Concurrent Asian monsoon strengthening and early modern human dispersal to East Asia during the last interglacial.

The relationship between initial Homo sapiens dispersal from Africa to East Asia and the orbitally paced evolution of the Asian summer monsoon (ASM)-currently the largest monsoon system-remains underexplored due to lack of coordinated synthesis of both Asian paleoanthropological and paleoclimatic data. Here, we investigate orbital-scale ASM dynamics during the last 280 thousand years (kyr) and their likely influences on early H. sapiens dispersal to East Asia, through a unique integration of i) new centennial-resolution ASM records from the Chinese Loess Plateau, ii) model-based East Asian hydroclimatic reconstructions, iii) paleoanthropological data compilations, and iv) global H. sapiens habitat suitability simulations. Our combined proxy- and model-based reconstructions suggest that ASM precipitation responded to a combination of Northern Hemisphere ice volume, greenhouse gas, and regional summer insolation forcing, with cooccurring primary orbital cycles of ~100-kyr, 41-kyr, and ~20-kyr. Between ~125 and 70 kyr ago, summer monsoon rains and temperatures increased in vast areas across Asia. This episode coincides with the earliest H. sapiens fossil occurrence at multiple localities in East Asia. Following the transcontinental increase in simulated habitat suitability, we suggest that ASM strengthening together with Southeast African climate deterioration may have promoted the initial H. sapiens dispersal from their African homeland to remote East Asia during the last interglacial.

CT23 knockdown attenuating malignant behaviors of hepatocellular carcinoma cell is associated with upregulation of metallothionein 1.

The cancer-testis antigen 23 (CT23) gene has been reported in association with the pathogenesis and progress of hepatocellular carcinoma (HCC). However, the alterations of gene expression profiling induced by CT23 knockdown in HCC cells remains largely unknown. In this study, the RNA interfering (RNAi) method was used to silence CT23 expression in BEL-7404 cells. Microarray analysis was performed on mRNA extracted from the CT23 knockdown cells and the control cells to determine the alterations of gene expression profiles. The result showed a total of 1051 genes expressed differentially (two-fold change), including 470 genes upregulated and 581 gene downregulated in the CT23 knockdown cells. A bioinformatic analysis showed that the functional differentially expressed genes (DEGs) were linked to cell proliferation, migration, and apoptosis, and metallothionein 1 (MT1) attained the maximum enrichment scores in functional annotation, classification, and pathway analysis of DEGs. Furthermore, Western blot analysis and cell behaviors assays verified that CT23 modulates cell proliferation, migration, and apoptosis by regulating MT1 expression in HCC cells and non-neoplastic hepatocytes. In summary, downregulated CT23 gene in BEL-7404 cells might change the expressions of carcinogenesis and progression related genes in HCC by upregulating MT1 expression, which would provide insight into searching for a novel therapeutic target for HCC.

The potential value of cancer-testis antigens in ovarian cancer: Prognostic markers and targets for immunotherapy.

BACKGROUND: Tumor immunotherapy has become an important adjuvant therapy after surgery, radiotherapy, and chemotherapy. In recent years, the role of tumor-associated antigen (TAA) in tumor immunotherapy has become increasingly prominent. Cancer-testis antigen (CTA) is a kind of TAA that is highly restricted in a variety of tumors and can induce an immune response. AIMS: This review article aimed to evaluate the role of CTA on the progression of ovarian cancer, its diagnostic efficacy, and the potential for immunotherapy. METHODS: We analyzed publications and outlined a comprehensive of overview the regulatory mechanism, immunogenicity, clinical expression significance, tumorigenesis, and application prospects of CTA in ovarian cancer, with a particular focus on recent progress in CTA-based immunotherapy. RESULTS: The expression of CTA affects the occurrence, development, and prognosis of ovarian cancer and is closely related to tumor immunity. CONCLUSION: CTA can be used as a biomarker for the diagnosis and prognosis evaluation of ovarian cancer and is an ideal target for antitumor immunotherapy. These findings provide novel insights on CTA in the improvement of diagnosis and treatment for ovarian cancer. The successes, current challenges and future prospects were also discussed to portray its significant potential.

The Crosstalk and Clinical Implications of CircRNAs and Glucose Metabolism in Gastrointestinal Cancers.

The majority of glucose in tumor cells is converted to lactate despite the presence of sufficient oxygen and functional mitochondria, a phenomenon known as the "Warburg effect" or "aerobic glycolysis". Aerobic glycolysis supplies large amounts of ATP, raw material for macromolecule synthesis, and also lactate, thereby contributing to cancer progression and immunosuppression. Increased aerobic glycolysis has been identified as a key hallmark of cancer. Circular RNAs (circRNAs) are a type of endogenous single-stranded RNAs characterized by covalently circular structures. Accumulating evidence suggests that circRNAs influence the glycolytic phenotype of various cancers. In gastrointestinal (GI) cancers, circRNAs are related to glucose metabolism by regulating specific glycolysis-associated enzymes and transporters as well as some pivotal signaling pathways. Here, we provide a comprehensive review of glucose-metabolism-associated circRNAs in GI cancers. Furthermore, we also discuss the potential clinical prospects of glycolysis-associated circRNAs as diagnostic and prognostic biomarkers and therapeutic targets in GI cancers.

P14.5 functions to inhibit cell migration and can be used as a prognostic marker in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with a high mortality rate. P14.5 is a member of the highly conserved YER057c/YIL051c/YjgF subfamily and is highly expressed in the liver. However, its low expression is associated with carcinogenesis in HCC. OBJECTIVE: This study aimed to investigate the role and prognostic significance of P14.5 in HCC. METHODS: The clinical significance of P14.5 in HCC was examined using ONCOMINE, UALCAN, Human Protein Atlas, and Kaplan-Meier plotter. The DNA methylation profile of the P14.5 promoter was examined in 103 HCC and paired precancerous tissues; the HCC cell lines HepG2, MHCC-97L, SMMC-7721, SK-Hep-1, and Huh7; and the normal hepatic cell line HL-7702 via MALDI-TOF mass spectrometry. In addition, in vitro experiments were performed to examine the effects of P14.5 overexpression on the proliferation and migration of SMMC-7721 cells. RESULTS: Low expression of P14.5 was correlated with shorter overall survival (OS) and disease-free survival (DFS) in HCC. Based on the results of MALDI-TOF mass spectrometry, no difference was observed in the methylation level between HCC cells and normal human hepatic cells and between HCC and paired precancerous tissues. Additionally, P14.5 overexpression promoted the proliferation and inhibited the migration of SMMC7721 cells in vitro. CONCLUSIONS: P14.5 may serve as a prognostic biomarker in HCC and plays a role in the migration and proliferation of HCC cells. Low expression of P14.5 during hepatocarcinogenesis is not attributed to DNA methylation.

Identification of potential biomarkers in cancer testis antigens for glioblastoma.

OBJECTIVE: To screen and validate cancer testis antigens (CTAs) as potential biomarkers and explore their molecular mechanisms in glioblastoma (GBM). METHODS: Ribonucleic acid sequencing (RNA-seq) and bioinformatics analyses were utilized to screen the highly expressed CTAs in GBM. Correlation analysis was used to identify potential biomarkers associated with tumor purity and prognosis. Immunohistochemistry was applied for detection of protein expression. Protein-protein interaction (PPI) network construction, functional enrichment analysis, and binding domain prediction were performed to investigate the underlying molecular mechanisms of GBM. RESULTS: A total of 8 highly expressed CTAs were identified in GBM. One of them was PDZ-binding kinase (PBK). PBK messenger RNA (mRNA) was most highly expressed in GBM and associated with tumor purity and prognosis, PBK protein expression was also significantly increased in GBM tissues and correlated with p53 expression. Functional enrichment analysis revealed that the PBK related genes were predominantly enriched in cell cycle pathway with 38 genes enriched. The proteins encoding by these 38 genes were performed by binding domain prediction analysis, which demonstrated 15 proteins interacting with PBK. Most of these proteins were up regulated in GBM. CONCLUSION: PBK is highly expressed in GBM. It may serve as a potential biomarker for GBM targeting therapy and the cell cycle modulator by interacting with certain key molecules of cell cycle in GBM.

Long non-coding RNA SNHG17 may function as a competitive endogenous RNA in diffuse large B-cell lymphoma progression by sponging miR-34a-5p.

We investigated the functional mechanism of long non-coding small nucleolar host gene 17 (SNHG17) in diffuse large B-cell lymphoma (DLBCL). lncRNAs related to the prognosis of patients with DLBCL were screened to analyze long non-coding small nucleolar host gene 17 (SNHG17) expression in DLBCL and normal tissues, and a nomogram established for predicting DLBCL prognosis. SNHG17 expression in B-cell lymphoma cells was detected using qPCR. The effects of SNHG17 with/without doxorubicin on the proliferation and apoptosis of DoHH2 and Daudi were detected. The effects of combined SNHG17 and doxorubicin were analyzed. The regulatory function of SNHG17 in DLBCL was investigated using a mouse tumor xenotransplantation model. RNA sequencing was used to analyze the signaling pathways involved in SNHG17 knockdown in B-cell lymphoma cell lines. The target relationships among SNHG17, microRNA, and downstream mRNA biomolecules were detected. A higher SNHG17 level predicted a lower survival rate. SNHG17 was highly expressed in DLBCL patient tissues and cell lines. We established a prognostic model containing SNHG17 expression, which could effectively predict the overall survival rate of DLBCL patients. SNHG17 knockdown inhibited the proliferation and induced the apoptosis of B-cell lymphoma cells, and the combination of SNHG17 and doxorubicin had a synergistic effect. SNHG17, miR-34a-5p, and ZESTE gene enhancer homolog 2 (EZH2) had common hypothetical binding sites, and the luciferase reporter assay verified that miR-34a-5p was the direct target of SNHG17, and EZH2 was the direct target of miR-34a-5p. The carcinogenic function of SNHG17 in the proliferation and apoptosis of DLBCL cells was partially reversed by a miR-34a-5p inhibitor. SNHG17 increases EZH2 levels by inhibiting miR-34a-5p. Our findings indicate SNHG17 as critical for promoting DLBCL progression by regulating the EZH2 signaling pathway and sponging miR-34a-5p. These findings provide a new prognostic marker and therapeutic target for the prognosis and treatment of DLBCL.

Prediction and identification of HLA-A*0201-restricted epitopes from cancer testis antigen CT23.

Cancer-testis antigen CT23 is a class of tumor-associated antigens (TAA) characterized by restricted expression in male germ cells and a variety of tumor tissues. Numerous studies have shown that CT23 is closely related to tumor cell viability, proliferation, metastasis and invasion. CT23 is immunogenic and can cause specific immune response in tumor patients. Therefore, it is considered to be one of the best target antigens for designing therapeutic tumor vaccines and T-cell-mediated tumor immunotherapy. In this study, we initially obtained seven HLA-A*0201-restricted CT23 epitope candidate peptides through the T cell epitope prediction program. Subsequently, a T2 cell binding assay revealed the potential binding of all candidate peptides with HLA-A2 molecules. Notably, peptide P7 (ALLVLCYSI) exhibited the highest affinity, as evidenced by a fluorescence index (FI) of 2.19. Dendritic cells (DCs) loaded with CT23 candidate peptide can stimulate CD8+T cell activation and proliferation, and compared with other candidate peptides, candidate peptide P7 is superior. The cytotoxic T lymphocytes (CTLs) stimulated by the peptide P7 had killing effect on tumor cells (HLA-A*0201+, CT23+), but no killing effect on tumor cells (HLA-A*0201-, CT23+). The CTLs induced by the peptide P7 also had a specific killing effect on T2 cells bearing the peptide P7. In summary, our findings suggest that the CT23 peptide P7 (ALLVLCYSI) can induce immune responses and holds potential for tumor-specific CTL therapy.

Knockdown of OY-TES-1 by RNAi causes cell cycle arrest and migration decrease in bone marrow-derived mesenchymal stem cells.

OY-TES-1 is a member of the CTA (cancer-testis antigen) group expressed in a variety of cancer and restrictedly expressed in adult normal tissues, except for testis. To determine whether MSCs (mesenchymal stem cells) express OY-TES-1 and its possible roles on MSCs, OY-TES-1 expression in MSCs isolated from human bone marrow was tested with RT (reverse transcription)-PCR, immunocytochemistry and Western blot. Using RNAi (RNA interference) technology, OY-TES-1 expression was knocked down followed by analysing cell viability, cell cycle, apoptosis and migration ability. MSCs expressed OY-TES-1 at both mRNA and protein levels. The down-regulation of OY-TES-1 expression in these MSCs caused cell growth inhibition, cell cycle arrest, apoptosis induction and migration ability attenuation. Through these primary results it was suggested that OY-TES-1 may influence the biological behaviour of MSCs.

Model-based orbital-scale precipitation δ18O variations and distinct mechanisms in Asian monsoon and arid regions.

The past Asian precipitation δ18O (δ18Op) records from stalagmites and other deposits have shown significant orbital-scale variations, but their climatic implications and regional differences are still not fully understood. This study, as the first attempt of a 300-kyr transient stable isotope-enabled simulation, investigated the characteristics and mechanisms of the orbital-scale δ18Op variations in three representative regions of Asia: arid Central Asia (CA), monsoonal South Asia (SA) and monsoonal East Asia (EA). The modelling results showed that the variations in the CA, SA and EA annual δ18Op exhibited significant but asynchronous 23-kyr precession cycles. Further analyses revealed that although the precession-induced insolation variation was the ultimate cause of the δ18Op variation in all three regions, the dominant mechanisms and the involved physical processes were distinct among them. For the CA region, the rainy-season (November-March) temperature effect and water vapour transport by the westerly circulation were identified as the key precession-scale processes linking the October-February boreal mid-latitude insolation to the rainy-season or annual δ18Op. In the SA region, the rainy-season (June-September) precipitation amount effect and upstream depletion of the monsoonal water vapour δ18O served as the main mechanisms linking the rainy-season or annual δ18Op to the April-July insolation variation at the precession scale. For the EA region, however, the precession-scale annual δ18Op was mainly controlled by the late-monsoon (August-September) and pre-monsoon (April-May) water vapour transport patterns, which were driven by the July-August insolation and the global ice volume, respectively. These results suggest that the climatic implications of the orbital-scale Asia δ18Op variations are sensitive to their geographic locations as determined by the combined effects of insolation and regional circulation patterns associated with the respective rainy seasons. This study provides new insights into understanding the regional differences and formation mechanisms of the Asian orbital-scale δ18Op variations.

Immunohistochemistry Study of OY-TES-1 Location in Fetal and Adult Human Tissues.

OY-TES-1 is reportedly involved in carcinogenesis and spermatogenesis. However, the tissue distribution of OY-TES-1 in the normal human body remains elusive. This study detected OY-TES-1 expression in human fetal and adult normal tissues by immunohistochemistry. We identified a general principle of OY-TES-1 expression. The expression of OY-TES-1 was found in neurons, smooth muscle cells, and cardiac muscle cells from both fetuses and adults. The connective tissue showed no specific staining throughout the fetal and adult samples. With OY-TES-1-positive staining of the epithelium irregular, OY-TES-1 was strongly expressed in the epithelium of the skin and bladder, as well as hepatocytes, pancreatic islets, and acinous cells during the fetal stage but was not detected in the postnatal period. In contrast to the epithelium of blood vessels, the fetal and adult central hepatic vein and glomeruli showed negative expression of the OY-TES-1 protein. Sex-dimorphism was observed in the distribution of OY-TES-1 in male and female germ cells. Collectively, our results indicate that OY-TES-1 is a member of the cancer-testis antigen and autoantigen, with tissue-specific and period-specific expression patterns, revealing potential contributions of OY-TES-1 to the diagnosis and therapeutic treatment for neoplasms and infertility.

Microrna-1224-5p Is a Potential Prognostic and Therapeutic Biomarker in Glioblastoma: Integrating Bioinformatics and Clinical Analyses.

OBJECTIVE: Glioblastoma (GBM) is the most common, invasive, and malignant primary brain tumor with a poor prognosis and high recurrence rate. It's known that some microRNAs (miRNAs) which are associated with tumorigenesis and progression can be considered as prognostic and therapeutic targets in tumors including GBM. This study aims to highlight the potential role of the core miRNAs in GBM and their potential use as a prognostic and therapeutic biomarker. METHODS: Differentially expressed miRNAs (DEmiRNAs) were identified in GBM by integrating miRNA-sequencing results and a GBM microarray dataset from the Gene Expression Omnibus (GEO) database through bioinformatics tools. The dysregulated miRNAs were identified by survival analysis through Chinese Glioma Genome Atlas (CGGA). Target genes of the dysregulated miRNAs were predicted on MiRWalk and miRTarBase database. TAM2.0 database, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were used to analyze the function of the dysregulated miRNAs. Subsequently, protein-protein interaction (PPI) network analysis was used to identify the top 20 hub targets of the up-regulated and down-regulated miRNAs, respectively. Then, core miRNAs in GBM were identified by constructing dysregulated miRNA-differentially expressed hub gene networks. Validation of the core miRNAs expression was detected in 41 GBM tissues compared to 8 normal brain tissues. Furthermore, the potential biomarkers were identified by clinical correlation analysis and survival analysis. RESULTS: Totally, 68 intersecting DEmiRNAs were identified, 40 of which were upregulated and the other 28 miRNAs were downregulated. Two upregulated and 4 downregulated miRNAs showed prognostic significance. Most differentially expressed hub genes were regulated by the miR-28-5p and miR-1224-5p, which were respectively upregulated and downregulated in GBM. The correlation between miR-1224-5p level and recurrence was statistically significant (P=0.011). Survival analysis showed that high miR-28-5p level and high miR-1224-5p level were both associated with better prognosis. Moreover, high miR-1224-5p level was an independent prognosis factor for GBM patients according to the cox regression analysis. CONCLUSION: MiRNA-1224-5p could be a potential target for the prognosis and treatment in GBM.

High Expression of Fibronectin 1 Predicts a Poor Prognosis in Glioblastoma.

OBJECTIVE: Glioblastoma multiforme (GBM), the most malignant intracranial neoplasm, is associated with a high mortality and recurrence rate due to the aggressive nature and heterogeneity of the tumor. Some of the molecular markers involved in the tumorigenesis of GBM are essential in prognosis, diagnosis, and treatment. Due to the limitations of therapeutic effects, this study aims to explore novel biomarkers with prognostic value and to provide new insights into therapeutic targets. METHODS: The expression profile of mRNAs in GBM was detected by RNA-sequencing, and differentially expressed genes were identified by integrating the data from RNA-seq results and the GEPIA2 database. Of the total 40 hub genes, FN1, P4HB, and PPIB showed prognostic significance based on both GEPIA2 and CGGA databases. The validation of FN1, P4HB, and PPIB expression by qPCR and correlation analysis with clinicopathological features were performed in 41 GBM tissues from our institution. RESULTS: Kaplan-Meier analysis revealed that FN1 and P4HB expressions levels were related to the overall survival (OS) of GBM patients (P<0.05). Multivariate analysis showed that FN1 overexpression (HR=9.199, P=0.002) was an independent and unfavorable prognostic factor for GBM patients. The median survival time was 8.5 months and 21 months for high and low expressions of FN1, respectively. CONCLUSION: It was suggested that FN1 could be an ideal target for prognosis and a potential therapeutic target in GBM.

Combined treatment with epigenetic agents enhances anti-tumor activity of MAGE-D4 peptide-specific T cells by upregulating the MAGE-D4 expression in glioma.

Objective: The study evaluated the efficacy of combined epigenetic drugs of decitabine (DAC), valproic acid (VPA), and trichostatin A (TSA) on immunotherapy against glioma. Methods: The expression and prognosis of MAGE-D4 in glioma were analyzed online, and the expression of MAGE-D4 and HLA-A2 in glioma induced by epigenetic drugs was detected by qRT-PCR, Western blot, and flow cytometry. The methylation status of the MAGE-D4 promoter was determined by pyrosequencing. An HLA-A2 restricted MAGE-D4 peptide was predicted and synthesized. An affinity assay and a peptide/HLA complex stability assay were performed to determine the affinity between peptide and HLA. CCK8 assay, CFSE assay, ELISA and ELISPOT were performed to detect the function of MAGE-D4 peptide-specific T cells. Flow cytometry, ELISA, and cytotoxicity assays were used to detect the cytotoxicity effect of MAGE-D4 peptide-specific T cells combined with epigenetic drugs against glioma in vitro. Finally, the glioma-loaded mouse model was applied to test the inhibitory effect of specific T cells on gliomas in vivo. Results: MAGE-D4 was highly expressed in glioma and correlated with poor prognosis. Glioma cells could be induced to express MAGE-D4 and HLA-A2 by epigenetic drugs. MAGE-D4-associated peptides were found that induce DCs to stimulate the highest T-cell activities of proliferation, IL-2 excretion, and IFN-γ secretion. MAGE-D4 peptide-specific T cells treated with TSA only or combining TSA and DAC had the most cytotoxicity effect, and its cytotoxicity effect on glioma cells decreased significantly after HLA blocking. In vivo experiments also confirmed that MAGE-D4-specific T cells inhibit TSA-treated glioma. Conclusion: MAGE-D4 is highly expressed in glioma and correlated with the prognosis of glioma. The novel MAGE-D4 peptide identified was capable of inducing MAGE-D4-specific T cells that can effectively inhibit glioma growth, and the epigenetic drug application can enhance this inhibition.

FMR1NB Involved in Glioma Tumorigenesis Is a Promising Target for Prognosis and Therapy.

OBJECTIVE: Cancer/testis antigen FMR1NB is aberrantly expressed in various types of cancer, but not in normal tissues except for testis. This study aimed to investigate the expression and functional role of FMR1NB in glioma. METHODS: The expression of FMR1NB mRNA and protein was determined using RT-PCR and immunohistochemistry, respectively, in glioma specimens from 83 patients at follow-up. The effects of siRNA-mediated FMR1NB silencing on malignant biological behaviors were evaluated in glioma cell lines A172 and U251. RESULTS: FMR1NB mRNA and protein expression was detected in 58.8% (77/131) and 46.34% (57/123) of glioma tissues, respectively. FMR1NB protein was positively correlated with World Health Organization grade and found to be an independent prognostic marker for poor outcome. Knockdown of FMR1NB induced apoptosis and suppressed proliferation, adhesion, migration, and invasion by modulating the expression of cyclin A, CDK2, caspase-3, E-cadherin, and N-cadherin in A172 and U251 cells. CONCLUSION: Our findings suggest that FMR1NB contributes to the tumorigenesis of glioma cells and may represent a potential prognostic biomarker and an attractive therapeutic target in glioma.

Comparative maternal protein profiling of mouse biparental and uniparental embryos.

BACKGROUND: Maternal proteins have important roles during early embryonic development. However, our understanding of maternal proteins is still very limited. The integrated analysis of mouse uniparental (parthenogenetic) and biparental (fertilized) embryos at the protein level creates a protein expression landscape that can be used to explore preimplantation mouse development. RESULTS: Using label-free quantitative mass spectrometry (MS) analysis, we report on the maternal proteome of mouse parthenogenetic embryos at pronucleus, 2-cell, 4-cell, 8-cell, morula, and blastocyst stages and highlight dynamic changes in protein expression. In addition, comparison of proteomic profiles of parthenogenotes and fertilized embryos highlights the different fates of maternal proteins. Enrichment analysis uncovered a set of maternal proteins that are strongly correlated with the subcortical maternal complex, and we report that in parthenogenotes, some of these maternal proteins escape the fate of protein degradation. Moreover, we identified a new maternal factor-Fbxw24, and highlight its importance in early embryonic development. We report that Fbxw24 interacts with Ddb1-Cul4b and may regulate maternal protein degradation in mouse. CONCLUSIONS: Our study provides an invaluable resource for mechanistic analysis of maternal proteins and highlights the role of the novel maternal factor Fbw24 in regulating maternal protein degradation during preimplantation embryo development.

Anthropogenic sulfate aerosol pollution in South and East Asia induces increased summer precipitation over arid Central Asia.

Precipitation has increased across the arid Central Asia region over recent decades. However, the underlying mechanisms of this trend are poorly understood. Here, we analyze multi-model simulations from the Precipitation Driver and Response Model Intercomparison Project (PDRMIP) to investigate potential drivers of the observed precipitation trend. We find that anthropogenic sulfate aerosols over remote polluted regions in South and East Asia lead to increased summer precipitation, especially convective and extreme precipitation, in arid Central Asia. Elevated concentrations of sulfate aerosols over remote polluted Asia cause an equatorward shift of the Asian Westerly Jet Stream through a fast response to cooling of the local atmosphere at mid-latitudes. This shift favours moisture supply from low-latitudes and moisture flux convergence over arid Central Asia, which is confirmed by a moisture budget analysis. High levels of absorbing black carbon lead to opposing changes in the Asian Westerly Jet Stream and reduced local precipitation, which can mask the impact of sulfate aerosols. This teleconnection between arid Central Asia precipitation and anthropogenic aerosols in remote Asian polluted regions highlights long-range impacts of anthropogenic aerosols on atmospheric circulations and the hydrological cycle.

Knockdown of hsa_circ_0008922 inhibits the progression of glioma.

Background: A glioma is a tumor originating from glial cells in the central nervous system. Although significant progress has been made in diagnosis and treatment, most high-grade glioma patients are prone to recurrence. Therefore, molecular targeted therapy may become a new direction for adjuvant therapy in glioma. In recent years, many studies have revealed that circular RNA (circRNA) may play an important role in the occurrence and development of many tumors including gliomas. Our previous study found that the expression of hsa_circ_0008922 was up-regulated in glioma tissues upon RNA sequencing. The biological mechanism of circ_0008922 is still unreported in gliomas. Therefore, in this study, we preliminarily outlined the expression of hsa_circ_0008922 in glioma and explored its biological functions. Methods: The expression of hsa_circ_0008922 in forty glioma tissues and four glioma cell lines (A172, U251, SF763 and U87) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The correlation between hsa_circ_0008922 expression and clinicopathological features of glioma patients was evaluated by Fisher's exact test. To understand the potential function of hsa_circ_0008922 in glioma, we constructed small interfering RNA (siRNA) to hsa_circ_0008922 to downregulate its expression in glioma cell lines A172 and U251. With these hsa_circ_0008922 downregulated cells, a series of assays were carried out as follows. Cell proliferation was detected by CCK8 assay, migration and invasion were determined by wound healing assay and transwell assay, respectively. Colony formation ability was evaluated by plate clonogenic assay. Moreover, flow cytometry combined with Western blot was performed to analyze apoptosis status and the expression of apoptotic related proteins (caspase 3 and caspase 9). Finally, the possible biological pathways and potential miRNA targets of hsa_circ_0008922 were predicted by bioinformatics. Results: We found that the expression of hsa_circ_0008922 in glioma tissues was 3.4 times higher than that in normal tissues. The expression of has_circ_0008922 was correlated with WHO tumor grade. After down-regulating the expression of hsa_circ_0008922, malignant biological behavior of glioma cells was inhibited, such as cell proliferation, colony formation, migration, and invasion. At the same time, it also induced apoptosis of glioma cells. Predicted analysis by bioinformatics demonstrated that hsa_circ_0008922 may be involved in tumor-related pathways by acting as a molecular sponge for multiple miRNAs (hsa-let-7e-5p, hsa-miR-506-5p, hsa-let-7b-5p, hsa-let-7c-5p and hsa-let-7a-5p). Finally, we integrated our observation to build a circRNA-miRNA-mRNA predictive network.

Circ_CEA promotes the interaction between the p53 and cyclin-dependent kinases 1 as a scaffold to inhibit the apoptosis of gastric cancer.

Circular RNAs (circRNAs) have been reported to play essential roles in tumorigenesis and progression. This study aimed to identify dysregulated circRNAs in gastric cancer (GC) and investigate the functions and underlying mechanism of these circRNAs in GC development. Here, we identify circ_CEA, a circRNA derived from the back-splicing of CEA cell adhesion molecule 5 (CEA) gene, as a novel oncogenic driver of GC. Circ_CEA is significantly upregulated in GC tissues and cell lines. Circ_CEA knockdown suppresses GC progression, and enhances stress-induced apoptosis in vitro and in vivo. Mechanistically, circ_CEA interacts with p53 and cyclin-dependent kinases 1 (CDK1) proteins. It serves as a scaffold to enhance the association between p53 and CDK1. As a result, circ_CEA promotes CDK1-mediated p53 phosphorylation at Ser315, then decreases p53 nuclear retention and suppresses its activity, leading to the downregulation of p53 target genes associated with apoptosis. These findings suggest that circ_CEA protects GC cells from stress-induced apoptosis, via acting as a protein scaffold and interacting with p53 and CDK1 proteins. Combinational therapy of targeting circ_CEA and chemo-drug caused more cell apoptosis, decreased tumor volume and alleviated side effect induced by chemo-drug. Therefore, targeting circ_CEA might present a novel treatment strategy for GC.

A Review of miR-326 and Female Related Diseases.

MicroRNA (miRNA), a non-coding single-stranded RNA molecule with 20-23 nucleotides encoded by endogenous genes, plays an essential role in maintaining normal cell function and regulating cell proliferation, differentiation, apoptosis, autophagy, and cell metabolism. The imbalance between miRNA and genes can cause a series of diseases, including malignancies. miRNA-326 (miR-326) is extensively known for its core regulation of various biological processes. This review presents an overview of the highlights of miR-326 in female-related diseases. To understand the impact of miR-326 on female disorders, we search all published studies about miR-326 having a high incidence in female conditions, including cervical cancer, endometrial cancer, breast cancer, intrauterine adhesion, and multiple autoimmune diseases. We aim to learn about the mutual regulation mechanism between miR-326 and related genes and signaling pathways, as well as to elaborate on the value of miR-326 as a potential biomarker and therapeutic target of female diseases. Our results provide reliable evidence and new strategies for treating female tumors and autoimmune diseases.