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Autophagy is a self-recycling and conserved process, in which the senescent cytoplasmic components are degraded in cells and then recycled to maintain homeostatic balance. Emerging evidence has suggested the involvement of autophagy in oncogenesis and progression of various cancers, such as ovarian cancer (OC). Meanwhile, the non-coding RNAs (ncRNAs) frequently regulate the mRNA transcription and other functional signaling pathways in cell autophagy, displaying promising roles in human cancer pathogenesis and therapeutic response. This article mainly reviews the cutting-edge research advances about the interactions between ncRNAs and autophagy in OC. This review not only summarizes the underlying mechanisms of dynamic ncRNA-autophagy association in OC, but also discusses their prognostic implications and therapeutic biomarkers. The aim of this review was to provide a more in-depth knowledge framework exploring the ncRNA-autophagy crosstalk and highlight the promising treatment strategies for OC patients.

Abstract Nonfullerene acceptors (NFAs) lead the continuous development of organic solar cells (OSCs) with competitive efficiency over 19%. Design and synthesis of novel photovoltaic materials are effective methods to improve the OSCs performance, which can regulate the optoelectric properties, such as energy level, absorption spectra, charge transport, and so on. So far, hundreds of NFAs have been reported. Meanwhile, it has been demonstrated that intrinsic morphology of active layer is partially determined by the chemical structures of NFAs. Hence, only in‐depth understanding of the relationship between different structures of NFAs and morphology can guide the molecular design of NFAs for highly efficient OSCs. Herein, we review some state‐of‐the‐art NFAs according to their functional moieties, that is, arene core, end group and side chain, and discuss the relationship between molecular structure, morphology and device parameter. Additionally, the challenges and prospects for further development of OSCs based on NFAs are briefly considered. This review brings a unique insight into structure–function correlation in this field, which may help to rapidly develop efficient OSCs.

Exosomes are nanoscale extracellular vesicles secreted by a variety of cells, affecting the physiological and pathological homeostasis. They carry various cargoes including proteins, lipids, DNA, and RNA and have emerged as critical mediators of intercellular communication. During cell–cell communication, they can internalize either by autologous or heterologous recipient cells, which activate different signaling pathways, facilitating malignant progression of cancer. Among different types of cargoes in exosomes, the endogenous non-coding RNAs, such as circular RNAs (or circRNAs), have gained tremendous attention for their high stability and concentration, playing promising functional roles in cancer chemotherapeutic response by regulating the targeted gene expression. In this review, we primarily described the emerging evidence demonstrating the important roles of circular RNAs derived from exosomes in the regulation of cancer-associated signaling pathways that were involved in cancer research and therapeutic interventions. Additionally, the relevant profiles of exosomal circRNAs and their biological implications have been discussed, which is under investigation for their potential effect on the control of cancer therapeutic resistance.

Pyruvate dehydrogenase E1 subunit beta (PDHB) is located in mitochondria and catalyzes the conversion of glucose-derived acetyl-CoA. The detailed roles of PDHB in human cancers is unclear. Here, through comprehensive bioinformatics analysis, we found that PDHB was aberrantly expressed in multiple human cancers and is associated with patients' clinical stage. The abnormal expression of PDHB was related to the prognostic values of cancers, such as kidney renal clear cell carcinoma (KIRC) and kidney renal papillary cell carcinoma (KIRP). The Wanderer database with clinical data from Cancer Genome Atlas (TCGA) showed a significant correlation between PDHB expression and the pathologic stage of KIRP patients. We also evaluated the mutation profiles of PDHB in pan-cancer, and showed its roles on the patients’ prognosis. At last, from several immunity algorithms, we demonstrated that the expression of PDHB was correlated with the infiltration of various immune cells in pan-cancer. Moreover, the aberrant PDHB had effects on the response to immune checkpoint inhibitors in cancer patients, such as anti-PD-1. Taken together, our study demonstrated the prognostic values of PDHB in pan-cancers. PDHB may be a potential molecular marker to predicting the immune response in cancer patients.

Ferroptosis is a novel type of cell death associated with iron accumulation and excessive lipid peroxidation. Elucidating the underlying molecular mechanisms of ferroptosis is intensively related to the development and treatment of multiple diseases, including musculoskeletal disorders. Moreover, in vitro and in vivo studies have shown the importance of oxidative stress in musculoskeletal conditions such as osteoporosis, osteoarthritis, rheumatoid arthritis, and osteosarcoma. Ferroptosis-derived clinical management of musculoskeletal diseases offers tremendous and attractive opportunities. Notably, ferroptosis agonists have been proven to enhance the sensitivity of osteosarcoma cells to conventional therapeutic strategies. In this review, we have mainly focused on the implications of ferroptosis regulation in the pathophysiology and therapeutic response of musculoskeletal disorders. Understanding roles of ferroptosis for controlling musculoskeletal diseases might provide directions for ferroptosis-driven therapies, which could be promising for the development of novel therapeutic strategies.

Since folic acid (FA) was officially recommended in 1998, concerns have emerged about the effect of excess FA intake, in particular with respect to negative clinical effects. Given this, a high-folate corn inbred line that we identified from a global germplasm collection was believed to become a valid alternative to FA supplementation. In this study, we proved this natural form of plant-sourced folates exhibited an effective restoration of folate deficiency. Folate metabolism and methylation modifications were restored in folate-deficient mice with folate-supplemented diets in 4 weeks. Restoration effects varies depending on folate sources, restricted retrotransposon activity and an orderly pattern of phospholipid/lipid metabolism protected by this high-folate corn partly ensures a healthy folate status for development. Totally, we proved in mice models that this kind of folate biofortification corn could provide a valid alternation of FA supplementation in alleviation of folate deficiency during pregnancy.

EMS(8p11 myeloproliferative syndrome, EMS) is an aggressive hematological neoplasm with/without eosinophilia caused by a rearrangement of the FGFR1 gene at 8p11-12. It was found that all cases carry chromosome abnormalities at the molecular level, not only the previously reported chromosome translocation and insertion but also a chromosome inversion. These abnormalities produced 17 FGFR1 fusion genes, of which the most common partner genes are ZNF198 on 13q11-12 and BCR of 22q11.2. The clinical manifestations can develop into AML (acute myeloid leukemia), T-LBL (T-cell lymphoblastic lymphoma), CML (chronic myeloid leukemia), CMML (chronic monomyelocytic leukemia), or mixed phenotype acute leukemia (MPAL). Most patients are resistant to traditional chemotherapy, and a minority of patients achieve long-term clinical remission after stem cell transplantation. Recently, the therapeutic effect of targeted tyrosine kinase inhibitors (such as pemigatinib and infigratinib) in 8p11 has been confirmed in vitro and clinical trials. The TKIs may become an 8p11 treatment option as an alternative to hematopoietic stem cell transplantation, which is worthy of further study.

Quorum sensing (QS) plays a vital role in multiple species' inter-communication in man-made ecosystems, especially in bioaugmentation technologies. The role of various acyl-homoserine lactone (AHL), especially thirteen AHL types mediated QS in bacterial communities has been widely explored in wastewater treatment plants (WWTPs), and the results indicated that various AHLs presented different functions. Here 47 types of AHL from 2680 references were collected for the first time, with 27 AHLs identified in three engineered ecosystems (i.e., oxidation ditch-, anaerobic-anoxic-oxic- and cyclic activated sludge technology-based bioprocesses) using liquid chromatography-high resolution mass spectrometry (LCHRMS) analysis. Specifically, 70.4% of the detected AHLs are newly reported, with C14:2-HSL and C18:2-HSL showing relatively high response values. These results emphasize the high complexity of AHL-based QS systems and that the newly detected AHLs need to be comprehensively investigated due to their high application potential.

Vitamin B and its derivatives possess diverse physiological functions and are essential micronutrients for humans. Their variation in crops is important for the identification of genetic resources used to develop new varieties with enhanced vitamin B. In this research, remarkable variations were observed in kernels of 156 maize inbred lines, ranging from 107.61 to 2654.54 μg per 100 g for vitamin B1, 1.19–37.37 μg per 100 g for B2, 19.60–213.75 μg per 100 g for B3, 43.47–590.86 μg per 100 g for B5, and 138.59–1065.11 μg per 100 g for B6. Growing inbreeds in Hainan and Hebei provinces of China revealed environmental and genotype interactions among these vitamins and the correlations between them in maize grain. Several inbred lines were identified as good sources of vitamin B and promising germplasms for maize breeding, namely By855 and Si273 are overall rich in all the studied vitamins, and GY386B and CML118 are specially enriched with derivatives of vitamin B6. The present study can assist maize breeders with germplasm resources of vitamin B for biofortification to offer people nutritious foods.

Background and ObjectivesAvian coccidiosis is an intestinal parasitic disease exerting a highly negative impact on the global poultry industry. The aim of the present study is to evaluate the immune protective efficacies against Eimeria tenella infection in chickens orally immunized with combined recombinant probiotics Entercoccus faecalis (E. faecalis) delivering surface-anchored E. tenella proteins.MethodsFour kinds of novel probiotics vaccines that surface-expressing four Eimeria tenella (E. tenella) proteins EtAMA1, EtIMP1, EtMIC2 and Et3-1E were produced, respectively. The expression of four target proteins on the surface of recombinant bacteria was detected by Western blot and indirect immunofluorescence assay (IFA). Then the four kinds of recombinant E. faecalis were combined to immunize chickens via oral route in different combinations. The immunizations were performed three times at two-week intervals, and each for three consecutive days. After immunizations, chickens in each immunized group were orally challenged with E. tenella sporulated oocysts. The immune responses and protective efficacies against homologous infection were evaluated.ResultsThe results showed that three or four live recombinant E. faecalis induced effective antigen-specific humoral, intestinal mucosal immune responses, stimulated peripheral T lymphocytes proliferation, and displayed partial protections against homologous challenge as measured by cecal lesions, oocyst shedding, and body weight gain (BWG). Notably, higher levels of protective efficacies were observed when the four recombinant E. faecalis delivering target proteins were combined.ConclusionChickens orally administrated with three or four, especially the four combined recombinant E. faecalis stimulated specific immune responses, which provided anti-coccidial effects. This study offers an idea for future development of novel vaccines based on multi-antigens delivered by probiotic bacteria.

Since most hepatocellular carcinoma (HCC) patients are diagnosed at advanced stages, there is no effective treatment to improve patient survival. Ferroptosis, a regulated cell death driven by iron accumulation and lipid peroxidation, has been reported to play an important role in tumorigenesis. However, the detailed mechanism and biological function of ferroptosis are still incompletely understood in HCC patients. In this study, we analyzed genomic profiles of three HCC datasets, GSE6764, GSE14520, and GSE14323. Venn diagrams were implemented to visualize the overlapping genes between differentially expressed genes and ferroptosis-related gene set. Then, one up-regulated gene, ACSL4, and five down-regulated genes, STEAP3, MT1G, GCH1, HAMP, and CXCL2, were screened. Based on the survival analysis performed by Kaplan-Meier plotter database, ferroptosis-related gene CXCL2 was demonstrated positively-correlated with the patients’ prognosis. Moreover, CXCL2 overexpression significantly inhibited cell growth and improved cellular ROS, Fe2+ and MDA levels in HCC cells Huh7 and MHCC97H, suggesting the roles of CXCL2 in inducing ferroptotic cell death. In addition, aberrantly expressed CXCL2 was negatively associated with malignancy clinical features, such as nodal metastasis and higher grades. The ssGSEA enrichment analysis revealed that CXCL2 co-expressed molecules were mainly involved in inflammation and immune-related pathways, such as acute inflammatory response, humoral immune response, adaptive immune response. TISIDB algorithm indicated the positive correlation between CXCL2 expression and tumor-infiltrating immune cells, including neutrophils and macrophages. Additionally, we also found that CXCL2 was positively correlated with immune infiltration score, and HCC patients with higher score harbored better prognosis. Together, these findings suggested that CXCL2 may enhance ferroptosis sensitivity and regulate immune microenvironment in HCC, and serve as a promising prognosis biomarker for HCC patients.

Allelopathy has garnered considerable attention, but the effects of different allelochemicals on invasive plants remain unclear. This study addressed the knowledge gap surrounding allelopathy and its impact on native and invasive plant species. We focused on the impact of caffeic acid and its derivatives on the growth and competitiveness of the native Lantana indica and the invasive plant Solidago canadensis. We selected three allelochemicals, caffeic acid, methyl caffeic acid, and ethyl caffeic acid, for evaluation at two concentrations (0.1 mM and 1.0 mM). Three planting methods were employed: (1) a single species of S. canadensis, (2) a single species of L. indica, and (3) a combination of S. canadensis and L. indica. In addition, a control group was also included. Results revealed that high concentrations (1 mM) of methyl caffeate (MC) and ethyl caffeate (EC) significantly reduced seed germination rate, seed germination index, and seed germination speed index of L. indica compared to a low concentration (0.1 mM). Plant height, stem diameter, biomass, and root length in the control group (CK) of S. canadensis were significantly higher than those in the treated groups. However, with increasing allelochemical concentration, L. indica’s relative competitiveness gradually decreased. These findings provide insights into the concentration-dependent effects of allelopathic compounds on the growth of L. indica and S. canadensis. By analyzing how these allelochemicals influence the growth and competitiveness of native and invasive plants, the study sheds light on the dynamics of allelochemical interactions between these species. This knowledge can be pivotal for understanding plant competition dynamics in ecosystems and could inform strategies to control invasive species or promote native plant growth.

Lipoic acid synthetase (LIAS) has been demonstrated to play a crucial role in the progression of cancer. Exploring the underlying mechanisms and biological functions of LIAS could have potential therapeutic guidance for cancer treatment. Our study has explored the expression levels and prognostic values of LIAS in pan-cancer through several bioinformatics platforms, including TIMER2.0, Gene Expression Profiling Interactive Analysis, version 2 (GEPIA2.0), and Human Protein Atlas (HPA). We found that a high LIAS expression was related to the good prognosis in patients with kidney renal clear cell carcinoma (KIRC), rectum adenocarcinoma (READ), breast cancer, and ovarian cancer. Inversely, a high LIAS expression showed unfavorable prognosis in lung cancer patients. In addition, the genetic alteration, methylation levels, and immune analysis of LIAS in pan-cancer have been evaluated. To elucidate the underlying molecular mechanism of LIAS, we conduct the single-cell sequencing to implicate that LIAS expression was related to hypoxia, angiogenesis, and DNA repair. Thus, these comprehensive pan-cancer analyses have conveyed that LIAS could be potentially significant in the progression of various cancers. Moreover, the LIAS expression could predict the efficacy of immunotherapy in cancer patients.

Pyroptosis is a cell death pathway that plays a significant role in lung adenocarcinoma (LUAD). Also, studies regarding the correlation between the expression of long non-coding RNAs (lncRNAs) and the mechanism of LUAD has aroused concern around the world. The purpose of this paper is to explore the underlying relationship of differentially expressed lncRNAs and pyroptosis-related genes. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression were applied to construct a prognostic risk score model from the TCGA database. A pyroptosis-related five-lncRNA signature (CRNDE, HHLA3, MIR193BHG, LINC00941, LINC01843) was considered to be correlated to the prognosis and immune response of LUAD patients. In addition, the cytological experiments revealed that aberrantly expressed HHLA3 displayed a proliferation promotion role in LUAD cells A549 and H460. Next, the forest and nomogram plots have shown this lncRNA signature could be served as an independent prognostic factor for LUAD. The ROC curves further identified the prognostic value of the five-lncRNA signature. The infiltration of immune cells, such as T cells CD8, T cells CD4 memory resting, T cells CD4 memory activated and M0 macrophages were greatly different between the high-risk group and the low-risk group. It implicated that the signature is significantly effective in immunotherapy of LUAD patients. This study has supplied a novel pyroptosis-related lncRNA signature and provided a predictive model for prognosis and immune response of LUAD patients.

The primary or acquired resistance to anti-VEGF inhibitors remains a common problem in cancer treatment. Therefore, identifying potential biomarkers enables a better understanding of the precise mechanism. Through the GEO database, three profiles associated with bevacizumab (BV) resistance to ovarian cancer, glioma, and non-small-cell lung carcinoma, respectively, were collected for the screening process, and two genes were found. A-kinase anchor protein 12 (AKAP12), one of these two genes, correlates with tumorigenesis of some cancers. However, the role of AKAP12 in pan-cancer remains poorly defined. The present study first systematically analyzed the association of AKAP12 with anti-VEGF inhibitors’ sensitivity, clinical prognosis, DNA methylation, protein phosphorylation, and immune cell infiltration across various cancers via bioinformatic tools. We found that AKAP12 was upregulated in anti-VEGF therapy-resistant cancers, including ovarian cancer (OV), glioblastoma (GBM), lung cancer, and colorectal cancer (CRC). A high AKAP12 expression revealed dismal prognoses in OV, GBM, and CRC patients receiving anti-VEGF inhibitors. Moreover, AKAP12 expression was negatively correlated with cancer sensitivity towards anti-VEGF therapy. Clinical prognosis analysis showed that AKAP12 expression predicted worse prognoses of various cancer types encompassing colon adenocarcinoma (COAD), OV, GBM, and lung squamous cell carcinoma (LUSC). Gene mutation status may be a critical cause for the involvement of AKAP12 in resistance. Furthermore, lower expression of AKAP12 was detected in nearly all cancer types, and hypermethylation may explain its decreased expression. A decreased phosphorylation of T1760 was observed in breast cancer, clear-cell renal cell carcinoma, and lung adenocarcinoma. For the immunologic significance, AKAP12 was positively related to the abundance of pro-tumor cancer-associated fibroblasts (CAFs) in various types of cancer. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis suggested that “cell junction organization” and “MAPK pathway” participated in the effect of AKAP12. Importantly, we discovered that AKAP12 expression was greatly associated with metastasis of lung adenocarcinoma as well as differential and angiogenesis of retinoblastoma through investigating the single-cell sequencing data. Our study showed that the dual role of AKAP12 in various cancers and AKAP12 could serve as a biomarker of anti-VEGF resistance in OV, GBM, LUSC, and COAD.

Abstract The molecular orientation has a profound influence on the performance of organic solar cells. Both donor and acceptor adopt face‐on orientation guarantees efficient exciton dissociation and charge transport, which is a key to achieving high device performance. However, the molecules usually adopt edge‐on orientation in some blend systems, take small molecules based on an oligothiophene (DRCN5T): fused‐ring electron acceptor based on indacenodithieno[3,2‐b]‐thiophene core and thienyl side‐chains (ITIC‐Th) blend, for instance, the orientation of DRCN5T is edge‐on, which is detrimental to the photophysical process of the device. Herein, a solid additive strategy, that is, adding N2200 as a nucleus for DRCN5T, was proposed, which combined the nucleation process with molecular diffusivity, thus realizing the orientation transformation of DRCN5T from edge‐on to face‐on. Consequently, the device performance was significantly improved, and a clear relationship between molecular orientation and energy loss/biomolecular recombination was established. More importantly, this study revealed not only the thermodynamic factors, including the crystallinity of solid additive, the lattice matching degree, and miscibility between DRCN5T and solid additive but also the kinetic parameter, such as the diffusivity of DRCN5T are very important to efficiently regulate the molecular orientation. Overall, this study presents the in‐depth mechanism of orientation transformation via adding solid additives, which may provide a guideline for solid additive choices.

B-Raf proto-oncogene serine/threonine-protein kinase (BRAF) is frequently altered in multiple cancer types, and BRAF V600 mutations act as a prime target for precision therapy. Although emerging evidence has investigated the role of BRAF, the comprehensive profiling of BRAF expression, alteration and clinical implications across various cancer types has not been reported. In this study, we used the TCGA dataset, covering 10,967 tumor samples across 32 cancer types, to analyze BRAF abnormal expression, DNA methylation, alterations (mutations and amplification/deletion), and their associations with patient survival. The results showed that BRAF expression, alteration frequency, mutation site distribution, and DNA methylation patterns varied tremendously among different cancer types. The expression of BRAF was found higher in PCPG and CHOL, and lower in TGCT and UCS compared to normal tissues. In terms of pathological stages, BRAF expression was significantly differentially expressed in COAD, KIRC, LUSC, and OV. The methylation levels of BRAF were significantly lower in LUSC, HNSC, and UCEC compared to normal tissue. The expression of BRAF and downstream gene (ETS2) was negatively correlated with methylation levels in various cancers. The overall somatic mutation frequency of BRAF was 7.7% for all cancer samples. Most fusion transcripts were found in THCA and SKCM with distinct fusion patterns. The majority of BRAF mutations were oncogenic and mainly distributed in the Pkinase_Tyr domain of THCA, SKCM, COADREAD, and LUAD. The BRAF mutations were divided into five levels according to the clinical targeted therapy implication. The results showed level 1 was mainly distributed in SKCM, COADREAD, and LUAD, while level 3B in THCA. The overall BRAF CNV frequency was about 42.7%, most of which was gain (75.9%), common in GBM, TGCT, and KIRP. In addition, the forest plot showed that increased BRAF expression was associated with poor patient overall survival in LIHC, OV, and UCEC. Taken together, this study provided a novel insight into the full alteration spectrum of BRAF and its implications for treatment and prognosis.

Bats are important hosts for various zoonotic viral diseases. However, they rarely show signs of disease infection with such viruses. As the first line for virus control, the innate immune system of bats attracted our full attention. In this study, the Tadarida brasiliensis MDA5 gene (batMDA5), a major sensor for anti-RNA viral infection, was first cloned, and its biological functions in antiviral innate immunity were identified. Bioinformatics analysis shows that the amino acid sequence of batMDA5 is poorly conserved among species, and it is evolutionarily closer to humans. The mRNA of batMDA5 was significantly upregulated in Newcastle disease virus (NDV), avian influenza virus (AIV), and vesicular stomatitis virus (VSV)-infected bat TB 1 Lu cells. Overexpression of batMDA5 could activate IFNβ and inhibit vesicular stomatitis virus (VSV-GFP) replication in TB 1 Lu cells, while knockdown of batMDA5 yielded the opposite result. In addition, we found that the CARD domain was essential for MDA5 to activate IFNβ by constructing MDA5 domain mutant plasmids. These results indicated that bat employs a conserved MDA5 gene to trigger anti-RNA virus innate immune response. This study helps understand the biological role of MDA5 in innate immunity during evolution.

Summary: In all polymer solar cells (all-PSCs), the domain size is critical for device performance. In highly crystalline polymer blends, however, precisely adjusting the domain size remains a significant challenge because of the simultaneous crystallization of both components. Herein, a strategy that promotes acceptor and donor to crystallize separately was proposed. Take PBDB-T/N2200 blends for instance; the solution state and confined crystallization were combined, which induced the crystallization of N2200, and PBDB-T occurred during the film-forming process and at thermal annealing stage. This separated crystallization process lowers the driving force of phase separation without affecting the degree of crystallinity of the blends. Thus, an interpenetrating network with high crystallinity and proper domain size was obtained, which boosted the power conversion efficiency to 7.59%. Importantly, the relation between pre-aggregation and domain size was established, which may be a guide to precisely adjust the active layer’s domain size in all-PSCs.

Glutathione (GSH) plays a crucial role in various physiological processes. Therefore, efficient detection of GSH is of great importance. In this study, we present a new and highly efficient ratiometric fluorescent biosensor through one-pot synthesis of coupling the self-assembly of polysaccharide (alginate dialdehyde, ADA)-dipeptide (diphenylalanine, FF) and in situ reduction of gold nanoparticles (Au NPs) simultaneously encapsulating a dye (5-aminofluorescein, FI-NH2) inside to form ADA-Au-FF-dye nanospheres. Because the fluorescence of the dye can be quenched by Au NPs and linearly recovered following the introduction of different GSH concentrations owing to nanometal surface energy transfer on and off, this new ADA-Au-FF-dye hybrid nanosphere-based sensor allows label-free and ratiometric detection of intracellular GSH and other biothiols in a wide linear range, which is of great significance for cancer diagnostics and therapy. [ABSTRACT FROM AUTHOR]

Endometrial cells and microenvironment are two important factors in the pathogenesis of adenomyosis. Our previous study demonstrated that macrophages can induce eutopic epithelial cells of adenomyosis to suffer from epithelial-mesenchymal transition (EMT). The aim of this study is to detect whether macrophages interacting with epithelial cells equally induce the EMT process in normal and eutopic endometria of healthy and adenomyotic patients and whether macrophages parallelly polarize to M2. We investigated the expression levels of epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), cytokeratin7 (CK7), vimentin, transforming growth factor-β1 (TGFB1), SMAD3 and pSMAD3 using immunohistochemistry and western blot and then estimated the genetic levels of CD163, IL10 and MMP12 using real-time quantitative polymerase chain reaction (RT-PCR) in macrophages. Eutopic and normal endometrial tissues were obtained from 20 patients with adenomyosis and 11 control patients without adenomyosis, respectively. The immunohistochemical analysis shows distinct EMT in eutopic endometria in secretory phase; the expression levels of TGFB1, SMAD3 and pSMAD3 that indicate signal pathway of EMT were also higher in secretory phase. Macrophages can induce EMT process in primary endometrial epithelial cells derived from normal and eutopic endometria. After co-culturing, THP-1-derived macrophages polarized to M2. Compared with the eutopic endometrium group, further polarization to M2 was observed in the normal endometrium group. These results indicate that adenomyosis may be promoted by the pathologic EMT of epithelial cells, which is induced by macrophages that incapably polarize to M2. [ABSTRACT FROM AUTHOR]

STUDY QUESTION: What are the features of peritoneal macrophage subgroups and T helper cells in the development of murine endometriosis? SUMMARY ANSWER: During the development of endometriosis in a murine model, large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs) are polarized into M1 and M2 cells, respectively, and the proportions of T helper (Th) 1, Th17 and T regulatory (Treg) cells are increased. WHAT IS KNOWN ALREADY: Numerous studies investigating the etiology and pathogenesis of endometriosis have focused on the polarization states of peritoneal macrophages in endometriosis models and patients, but the results are inconclusive. Further studies indicate that peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs, although their roles in endometriosis are unknown. STUDY DESIGN, SIZE, DURATION: This study involves a prospective and randomized experiment. Fifty C57BL/6 female mice were randomly allocated to five control and five experimental groups (n = 5/group) according to the presence or absence of transplantation. The transplant periods are 0.25, 3, 14, 28 and 42 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: C57BL/6 mice were utilized to establish an endometriosis model by i.p. injection of allogeneic endometrial segments. Dynamic changes of peritoneal macrophage subsets and polarization profiles were evaluated by flow cytometry (FCM). Macrophage morphology and density were assessed by cell counting under a microscope. Dynamic changes of Th1, Th2, Th17 and Treg cells were estimated by FCM. MAIN RESULTS AND THE ROLE OF CHANCE: Peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs. The proportion of SPMs increased immediately after peritoneal injection of endometrial tissues, whereas LPMs showed an opposite trend. Peritoneal macrophages differentiated into both M1 and M2 macrophages. The bidirectional polarization of macrophages was caused by the inverse trends of polarization of LPMs and SPMs. Consistently, the proportions of Th1, Th17 and Treg cells were all increased in mice with endometriosis. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: In this study, detection was only performed in a murine endometriosis model. Clinical data and more intervention experiments are required in understanding the roles of LPMs and SPMs in endometriosis. WIDER IMPLICATIONS OF THE FINDINGS: The dramatic changes of LPMs and SPMs in proportion and polarization profiles clarified the varying differentiation states of peritoneal macrophages. In addition, LPMs and SPMs may play different roles in the pathogenesis of endometriosis in different stages of endometriosis. Therefore, the new classification should be included in future relevant basic and clinical studies on endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This research was supported totally by grant 81270671 from the National Natural Science Foundation of China. [ABSTRACT FROM AUTHOR]

Chemoresistance, especially temozolomide (TMZ) resistance, is a major clinical challenge in the treatment of glioblastoma (GBM). Exploring the mechanisms of TMZ resistance could help us identify effective therapies. Adenosine deaminases acting on RNA (ADARs) are very important in RNA modification through regulating the A-to-I RNA editing. Recent studies have shown that ADARs regulate multiple neurotransmitter receptors, which have been linked with the occurrence and progress of GBM. Here, data from several bioinformatics databases demonstrated that adenosine deaminase RNA specific B1 (ADARB1), also named ADAR2, was upregulated in both GBM tissues and cells, and had the prognostic value in GBM patients. Moreover, ADARB1 was found to be involved in AKT-mediated TMZ resistance in GBM cells. The KEGG analysis of ADARB1-associated co-expressed genes showed that ADARB1 was potentially involved in the mitochondrial respiratory chain complex. TISIDB and GEPIA databases were further used to analyze the role of ADARB1 in tumor-immune system interactions in GBM. These findings deepened our understanding of the function of ADARB1 in tumorigenesis and therapeutic response in GBM.