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هذا الكتاب يحتوي على قصص مختارة من المؤتمر الدولي الرابع عشر للقصة القصيرة وهذا اللقاء الذي نظم ‏من قبل جمعية دراسة القصص القصيرة الإنجليزية (أس أس أس أس إي) وهي جمعية عالمية ‏أنشئت في الولايات المتحدة عام 1992 وينعقد كل عامين ويعتبر اللقاء العالمي الوحيد الذي ‏يركز بشكل خاص على دراسات القصة القصيرة أما القصص المشاركة في اللقاء فهي مكتوبة ‏من قبل 29 كاتبا ينتمون إلى عشرة دول هي الصين وتايوان والهند والولايات المتحدة وكندا ‏ونيوزلندا وفرنسا وإيرلندا والنمسا وسنغافورا وجامايكا.

Endophytic actinobacteria, which exist in the inner tissues of living plants, have attracted increasing attention among taxonomists, ecologists, agronomists, chemists and evolutionary biologists. Numerous studies have indicated that these prolific actinobacteria appear to have a capacity to produce an impressive array of secondary metabolites exhibiting a wide variety of biological activity, such as antibiotics, antitumor and anti-infection agents, plant growth promoters and enzymes, and may contribute to their host plants by promoting growth and enhancing their ability of withstanding the environmental stresses. These microorganisms may represent an underexplored reservoir of novel species of potential interest in the discovery of novel lead compounds and for exploitation in pharmaceutical, agriculture and industry. This review focuses on new findings in the isolation methods, bio- and chemical diversity of endophytic actinobacteria and reveals the potential biotechnological application. The facing problems and strategies for biodiversity research and bioactive natural products producing are also discussed.

The incidence of recurrent t(6;9) translocation of the MYB proto-oncogene to NFIB (the gene that encodes nuclear factor 1 B-type) in adenoid cystic carcinoma (ACC) tumour tissues is high. However, MYB [the gene that encodes transcriptional activator Myb (MYB)] overexpression is more common, indicating that MYB serves a key role in ACC. The current study aimed to investigate the role of MYB in salivary (S)ACC growth and metastasis. A total of 50 fresh-frozen SACC tissues and 41 fresh-frozen normal submandibular gland (SMG) tissues were collected to measure MYB mRNA expression, and to analyse the associations between MYB and epithelial-mesenchymal transition (EMT) markers. Compared with normal SMG tissue, SACC tissues demonstrated significantly increased MYB expression, with a high expression rate of 90%. Interestingly, MYB tended to be negatively correlated with CDH1 [the gene that encodes cadherin-1 (E-cadherin)] and positively correlated with VIM (the gene that encodes vimentin), suggesting that MYB is associated with SACC metastasis. To explore the role of MYB in SACC, the authors stably overexpressed and knocked down MYB in SACC cells. The authors of the current study demonstrated that MYB overexpression promoted SACC cell proliferation, migration and invasion, whereas its knockdown inhibited these activities. Additionally, when MYB was overexpressed, CDH1 expression was downregulated, and CDH2 (the gene that encodes cadherin-2), VIM and ACTA2 (the gene that encodes actin, aortic smooth muscle) expression was upregulated. Then, the effect of MYB on lung tumour metastasis was investigated in vivo in non-obese diabetic/severe combined immunodeficiency mice. MYB overexpressing and control cells were injected into the mice through the tail vein. The results revealed that MYB promoted SACC lung metastasis. Collectively, these results demonstrated that MYB is aberrantly overexpressed in SACC tissues, and promotes SACC cell proliferation and metastasis, indicating that MYB may be a novel therapeutic target for SACC.

Background and aim We previously identified forkhead box (FOX) O4 mRNA as a predictor in gastric cancer (GC). However, the underlying mechanism has yet to be elucidated. We aimed to illustrate the mechanism by which FOXO4 regulated glycolysis under hypoxia in GC. Methods FOXO4 protein expression was investigated by immunohistochemical staining of 252 GC and their normal adjacent tissues. We restored or silenced FOXO4 expression in GC cell lines to explore the underlying mechanisms. Results FOXO4 was downregulated in GC. Loss of FOXO4 expression was validated in univariate and multivariate survival analysis as an independent prognostic predictor for overall survival (P < 0.05) and disease‐free survival (P<0.05). Restored FOXO4 expression significantly impaired the glycolysis rate in GC cells, while silencing FOXO4 expression enhanced glycolysis rate. FOXO4 expression was inversely associated with maximum standardized uptake value in mice models and patient samples. Mechanistically, FOXO4 bound to the glycolytic enzyme lactate dehydrogenase (LDH)A promoter and inactivated its activity in a dose‐dependent manner (P < 0.05). Finally, we determined that FOXO4 was a transcriptional target of hypoxia‐inducible factor (HIF) ‐1α, which is central in response to hypoxia. Conclusions Our data suggested that FOXO4 plays a key role in the regulation of glycolysis in GC, and disrupting the HIF‐1α‐FOXO4‐LDHA axis might be a promising therapeutic strategy for GC. FOXO4 was frequently downregulated in gastric cancer and may serve as a biomarker for prognosis. FOXO4 expression was associated with glycolysis rate both in vitro and in vivo. Mechanistically, FOXO4 impaired glycolysis by transcriptional inhibiting glycolytic enzyme LDHA, and FOXO4 itself was directly by HIF‐1α.

Objective. Panax ginseng is used widely for treatment of cardiovascular disorders in China. Ginsenoside Re is the main chemical component of P. ginseng. We aimed to investigate the protective effect of ginsenoside Re on isoproterenol-induced myocardial fibrosis and heart failure in rats. Methods. A model of myocardial fibrosis and heart failure was established by once-daily subcutaneous injection of isoproterenol (5 mg/kg/day) to rats for 7 days. Simultaneously, rats were orally administrated ginsenoside Re (5 or 20 mg/kg) or vehicle daily for 4 weeks. Results. Isoproterenol enhanced the heart weight, myocardial fibrosis, and hydroxyproline content in rat hearts. Ginsenoside Re inhibited (at least in part) the isoproterenol-induced increase in heart weight, myocardial fibrosis, and hydroxyproline content. Compared with the isoproterenol group, treatment with ginsenoside Re ameliorated changes in left ventricular systolic pressure, left ventricular end diastolic pressure, and the positive and negative maximal values of the first derivative of left ventricular pressure. Ginsenoside Re administration also resulted in decreased expression of transforming growth factor (TGF)-β1 in serum and decreased expression of Smad3 and collagen I in heart tissue. Conclusion. Ginsenoside Re can improve isoproterenol-induced myocardial fibrosis and heart failure by regulation of the TGF-β1/Smad3 pathway.

Endophytic actinobacteria colonize internal tissues of their host plants and are considered as a rich and reliable source of diverse species and functional microorganisms. In this study, endophytic actinobacterial strain YIM 63111 was isolated from surface-sterilized tissue of the medicinal plant Artemisia annua. We identified strain YIM 63111 as a member of the genus Pseudonocardia. A. annua seedlings grown under both sterile and greenhouse conditions were inoculated with strain YIM 63111. The growth of A. annua seedlings was strongly reduced when YIM 63111 was inoculated at higher concentrations under sterile conditions. However, no growth inhibition was observed when A. annua was grown under greenhouse conditions. Using an enhanced green fluorescent protein (EGFP) expressing YIM 63111 strain, we also observed the endophytic colonization of A. annua seedling using confocal laser-scanning microscopy. The transcription levels of the key genes involved in artemisinin biosynthesis were investigated using real time RT-PCR, revealing that cytochrome P450 monooxygenase (CYP71AV1) and cytochrome P450 oxidoreductase (CPR) expression were up-regulated in A. annua upon inoculation with strain YIM 63111 under certain conditions. The up-regulation of these genes was associated with the increased accumulation of artemisinin. These results suggest that endophytic actinobacteria effectively stimulate certain plant defense responses. Our data also demonstrate the use of Pseudonocardia sp. strain YIM 63111 as a promising means to enhance artemisinin production in plants.

( ) is a widely prevalent intracellular parasite that infects almost all warm-blooded animals and causes serious public health problems. The drugs currently used to treat toxoplasmosis have the disadvantage of being toxic and prone to the development of resistance, and the only licensed vaccine entails a risk of virulence restoration. The development of a safe and effective vaccine against is urgently needed. ( ) has been used as a potential vaccine expression vector for the treatment and prevention of various diseases. GRA12 is a key virulence factor that resists host innate immunity and exhibits good antigenicity with several excellent B and T cell epitopes. A recombinant spore named rBS-GRA12 was constructed by fusing the GRA12 protein to the coat protein B (CotB). rBS-GRA12 spores were identified by PCR, western blotting, immunofluorescence assays, amylase activity, and ultrastructural analysis. Immunological experiments were then conducted to assess the immunoprotective effects of rBS-GRA12. Groups of mice immunized with rBS-GRA12 (10 , 10 , or 10 colony-forming units), GRA12 protein emulsified with Freund's adjuvant (FA+GRA12), Freund's adjuvant alone (FA), phosphate buffered saline (PBS), or wild-type spores (WT). Splenocyte proliferation, antibodies, and cytokine expression levels were used to assess immune responses induced by the immunizations. All groups were inoculated with RH strain, and survival times and parasite loads in tissues were used to assess protective effects against infection. Amylase activity assays confirmed the generation of recombinant . PCR, western blotting and immunofluorescence assays confirmed that the rBS-GRA12 spores expressed GRA12. Observation of rBS-GRA12 spores via transmission and scanning electron microscopy indicated that GRA12 expression had no effect on spore morphology or structure. Splenocyte proliferation was significantly greater in all three rBS-GRA12 groups than in the FA+GRA12 group, and IgG and IgG2a subclass titers were higher. Substantial production of interferon gamma (IFN-γ), interleukin (IL)-12, and an increase in IL-4 production were evident in the rBS-GRA12-10 group. Secretory sIgA levels were significantly elevated in all three rBS-GRA12 groups than in the FA+GRA12 group and the control groups. Brain and liver tissues parasite loads were significantly lower in the three rBS-GRA12 groups than in any other group. Compared to all other groups, mice in the three rBS-GRA12 groups exhibited longer survival times when challenged with acute infection. Mice immunized with rBS-GRA12 exhibited higher levels of cellular, humoral, and mucosal immune responses than control mice. These results provide a new perspective for the development of vaccines.

Background B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various tumors, and its overexpression correlates with a poor outcome in several human cancers. Ectopic expression of Bmi-1 can induce epithelial-mesenchymal transition (EMT) and enhance the motility and invasiveness of human nasopharyngeal epithelial cells (NPECs), whereas silencing endogenous Bmi-1 expression can reverse EMT and reduce the metastatic potential of nasopharyngeal cancer cells (NPCs). Mouse xenograft studies indicate that coexpression of Bmi-1 and H-Ras in breast cancer cells can induce an aggressive and metastatic phenotype with an unusual occurrence of brain metastasis; although, Bmi-1 overexpression did not result in oncogenic transformation of MCF-10A cells. However, the underlying molecular mechanism of Bmi-1-mediated progression and the metastasis of breast cancer are not fully elucidated at this time. Results Bmi-1 expression is more pronouncedly increased in primary cancer tissues compared to matched adjacent non-cancerous tissues. High Bmi-1 expression is correlated with advanced clinicopathologic classifications (T, N, and M) and clinical stages. Furthermore, a high level of Bmi-1 indicates an unfavorable overall survival and serves as a high risk marker for breast cancer. In addition, inverse transcriptional expression levels of Bmi-1 and E-cadherin are detected between the primary cancer tissues and the matched adjacent non-cancerous tissues. Higher Bmi-1 levels are found in the cancer tissue, whereas the paired adjacent non-cancer tissue shows higher E-cadherin levels. Overexpression of Bmi-1 increases the motility and invasive properties of immortalized human mammary epithelial cells, which is concurrent with the increased expression of mesenchymal markers, the decreased expression of epithelial markers, the stabilization of Snail and the dysregulation of the Akt/GSK3β pathway. Consistent with these observations, the repression of Bmi-1 in highly metastatic breast cancer cells remarkably reduces cellular motility, invasion and transformation, as well as tumorigenesis and lung metastases in nude mice. In addition, the repression of Bmi-1 reverses the expression of EMT markers and inhibits the Akt/GSK3β/Snail pathway. Conclusions This study demonstrates that Bmi-1 promotes the invasion and metastasis of human breast cancer and predicts poor survival.

Background Single-cell RNA sequencing (scRNA-seq) enables high-resolution transcriptomic analysis but loses spatial context due to tissue dissociation, thereby limiting insights into spatially regulated cell–cell interactions critical for tissue function and disease, including cancer. Consequently, developing approaches capable of extracting spatially relevant intercellular interaction information from scRNA-seq data is of substantial importance for elucidating mechanisms underlying disease initiation and progression. Methods Here, we present DeepPNCC, a novel deep learning framework that reconstructs pseudo-spatial cell-cell interaction networks (PSCCIs) from scRNA-seq data by leveraging latent spatial cues preserved in undissociated cell aggregates. Built on a variational graph autoencoder (VGAE) enhanced with adversarial regularization, DeepPNCC uniquely integrates local adjacency matrices derived from multiplet data, without relying on prior knowledge such as ligand-receptor pairs, to infer global, spatially informed interaction landscapes. DeepPNCC is available as an open-source Python package. Results DeepPNCC outperforms existing methods in recovering interactions aligned with spatial transcriptomics across mouse brain and breast cancer datasets. In breast cancer, the inferred cell-cell interaction network reveals a closed-loop signaling axis in triple-negative breast cancer, in which cancer-associated fibroblasts (CAFs) and perivascular-like cells (PVL) promote angiogenesis through the ADM-CALCRL-STAT1-CD40/CCL2/ICAM1 pathway. These findings provide important clues for elucidating the regulatory mechanisms of the tumor microenvironment. Conclusions DeepPNCC provides an efficient tool for spatially informed analysis of scRNA-seq data, enabling the reconstruction of pseudo-spatial cell–cell interaction networks from datasets lacking explicit spatial information. This approach expands the spatial analytical scope of scRNA-seq and facilitates mechanistic dissection of cellular ecosystems in both health and disease.

The polycomb group protein B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1) is dysregulated in various cancers, and its upregulation strongly correlates with an invasive phenotype and poor prognosis in patients with nasopharyngeal carcinomas. However, the underlying mechanism of Bmi-1-mediated invasiveness remains unknown. In the current study, we found that upregulation of Bmi-1 induced epithelial-mesenchymal transition (EMT) and enhanced the motility and invasiveness of human nasopharyngeal epithelial cells, whereas silencing endogenous Bmi-1 expression reversed EMT and reduced motility. Furthermore, upregulation of Bmi-1 led to the stabilization of Snail, a transcriptional repressor associated with EMT, via modulation of PI3K/Akt/GSK-3beta signaling. Chromatin immunoprecipitation assays revealed that Bmi-1 transcriptionally downregulated expression of the tumor suppressor PTEN in tumor cells through direct association with the PTEN locus. This in vitro analysis was consistent with the statistical inverse correlation detected between Bmi-1 and PTEN expression in a cohort of human nasopharyngeal carcinoma biopsies. Moreover, ablation of PTEN expression partially rescued the migratory/invasive phenotype of Bmi-1-silenced cells, indicating that PTEN might be a major mediator of Bmi-1-induced EMT. Our results provide functional and mechanistic links between the oncoprotein Bmi-1 and the tumor suppressor PTEN in the development and progression of cancer.