LXA4 protected mice from renal ischemia/reperfusion injury by promoting IRG1/Nrf2 and IRAK-M-TRAF6 signal pathways.

Excessive inflammatory response and increased oxidative stress play an essential role in the pathophysiology of ischemia/reperfusion (I/R)-induced acute kidney injury (IRI-AKI). Emerging evidence suggests that lipoxin A4 (LXA4), as an endogenous negative regulator in inflammation, can ameliorate several I/R injuries. However, the mechanisms and effects of LXA4 on IRI-AKI remain unknown. In this study, A bilateral renal I/R mouse model was used to evaluate the role of LXA4 in wild-type, IRG1 knockout, and IRAK-M knockout mice. Our results showed that LXA4, as well as 5-LOX and ALXR, were quickly induced, and subsequently decreased by renal I/R. LXA4 pretreatment improved renal I/R-induced renal function impairment and renal damage and inhibited inflammatory responses and oxidative stresses in mice kidneys. Notably, LXA4 inhibited I/R-induced the activation of TLR4 signal pathway including decreased phosphorylation of TAK1, p36, and p65, but did not affect TLR4 and p-IRAK-1. The analysis of transcriptomic sequencing data and immunoblotting suggested that innate immune signal molecules interleukin-1 receptor-associated kinase-M (IRAK-M) and immunoresponsive gene 1 (IRG1) might be the key targets of LXA4. Further, the knockout of IRG1 or IRAK-M abolished the beneficial effects of LXA4 on IRI-AKI. In addition, IRG1 deficiency reversed the up-regulation of IRAK-M by LXA4, while IRAK-M knockout had no impact on the IRG1 expression, indicating that IRAK-M is a downstream molecule of IRG1. Mechanistically, we found that LXA4-promoted IRG1-itaconate not only enhanced Nrf2 activation and increased HO-1 and NQO1, but also upregulated IRAK-M, which interacted with TRAF6 by competing with IRAK-1, resulting in deactivation of TLR4 downstream signal in IRI-AKI. These data suggested that LXA4 protected against IRI-AKI via promoting IRG1/Itaconate-Nrf2 and IRAK-M-TRAF6 signaling pathways, providing the rationale for a novel strategy for preventing and treating IRI-AKI.

A Ribosome-Related Prognostic Signature of Breast Cancer Subtypes Based on Changes in Breast Cancer Patients' Immunological Activity.

Background and Objectives. The prognostic role of adjacent nontumor tissue in patients with breast cancer (BC) is still unclear. The activity changes in immunologic and hallmark gene sets in normal tissues adjacent to BC may play a crucial role in predicting the prognosis of BC patients. The aim of this study was to identify BC subtypes and ribosome-associated prognostic genes based on activity changes of immunologic and hallmark gene sets in tumor and adjacent nontumor tissues to improve patient prognosis. Materials and Methods. Gene set variation analysis (GSVA) was applied to assess immunoreactivity changes in the overall sample and three immune-related BC subtypes were identified by non-negative matrix factorization (NMF). KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) analyses were after determining the prognostic gene set using the least absolute shrinkage and selection operator (LASSO) method. Ribosome-related genes were identified by PPI (protein-protein interaction) analysis, and finally a prognostic risk model was constructed based on the expression of five ribosomal genes (RPS18, RPL11, PRLP1, RPL27A, and RPL38). Results. A comprehensive analysis of immune and marker genomic activity changes in normal breast tissue and BC tissue identified three immune-related BC subtypes. BC subtype 1 has the best prognosis, and subtype 3 has the worst overall survival rate. We identified a prognostic gene set in nontumor tissue by the least absolute shrinkage and selection operator (LASSO) method. We found that the results of both KEGG and GO analyses were indistinguishable from those of ribosome-associated genes. Finally, we determined that genes associated with ribosomes exhibit potential as a reliable predictor of overall survival in breast cancer patients. Conclusions. Our research provides an important guidance for the treatment of BC. After a mastectomy, the changes in gene set activity of both BC tissues and the nontumor tissues adjacent to it should be thoroughly evaluated, with special attention to changes in ribosome-related genes in the nontumor tissues.

Pharmaceutical targeting Th2-mediated immunity enhances immunotherapy response in breast cancer.

BACKGROUND: Breast cancer is a complex disease with a highly immunosuppressive tumor microenvironment, and has limited clinical response to immune checkpoint blockade (ICB) therapy. T-helper 2 (Th2) cells, an important component of the tumor microenvironment (TME), play an essential role in regulation of tumor immunity. However, the deep relationship between Th2-mediated immunity and immune evasion in breast cancer remains enigmatic. METHODS: Here, we first used bioinformatics analysis to explore the correlation between Th2 infiltration and immune landscape in breast cancer. Suplatast tosilate (IPD-1151 T, IPD), an inhibitor of Th2 function, was then employed to investigate the biological effects of Th2 blockade on tumor growth and immune microenvironment in immunocompetent murine breast cancer models. The tumor microenvironment was analyzed by flow cytometry, mass cytometry, and immunofluorescence staining. Furthermore, we examined the efficacy of IPD combination with ICB treatment by evaluating TME, tumor growth and mice survival. RESULTS: Our bioinformatics analysis suggested that higher infiltration of Th2 cells indicates a tumor immunosuppressive microenvironment in breast cancer. In three murine breast cancer models (EO771, 4T1 and EMT6), IPD significantly inhibited the IL-4 secretion by Th2 cells, promoted Th2 to Th1 switching, remodeled the immune landscape and inhibited tumor growth. Remarkably, CD8+ T cell infiltration and the cytotoxic activity of cytotoxic T lymphocyte (CTL) in tumor tissues were evidently enhanced after IPD treatment. Furthermore, increased effector CD4+ T cells and decreased myeloid-derived suppressor cells and M2-like macrophages were also demonstrated in IPD-treated tumors. Importantly, we found IPD reinforced the therapeutic response of ICB without increasing potential adverse effects. CONCLUSIONS: Our findings demonstrate that pharmaceutical inhibition of Th2 cell function improves ICB response via remodeling immune landscape of TME, which illustrates a promising combinatorial immunotherapy.

Lipid Metabolism in Tumor-Associated Fibroblasts.

Tumor- or cancer-associated fibroblasts (TAFs), one of the most abundant stromal cell types in various carcinomas, consist of a heterogeneous cell population. Typically, TAFs are assigned with pro-tumor activities to promote tumor growth and progression. One of the key features of solid tumors is the metabolic reprogramming that induces alterations of bioenergetics and biosynthesis in both tumor cells and TAFs. Therefore, this review emphasizes TAFs lipid metabolism related to both TAFs differentiation process and TAFs crosstalk with cancer cells. We hope that this review will help understand lipid metabolism in tumor microenvironment, and support the rational design of metabolism-based approaches to improve the efficacy of cancer therapy.

Echocardiographic diagnosis of congenital double orifice mitral valve malformation: A case report.

Double orifice mitral valve (DOMV) is a rare congenital valve malformation. Due to the insufficient understanding and awareness of its echocardiographic characteristics, there is a risk of misdiagnosis. Here, we report a case of echocardiographic diagnosis of congenital DOMV malformation in a 56-year-old male patient who visited our hospital for systematic physical examination, during which DOMV was not diagnosed. The following year, the patient visited our hospital again, and echocardiography showed two approximately circular orifices on the short axis view of the mitral valve. During diastole, two red Doppler blood flow signals were observed entering the left ventricle simultaneously. A small amount of blue Doppler signal revealed reflux into the left atrium during systole, leading to the diagnose of congenital heart disease with DOMV malformation, without other cardiac structural abnormality. Because the patient did not have obvious discomfort, he did not receive any special treatment and is regularly followed-up.

CircEHMT1 inhibits metastatic potential of breast cancer cells by modulating miR-1233-3p/KLF4/MMP2 axis.

CircRNA is a kind of covalent head-to-tail looped RNA and plays an important role in tumor development. However, the identification of new potential targetable circRNAs to inhibit cancer development is still a huge challenge. In this study, we found that circEHMT1 inhibited migration and invasion of breast cancer cells. Mechanistically, we identified miR-1233-3p as a target of circEHMT1, and the circEHMT1/miR-1233-3p axis regulated matrix metalloprotease 2 (MMP2) by modulating the transcription factor Krϋppel-like factor 4 (KLF4). In summary, we showed that circEHMT1 has potential as a prognostic factor in breast cancer and played a tumor suppressor role via the circEHMT1/miR-1233-3p/KLF4/MMP2 axis.

DNA damage-inducible transcript 4 is an innate guardian for human squamous cell carcinoma and an molecular vector for anti-carcinoma effect of 1,25(OH)2 D3.

Cutaneous squamous cell carcinoma (SCC) is one of the most common non-melanoma skin cancers worldwide. While its exact tumorigenesis mechanisms is far from well-established and less satisfied therapeutic strategy can be clinically used nowadays. In this study, we intended to investigate the role of DNA damage-inducible transcript 4 (DDIT4) in human SCC. Firstly, we identified DDIT4 is significantly suppressed in human SCC tissue and cultured A431 cell line, and reduced DDIT4 accelerates keratinocytes proliferation but impedes the autophagy flux through mTORC1 pathway by affecting the downstream S6 Kinase1, 4E-BP1, Beclin1 and LC3 II/I. While 1,25(OH)2 D3 enhanced DDIT4 expression and activated autophagy and inhibit mTORC1 to take the effect of anti-proliferation and activating autophagy. Further, formation of direct vitamin D receptor (VDR)-DDIT4 transcription complex was verified by ChIP-qPCR, which showed the molecular mechanism of how 1,25(OH)2 D3 promotes DDIT4 transcription. Thirdly, xenograft tumor-bearing mice model treated by gradient concentrations of 1,25(OH)2 D3 revealed the obvious anti-carcinoma effect of 1,25(OH)2 D3 in vivo and DDIT4 acted the molecular vector of 1,25(OH)2 D3 through mTORC1. Lastly, elevated DDIT4 expression was verified in human actinic keratoses tissue, and chronic long-term ultraviolet (UV) irradiation on mouse disclosed UV could promote DDIT4 expression inside epidermis. Conclusively, our research suggested a novel molecular mechanism about the human SCC tumorigenesis and the pharmacological mechanism about how 1,25(OH)2 D3 take its anti-carcinoma role on human SCC, as well as a striking paradoxes that how UV irradiation plays the tumorigenesis effect but synchronously take a protective role in the early stage of SCC carcinogenesis.

Downregulated CDKN1C/p57kip2 drives tumorigenesis and associates with poor overall survival in breast cancer.

CDKN1C, also known as p57kip2, is considered to be a potential tumor suppressor implicated in several kinds of human cancers. However, the current knowledge of CDKN1C in breast cancer remains obscure. In the present study, we demonstrated that CDKN1C was dramatically downregulated in breast cancer compared with normal tissues by using real-time quantitative polymerase chain reaction, western blot and two public data portals: The Cancer Genome Atlas (TCGA) and Oncomine datasets. Moreover, the expression of CDKN1C was correlated with age and tumor size in the TCGA cohort containing 708 cases of breast cancer. Low expression of CDKN1C was significantly associated with poor overall survival (OS) in the TCGA cohort and validated cohort composed of 1402 patients. Multivariate Cox regression analysis indicated that CDKN1C was an independent prognostic factor for worse OS (HR = 1.78, 95% CI: 1.09-2.89, p = 0.020). Furthermore, gene set enrichment analysis (GSEA) revealed that CDKN1C was significantly correlated with gene signatures involving DNA repair, cell cycle, glycolysis, adipogenesis, and two critical signaling pathways mTORC1 and PI3K/Akt/mTOR. In conclusion, our data suggested an essential role of CDKN1C in the tumorgenesis of breast cancer. Targeting CDKN1C may be a promising strategy for anticancer therapeutics.

Downregulated miR-1247-5p associates with poor prognosis and facilitates tumor cell growth via DVL1/Wnt/ß-catenin signaling in breast cancer.

The abnormal expression of microRNAs is a key hallmark of breast cancer. Nevertheless, the biological roles of miR-1247-5p in breast cancer remain unknown. In this study, we revealed that miR-1247-5p expression was markedly decreased in breast cancer. It was a valuable diagnostic biomarker for breast cancer with the area under the curve of more than 0.80. Reduced miR-1247-5p expression was significantly correlated with patient age, tumor size, and poor prognosis in The Cancer Genome Atlas cohort including 839 breast cancer patients. Multivariate Cox regression analysis demonstrated that miR-1247-5p was an independent prognostic indicator for overall survival (hazard radio [HR] = 1.683, 95% confidence interval [CI] = 1.087-2.606, p = 0.020) and recurrence-free survival (HR = 2.496, 95% CI = 1.576-3.951, p < 0.001). Moreover, functional studies showed that overexpression of miR-1247-5p inhibited proliferation and induced apoptosis in breast cancer cells. Bioinformatics analysis and mechanistic investigations revealed that Dishevelled 1 (DVL1) was a direct target of miR-1247-5p. Inhibition of DVL1 by miR-1247-5p resulted in the suppression of Wnt/ß-catenin signaling, whereas overexpression of DVL1 abrogated the miR-1247-5p-mediated effect. These data reveal that miR-1247-5p, as an oncosuppressor in breast cancer, may be a promising prognostic biomarker and therapeutic target.

Urban spring phenology in the middle temperate zone of China: dynamics and influence factors.

Urbanization and its resultant urban heat island provide a means for evaluating the impact of climate warming on vegetation phenology. To predict the possible response of vegetation phenology to rise of temperature, it is necessary to investigate factors influencing vegetation phenology in different climate zones. The start of growing season (SOS) in seven cities located in the middle temperate humid, semi-humid, semi-arid, and arid climate zones in China was extracted based on satellite-derived normalized difference vegetation index (NDVI) data. The dynamics of urban SOS from 2000 to 2009 and the correlations between urban SOS and land surface temperatures (LST), precipitation, and sunshine duration, respectively, were analyzed. The results showed that there were no obvious change trends for urban SOS, and the heat island induced by urbanization can make SOS earlier in urban areas than that in adjacent rural areas. And the impact of altitude on SOS was also not negligible in regions with obvious altitude difference between urban and adjacent rural areas. Precipitation and temperature were two main natural factors influencing urban SOS in the middle temperate zone, but their impacts varied with climate zones. Only in Harbin city with lower sunshine duration in spring, sunshine duration had more significant impact than temperature and precipitation. Interference of human activities on urban vegetation was non-negligible, which can lower the dependence of urban SOS on natural climatic factors.

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.

[Analysis of X-Ray Fluorescence Spectroscopy and Plasma Mass Spectrometry of Pangxidong Composite Granitoid Pluton and Its Implications for Magmatic Differentiation].

Pangxidong composite granitoid pluton located in the southwestern margin of Yunkai massif. The metamorphic grade of this pluton increases from outside to inside, that is, banded-augen granitic gneisses, gneissoid granites and granites distribute in order from edge to core. X-Ray Fluorescence Spectroscopy and Plasma Mass Spectrometry are conducted to study the geochemical characteristics of the three types of rocks. The result shows that all the three types of rocks are peraluminous rocks and their contents of main elements and rare earth elements change gradually. From granitic gneisses to granites, the contents of Al2O3, CaO, MgO, TiO2, total rare earth elements and light rare earth elements increase, but the contents of SiO2 and heavy rare earth elements decrease. It is suggested that the phylogenetic relationship exists between granitic gneisses, gneissoid granites and granites during the multi-stage tectonic evolution process. Furthermore, the remelting of metamorphosed supracrustal rocks in Yunkai massif is probably an important cause of granitoid rocks forming. The evolutionary mechanism is probably that SiO2 and heavy rare earth elements were melt out from the protolith and gradually enriched upward, but Al2O3, CaO, MgO, TiO2 and light rare earth elements enriched downward.

[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.

Chrysin inhibits metastatic potential of human triple-negative breast cancer cells by modulating matrix metalloproteinase-10, epithelial to mesenchymal transition, and PI3K/Akt signaling pathway.

Chrysin, a naturally occurring flavone, has been shown to inhibit cell proliferation and induce cell apoptosis in various cancers. However, the effect and mechanisms of chrysin on cancer metastasis are still enigmatic. In this study, metastatic triple-negative breast cancer (TNBC) cell lines were used to evaluate the antimetastatic activity of chrysin. The results showed that chrysin (5, 10 and 20 µM) significantly suppressed TNBC cell migration and invasion in a dose-dependent manner. Human matrix metalloproteinase (MMP) antibody array demonstrated that MMP-10 was downregulated by chrysin, which was further verified by Western blotting and ELISA. Moreover, it was shown that chrysin induced increased E-cadherin expression and decreased expression of vimentin, snail and slug in TNBC cells, suggesting that chrysin had a reversal effect on epithelial-mesenchymal transition. More importantly, it was demonstrated that inhibiting the Akt signal pathway might play a central role in chrysin-induced antimetastatic activity by regulating MMP-10 and epithelial-mesenchymal transition. In conclusion, our study indicates that chrysin exerts antimetastatic activities in TNBC cells, which suggests that chrysin might be a potential therapeutic candidate for the treatment of advanced or metastatic breast cancer.

Distribution, microfabric, and geochemical characteristics of siliceous rocks in central orogenic belt, China: implications for a hydrothermal sedimentation model.

Marine siliceous rocks are widely distributed in the central orogenic belt (COB) of China and have a close connection to the geological evolution and metallogenesis. They display periodic distributions from Mesoproterozoic to Jurassic with positive peaks in the Mesoproterozoic, Cambrian--Ordovician, and Carboniferous--Permian and their deposition is enhanced by the tensional geological settings. The compressional regimes during the Jinning, Caledonian, Hercynian, Indosinian, and Yanshanian orogenies resulted in sudden descent in their distribution. The siliceous rocks of the Bafangshan-Erlihe ore deposit include authigenic quartz, syn-depositional metal sulphides, and scattered carbonate minerals. Their SiO2 content (71.08-95.30%), Ba (42.45-503.0 ppm), and ΣREE (3.28-19.75 ppm) suggest a hydrothermal sedimentation origin. As evidenced by the Al/(Al + Fe + Mn), Sc/Th, (La/Yb) N, and (La/Ce) N ratios and δCe values, the studied siliceous rocks were deposited in a marginal sea basin of a limited ocean. We suggest that the Bafangshan-Erlihe area experienced high- and low-temperature stages of hydrothermal activities. The hydrothermal sediments of the former stage include metal sulphides and silica, while the latter was mainly composed of silica. Despite the hydrothermal sedimentation of the siliceous rocks, minor terrigenous input, magmatism, and biological activity partly contributed to geochemical features deviating from the typical hydrothermal characteristics.

[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.

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.

Novel prognostic biomarker TBC1D1 is associated with immunotherapy resistance in gliomas.

Background: Glioma, an aggressive brain tumor, poses a challenge in understanding the mechanisms of treatment resistance, despite promising results from immunotherapy. Methods: We identified genes associated with immunotherapy resistance through an analysis of The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and Gene Expression Omnibus (GEO) databases. Subsequently, qRT-PCR and western blot analyses were conducted to measure the mRNA and protein levels of TBC1 Domain Family Member 1 (TBC1D1), respectively. Additionally, Gene Set Enrichment Analysis (GSEA) was employed to reveal relevant signaling pathways, and the expression of TBC1D1 in immune cells was analyzed using single-cell RNA sequencing (scRNA-seq) data from GEO database. Tumor Immune Dysfunction and Exclusion (TIDE) database was utilized to assess T-cell function, while Tumor Immunotherapy Gene Expression Resource (TIGER) database was employed to evaluate immunotherapy resistance in relation to TBC1D1. Furthermore, the predictive performance of molecules on prognosis was assessed using Kaplan-Meier plots, nomograms, and ROC curves. Results: The levels of TBC1D1 were significantly elevated in tumor tissue from glioma patients. Furthermore, high TBC1D1 expression was observed in macrophages compared to other cells, which negatively impacted T cell function, impaired immunotherapy response, promoted treatment tolerance, and led to poor prognosis. Inhibition of TBC1D1 was found to potentially synergistically enhance the efficacy of immunotherapy and prolong the survival of cancer patients with gliomas. Conclusion: Heightened expression of TBC1D1 may facilitate an immunosuppressive microenvironment and predict a poor prognosis. Blocking TBC1D1 could minimize immunotherapy resistance in cancer patients with gliomas.

Acetylation-dependent deubiquitinase USP26 stabilizes BAG3 to promote breast cancer progression.

Deubiquitylases (DUBs) have emerged as promising targets for cancer therapy due to their role in stabilizing substrate proteins within the ubiquitin machinery. Here, we identified ubiquitin-specific protease 26 (USP26) as an oncogene via screening prognostic DUBs in breast cancer. Through in vitro and in vivo experiments, we found that depletion of USP26 inhibited breast cancer cell proliferation and invasion, and suppressed tumor growth and metastasis in nude mice. Further investigation identified co-chaperone Bcl-2-associated athanogene 3 (BAG3) as the direct substrate of USP26, and ectopic expression of BAG3 partially reversed antitumor effect induced by USP26 knockdown. Mechanistically, the lysine acetyltransferase Tip60 targeted USP26 at K134 for acetylation, which enhanced USP26 binding affinity to BAG3, leading to BAG3 deubiquitination and increased protein stability. Importantly, we employed a structure-based virtual screening and discovered a drug-like molecule called 5813669 that targets USP26, destabilizing BAG3 and effectively mitigating tumor growth and metastasis in vivo. Clinically, high expression levels of USP26 were correlated with elevated BAG3 levels and poor prognosis in breast cancer patients. Overall, our findings highlight the critical role of USP26 in BAG3 protein stabilization and provide a promising therapeutic target for breast cancer.

An immune-related prognostic gene ULBP2 is correlated with immunosuppressive tumor microenvironment and immunotherapy in breast cancer.

Breast cancer (BC) is one of the major dangerous tumors threatening women's lives. We here aimed to sort out prognostic immune-related genes by univariate Cox regression analysis and build a model of immune-related genes for forecasting the prognosis of BC patients. We identified UL16 binding protein 2 (ULBP2) as a valuable gene for study in the model using related databases and algorithms analysis. We found the stromal and immune cells scores were higher in ULBP2 high expression group and ULBP2 was related to kinds of immune cells, most importantly had negative correlation with CD8+ T cell. Notably, ULBP2 was positively correlated with tumor mutational burden (TMB) and had relationship with many immune checkpoints. Correlation analysis revealed that ULBP2 expression was closely linked to the clinicopathological characters and negatively related to BC patient survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed the functional enrichment of differential genes related to ULBP2. Gene Set Enrichment Analysis (GSEA) indicated pathway enrichment in ULBP2 high and low expression groups. In short, this study comprehensively investigated the potential function of ULBP2 in BC, which might make ULBP2 to be an important therapeutic target for BC.