Microwave-Assisted Synthesis of SnO2@ZnIn2S4 Composites for Highly Efficient Photocatalytic Hydrogen Evolution.

This research successfully synthesized SnO2@ZnIn2S4 composites for photocatalytic tap water splitting using a rapid two-step microwave-assisted synthesis method. This study investigated the impact of incorporating a fixed quantity of SnO2 nanoparticles and combining them with various materials to form composites, aiming to enhance photocatalytic hydrogen production. Additionally, different weights of SnO2 nanoparticles were added to the ZnIn2S4 reaction precursor to prepare SnO2@ZnIn2S4 composites for photocatalytic hydrogen production. Notably, the photocatalytic efficiency of SnO2@ZnIn2S4 composites is substantially higher than that of pure SnO2 nanoparticles and ZnIn2S4 nanosheets: 17.9-fold and 6.3-fold, respectively. The enhancement is credited to the successful use of visible light and the facilitation of electron transfer across the heterojunction, leading to the efficient dissociation of electron-hole pairs. Additionally, evaluations of recyclability demonstrated the remarkable longevity of SnO2@ZnIn2S4 composites, maintaining high levels of photocatalytic hydrogen production over eight cycles without significant efficiency loss, indicating their impressive durability. This investigation presents a promising strategy for crafting and producing environmentally sustainable SnO2@ZnIn2S4 composites with prospective implementations in photocatalytic hydrogen generation.

[Spatial-temporal Distribution and Source Analysis of Polycyclic Aromatic Hydrocarbons in the Sediments of Poyang Lake].

The concentrations, spatial-temporal distribution, and influencing factors of 16 polycyclic aromatic hydrocarbons (PAHs) in the sediments of Poyang Lake were studied, and a quantitative source analysis of PAHs in different areas of the lake was conducted. PAHs were widespread within the sediments. The concentrations of ∑16PAHs in the surface sediments of all sites ranged from 203 to 2 318 µg·kg-1. The concentrations of PAHs in the surface sediments of the lake body were higher than those in the surface sediments of the inlet rivers. The ratio of PAHs in Poyang Lake was 4 rings > 5 rings > 6 rings > 3 rings > 2 rings; the composition of 4-ring PAHs was dominant, and its content accounted for 86.11% of ∑16PAHs. The 2- and 3-ring and some 4-ring PAHs, including Flua and Pyr, were more susceptible to SOM, and the 4 through 6-ring PAHs were more susceptible to ORP and heavy metals and other environmental factors. Spatially, the higher concentration of ∑16PAHs occurred in the area of the lake adjacent to Duchang County and Poyang County, where the terrain was relatively closed, and the water exchange with the surrounding area was less than that in other sections, which was not conducive to the migration, transformation, and degradation of pollutants. In the temporal distribution, the changes in PAHs concentration level and the development of GDP in Jiangxi Province showed high consistency, and the influence of economic development and human activities might have been the main reason for the increasing PAHs concentration level. The main sources of PAHs in surface sediments of Poyang Lake included petroleum pollution and oil and coal and biomass combustion sources, and there were some spatial differences in PAHs sources in different regions. This study can provide a reference for PAHs pollution in surface sediments of Poyang Lake, which is important for the ecological environmental protection and management of Poyang Lake.

Commonalities and distinctions between the type 2 diabetes mellitus and Alzheimer's disease: a systematic review and multimodal neuroimaging meta-analysis.

Background: Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are aging related diseases with high incidence. Because of the correlation of incidence rate and some possible mechanisms of comorbidity, the two diseases have been studied in combination by many researchers, and even some scholars call AD type 3 diabetes. But the relationship between the two is still controversial. Methods: This study used seed-based d mapping software to conduct a meta-analysis of the whole brain resting state functional magnetic resonance imaging (rs-fMRI) study, exploring the differences in amplitude low-frequency fluctuation (ALFF) and cerebral blood flow (CBF) between patients (AD or T2DM) and healthy controls (HCs), and searching for neuroimaging evidence that can explain the relationship between the two diseases. Results: The final study included 22 datasets of ALFF and 22 datasets of CBF. The results of T2DM group showed that ALFF increased in both cerebellum and left inferior temporal gyrus regions, but decreased in left middle occipital gyrus, right inferior occipital gyrus, and left anterior central gyrus regions. In the T2DM group, CBF increased in the right supplementary motor area, while decreased in the middle occipital gyrus and inferior parietal gyrus. The results of the AD group showed that the ALFF increased in the right cerebellum, right hippocampus, and right striatum, while decreased in the precuneus gyrus and right superior temporal gyrus. In the AD group, CBF in the anterior precuneus gyrus and inferior parietal gyrus decreased. Multimodal analysis within a disease showed that ALFF and CBF both decreased in the occipital lobe of the T2DM group and in the precuneus and parietal lobe of the AD group. In addition, there was a common decrease of CBF in the right middle occipital gyrus in both groups. Conclusion: Based on neuroimaging evidence, we believe that T2DM and AD are two diseases with their respective characteristics of central nervous activity and cerebral perfusion. The changes in CBF between the two diseases partially overlap, which is consistent with their respective clinical characteristics and also indicates a close relationship between them. Systematic review registration: PROSPERO [CRD42022370014].

[Optimization of extraction process for classic prescription Yihuang Decoction based on Box-Behnken design-response surface methodology, standard relation, and analytic hierarchy process combined with entropy weight method].

Based on the concept of quality by design(QbD), the Box-Behnken design-response surface methodology combined with standard relation(SR) and analytic hierarchy process(AHP)-entropy weight method(EWM) was applied to optimize the extraction process of the classic prescription Yihuang Decoction. The content of geniposidic acid, phellodendrine hydrochloride, and berberine hydrochloride in Yihuang Decoction, the extract yield, and fingerprint similarity were used as the critical quality attributes(CQAs) of the extraction process. The extraction time, water addition, and extraction times were used as the critical process parameters(CPPs). After determining the levels of each factor and level through single-factor experiments, response surface experiments were designed according to the Box-Behnken principle, and the experimental results were analyzed. The SR between each sample and the reference sample under various evaluation indicators of different extraction parameters was calculated. The weights of the five evaluation indicators were determined using AHP-EWM, followed by comprehensive evaluation. A function model between CPPs and CQAs characterized by comprehensive scores was established to predict the optimal extraction process parameters. In the final comprehensive weight coefficients, the yield rate accounted for 43.1%, and the content of berberine hydrochloride, phellodendrine hydrochloride, and geniposidic acid accounted for 35.1%, 6.3%, and 15.5%, respectively. After comprehensive score analysis with SR, the established second-order polynomial model was statistically significant(P<0.01, and the lack of fit was not significant). The predicted optimal extraction conditions for Yihuang Decoction were determined as follows: 8-fold volume of water, extraction time of 1.5 h, and extraction once. The mean comprehensive score of the validation experiment was 85.77, with an RSD of 0.99%, and it met the quality control stan-dards for the reference sample of Yihuang Decoction. The results indicate that the optimized extraction process for Yihuang Decoction is stable and reliable, and the water extract is close in quality attributes to the reference sample. This can serve as a foundation for the research and development of granules in the future. Box-Behnken design-response surface methodology combined with SR and AHP-EWM can provide references for the modern extraction process research of other classic prescriptions.

HSF4/COIL complex-dependent R-loop mediates ultraviolet-induced inflammatory skin injury.

Intense ultraviolet (UV) exposure can cause phototoxic reactions, such as skin inflammation, resulting in injury. UV is a direct cause of DNA damage, but the mechanisms underlying transcriptional regulation within cells after DNA damage are unclear. The bioinformatics analysis of transcriptome sequencing data from UV-irradiated and non-UV-irradiated skin showed that transcription-related proteins, such as HSF4 and COIL, mediate cellular response to UV irradiation. HSF4 and COIL can form a complex under UV irradiation, and the preference for binding target genes changed because of the presence of a large number of R-loops in cells under UV irradiation and the ability of COIL to recognize R-loops. The regulation of target genes was altered by the HSF4-COIL complex, and the expression of inflammation and ageing-related genes, such as Atg7, Tfpi, and Lims1, was enhanced. A drug screen was performed for the recognition sites of COIL and R-loop. N6-(2-hydroxyethyl)-adenosine can competitively bind COIL and inhibit the binding of COIL to the R-loop. Thus, the activation of downstream inflammation-related genes and inflammatory skin injury was inhibited.

Landslide Susceptibility Evaluation Based on Potential Disaster Identification and Ensemble Learning.

Catastrophic landslides have much more frequently occurred worldwide due to increasing extreme rainfall events and intensified human engineering activity. Landslide susceptibility evaluation (LSE) is a vital and effective technique for the prevention and control of disastrous landslides. Moreover, about 80% of disastrous landslides had not been discovered ahead and significantly impeded social and economic sustainability development. However, the present studies on LSE mainly focus on the known landslides, neglect the great threat posed by the potential landslides, and thus to some degree constrain the precision and rationality of LSE maps. Moreover, at present, potential landslides are generally identified by the characteristics of surface deformation, terrain, and/or geomorphology. The essential disaster-inducing mechanism is neglected, which has caused relatively low accuracies and relatively high false alarms. Therefore, this work suggests new synthetic criteria of potential landslide identification. The criteria involve surface deformation, disaster-controlling features, and disaster-triggering characteristics and improve the recognition accuracy and lower the false alarm. Furthermore, this work combines the known landslides and discovered potential landslides to improve the precision and rationality of LSE. This work selects Chaya County, a representative region significantly threatened by landslides, as the study area and employs multisource data (geological, topographical, geographical, hydrological, meteorological, seismic, and remote sensing data) to identify potential landslides and realize LSE based on the time-series InSAR technique and XGBoost algorithm. The LSE precision indices of AUC, Accuracy, TPR, F1-score, and Kappa coefficient reach 0.996, 97.98%, 98.77%, 0.98, and 0.96, respectively, and 16 potential landslides are newly discovered. Moreover, the development characteristics of potential landslides and the cause of high landslide susceptibility are illuminated. The proposed synthetic criteria of potential landslide identification and the LSE idea of combining known and potential landslides can be utilized to other disaster-serious regions in the world.

Computational Recognition of a Regulatory T-cell-specific Signature With Potential Implications in Prognosis, Immunotherapy, and Therapeutic Resistance of Prostate Cancer.

Prostate cancer, recognized as a "cold" tumor, has an immunosuppressive microenvironment in which regulatory T cells (Tregs) usually play a major role. Therefore, identifying a prognostic signature of Tregs has promising benefits of improving survival of prostate cancer patients. However, the traditional methods of Treg quantification usually suffer from bias and variability. Transcriptional characteristics have recently been found to have a predictive power for the infiltration of Tregs. Thus, a novel machine learning-based computational framework has been presented using Tregs and 19 other immune cell types using 42 purified immune cell datasets from GEO to identify Treg-specific mRNAs, and a prognostic signature of Tregs (named "TILTregSig") consisting of five mRNAs (SOCS2, EGR1, RRM2, TPP1, and C11orf54) was developed and validated to monitor the prognosis of prostate cancer using the TCGA and ICGC datasets. The TILTregSig showed a stronger predictive power for tumor immunity compared with tumor mutation burden and glycolytic activity, which have been reported as immune predictors. Further analyses indicate that the TILTregSig might influence tumor immunity mainly by mediating tumor-infiltrating Tregs and could be a powerful predictor for Tregs in prostate cancer. Moreover, the TILTregSig showed a promising potential for predicting cancer immunotherapy (CIT) response in five CIT response datasets and therapeutic resistance in the GSCALite dataset in multiple cancers. Our TILTregSig derived from PBMCs makes it possible to achieve a straightforward, noninvasive, and inexpensive detection assay for prostate cancer compared with the current histopathological examination that requires invasive tissue puncture, which lays the foundation for the future development of a panel of different molecules in peripheral blood comprising a biomarker of prostate cancer.

Retraction Notice to: miR-181a Induces Macrophage Polarized to M2 Phenotype and Promotes M2 Macrophage-mediated Tumor Cell Metastasis by Targeting KLF6 and C/EBPα.

[This retracts the article DOI: 10.1038/mtna.2016.71.].

[Puerarin-Chuanxiong oil submicron emulsion combining medicine and adjuvant].

This study was mainly based on the compatibility of Puerariae Lobatae Radix and Chuanxiong Rhizoma to prepare submicron emulsion and evaluated its physical and pharmaceutical properties. Firstly, pseudo-ternary phase diagrams were drawn by dripping method which took Chuanxiong oil as the oil phase and the area of microemulsion region as the index. On this basis, suitable emulsifier and co-emulsifier were screened for the preparation of Chuanxiong oil submicron emulsion. Then, the formula realizing the largest oil loading was selected. Finally, puerarin substituted part of emulsifier and co-emulsifier to lower their content, so as to form puerarin-Chuanxiong oil submicron emulsion featuring the combination of medicine and adjuvant. Its particle size, zeta potential, centrifugal stability and storage stability were determined, and the in vitro drug release behavior was investigated by dialysis bag method, based on which the quality of the as-prepared submicron emulsion was evaluated comprehensively. The proposed method was proved feasible for the preparation of Chuanxiong oil submicron emulsion, which adopted polyoxyethylene castor oil(EL-40) as the emulsifier and was free from co-emulsifier. The formula of the maximum oil loading was found as Chuanxiong oil∶EL-40∶water 3∶7∶90. Further, puera-rin successfully replaced up to 10% of the emulsifier in submicron emulsion. Eventually, the optimal drug-loading formula was determined as puerarin∶Chuanxiong oil∶EL-40∶water 7∶30∶63∶900. The quality evaluation results of the as-prepared submicron emulsion demonstrated that the average emulsion droplet size was 333.9 nm, the PDI 0.26, and the zeta potential-10.12 mV. The submicron emulsion had a good centrifugal stability and did not present any instable phenomena such as delamination and precipitation during its standing still for 50 days. The evaluation of in vitro drug release behavior indicated that the submicron emulsion was capable of releasing the drug completely. The puerarin-chuanxiong oil submicron emulsion prepared in this study possessed a stable quality and to some extent increased the solubility of puerarin along with a sustained-release effect. This study provided ideas for the clinical application of puerarin.

Development of a Novel Prognostic Signature Based on Antigen Processing and Presentation in Patients with Breast Cancer.

Background: Complex antigen processing and presentation processes are involved in the development and progression of breast cancer (BC). A single biomarker is unlikely to adequately reflect the complex interplay between immune cells and cancer; however, there have been few attempts to find a robust antigen processing and presentation-related signature to predict the survival outcome of BC patients with respect to tumor immunology. Therefore, we aimed to develop an accurate gene signature based on immune-related genes for prognosis prediction of BC. Methods: Information on BC patients was obtained from The Cancer Genome Atlas. Gene set enrichment analysis was used to confirm the gene set related to antigen processing and presentation that contributed to BC. Cox proportional regression, multivariate Cox regression, and stratified analysis were used to identify the prognostic power of the gene signature. Differentially expressed mRNAs between high- and low-risk groups were determined by KEGG analysis. Results: A three-gene signature comprising HSPA5 (heat shock protein family A member 5), PSME2 (proteasome activator subunit 2), and HLA-F (major histocompatibility complex, class I, F) was significantly associated with OS. HSPA5 and PSME2 were protective (hazard ratio (HR) < 1), and HLA-F was risky (HR > 1). Risk score, estrogen receptor (ER), progesterone receptor (PR) and PD-L1 were independent prognostic indicators. KIT and ACACB may have important roles in the mechanism by which the gene signature regulates prognosis of BC. Conclusion: The proposed three-gene signature is a promising biomarker for estimating survival outcomes in BC patients.

lncRNA-Xist/miR-101-3p/KLF6/C/EBPα axis promotes TAM polarization to regulate cancer cell proliferation and migration.

The phenotypic switch in tumor-associated macrophages (TAMs) mediates immunity escape of cancer. However, the underlying mechanisms in the TAM phenotypic switch have not been systematically elucidated. In this study, long noncoding RNA (lncRNA)-Xist, CCAAT/enhancer-binding protein (C/EBP)α, and Kruppel-like factor 6 (KLF6) were upregulated, whereas microRNA (miR)-101 was downregulated in M1 macrophages-type (M1). Knockdown of Xist or overexpression of miR-101 in M1 could induce M1-to-M2 macrophage-type (M2) conversion to promote cell proliferation and migration of breast and ovarian cancer by inhibiting C/EBPα and KLF6 expression. Furthermore, miR-101 could combine with both Xist and C/EBPα and KLF6 through the same microRNA response element (MRE) predicted by bioinformatics and verified by luciferase reporter assays. Moreover, we found that miR-101 knockdown restored the decreased M1 marker and the increased M2 marker expression and also reversed the promotion of proliferation and migration of human breast cancer cells (MCF-7) and human ovarian cancer (OV) cells caused by silencing Xist. Generally, the present study indicates that Xist could mediate macrophage polarization to affect cell proliferation and migration of breast and ovarian cancer by competing with miR-101 to regulate C/EBPα and KLF6 expression. The promotion of Xist expression in M1 macrophages and inhibition of miR-101 expression in M2 macrophages might play an important role in inhibiting breast and ovarian tumor proliferation and migration abilities.

Pan-cancer analysis of NLRP3 inflammasome with potential implications in prognosis and immunotherapy in human cancer.

NLRP3 inflammasome was introduced as a double-edged sword in tumorigenesis and influenced immunotherapy response by modulating host immunity. However, a systematic assessment of the NLRP3-inflammasome-related genes across human cancers is lacking, and the predictive role of NLRP3 inflammasome in cancer immunotherapy (CIT) response remains unexplored. Thus, in this study, we performed a pan-cancer analysis of NLRP3-inflammasome-related genes across 24 human cancers. Out of these 24 cancers, 15 cancers had significantly different expression of NLRP3-inflammasome-related genes between normal and tumor samples. Meanwhile, Cox regression analysis showed that the NLRP3 inflammasome score could be served as an independent prognostic factor in skin cutaneous melanoma. Further analysis indicated that NLRP3 inflammasome may influence tumor immunity mainly by mediating tumor-infiltrating lymphocytes and macrophages, and the effect of NLRP3 inflammasome on immunity is diverse across tumor types in tumor microenvironment. We also found that the NLRP3 inflammasome score could be a stronger predictor for immune signatures compared with tumor mutation burden (TMB) and glycolytic activity, which have been reported as immune predictors. Furthermore, analysis of the association between NLRP3 inflammasome and CIT response using six CIT response datasets revealed the predictive value of NLRP3 inflammasome for immunotherapy response of patients in diverse cancers. Our study illustrates the characterization of NLRP3 inflammasome in multiple cancer types and highlights its potential value as a predictive biomarker of CIT response, which can pave the way for further investigation of the prognostic and therapeutic potentials of NLRP3 inflammasome.

Prognostic alternative splicing signature reveals the landscape of immune infiltration in Pancreatic Cancer.

Background: Pancreatic cancer (PC) is an aggressive cancer with worse survival in the world. Emerging evidence suggested that the imbalance of alternative splicing (AS) is a hallmark of cancer and indicated poor prognosis of patients. Genes-derived splicing events can produce neoepitopes for immunotherapy. However, the profound study of splicing profiling in PC is still elusive. We aimed to identification of novel prognostic signature across a comprehensive splicing landscape and reveal their relationship with tumor-infiltrating immune cells in pancreatic cancer microenvironment. Methods: Based on integrated analysis of splicing profiling and clinical data, differentially splicing events were filtered out. Then, stepwise Cox regression analysis was applied to identify survival-related splicing events and construct prognostic signature. Functional enrichment analysis was performed to explore biology function. Kaplan-Meier curves and receiver operating characteristic (ROC) curves were performed to validate the predictive effect of predictive signature. We also verified the clinical value of prognostic signature under the influence of different clinical parameters. For deeper analysis, we evaluated the correlation between prognostic signature and infiltrating immune cells by CIBERSORT. Results: According to systematic analyzing, a final six splicing events were identified and validated the good prognostic capability in entire TCGA dataset, validation set 1 and validation set 2 by Kaplan-Meier curves (P < 0.0001). The area under the curve (AUC) of ROC curves were also confirmed the high predictive efficiency of the prognostic signature in these three cohorts (AUC = 0.857, 0.895 and 0.788). In order to validate whether prognostic signature highlights a correlation between AS and immune contexture, CIBERSORT was performed to analyze the proportion of tumor-infiltrating immune cells in PC. Based on prognostic signature, we identified survival-related immune cells including CD8 T cells (P = 0.0111), activated CD4 memory T cells (P = 0.0329) and resting mast cells (P = 0.0352). Conclusion: In conclusion, our study contribute to provide a promising prognostic signature based on six splicing events and revealed prognosis-related immune cells which indeed represented novel tumor drivers and provide potential targets for personalized therapeutic.

A five-mRNA signature associated with post-translational modifications can better predict recurrence and survival in cervical cancer.

High mortality of patients with cervical cancer (CC) stresses the imperative of prognostic biomarkers for CC patients. Additionally, the vital status of post-translational modifications (PTMs) in the progression of cancers has been reported by numerous researches. Therefore, the purpose of this research was to dig a prognostic signature correlated with PTMs for CC. We built a five-mRNA (GALNTL6, ARSE, DPAGT1, GANAB and FURIN) prognostic signature associated with PTMs to predict both disease-free survival (DFS) (hazard ratio [HR] = 3.967, 95% CI = 1.985-7.927; P < .001) and overall survival (HR = 2.092, 95% CI = 1.138-3.847; P = .018) for CC using data from The Cancer Genome Atlas database. Then, the robustness of the signature was validated using GSE44001 and the Human Protein Atlas (HPA) database. CIBERSORT algorithm analysis displayed that activated CD4 memory T cell was also an independent indicator for DFS (HR = 0.426, 95% CI = 0.186-0.978; P = .044) which could add additional prognostic value to the signature. Collectively, the PTM-related signature and activated CD4 memory T cell can provide new avenues for the prognostic predication of CC. These findings give further insights into effective treatment strategies for CC, providing opportunities for further experimental and clinical validations.

Neural cell adhesion molecule regulates chondrocyte hypertrophy in chondrogenic differentiation and experimental osteoarthritis.

Chondrocyte hypertrophy-like change is an important pathological process of osteoarthritis (OA), but the mechanism remains largely unknown. Neural cell adhesion molecule (NCAM) is highly expressed and involved in the chondrocyte differentiation of mesenchymal stem cells (MSCs). In this study, we found that NCAM deficiency accelerates chondrocyte hypertrophy in articular cartilage and growth plate of OA mice. NCAM deficiency leads to hypertrophic chondrocyte differentiation in both murine MSCs and chondrogenic cells, in which extracellular signal-regulated kinase (ERK) signaling plays an important role. Moreover, NCAM expression is downregulated in an interleukin-1ß-stimulated OA cellular model and monosodium iodoacetate-induced OA rats. Overexpression of NCAM substantially inhibits hypertrophic differentiation in the OA cellular model. In conclusion, NCAM could inhibit hypertrophic chondrocyte differentiation of MSCs by inhibiting ERK signaling and reduce chondrocyte hypertrophy in experimental OA model, suggesting the potential utility of NCAM as a novel therapeutic target for alleviating chondrocyte hypertrophy of OA.

Glycolysis gene expression profilings screen for prognostic risk signature of hepatocellular carcinoma.

Metabolic changes are the markers of cancer and have attracted wide attention in recent years. One of the main metabolic features of tumor cells is the high level of glycolysis, even if there is oxygen. The transformation and preference of metabolic pathways is usually regulated by specific gene expression. The aim of this study is to develop a glycolysis-related risk signature as a biomarker via four common cancer types. Only hepatocellular carcinoma was shown the strong relationship with glycolysis. The mRNA sequencing and chip data of hepatocellular carcinoma, breast invasive carcinoma, renal clear cell carcinoma, colorectal adenocarcinoma were included in the study. Gene set enrichment analysis was performed, profiling three glycolysis-related gene sets, it revealed genes associated with the biological process. Univariate and multivariate Cox proportional regression models were used to screen out prognostic-related gene signature. We identified six mRNAs (DPYSL4, HOMER1, ABCB6, CENPA, CDK1, STMN1) significantly associated with overall survival in the Cox proportional regression model for hepatocellular carcinoma. Based on this gene signature, we were able to divide patients into high-risk and low-risk subgroups. Multivariate Cox regression analysis showed that prognostic power of this six gene signature is independent of clinical variables. Further, we validated this data in our own 55 paired hepatocellular carcinoma and adjacent tissues. The results showed that these proteins were highly expressed in hepatocellular carcinoma tissues compared with adjacent tissue. The survival time of high-risk group was significantly shorter than that of low-risk group, indicating that high-risk group had poor prognosis. We calculated the correlation coefficients between six proteins and found that these six proteins were independent of each other. In conclusions, we developed a glycolysis-related gene signature that could predict survival in hepatocellular carcinoma patients. Our findings provide novel insight to the mechanisms of glycolysis and it is useful for identifying patients with hepatocellular carcinoma with poor prognoses.

Intrinsic adriamycin resistance in p53-mutated breast cancer is related to the miR-30c/FANCF/REV1-mediated DNA damage response.

Adriamycin(ADR) is still considered to be one of the most effective agents in the treatment of breast cancer (BrCa), its efficacy is compromised by intrinsic resistance or acquire characteristics of multidrug resistance. At present, there are few genetic alterations that can be exploited as biomarkers to guide targeted use of ADR in clinical. Therefore, exploring the determinants of ADR sensitivity is pertinent for their optimal clinical application. TP53 is the most frequently mutated gene in human BrCa, p53 mutation has been reported to be closely related to ADR resistance, whereas the underlying mechanisms that cause endogenous ADR resistance in p53-mutant BrCa cells are not completely understood. The aim of the present study was to investigate the potential roles of miRNA in the response to ADR in p53-mutated breast cancer. Here, we report that BrCa cells expressing mutp53 are more resistant to ADR than cells with wild-type p53 (wtp53). The DNA repair protein- Fanconi anemia complementation group F protein (FANCF) and the translesion synthesis DNA polymerase REV1 protein is frequently abundant in the context of mutant p53 of BrCa. By targeting two key factors, miR-30c increases the sensitivity of BrCa cells to ADR. Furthermore, p53 directly activates the transcription of miR-30c by binding to its promoter. Subsequent analyses revealed that p53 regulates REV1 and FANCF by modulating miR-30c expression. Mutation of the p53 abolished this response. Consistently, reduced miR-30c expression is highly correlated with human BrCa with p53 mutational status and is associated with poor survival. We propose that one of the pathways affected by mutant p53 to increase intrinsic resistance to ADR involves miR-30c downregulation and the consequent upregulation of FANCF and REV1. The novel miRNA-mediated pathway that regulates chemoresistance in breast cancer will facilitate the development of novel therapeutic strategies.

SNORD89 promotes stemness phenotype of ovarian cancer cells by regulating Notch1-c-Myc pathway.

BACKGROUND: Ovarian cancer is the leading cause of death in gynecological cancer. Cancer stem cells (CSCs) contribute to the occurrence, progression and resistance. Small nucleolar RNAs (SnoRNAs), a class of small molecule non-coding RNA, involve in the cancer cell stemness and tumorigenesis. METHODS: In this study, we screened out SNORNAs related to ovarian patient's prognosis by analyzing the data of 379 cases of ovarian cancer patients in the TCGA database, and analyzed the difference of SNORNAs expression between OVCAR-3 (OV) sphere-forming (OS) cells and OV cells. After overexpression or knockdown SNORD89, the expression of Nanog, CD44, and CD133 was measured by qRT-PCR or flow cytometry analysis in OV, CAOV-3 (CA) and OS cells, respectively. CCK-8 assays, plate clone formation assay and soft agar colony formation assay were carried out to evaluate the changes of cell proliferation and self-renewal ability. Scratch migration assay and trans-well invasion analysis were used for assessing the changes of migration and invasion ability. RESULTS: High expression of SNORD89 indicates the poor prognosis of ovarian cancer patients and was associated with patients' age, therapy outcome. SNORD89 highly expressed in ovarian cancer stem cells. The overexpression of SNORD89 resulted in the increased stemness markers, S phase cell cycle, cell proliferation, invasion and migration ability in OV and CA cells. Conversely, these phenomena were reversed after SNORD89 silencing in OS cells. Further, we found that SNORD89 could upregulate c-Myc and Notch1 expression in mRNA and protein levels. SNORD89 deteriorates the prognosis of ovarian cancer patients by regulating Notch1-c-Myc pathway to promote cell stemness and acts as an oncogene in ovarian tumorigenesis. Consequently, SNORD89 can be a novel prognostic biomarker and therapeutic target for ovarian cancer.