PC-3 and DU145.We found that miR-199b expression level was decreased in prostate cancer while HIF-1α was significantly over-expressed. Furthermore, we postulated the posttranscriptional regulation of HIF-1α by miR199b through bioinformatics analysis, and herein we experimentally demonstrated that miR199b negatively regulated HIF-1α by targeting its 3'-untranslated region. Artificial over-expression of miR199b by using adenoviral vectors in prostate cancer PC-3 and DU145 cells significantly down-regulated HIF-1α, together with reduced cell growth and increased cell death.

[The expression and function of anti-apoptotic Bfl-1 in prostate cancer].

OBJECTIVE: To determine the expression of Bcl2 related protein A1(Bfl-1) mRNA in prostate cancer cell lines and tissues, and to explore the functions of Bfl-1 in prostate adenocarcinoma. METHODS: RT-PCR, real-time quantitative PCR (Q-PCR)and in situ hybridization (ISH) were used to detect the expression of Bfl-1 mRNA in prostate cancer cell lines, tissues and benign prostate hyperplasia (BPH) tissue samples. The relationship between Bfl-1 expression and clinicopathological parameters was analyzed. Antisense oligonucleotides (ASONs) were used to interfere the expression of Bfl-1 and its effects on prostate cancer cells. MTT was used to detect the survival, morphologic changes of prostate cancer cells was observed by inverted microscope. RESULTS: Bfl-1 mRNA, detected by RT-PCR, Q-PCR and ISH, was overexpressed in the androgen-independent prostate cancer cell lines PC-3 and DU145, but not detectable in the androgen-dependent prostate cancer cell line LNCaP and BPH tissue samples (P < 0.05). Significantly higher Bfl-1 mRNA levels were observed in higher stage and metastatic prostate cancer cases than those without metastasis or of low stage. ASONs targeting Bfl-1 significantly inhibited androgen-independent prostate cancer cell growth (P < 0.05), cell was rounding off or fragmentation. CONCLUSION: Bfl-1 is involved in maintaining the hormone-independent prostate cancer cell growth. Bfl-1 may become a new therapeutic target in advanced prostate cancer.