Constituting approximately 10% of flowering plant species, orchids (Orchidaceae) display unique flower morphologies, possess an extraordinary diversity in lifestyle, and have successfully colonized ...almost every habitat on Earth. Here we report the draft genome sequence of Apostasia shenzhenica, a representative of one of two genera that form a sister lineage to the rest of the Orchidaceae, providing a reference for inferring the genome content and structure of the most recent common ancestor of all extant orchids and improving our understanding of their origins and evolution. In addition, we present transcriptome data for representatives of Vanilloideae, Cypripedioideae and Orchidoideae, and novel third-generation genome data for two species of Epidendroideae, covering all five orchid subfamilies. A. shenzhenica shows clear evidence of a whole-genome duplication, which is shared by all orchids and occurred shortly before their divergence. Comparisons between A. shenzhenica and other orchids and angiosperms also permitted the reconstruction of an ancestral orchid gene toolkit. We identify new gene families, gene family expansions and contractions, and changes within MADS-box gene classes, which control a diverse suite of developmental processes, during orchid evolution. This study sheds new light on the genetic mechanisms underpinning key orchid innovations, including the development of the labellum and gynostemium, pollinia, and seeds without endosperm, as well as the evolution of epiphytism; reveals relationships between the Orchidaceae subfamilies; and helps clarify the evolutionary history of orchids within the angiosperms.
Prostate stromal cells play a crucial role in the promotion of tumor growth and immune evasion in the tumor microenvironment (TME) through intricate molecular alterations in their interaction with ...prostate cancer (PCa) cells. While the impact of these cells on establishing an immunosuppressive response and influencing PCa aggressiveness remains incompletely understood. Our study shows that the activation of the leukemia inhibitory factor (LIF)/LIF receptor (LIFR) pathway in both prostate tumor and stromal cells, following androgen deprivation therapy (ADT), leads to the development of an immunosuppressive TME. Activation of LIF/LIFR signaling in PCa cells induces neuroendocrine differentiation (NED) and upregulates immune checkpoint expression. Inhibition of LIF/LIFR attenuates these effects, underscoring the crucial role of LIF/LIFR in linking NED to immunosuppression. Prostate stromal cells expressing LIFR contribute to NED and immunosuppressive marker abundance in PCa cells, while LIFR knockdown in prostate stromal cells reverses these effects. ADT‐driven LIF/LIFR signaling induces brain‐derived neurotrophic factor (BDNF) expression, which, in turn, promotes NED, aggressiveness, and immune evasion in PCa cells. Clinical analyses demonstrate elevated BDNF levels in metastatic castration‐resistant PCa (CRPC) and a positive correlation with programmed death‐ligand 1 (PDL1) and immunosuppressive signatures. This study shows that the crosstalk between PCa cells and prostate stromal cells enhances LIF/LIFR signaling, contributing to an immunosuppressive TME and NED in PCa cells through the upregulation of BDNF.
Activation of LIF/LIFR/STAT3 signaling in the prostate cancer tumor microenvironment triggers BDNF production, linked to heightened PDL1 expression and neuroendocrine differentiation in prostate cancer cells. This pathway is crucial in stromal cells for regulating immune suppression and checkpoint responses, suggesting potential prognostic markers and therapies to combat immune evasion and neuroendocrine differentiation in prostate cancer.
Drug resistance is an obstacle to the treatment of ovarian cancer. Using a unique cell model, we have proven previously that a subpopulation of ovarian cancer cells is more resistant to cisplatin ...than are the original cells. MicroRNAs (miRNAs), small noncoding RNAs, are involved in many biological events in cancer cells. In our study, we explored whether miRNAs are involved in cisplatin resistance of ovarian cancer cells. Cisplatin‐resistant cells expressed a lower level of miR‐29a/b/c. Manipulation of microRNA‐29 (miR‐29) expression modulated cisplatin sensitivity of CP70, HeyC2, SKOV3 and A2780 ovarian cancer cells. Knockdown of miR‐29a/b/c increased the ability of cells to escape cisplatin‐induced cell death partly through upregulation of collagen type I alpha 1 (COL1A1) and increased the activation of extracellular signal‐regulated kinase 1/2 and inactivation of glycogen synthase kinase 3 beta. When combined with cisplatin treatment, knockdown of miR‐29 decreased the amount of the active form of caspase‐9 and caspase‐3. Ectopic expression of miR‐29 alone or in combination with cisplatin treatment efficaciously reduced the tumorigenicity of CP70 cells in vivo. Our data show that downregulation of miR‐29 increases cisplatin resistance in ovarian cancer cells. Taken together, these data suggest that overexpression of miR‐29 is a potential sensitizer to cisplatin treatment that may have therapeutic implications.
What's new?
MicroRNAs (miRNAs) are small, noncoding RNAs that are involved in a number of processes in cancer cells. In this study, the authors found that overexpression of miR‐29 can reduce drug resistance in ovarian cancer cells, in part through increased expression of collagen. Ectopic expression of miR‐29 alone or in combination with cisplatin treatment also reduced the tumorigenicity of CP70 cells in vivo. These data suggest that overexpression of miR‐29 may sensitize tumor cells to cisplatin treatment, and that this miRNA may therefore have therapeutic potential.
Prostate cancer (PCa) is considered one of the most prevalent malignancy globally, and metastasis is a major cause of death. Apigenin (API) is a dietary flavonoid which exerts an antimetastatic ...effect in various cancer types. Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1) is a crucial modulator of tumor growth and metastasis in cancers. However, the role and underlying regulatory mechanisms of SPOCK1 in the API-mediated antimetastatic effects of PCa remain unclear.
MTS, colony formation, wound-healing, and transwell assays were conducted to evaluate the effects of API on PCa cell proliferative, migratory, and invasive potentials. In vivo orthotopic bioluminescent xenograft model were employed to determine antitumor activity of API. PCa cells were transfected with either Snail-, Slug-, SPOCK1-overexpressing vector, or small hairpin (sh)SPOCK1 to determine the invasive abilities and expression levels of SPOCK1 and epithelial-to-mesenchymal transition (EMT) biomarkers in response to API treatment. Immunohistochemical (IHC) assays were carried out to evaluate the expression level of SPOCK1 in PCa xenografts and a PCa tissue array. Associations of SPOCK1 expression with clinicopathological features and prognoses of patients with PCa were analyzed by GEO or TCGA RNA-sequencing data.
API significantly suppressed in vitro PCa cell proliferation, migration, and invasion and inhibited in vivo PCa tumor growth and metastasis. Moreover, survival times of animals were also prolonged after API treatment. Mechanistic studies revealed that API treatment resulted in downregulation of SPOCK1, which was accompanied by reduced expressions of mesenchymal markers and subsequent attenuation of invasive abilities of PCa cells. Overexpression of SPOCK1 in PCa xenografts resulted in significant promotion of tumor progression and relieved the anticancer activities induced by API, whereas knockdown of SPOCK1 had opposite effects. In clinical, SPOCK1 levels were higher in tumor tissues compared to non-tumor tissues, which was also significantly correlated with shorter disease-free survival in PCa patients.
Levels of SPOCK1 increase with the progression of human PCa which suggests that SPOCK1 may act as a prognostic marker or therapeutic target for patients with PCa. Suppression of SPOCK1-mediated EMT signaling contributes to the antiproliferative and antimetastatic activities of API in vitro and in vivo.
The performance of hybrid perovskite‐based light‐emitting diodes (LEDs) is markedly enhanced by the application of a NiOx electrode interlayer and moderate methylamine treatment. A hybrid ...perovskite‐based LED exhibits a peak luminous efficiency of 15.9 cd A−1 biased at 8.5 V, 407.65 mA cm−2, and 65 300 cd m−2, showing a distinctive impact for future applications.
CD26/dipeptidyl peptidase IV (DPP4) is a multifunctional cell‐surface glycoprotein widely found in many cell types, and a soluble form is present in body fluids. There is longstanding evidence ...indicating a tumour‐promoting or ‐suppressive role of DPP4 in different cancer types. However, studies focusing on the impacts of genetic variants of DPP4 on cancers are very rare. Herein, we conducted a case–control study to evaluate whether single‐nucleotide polymorphisms (SNPs) of DPP4 were associated with the risk or clinicopathologic development of prostate cancer (PCa). We genotyped four loci of DPP4 SNPs, including rs7608798 (A/G), rs3788979 (C/T), rs2268889 (T/C) and rs6741949 (G/C), using a TaqMan allelic discrimination assay in 704 PCa patients and 704 healthy controls. Our results showed that PCa patients with the DPP4 rs7608798 AG+GG genotype or rs2268889 TC+CC genotype had a higher risk of developing an advanced clinical primary tumour (cT) stage (adjusted odds ratio (AOR): 1.680, 95% confidence interval (CI): 1.062–2.659, p = 0.025; AOR: 1.693, 95% CI: 1.092–2.624, p = 0.018). Additionally, in The Cancer Genome Atlas (TCGA) database, we observed that lower DPP4 expression levels were correlated with higher Gleason scores, advanced cT and pathological stages, tumour metastasis, and shorter progression‐free survival rates in PCa patients. Furthermore, overexpression of DPP4 suppressed migration/invasion of metastatic PC3 PCa cells. Our findings suggest that DPP4 levels may affect the progression of PCa, and the DPP4 rs7608798 and rs2268889 SNPs are associated with the clinicopathologic development of PCa in a Taiwanese population.
This retrospective cohort study is to investigate the association between herpes simplex virus (HSV) infections and dementia, and the effects of anti-herpetic medications on the risk involved, using ...Taiwan’s National Health Insurance Research Database (NHIRD). We enrolled a total of 33,448 subjects, and identified 8362 with newly diagnosed HSV infections and 25,086 randomly selected sex- and age-matched controls without HSV infections in a ratio of 1:3, selected from January 1, to December 31, 2000. A multivariable Cox proportional hazards regression model was used to evaluate the risk of developing dementia in the HSV cohort. This analysis revealed an adjusted hazard ratio of 2.564 (95% CI: 2.351-2.795,
P
< 0.001) for the development of dementia in the HSV-infected cohort relative to the non-HSV cohort. Thus, patients with HSV infections may have a 2.56-fold increased risk of developing dementia. A risk reduction of dementia development in patients affected by HSV infections was found upon treatment with anti-herpetic medications (adjusted HR = 0.092 95% CI 0.079-0.108,
P
< 0.001). The usage of anti-herpetic medications in the treatment of HSV infections was associated with a decreased risk of dementia. These findings could be a signal to clinicians caring for patients with HSV infections. Further research is, therefore, necessary to explore the underlying mechanism(s) of these associations.
ABSTRACT
Disseminated castration‐resistant prostate cancer (CRPC) is a common disease in men that is characterized by limited survival and resistance to androgen‐deprivation therapy. The increase in ...human epidermal growth factor receptor 2 (HER2) signaling contributes to androgen receptor activity in a subset of patients with CRPC; however, enigmatically, HER2‐targeted therapies have demonstrated a lack of efficacy in patients with CRPC. Aberrant glycosylation is a hallmark of cancer and involves key processes that support cancer progression. Using transcriptomic analysis of prostate cancer data sets, histopathologic examination of clinical specimens, and in vivo experiments of xenograft models, we reveal in this study a coordinated increase in glycan‐binding protein, galectin‐4, specific glycosyltransferases of core 1 synthase, glycoprotein‐N‐acetylgalactosamine 3‐β‐galactosyltransferase 1 (C1GALT1) and ST3 β‐galactoside α‐2,3‐sialyltransferase 1 (ST3GAL1), and resulting mucin‐type O‐glycans during the progression of CRPC. Furthermore, galectin‐4 engaged with C1GALT1‐dependent O‐glycans to promote castration resistance and metastasis by activating receptor tyrosine kinase signaling and cancer cell sternness properties mediated by SRY‐box 9 (SOX9). This galectin‐glycan interaction up‐regulated the MYC‐dependent expression of C1GALT1 and ST3GAL1, which altered cellular mucin‐type O‐glycosylation to allow for galectin‐4 binding. In clinical prostate cancer, high‐level expression of C1GALT1 and galectin‐4 together predict poor overall survival compared with low‐level expression of C1GALT1 and galectin‐4. In summary, MYC regulates abnormal O‐glycosylation, thus priming cells for binding to galectin‐4 and downstream signaling, which promotes castration resistance and metastasis.—Tzeng, S.‐F., Tsai, C.‐H., Chao, T.‐K., Chou, Y.‐C., Yang, Y.‐C., Tsai, M.‐H., Cha, T.‐L., Hsiao, P.‐W. O‐Glycosylation‐mediated signaling circuit drives metastatic castration‐resistant prostate cancer. FASEB J. 32, 6869–6882 (2018). www.fasebj.org
In this study, a novel perovskite quantum dot (QD) spray‐synthesis method is developed by combining traditional perovskite QD synthesis with the technique of spray pyrolysis. By utilizing this new ...technique, the synthesis of cubic‐shaped perovskite QDs with a homogeneous size of 14 nm is demonstrated, which shows an unprecedented stable absolute photoluminescence quantum yield ≈100% in the solution and even in the solid‐state neat film. The highly emissive thin films are integrated with light emission devices (LEDs) and organic light emission displays (OLEDs). The color conversion type QD‐LED (ccQD‐LED) hybrid devices exhibit an extremely saturated green emission, excellent external quantum efficiency of 28.1%, power efficiency of 121 lm W−1, and extraordinary forward‐direction luminescence of 8 500 000 cd m−2. The conceptual ccQD‐OLED hybrid display also successfully demonstrates high‐definition still images and moving pictures with a 119% National Television System Committee 1931 color gamut and 123% Digital Cinema Initiatives‐P3 color gamut. These very‐stable, ultra‐bright perovskite QDs have the properties necessary for a variety of useful applications in optoelectronics.
Spray‐synthesized perovskite quantum dots (QDs) show an unprecedented cubic shape, and a stable photoluminescence quantum yield of ≈100% in both solution and the solid‐state neat film. QD‐LED (light emission device) and QD‐OLED (organic light emission display) hybrid devices exhibit an excellent external quantum efficiency of 28.1%, a power efficiency of 121 lm W−1, and successfully demonstrate high‐definition motion pictures.
We applied Simmons-Balluffi methods, positron measurements, and neutron diffraction to estimate the vacancy of CoCrFeNi and CoCrFeMnNi high-entropy alloys (HEAs) using Cu as a benchmark. The ...corresponding formation enthalpies and associated entropies of the HEAs and Cu were calculated. The vacancy-dependent effective free volumes in both CoCrFeNi and CoCrFeMnNi alloys are greater than those in Cu, implying the easier formation of vacancies by lattice structure relaxation of HEAs at elevated temperatures. Spatially resolved synchrotron X-ray measurements revealed different characteristics of CoCrFeNi and CoCrFeMnNi HEAs subjected to quasi-equilibrium conditions at high temperatures. Element-dependent behavior revealed by X-ray fluorescence (XRF) mapping indicates the effect of Mn on the Cantor Alloy.
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