The promoting effects of Grin2d expression in tumorigenesis and the aggressiveness of esophageal cancer.

Grin2d is an ionotropic NMDA receptor, a subunit of glutamate-dependent, and a facilitator of cellular calcium influx in neuronal tissue. In this study, we found that Grin2d expression was higher in esophageal cancer than in normal mucosa at both the mRNA and protein level using RT-PCR, bioinformatics analysis, and western blotting (p<0.05). Grin2d mRNA expression was positively correlated with old age, white race, heavy weight, distal location, adenocarcinoma, cancer with Barrett's lesion, or high-grade columnar dysplasia (p<0.05). The differential genes associated with Grin2d mRNA were involved in fat digestion and absorption, cholesterol metabolism, lipid transfer, lipoproteins, synaptic membranes, and ABC transporters (p<0.05). The Grin2d-related genes were classified into the following categories: metabolism of glycerolipids, galactose, and O-glycan, cell adhesion binding, actin binding, cadherin binding, the Hippo signaling pathway, cell-cell junctions, desmosomes, DNA-transcription activator binding, and skin development and differentiation (p<0.05). Grin2d immunoreactivity was positively correlated with distal metastasis and unfavorable overall survival in esophageal cancer (p<0.05). Grin2d overexpression promoted proliferation, migration, and invasion in esophageal cancer cells but blocked apoptosis (p<0.05) and increased the expression of PI3K, Akt and p-mTOR. Grin2d knockout caused the opposite effects. These findings indicated that upregulated Grin2d expression played an important role in esophageal carcinogenesis via the PI3K/Akt/mTOR pathway and might be a biological marker for aggressive tumor behavior and poor prognosis. Its silencing might represent a targeted therapy approach against esophageal cancer.

FAM64A aggravates proliferation, invasion, lipid droplet formation, and chemoresistance in gastric cancer: A biomarker for aggressiveness and a gene therapy target.

FAM64A is a mitogen-induced regulator of the metaphase and anaphase transition. Here, we found that FAM64A messenger RNA (mRNA) and protein expression levels were higher in gastric cancer tissue than in normal mucosa (p < .05). FAM64A methylation was negatively correlated with FAM64A mRNA expression (p < .05). The differentially expressed genes of FAM64A were mainly involved in digestion, potassium transporting or exchanging ATPase, contractile fibers, endopeptidase, and pancreatic secretion (p < .05). The FAM64A-related genes were principally categorized into ubiquitin-mediated proteolysis, cell cycle, chromosome segregation and mitosis, microtubule binding and organization, metabolism of amino acids, cytokine receptors, lipid droplet, central nervous system, and collagen trimer (p < .05). FAM64A protein expression was lower in normal gastric mucosa than intestinal metaplasia, adenoma, and primary cancer (p < .05), negatively correlated with older age, T stage, lymphatic and venous invasion, tumor, node, metastasis stage, and dedifferentiation (p < .05), and associated with a favorable overall survival of gastric cancer patients. FAM64A overexpression promoted proliferation, antiapoptosis, migration, invasion, and epithelial-mesenchymal transition via the EGFR/Akt/mTOR/NF-κB, while the opposite effect was observed for FAM64A knockdown. FAM64A also induced chemoresistance directly or indirectly through lipid droplet formation via ING5. These results suggested that upregulation of FAM64A expression might induce aggressive phenotypes, leading to gastric carcinogenesis and its subsequent progression. Thus, FAM64A could be regarded as a prognosis biomarker and a target for gene therapy.

The clinicopathological and prognostic significances of CDC73 expression in breast cancer: A pathological and bioinformatics analysis.

Parafibromin is a protein encoded by the oncosuppressor CDC73 gene, whose mutation results in hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid carcinoma. Down-regulation of parafibromin is linked to lung, gastric, colorectal, and ovarian cancer tumorigenesis. Parafibromin expression was detected by RT-PCR, bioinformatics analysis, Western blot, and immunohistochemistry; and compared with clinicopathological characteristics of breast cancer. CDC73-related genes and pathways were analyzed using bioinformatics analysis. Parafibromin expression was increased in breast cancer compared to normal tissues at both mRNA and protein levels (p<0.05). Among triple-negative breast cancers, it was higher in basal-like 1 than basal-like 2 patients (p<0.05) and mesenchymal than immunomodulatory patients (p<0.05). CDC73 mRNA expression was positively correlated with white race, non-infiltrating immune cells, favorable luminal subtypes of PAM50, and prognosis of breast cancer patients (p<0.05). The differential genes of CDC73 were classified into enzyme inhibitors, peptidase, and keratinization by KEGG (p<0.05). Similarly, it was classified into ribosomes, TGF-ß, oxidation phosphorylation, inositol phosphate metabolism, arachidonic acid metabolism, linoleic acid metabolism, ERBB, and VEGF signaling pathways by GSEA (p<0.05). The positively-correlated genes of CDC73 were involved in cell mobility, response to interferon α, nuclear pore and basket, and histone methyltransferase. The negatively-correlated genes of CDC73 were involved in the mitochondrial respiratory chain, thermogenesis, and ribosomes. Parafibromin expression was higher in invasive ductal than lobular carcinoma (p<0.05) and mucinous adenocarcinoma than others (p<0.05). Parafibromin immunoreactivity as an independent factor was positively associated with an increased overall survival rate of breast cancer patients (p<0.05). These findings suggest that up-regulation of parafibromin in breast cancer patients is closely linked to a favorable prognosis. It is involved in tumorigenesis and subsequent progression by regulating metabolism, ribosomes, and cytokines.

The clinicopathological and prognostic significances of LATS1 expression in breast cancer.

AIM: Large tumor suppressor gene 1 (LATS1) belongs to the PKA/PKG/PKC serine/threonine kinase subfamily of the Hippo signaling pathway and inactivates nuclear co-activators YAP1 and WWTR1 by phosphorylation. This study aimed to discern the clinicopathological and prognostic significances of LATS1 expression in breast cancer. METHODS: We examined LATS1 expression in breast carcinogenesis and compared it with clinicopathological parameters and survival information of breast cancer patients using immunohistochemistry, western blotting, RT-PCR, and bioinformatics analysis. RESULTS: LATS1 expression was downregulated in breast cancer at both mRNA and protein levels (P<0.05). LATS1 mRNA expression was negatively correlated with low ER and PR expression, aggressive subtypes (TNBC and HER2+ vs. luminal), and poor survival (P<0.05). Its protein expression was negatively linked to patient age, T stage, N stage, M stage histological grade, PR status, and unfavorable prognosis (P<0.05). There was a positive correlationship between nuclar and cytoplasmic LATS1 expression in breast cancer (P<0.05). CONCLUSIONS: The downregulation of LATS1 expression plays a vital role in the carcinogenesis and progression of breast cancer. Thus, LATS1 loss was employed to indicate the aggressive behaviors and poor prognosis of breast cancer.

HA of H1N1 enhanced the expression of ICAM-1 and IL-6 in HUVECs and pathological injury in the lungs in mice.

OBJECTIVE: Both COVID-19 and influenza are viral respiratory tract infections and the epidemics of viral respiratory tract infections remain highly prevalent with lethal consequences in susceptible individuals. Expression of ICAM-1 on vascular endothelium recruits leukocytes which initiates inflammation. IL-6 induces ICAM-1. Both ICAM-1 and IL-6 can be enhanced in influenza virus infection and COVID-19 patients. Besides initiation of virus entry host cells, whether HA alone, instead of whole virus, of influenza has the effects on expression of ICAM-1 and IL-6 in vascular endothelium with injury in the lungs, remains to be demonstrated. METHODS: RT-qPCR and Western blot as well as histopathologic examination were used to examine mRNA and protein of ICAM-1 and IL-6 as well as pathological injury in the lung tissues, respectively. RESULTS: After incubation of the Human Umbilical Vein Endothelial Cells (HUVECs) with HA of H1N1 for 24 h, the mRNA and protein of ICAM-1 and IL-6 in HUVECs were increased in group of 5 µg/ml concentration with statistical significance (p < 0.05). Pathological injury in lung tissues of the mice was shown 12 h after tail intravenous injection with 100 µl of HA (50 µg/ml and 100 µg/ml in normal saline), including widened alveolar spaces with angiotelectasis in alveolar wall, alveolar luminal and interstitial inflammatory infiltrates, alveolar luminal erythrocyte effusion. CONCLUSIONS: HA alone, instead of whole H1N1 virus, induced more expression of ICAM-1 and IL-6, two molecules involving in pathological and inflammatory responses, in HUVECs and pathological injury in lung tissues of the mice. This knowledge provides a new HA-targeted potential direction for prevention and treatment of disease related to H1N1 infection.

Promotion on NLRC5 upregulating MHC-I expression by IFN-γ in MHC-I-deficient breast cancer cells.

Breast cancer is the most dominant cancer in women and the second most frequent cancer in the general population worldwide. NLRC5 critically transactivates MHC class I (classically HLA-ABC in human) which is crucial for cancer immunosurveillance. But the expressional and functional impairments of NLRC5 have been found in many cancers as a major mechanism of immune evasion. Promotion of NLRC5 with the enhancement of MHC class I contributes to cancer immunotherapy and counteraction against cancer immune evasion. In many cancers, IFN-γ promotes the expression of MHC class I involving NLRC5; however, it is unclear in breast cancer cells. In this study, qRT-PCR, western blot, and flow cytometry were used to detect the mRNAs and proteins of NLRC5, ß2m, and HLA-ABC in MHC class I-deficient human SKBR3 breast cancer cells after IFN-γ treatment. It was shown that the relative levels of NLRC5 mRNA, ß2m mRNA, and HLA-ABC α heavy chain mRNA, in concentrations of 50 U/ml and 100 U/ml IFN-γ groups, were statistically increased (p < 0.05) with dose dependent tendency compared with the control group. The protein levels of NLRC5 and ß2m in concentrations of 50 U/ml and 100 U/ml IFN-γ groups, HLA-ABC (positive rates) in different concentrations of IFN-γ groups, were statistically increased (p < 0.05), with dose dependent tendency for NLRC5 and HLA-ABC, compared with the control group. Promotion of NLRC5 by IFN-γ with upregulation of MHC class I (HLA-ABC) in SKBR3 breast cancer cells, suggesting the contribution to counteracting cancer evasion from immunosurveillance and benefiting cancer immunotherapy.

Raman Spectra of Bredigite at High Temperature and High Pressure.

Bredigite was synthesized by using the Piston-Cylinder in 1.2 GPa and 1 473 K. With external heating device and diamond anvil cell, high temperature and high pressure Raman spectra of bredigite were collected at temperatures 298, 353, 463, 543, 663, 773 and 873 K and with pressure from 1 atm up to 14.36 GPa (room temperature). The SEM image showed that the sample consisted of one crystalline phase with grain size ranging from 10～20 µm. The EPMA data suggest a chemical formula of Ca7.03(2)Mg0.98(2)Si3.94(2)O16 which was identical to the theoretical component of bredigite. The Raman spectroscopic results indicate there were 29 vibration bands of bredigite at high temperature. Some bands were merging, weakening and disappearing increasingly with the temperature, which was obvious in the range of 800~1 200 cm-1. The vibration bands of 909, 927 and 950 cm-1 disappeared at 873, 773 and 873 K, respectively. The results primarily indicated that the structure of bredigite was stable under experimental condition. In addition, isobaric mode-Grüneisen parameters and isothermal mode-Grüneisen parameters were calculated, yielding 1.47(2) and 0.45(3) as their mean values, respectively. Anharmonic coefficients were estimated based on the high temperature and high pressure Raman experiments, showing that the contributions to anharmonic-effect induced with the Si­O vibration modes were smaller than other modes.

[Study on Mineralogical Characteristics of Quartz and Calcite from Feieling Skarn-Type Pb-Zn Deposit in Southwest Margin of Yunkai Massif].

The Feieling Pb-Zn deposit of skarn-type is located the in Southwest margin of Yunkai massif, China. This ore deposit can be divided into wall rock near ore, concealed rock mass, endoskarn, exoskarn and orebody. The Raman and FTIR spectrum are conducted to study the mineralogical characteristics of quartz and calcite from five types of rocks from Feieling skarn-type deposit. The analysis shows that the quartz included in the near ore wall rock, endoskarn and exoskarn, comparing with recrystallized quartz of concealed rock mass, has a tend to change into low symmetry quartz in varying degrees. The crystalinity and order degree of quartz from near ore wall rock to concealed rock mass and to endoskarn are becoming higher, but that of quartz from different exoskarn samples display no regular. The origin or the quartz microstructure changes may be related to the multi-stage evolution of skarn mineralization process. The quartz, included in near ore wall rock, endoskarn and exoskarn, become easier to recrystallize and adjust microstructure under the influence of the multi-stage hydrothermal and temperature effect. In anyone sample, the earlier crystalline calcite, showing subhedral-euhedral crystal, display higher crystalinity and order degree. On the contrary, the later crystalline calcite, showing xenomorphic crystal, display lower crystalinity and order degree. Calcite crystal of exoskarn rock contains some silica impurity, while endoskarn and orebody rock is pure. The purity of calcite crystal may relate to Multi-stage evolution of skarn mineralization process. At the early and late skarn stage, active silica-containing fluid is easier to join into calcite, which is under higher temperature environments. On the contrary, at the late quartz-surfide stage, the later crystalized calcite displays higher purity, which is under lower temperature environments. Therefore, spectral characteristics of quartz and calcite reflect multi-stage evolution of skarn mineralization process.

Statistical analysis of twenty years (1993 to 2012) of data from mainland China's first intervention center for children with autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and interaction, and restrictive and repetitive patterns of behavior, interests or activities. This study aimed to analyze trends in ASD diagnosis and intervention in 20 years of data from the Beijing Stars and Rain Education Institute for Autism (SR), the first autism intervention center in mainland China, and from a recent survey of members of the Heart Alliance, an industry association of autism intervention centers in China. METHODS: We analyzed the registration data at the SR from 1993 to 2012 for a total of 2,222 children who had a parent-reported diagnosis of ASD and 612 of 'autistic tendencies'. Most of the children who were the primary focus of our analyses were age six and under. We also analyzed results of a survey we conducted in 2013 of 100 member centers of the Heart Alliance. Generalized Estimating Equations, multiple linear regression and the Mann-Whitney test were used for data analysis. Statistically significant findings are reported here. RESULTS: The number of hospitals where SR children received their diagnosis increased from several in the early 1990s to 276 at present. The proportion of 'autistic tendencies' diagnosis increased 2.04-fold from 1998 to 2012 and was higher for children diagnosed at a younger age. The mean age at first diagnosis of ASD or 'autistic tendencies' decreased by 0.27 years every decade. A higher level of parental education was statistically significantly associated with an earlier diagnosis of the child. The mean parental age at childbirth increased by about 1.48 years per decade, and the mean maternal age was 1.40 and 2.10 years higher than that in the national population censuses of 2000 and 2010, respectively. At the time of the survey 3,957 children with ASD were being trained at the 100 autism intervention centers. Ninety-seven of these centers opened after the year 2000. Economically underdeveloped regions are still underserved. CONCLUSIONS: This study revealed encouraging trends and remaining challenges in ASD diagnosis and intervention among children at the SR over the past 20 years and the 100 autism intervention centers in China at present.

Study on the order degree and geochemical characteristics of major elements of siliceous rock in eastern Qinling area, China.

Siliceous rocks were extensively distributed in the marine volcanic sedimentary formation of Erlangping Group in the Early Paleozoic in eastern Qinling area. These siliceous rocks formed in the same age, but had differences in the degree of crystallization and order because of the late diagenetic evolution. In the present study, the major elements and order degree of the siliceous rocks were studied, which were from the Erlangping Group in Xixia area, Songxian area and Nanzhao area of eartern Qinling orogenic belt. As shown in the results, the siliceous rocks contained SiO2 with percentage between 84.75% and 94.12% and average of 89.09%. The SiO2/(K2O+Na2O) values were from 26.69 to 114.78 with 65.67 as its average, and the values of SiO2/Al2O3 were from 10.48 to 61.52 with average of 30.58. These above characteristics excellently agreed with the geochemical characteristics of hydrothermal siliceous rocks, which deposited in the continental margin environment. In the Raman analytical results, the quartz contributed to the characteristic Raman shifts at 394, 464, 465 and 467 cm(-1). In the results of Gaussian fitting the degrees of order increased with the order of siliceous rocks of Songxian area, Nanzhao area and Xixia area, which were witnessed by the descending in FWHM values of quartz in the siliceous rocks of Songxian area, Nanzhao area and Xixia area orderly. Disagreeing with the FWHM values of Gaussian fitting, the silica contents of the siliceous rocks had a rising trend of Songxian (87.36%), Nanzhao (89.57%), Xixia area (90.35%), which meant a descending in impurity elements with the order of Songxian area, Nanzhao area and Xixia areas. According to this, there was high agreement between lower crystallinity degree and higher purity of silica, and this denoted that the rising in order degree of silica would result in lower impurity in siliceous rocks. Although the crystallinity degrees could change with the influences of temperature, pressure and its natural property, the impurity elements decreased with the rising in crystallinity degrees of silica. Although there was excluding of impurity elements during the increase in degrees of crystallinity and order, the key factor for the diversities of major elements in siliceous rocks was not likely to be the excluding of impurity elements during the increase in the crystallinity degrees in silica In this study, the Raman analysis exhibited to be an effective way to understand the degree of order for the silica of the siliceous rocks, which would be a potential way to study the subsequent diagenetic evolution of siliceous rocks.

[Micro-area characteristics of laminated chert in the volcanic rocks of Xionger Group of Ruyang area and its geological significances].

The Xionger Group was originated from the volcanic eruption and sedimentation in Precambrian, whose sedimentary strata at the top were named Majiahe Formation. In the Majiahe Formation, there were hydrothermal chert widely distributed, which were exhibited to be interlayers in the volcanic rocks. The polarized microscope, X-ray diffraction (XRD), Raman and electron back scatter diffraction (EBSD) were conducted to study the characteristics in micro area of the jasperite samples, which were from the sedimentary interlayers in the volcanic rocks of Majiahe Formation in Xionger Group. As shown in the microphotographs and EBSD images, the quartz in the chert had small grain size, low degree of crystallinity and close packed structure, which quite agreed with the characteristics of hydrothermal sedimentary chert. In the chert of Xionger Group, there were clear banded (or lamellar) structures which were contributed by the diversities of the grain size and mineral composition. The different bands (or lamellars) had alternative appearance repeatedly, and denoted the diversities and periodic changes in the substance supply during the precipitation. According to the results of the XRD analysis, the majority minerals of the chert was low temperature quartz, whose lattice parameters were a=b=0.4913 nm, c=0.5405 nm and Z=3. As denoted in the EBSD image and result of Raman analysis, several impurity minerals were formed in the chert in different stages, whose geneses and formation time were quite different. The clay minerals and pyrite were scattered in distribution, and should be contributed by the original sedimentation. On contrary, the felsic minerals and mafic silicate minerals were originated from the sedimentation of tuffaceous substance during the volcanic eruption. The minerals of volcanic genesis had relatively larger grain size, and they deposited together with the hydrothermal sediments to form the bands (or lamellars) of coarse minerals. However, the hydrothermal sedimentation contributed to the bands (or lamellars) with minerals of much smaller grain size, which therefore resulted in diversities from the other bands (or lamellars). According to this, the repeated bands (or lamellars) denoted the volcanic activities were cyclic during the formation of the chert. What's more, the carbonate vein came from the precipitation of subsequent hydrothermal fluids in the fracture of the chert, which contributed to the changes (e. g. rising in crystallinity degree of silica and formation of micro-structure of new silicate) near the interface between chert and the carbonate vein. Although there were many impurity minerals with complex genesis, the relatively lower content of silica in the chert of Xionger Group was due to the volcanic mineral mainly. Since there were impurity minerals of volcanic genesis in relatively large amount, the content of silica in the chert of Xionger Group was hence relatively low. In this study, the Raman analysis was witnessed to be an effective way in the researches on the chert, and could open out the type of mineral, micro-structure and degrees of crystallinity (or order). These characteristics were well kept in the micro-area, and played significant roles to reflect and understand the formation mechanism and subsequent evolution of the chert.