Kidney renal clear cell carcinoma (KIRC) is the most common type of kidney cell carcinoma which has the worst overall survival rate. Almost 30% of patients with localized cancers eventually develop ...to metastases despite of early surgical treatment carried out. MicroRNAs (miRNAs) play a critical role in human cancer initiation, progression, and prognosis. The aim of our study was to identify potential prognosis biomarkers to predict overall survival of KIRC.
All data were downloaded from an open access database The Cancer Genome Atlas. DESeq2 package in R was used to screening the differential expression miRNAs (DEMs) and genes (DEGs). RegParallel and Survival packages in R was used to analysis their relationships with the KIRC patients. David version 6.8 and STRING version 11 were used to take the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.
We found 2 DEGs (TIMP3 and HMGCS1) and 3 DEMs (hsa-miR-21-5p, hsa-miR-223-3p, and hsa-miR-365a-3p) could be prognosis biomarkers for the prediction of KIRC patients. The constructed prognostic model based on those 2 DEGs could effectively predict the survival status of KIRC. And the constructed prognostic model based on those 3 DEMs could effectively predict the survival status of KIRC in 3-year and 5-year.
The current study provided novel insights into the miRNA related mRNA network in KIRC and those 2 DEGs biomarkers and 3 DEMs biomarkers may be independent prognostic signatures in predicting the survival of KIRC patients.
Aberrant expressions of desmoglein 2 (Dsg2) and desmocollin 2(Dsc2), the two most widely distributed desmosomal cadherins, have been found to play various roles in cancer in a context-dependent ...manner. Their specific roles on breast cancer (BC) and the potential mechanisms remain unclear.
The expressions of Dsg2 and Dsc2 in human BC tissues and cell lines were assessed by using bioinformatics analysis, immunohistochemistry and western blotting assays. Wound-healing and Transwell assays were performed to evaluate the cells' migration and invasion abilities. Plate colony-forming and MTT assays were used to examine the cells' capacity of proliferation. Mechanically, Dsg2 and Dsc2 knockdown-induced malignant behaviors were elucidated using western blotting assay as well as three inhibitors including MK2206 for AKT, PD98059 for ERK, and XAV-939 for β-catenin.
We found reduced expressions of Dsg2 and Dsc2 in human BC tissues and cell lines compared to normal counterparts. Furthermore, shRNA-mediated downregulation of Dsg2 and Dsc2 could significantly enhance cell proliferation, migration and invasion in triple-negative MDA-MB-231 and luminal MCF-7 BC cells. Mechanistically, EGFR activity was decreased but downstream AKT and ERK pathways were both activated maybe through other activated protein tyrosine kinases in shDsg2 and shDsc2 MDA-MB-231 cells since protein tyrosine kinases are key drivers of triple-negative BC survival. Additionally, AKT inhibitor treatment displayed much stronger capacity to abolish shDsg2 and shDsc2 induced progression compared to ERK inhibition, which was due to feedback activation of AKT pathway induced by ERK inhibition. In contrast, all of EGFR, AKT and ERK activities were attenuated, whereas β-catenin was accumulated in shDsg2 and shDsc2 MCF-7 cells. These results indicate that EGFR-targeted therapy is not a good choice for BC patients with low Dsg2 or Dsc2 expression. Comparatively, AKT inhibitors may be more helpful to triple-negative BC patients with low Dsg2 or Dsc2 expression, while therapies targeting β-catenin can be considered for luminal BC patients with low Dsg2 or Dsc2 expression.
Our finding demonstrate that single knockdown of Dsg2 or Dsc2 could promote proliferation, motility and invasion in triple-negative MDA-MB-231 and luminal MCF-7 cells. Nevertheless, the underlying mechanisms were cellular context-specific and distinct.
•Melt-related textures were derived from breakdown of phengite and amphibole.•Rutile in core to ilmenite in rim of garnet suggests garnet growth with exhumation.•Pseudosection modeling constrained ...partial melting along an exhumation P–T path.
Characterizing partial melting of eclogite in Precambrian orogens is critical to understanding the petrological processes that operate in the deep orogenic crust. Retrogressed eclogite from the Algonquin terrane in the western Grenville Province, Canada, was taken as an example to study such processes. The studied samples contained the assemblage of garnet, omphacite, amphibole, phengite, biotite, and rutile at peak pressure. Various exhumation- and melt-related textures formed show evidence for a complex post-peak pressure history. Rutile is only found in the core of garnet, whereas ilmenite-bearing assemblages predominate in the garnet rim and the matrix. Symplectite of diopside + plagioclase + amphibole replaced former omphacite. Symplectite of amphibole and plagioclase formed as a corona around garnet. Polymineralic inclusions of plagioclase + K-feldspar ± ilmenite ± biotite ± amphibole ± apatite ± sulfides in garnet crystallized from melt, which was captured during garnet growth and reacted with the host. Cusps of plagioclase into the boundaries of other phases (e.g. garnet and clinopyroxene) mimic the original melt-solid interface. Neoblasts of garnet with euhedral crystal faces were formed as a peritectic phase during eclogite melting. Leucocratic veins without external connection, present in the sampled mafic pod at outcrop scale, are interpreted as crystallized pockets of melt which derived internally. Pseudosection modeling of the studied samples along with compositional isopleths of chemically zoned garnet yielded an exhumation path from 1.7 ± 0.1 GPa, 680 ± 50 °C to 1.3 ± 0.1 GPa, 920 ± 50 °C. Along this path, the modal content of melt increased in response to the breakdown of phengite and amphibole along with involvement of omphacite and rutile. The melt crystallized during cooling and equilibrated at 0.6–0.8 GPa, 710–750 °C, estimated using empirical thermobarometry. This study shows that metabasite from Proterozoic collisional orogens can be partially melted on the exhumation and heating path through phengite- and amphibole-dehydration melting.
In this letter, we proposed an efficient underwater acoustic (UWA) image communication algorithm based on reinforcement learning which can improve the image quality while reduce the energy ...consumption and time delay in fast time variant UWA channels. In the proposed algorithm, the received image quality and other communication performance parameters are estimated at the sink continuously and then feedback to the sensor by an independent channel in order to avoid bandwidth loss caused by large time delay. At the sensor, the most suitable modulation and coding method is chosen to maximize a special designed value function in order to achieve the best efficient underwater image communication. Sea test results show that the proposed UWA image communication algorithm can reduce the bit-error rate by 3.1 dB, the energy consumption of the sensor by 26.9% and the time delay by 58.2%. The proposed algorithm can also shorten the convergence time by 47.4% compared with the model-free reinforcement learning underwater communication algorithm.
Published research suggests that the total phosphorus (TP) thresholds for the regime shifts between a clear‐water state dominated by submersed macrophytes and a turbid‐water state dominated by ...phytoplankton in shallow lakes vary with forms of lake basins and climates. However, such hypotheses remain untested by direct field evidence. We therefore tested the hypotheses with empirical data from subtropical lakes on the Yangtze floodplain and also from other lakes in temperate to tropical zones. TP thresholds were found to vary little at moderate depths, but to decrease notably when depth exceeds a level of probably 3–4 m, and increase sharply when depth is below a level of around 1–2 m. TP thresholds were found to be nearly equal in shallow lakes (1–2 m <mean depth <3–4 m; c. 0.1 km² <area <at least 350 km²) from temperate to subtropical (probably to tropical) zones, being 80–120 mg m⁻³ for the forward shift from a clear‐water state to a turbid‐water state and 40–60 mg m⁻³ for the backward shift. The threshold of turbidity for the forward shift was found to be higher than that for the backward shift, amending the previous hypothesis of the equality of turbidity thresholds for both shifts. Our findings suggest that according to the subequality of TP thresholds, similar target concentrations for in‐lake TP can be set in most shallow lakes world‐wide to mitigate eutrophication.
Breast cancer (BC) is one of the most common malignancies affecting women. Ferroptosis is a novel cancer treatment option. The present study is aimed to identify suitable ferroptosis-related lncRNAs ...to predict and diagnose BC. Differential expression and Cox regression analyses were used to screen suitable prognostic biomarkers and construct a suitable risk model. We identified four ferroptosis-related differentially expressed lncRNAs (FR-DELs) (LINC01152, AC004585.1, MAPT-IT1, and AC026401.3), which were independently correlated with the overall survival of BC patients. The area under the curve value of the prognostic model using those four biomarkers was over 0.60 in all three groups. The sensitivity and specificity of the diagnostic model using those four biomarkers were 86.89% and 86.73%, respectively. Our present study indicated that these four FR-DELs (LINC01152, AC004585.1, MAPT-IT1, and AC026401.3) could be prognostic biomarkers for BC, although clinical validation studies are required.
Excessive mechanical tension can lead to the degeneration of endplate chondrocytes. The presence of tension‐sensitive circRNA_0058097 molecules has been detected in human endplate chondrocytes, where ...it was found to be a potential competing endogenous RNA. Indeed, inhibiting the expression of circRNA_0058097 effectively enhanced the stress resistance of endplate chondrocytes, suggesting that it may be an important trigger point for the degeneration of endplate cartilage. Through a series of experiments, we reveal that circRNA_0058097 can upregulate the expression of downstream target gene histone deacetylase 4 by sponge adsorption of miR‐365a‐5p, which promoted morphological changes of endplate chondrocytes, and increased extracellular matrix degradation and degeneration of endplate cartilage. Therefore, circRNA_0058097 may provide a new way to prevent and treat endplate cartilage degeneration.
Excessive intermittent cyclic mechanical tension can induce the degeneration of endplate chondrocytes. Tension‐sensitive circRNA_0058097 can upregulate the expression of downstream target gene histone deacetylase 4 by sponge adsorption of miR‐365a‐5p, which promoted morphological changes of endplate chondrocytes, and increased extracellular matrix degradation and degeneration of endplate cartilage.
To improve patient outcome and decrease overall health-care costs, highly sensitive and precise detection of a tumor is required for its accurate diagnosis and efficient therapy; however, this ...remains a challenge when using conventional single mode imaging. Here, we successfully designed a near-infrared (NIR)-response photothermal therapy (PTT) platform (Au@MSNs-ICG) for the location, diagnosis, and NIR/computer tomography (CT) bimodal imaging-guided PTT of tumor tissues, using gold (Au) nanospheres coated with indocyanine green (ICG)-loaded mesoporous silica nanoparticles (MSNs), which would have high sensitivity and precision. The nanoparticles (NPs) exhibited good monodispersity, fluorescence stability, biocompatibility, and NIR/CT signaling and had a preferable temperature response under NIR laser irradiation in vitro or in vivo. Using a combination of NIR/CT imaging and PTT treatment, the tumor could be accurately positioned and thoroughly eradicated in vivo by Au@MSNs-ICG injection. Hence, the multifunctional NPs could play an important role in facilitating the accurate treatment of tumors in future clinical applications.
Pain is one critical hallmark of inflammatory responses. A large number of studies have demonstrated that stromal cell-derived factor 1 (SDF1, also named as CXCL12) and its cognate receptor C-X-C ...chemokine receptor type 4 (CXCR4) play an important role in immune reaction and inflammatory processes. However, whether and how SDF1-CXCR4 signaling is involved in inflammatory pain remains unclear.
Under the intraplantar (i.pl.) bee venom (BV) injection-induced persistent inflammatory pain state, the changes of SDF1 and CXCR4 expression and cellular localization in the rat dorsal root ganglion (DRG) were detected by immunofluorescent staining. The role of SDF1 and CXCR4 in the hyperexcitability of primary nociceptor neurons was assessed by electrophysiological recording. Western blot analysis was used to quantify the DRG Nav1.8 and phosphorylation of ERK (pERK) expression. Behavioral tests were conducted to evaluate the roles of CXCR4 as well as extracellular signal-regulated kinase (ERK) and Nav1.8 in the BV-induced persistent pain and hypersensitivity.
We showed that both SDF1 and CXCR4 were dramatically up-regulated in the DRG in i.pl. BV-induced inflammatory pain model. Double immunofluorescent staining showed that CXCR4 was localized in all sizes (large, medium, and small) of DRG neuronal soma, while SDF1 was exclusively expressed in satellite glial cells (SGCs). Electrophysiological recording showed that bath application with AMD3100, a potent and selective CXCR4 inhibitor, could reverse the hyperexcitability of medium- and small-sized DRG neurons harvested from rats following i.pl. BV injection. Furthermore, we demonstrated that the BV-induced ERK activation and Nav1.8 up-regulation in the DRG could be blocked by pre-antagonism against CXCR4 in the periphery with AMD3100 as well as by blockade of ERK activation by intrathecal (i.t.) or intraplantar (i.pl.) U0126. At behavioral level, the BV-induced persistent spontaneous pain as well as primary mechanical and thermal hypersensitivity could also be significantly suppressed by blocking CXCR4 and Nav1.8 in the periphery as well as by inhibition of ERK activation at the DRG level.
The present results suggest that peripheral inflammatory pain state can trigger over release of SDF1 from the activated SGCs in the DRG by which SGC-neuronal cross-talk is mediated by SDF1-CXCR4 coupling that result in subsequent ERK-dependent Nav1.8 up-regulation, leading to hyperexcitability of tonic type of the primary nociceptor cells and development and maintenance of persistent spontaneous pain and hypersensitivity.
Aseptic loosening caused by wear particles is a common complication after total hip arthroplasty. We investigated the effect of the quercetin on wear particle‐mediated macrophage polarization, ...inflammatory response and osteolysis. In vitro, we verified that Ti particles promoted the differentiation of RAW264.7 cells into M1 macrophages through p‐38α/β signalling pathway by using flow cytometry, immunofluorescence assay and small interfering p‐38α/β RNA. We used enzyme‐linked immunosorbent assays to confirm that the protein expression of M1 macrophages increased in the presence of Ti particles and that these pro‐inflammatory factors further regulated the imbalance of OPG/RANKL and promoted the differentiation of osteoclasts. However, this could be suppressed, and the protein expression of M2 macrophages was increased by the presence of the quercetin. In vivo, we revealed similar results in the mouse skull by μ‐CT, H&E staining, immunohistochemistry and immunofluorescence assay. We obtained samples from patients with osteolytic tissue. Immunofluorescence analysis indicated that most of the macrophages surrounding the wear particles were M1 macrophages and that pro‐inflammatory factors were released. Titanium particle‐mediated M1 macrophage polarization, which caused the release of pro‐inflammatory factors through the p‐38α/β signalling pathway, regulated OPG/RANKL balance. Macrophage polarization is expected to become a new clinical drug therapeutic target.
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