Progress of immunotherapies in gestational trophoblastic neoplasms.

BACKGROUND: Different from other malignant gynecologic tumors, gestational trophoblastic neoplasms (GTNs) exhibit an exceptionally high cure rate primarily through chemotherapeutic interventions. However, there exists a small subset of refractory GTNs that do not respond to conventional chemotherapies. In such cases, the emergence of immunotherapies has demonstrated significant benefits in managing various challenging GTNs. PURPOSE: This article aims to provide a comprehensive and systematic review of the immune microenvironment and immunotherapeutic approaches for GTNs. The purpose is to identify potential biomarkers that could enhance disease management and summarize the available immunotherapies for ease of reference. METHODS: We reviewed the relevant literatures toward immunotherapies of GTNs from PubMed. CONCLUSION: Current immunotherapeutic strategies for GTNs mainly revolve around immune checkpoint inhibitors (ICIs) targeting programmed death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1). Prominent examples include avelumab, pembrolizumab, and camrelizumab. However, existing researches into the underlying mechanisms are still limited.

Novel insights into tumorigenesis and prognosis of endometrial cancer through systematic investigation and validation on mitophagy-related signature.

In-depth studies on the pathogenesis of endometrial cancer (EC) are critical because of the increasing global incidence of EC. Mitophagy, a mitochondrial quality control process, plays an important role in carcinogenesis and tumor progression. This study aimed to develop a novel mitophagy-based signature to predict the tumorigenesis and prognosis of EC. Data was downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases, and 29 mitophagy-related genes were downloaded from the Pathway Unification Database. EC patients were classified into two risk groups based on the two-key- gene signature, TOMM40 and MFN1, which were constructed using Cox regression analysis. A better prognosis was noted in the low-risk group. The model was validated for four aspects: clinical features, mutation status, clinical therapeutic response, and immune cell infiltration status. Moreover, according to the contribution to the risk model, TOMM40 was selected for further in vitro experiments. The silencing of TOMM40 inhibited mitochondrial degradation; suppressed cell proliferation; induced cell apoptosis and G1 phase cell cycle arrest; inhibited migration, invasion, and epithelial-mesenchymal transition; and suppressed cell stemness. In conclusion, the mitophagy-related risk score provides a novel perspective for survival and drug selection during the individual treatment of EC patients. TOMM40 serves as an oncogene in EC and promotes tumor progression via a mitophagy-related pathway. Thus, TOMM40 is a potential therapeutic target in EC.

Multi-granularity knowledge distillation and prototype consistency regularization for class-incremental learning.

Deep neural networks (DNNs) are prone to the notorious catastrophic forgetting problem when learning new tasks incrementally. Class-incremental learning (CIL) is a promising solution to tackle the challenge and learn new classes while not forgetting old ones. Existing CIL approaches adopted stored representative exemplars or complex generative models to achieve good performance. However, storing data from previous tasks causes memory or privacy issues, and the training of generative models is unstable and inefficient. This paper proposes a method based on multi-granularity knowledge distillation and prototype consistency regularization (MDPCR) that performs well even when the previous training data is unavailable. First, we propose to design knowledge distillation losses in the deep feature space to constrain the incremental model trained on the new data. Thereby, multi-granularity is captured from three aspects: by distilling multi-scale self-attentive features, the feature similarity probability, and global features to maximize the retention of previous knowledge, effectively alleviating catastrophic forgetting. Conversely, we preserve the prototype of each old class and employ prototype consistency regularization (PCR) to ensure that the old prototypes and semantically enhanced prototypes produce consistent prediction, which excels in enhancing the robustness of old prototypes and reduces the classification bias. Extensive experiments on three CIL benchmark datasets confirm that MDPCR performs significantly better over exemplar-free methods and outperforms typical exemplar-based approaches.

LncRNA HOXB-AS3 binding to PTBP1 protein regulates lipid metabolism by targeting SREBP1 in endometrioid carcinoma.

Endometrial cancer (EC) is a malignant tumor with a high incidence in women, and the survival rate of high-risk patients decreases significantly after disease progression. The regulatory role of long non-coding RNAs (LncRNAs) in tumors has been widely appreciated, but there have been few studies in EC. To investigate the effect of HOXB-AS3 in EC, we used bioinformatics tools for prediction and collected clinical samples to detect the expression of HOXB-AS3. Colony formation assay, MTT assay, flow cytometry and apoptosis assay, and transwell assay were used to verify the role of HOXB-AS3 in EC. HOXB-AS3 was upregulated in EC, promoted the proliferation and invasive ability of EC cells, and inhibited apoptosis. In addition, the ROC curve illustrated its diagnostic value. We explored experiments via lentiviral transduction, FISH, Oil Red O staining, TC and FFA content detection, RNA-pulldown, RIP, and other mechanisms to reveal that HOXB-AS3 can bind to PTBP1 and co-regulate the expression of SREBP1, thereby regulating lipid metabolism in EC cells. To the best of our knowledge, this is the first study on HOXB-AS3 in disorders of lipid metabolism in EC. In addition, we believe HOXB-AS3 has the potential to be a neoplastic marker or a therapeutic target.

Verteporfin reverses progestin resistance through YAP/TAZ-PI3K-Akt pathway in endometrial carcinoma.

Progestin resistance is a problem for patients with endometrial carcinoma (EC) who require conservative treatment with progestin, and its underlying mechanisms remain unclear. YAP and TAZ (YAP/TAZ), downstream transcription coactivators of Hippo pathway, promote viability, metastasis and also drug resistance of malignant tumors. According to our microarray analysis, YAP/TAZ were upregulated in progestin resistant IshikawaPR cell versus progestin sensitive Ishikawa cell, which implied that YAP/TAZ may be a vital promotor of resistance to progestin. We found YAP/TAZ had higher expression levels among the resistant tissues than sensitive tissues. In addition, knocking down YAP/TAZ decreased cell viability, inhibited cell migration and invasion and increased the sensitivity of IshikawaPR cell to progestin. On the contrary, overexpression of YAP/TAZ increased cell proliferation, metastasis and promoted progestin resistance. We also confirmed YAP/TAZ were involved in progestin resistant process by regulating PI3K-Akt pathway. Furthermore, Verteporfin as an inhibitor of YAP/TAZ could increase sensitivity of IshikawaPR cells to progestin in vivo and in vitro. Our study for the first time indicated that YAP/TAZ play an important role in progestin resistance by regulating PI3K-Akt pathway in EC, which may provide ideas for clinical targeted therapy of progestin resistance.

ABX-1431 inhibits the development of endometrial adenocarcinoma and reverses progesterone resistance by targeting MGLL.

Endometrial cancer is a common gynecological malignancy. With the onset of EC patients younger, conservative treatment with progesterone has become an important option for patients trying to preserve reproductive function. However, progesterone resistance is a key factor affecting the efficacy of therapy and it is urgent to clarify the mechanism so as to propose a potential target and inhibit the development of endometrial adenocarcinoma and progesterone resistance. MGLL, an important factor involved in lipid mobilization, is overexpressed in many tumors, however the biological function of MGLL in the development of endometrial adenocarcinoma and the process of progesterone resistance still remains unclear. In this study, we first found MGLL was highly expressed in progesterone resistant samples of endometrial adenocarcinoma, and then we verified its expression was increased in endometrial adenocarcinoma. Through in vitro and in vivo experiments, we demonstrated that overexpression of MGLL promoted tumor proliferation, metastasis and the occurrence of progestogen resistance, knockdown MGLL inhibited tumor proliferation, metastasis and reversed progestogen resistance. In addition, knockdown of MGLL can sensitize endometrial adenocarcinoma cells to progesterone, possibly by affecting ROS generation and reducing the expression of AKR1C1. Finally, it was verified that ABX-1431, MGLL inhibitor, reversed progesterone resistance and enhanced the sensitivity of endometrial adenocarcinoma to progesterone both in vitro and in vivo. In conclusion, the high expression of MGLL is involved in the occurrence and development of endometrial adenocarcinoma and progesterone resistance. Targeted inhibition of MGLL by inhibitors may be an effective method for the treatment of progesterone resistance in endometrial adenocarcinoma.

MEX3A promotes the malignant progression of ovarian cancer by regulating intron retention in TIMELESS.

The latest research shows that RNA-binding proteins (RBPs) could serve as novel potential targets for cancer therapy. We used bioinformatics analysis to screen and identify the key RBPs in ovarian cancer, from which we found that Mex-3 RNA Binding Family Member A (MEX3A) was intimately associated with the clinical prognosis of ovarian cancer. Nevertheless, little is known about its biological roles in ovarian cancer. In this case, we observed that MEX3A was highly overexpressed in fresh-frozen ovarian cancer tissues. MEX3A knockdown suppressed the development and invasion of ovarian cancer cells, while MEX3A overexpression promoted the proliferation and invasion of ovarian cancer cells. Mechanistically, TIMELESS was the critical downstream target gene of MEX3A, as demonstrated through alternative splicing event analysis based on RNA-seq. MEX3A knockdown resulted in retention of intron twenty-three of TIMELESS mRNA and decreased TIMELESS mRNA owing to stimulation of nonsense-mediated RNA decay (NMD). Additionally, we found that TIMELESS overexpression with MEX3A knockdown partially restored the proliferation ability of ovarian cancer cells. The results of this paper demonstrated that the MEX3A/TIMELESS signaling pathway was a key regulator of ovarian cancer, and MEX3A was a novel possible treatment target for ovarian cancer patients.

HJURP Promotes Malignant Progression and Mediates Sensitivity to Cisplatin and WEE1-inhibitor in Serous Ovarian Cancer.

Ovarian cancer is the most lethal gynecological malignancy. Recurrence and chemoresistance are tough challenges leading to poor prognosis. HJURP is a molecular chaperone of CENP-A, which is associated with aggressive progression in multiple tumors. However, the function of HJURP in ovarian cancer has not been elucidated. In our study, we found HJURP was over-expressed in ovarian cancer and high expression of HJURP was correlated to unfavorable prognosis. HJURP knockdown could inhibit proliferation, metastasis and induce G0/G1 stagnation of ovarian cancer cells. Besides, next-generation sequencing (NGS) unveiled that WEE1 was down-regulated by silencing HJURP. Further mechanistic research revealed that HJURP regulated WEE1 through MYC, and luciferase assay indicated that MYC was a transcription factor of WEE1. Additionally, we investigated that silencing HJURP increased sensitivity of ovarian cancer cells to cisplatin via MYC/WEE1 axis, and HJURP participated in DNA repair of cisplatin-induced damage. More interestingly, silencing HJURP could enhance sensitivity of ovarian cancer cells to AZD1775 and improve the synergistic effect of cisplatin plus AZD1775 combined therapy. Collectively, our data displays that HJURP promotes tumor progression and chemoresistance of ovarian cancer, and HJURP has potential to be a novel therapeutic target in the combined treatment with cisplatin and AZD1775 in ovarian cancer.

The urban morphology on our planet - Global perspectives from space.

Urbanization is the second largest mega-trend right after climate change. Accurate measurements of urban morphological and demographic figures are at the core of many international endeavors to address issues of urbanization, such as the United Nations' call for "Sustainable Cities and Communities". In many countries - particularly developing countries -, however, this database does not yet exist. Here, we demonstrate a novel deep learning and big data analytics approach to fuse freely available global radar and multi-spectral satellite data, acquired by the Sentinel-1 and Sentinel-2 satellites. Via this approach, we created the first-ever global and quality controlled urban local climate zones classification covering all cities across the globe with a population greater than 300,000 and made it available to the community (https://doi.org/10.14459/2021mp1633461). Statistical analysis of the data quantifies a global inequality problem: approximately 40% of the area defined as compact or light/large low-rise accommodates about 60% of the total population, whereas approximately 30% of the area defined as sparsely built accommodates only about 10% of the total population. Beyond, patterns of urban morphology were discovered from the global classification map, confirming a morphologic relationship to the geographical region and related cultural heritage. We expect the open access of our dataset to encourage research on the global change process of urbanization, as a multidisciplinary crowd of researchers will use this baseline for spatial perspective in their work. In addition, it can serve as a unique dataset for stakeholders such as the United Nations to improve their spatial assessments of urbanization.

Splicing Factor DDX23, Transcriptionally Activated by E2F1, Promotes Ovarian Cancer Progression by Regulating FOXM1.

Ovarian carcinoma remains the most lethal gynecological carcinoma. Abnormal expression of splicing factors is closely related to the occurrence and development of tumors. The DEAD-box RNA helicases are important members of the splicing factor family. However, their role in the occurrence and progression of ovarian cancer is still unclear. In this study, we identified DEAD-box helicase 23 (DDX23) as a key DEAD-box RNA helicase in ovarian cancer using bioinformatics methods. We determined that DDX23 was upregulated in ovarian cancer and its high expression predicted poor prognosis. Functional assays indicated that DDX23 silencing significantly impeded cell proliferation/invasion in vitro and tumor growth in vivo. Mechanistically, transcriptomic analysis showed that DDX23 was involved in mRNA processing in ovarian cancer cells. Specifically, DDX23 regulated the mRNA processing of FOXM1. DDX23 silencing reduced the production of FOXM1C, the major oncogenic transcript of FOXM1 in ovarian cancer, thereby decreasing the FOXM1 protein expression and attenuating the malignant progression of ovarian cancer. Rescue assays indicated that FOXM1 was a key executor in DDX23-induced malignant phenotype of ovarian cancer. Furthermore, we confirmed that DDX23 was transcriptionally activated by the transcription factor (TF) E2F1 in ovarian cancer using luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays. In conclusion, our study demonstrates that high DDX23 expression is involved in malignant behavior of ovarian cancer and DDX23 may become a potential target for precision therapy of ovarian cancer.

Fatostatin reverses progesterone resistance by inhibiting the SREBP1-NF-κB pathway in endometrial carcinoma.

Progesterone resistance can significantly restrict the efficacy of conservative treatment for patients with endometrial cancer who wish to preserve their fertility or those who suffer from advanced and recurrent cancer. SREBP1 is known to be involved in the occurrence and progression of endometrial cancer, although the precise mechanism involved remains unclear. In the present study, we carried out microarray analysis in progesterone-sensitive and progesterone-resistant cell lines and demonstrated that SREBP1 is related to progesterone resistance. Furthermore, we verified that SREBP1 is over-expressed in both drug-resistant tissues and cells. Functional studies further demonstrated that the inhibition of SREBP1 restored the sensitivity of endometrial cancer to progesterone both in vitro and in vivo, and that the over-expression of SREBP1 promoted resistance to progesterone. With regards to the mechanism involved, we found that SREBP1 promoted the proliferation of endometrial cancer cells and inhibited their apoptosis by activating the NF-κB pathway. To solve the problem of clinical application, we found that Fatostatin, an inhibitor of SREBP1, could increase the sensitivity of endometrial cancer to progesterone and reverse progesterone resistance by inhibiting SREBP1 both in vitro and in vivo. Our results highlight the important role of SREBP1 in progesterone resistance and suggest that the use of Fatostatin to target SREBP1 may represent a new method to solve progesterone resistance in patients with endometrial cancer.

MiR-501 promotes tumor proliferation and metastasis by targeting HOXD10 in endometrial cancer.

BACKGROUND: Several studies have shown the crucial role of miR-501 in regulating cellular pathology in various cancers. However, the function and expression of miR-501 in endometrial cancer (EC) remain obscure. METHODS: The expression of miR-501 was determined using quantitative real-time PCR. MTT assay, colony formation assay and cell cycle analysis were used to evaluate the proliferation ability. Migration and invasion were assessed using transwell assay. Tumor formation in nude mice was used to observe the effects of miR-501 on cell proliferation and migration in vivo. Luciferase assay, quantitative real-time PCR and western blot were applied to determine that HOXD10 was the target gene of miR-501. RESULTS: In this study, we observed significantly up-regulated expression of miR-501 in endometrial cancer, which correlated with higher pelvic lymph node metastasis and shorter overall survival in high-grade endometrial cancer. High expression of miR-501 was also found in the copy-number-high group than other groups. Moreover, in vitro and in vivo assay showed that overexpression of miR-501 can promote proliferation and metastasis. Mechanistically, we found that miR-501 promotes tumor progression by directly targeting HOXD10. Further study also indicated that miR-501 overexpression can activate the AKT/mTOR pathway. CONCLUSIONS: MiR-501, which functions as an oncomir in endometrial cancer, might be a potential therapeutic target in high grade endometrial cancer.

CNR1 may reverse progesterone-resistance of endometrial cancer through the ERK pathway.

Endocrine therapy is a promising treatment for endometrial cancer (EC) that preserves fertility, however, progesterone-resistance is currently the major challenges. The Cancer Genome Atlas (TCGA) database analysis showed that CNR1 was closely have a negative correlation with overall survival (OS) and relapse-free survival (RFS) in endometrial cancer. To explore the role of CNR1 in progesterone resistance and possible molecular regulation mechanism, we established stable progesterone-resistant cell lines (IshikawaPR) via progesterone tolerance of ordinary cancer cells (Ishikawa). The difference of CNR1 level in two cell lines was assessed by MTT, RT-PCR, Western blot, immunofluorescence. Then, lentiviruses constructed CNR1-knockdown with GV248 as the tool vector were used to transfect IshikwaPR cells, and the changes of biological behavior and progesterone sensitivity was verified respectively through plate cloning experiment, EdU assay, flow cytometry cycle analysis, transwell, Scratch test, etc. We founded after CNR1 was knocked down, the proliferative activity and ability to migrate of IshikawaPR cells decreased, progesterone-response sensitivity could be improved. Moreover, knockdown of CNR1 can also down-regulate ERK and NFκ B expression and activation. Furthermore, subcutaneous xenograft in nude mice was tested similarly in vivo. The above datas suggest that targeting CNR1 may reverse the progesterone resistance in endometrial cancer and may coordinate the role of ERK pathway activation.

IQGAP3 promotes cancer proliferation and metastasis in high-grade serous ovarian cancer.

Ovarian cancer is a type of gynecological cancer with the highest mortality rate worldwide. Due to a lack of effective screening methods, most cases are diagnosed at later stages where the survival rates are poor. Thus, it is termed a 'silent killer' and is the most lethal of all the malignancies in women. IQ motif containing GTPase Activating Protein 3 (IQGAP3) is a member of the Rho family of GTPases, and plays a crucial role in the development and progression of several types of cancer. The aim of the present study was to investigate the oncogenic functions and mechanisms of IQGAP3 on the proliferation and metastasis of high-grade serous ovarian cancer (HGSOC). Therefore, the expression levels of IQGAP3 in HGSOC and normal tissue samples were compared, and IQGAP3 knockdown was performed to examine its functional role using various in vitro and in vivo experiments. It was demonstrated that the expression of IQGAP3 was upregulated in HGSOC tissues compared with the healthy tissues; this differential expression was also observed in the ovarian cancer cell lines. Functional experimental results suggested that IQGAP3 silencing significantly reduced proliferation, migration and invasion in ovarian cancer cell lines. Moreover, in vivo experimental findings validated the in vitro results, where the tumorigenic and metastatic capacities of IQGAP3-silenced cells were significantly lower in the nude mice compared with the mice implanted with the control cells. Furthermore, knockdown of IQGAP3 resulted in increased apoptosis, and the effects of IQGAP3 expression on various epithelial-mesenchymal transition markers were identified, suggesting a possible mechanism associated with the role of IQGAP3 in metastasis. The effect of IQGAP3 silencing on chemosensitivity towards olaparib was also assessed. Collectively, the present results indicated that IQGAP3 is a potential diagnostic and prognostic marker, and a putative therapeutic target of HGSOC.

A framework for large-scale mapping of human settlement extent from Sentinel-2 images via fully convolutional neural networks.

Human settlement extent (HSE) information is a valuable indicator of world-wide urbanization as well as the resulting human pressure on the natural environment. Therefore, mapping HSE is critical for various environmental issues at local, regional, and even global scales. This paper presents a deep-learning-based framework to automatically map HSE from multi-spectral Sentinel-2 data using regionally available geo-products as training labels. A straightforward, simple, yet effective fully convolutional network-based architecture, Sen2HSE, is implemented as an example for semantic segmentation within the framework. The framework is validated against both manually labelled checking points distributed evenly over the test areas, and the OpenStreetMap building layer. The HSE mapping results were extensively compared to several baseline products in order to thoroughly evaluate the effectiveness of the proposed HSE mapping framework. The HSE mapping power is consistently demonstrated over 10 representative areas across the world. We also present one regional-scale and one country-wide HSE mapping example from our framework to show the potential for upscaling. The results of this study contribute to the generalization of the applicability of CNN-based approaches for large-scale urban mapping to cases where no up-to-date and accurate ground truth is available, as well as the subsequent monitor of global urbanization.

MiR-509-3 augments the synthetic lethality of PARPi by regulating HR repair in PDX model of HGSOC.

BACKGROUND: PARP inhibitors have been the most promising target drugs with widely proven benefits among ovarian cancer patients. Although platinum-response, HR-related genes, or HRD genomic scar detection are acceptably used in assessment of Olaparib response, there are still evident limitations in the present approaches. Therefore, we aim to investigate more accurate approaches to predict Olaparib sensitivity and effective synergistic treatment strategies. METHODS: We probed two databases (TCGA and Qilu Hospital) in order to quest novel miRNAs associated with platinum-sensitivity or HR-related genes. Cellular experiments in vitro or in vivo and PDX models were utilized to validate their role in tumor suppression and Olaparib sensitizing. Furthermore, HR gene mutation was analyzed through WES to explore the relation between HR gene mutation and Olaparib response. RESULTS: High miR-509-3 expression indicated better response to platinum and longer progression-free and overall survival in two independent ovarian cancer patient cohorts (high vs. low miR-509-3 expression; PFS: TCGA P < 0.05, Qilu P < 0.05; OS: TCGA P < 0.05, Qilu P < 0.01). MiR-509-3 could impair the proliferation, migration, and invasion ability but enhance the sensitivity to Olaparib of ovarian cancer cell in vitro and in vivo by directly targeting HMGA2 and RAD51. In two PDX cases (PDX1 and PDX9), miR-509-3 could significantly increase the sensitivity to Olaparib along with the decrease of RAD51 positive rate (mean tumor weight NC + Olaparib vs. miR-509 + Olaparib; PDX1 P < 0.05, PDX9 P < 0.05). Additionally, in PDX8, miR-509-3 treatment dramatically reversed the Olaparib insensitivity (P < 0.05) by downregulating RAD51 expression. RAD51 functional detection revealed that all Olaparib sensitive cases exhibited low RAD51 positive rate (lesser than 50%) in treated groups. Furthermore, among the four HR gene mutation patients, three harbored HR core gene mutation and were sensitive to Olaparib while the remaining one with non-HR core gene mutation did not respond well to Olaparib. CONCLUSIONS: MiR-509-3 can sensitize ovarian cancer cells to Olaparib by impeding HR, which makes it a potential target in PARPi synergistic treatment. HR core gene analysis and RAD51 functional detection are prospectively feasible in prediction of PARPi response.

The diagnosis and treatment of adrenocortical carcinoma in pregnancy: a case report.

BACKGROUND: Pregnancy complicated with adrenocortical carcinoma (ACC) is a sporadic syndrome that is characterized by hypertension, uncontrolled hypokalemia, severe heart failure, premature delivery and other adverse effects. The clinical presentation of adrenocortical carcinoma is vague and nonspecific, it is challenging to identify complications of pregnancy with adrenocortical carcinoma. Here we present a case of adrenocortical carcinoma during pregnancy. We describe how to distinguish secondary hypertension from other conditions and the importance of timely detection and treatment of such patients. CASE PRESENTATION: A 22-year-old woman 30 weeks pregnant was hospitalized with uncontrolled hypertension and hypokalemia. An ultrasound examination of the right adrenal gland revealed a large mass. She underwent transabdominal adrenalectomy, and histopathology from the sample removed revealed an adrenocortical carcinoma. Five days after surgery, the patient had a premature rupture of the fetal membranes and gave birth to a newborn girl via vaginal delivery at 32 weeks of gestation. The newborn was transferred to the neonatal pediatrics ward, and the woman started receiving chemotherapy. CONCLUSIONS: Pregnancy with adrenocortical carcinoma is a rare condition. This case alerts the obstetricians that analysis of hypertension, hypokalemia, the plasma level and circadian rhythm of plasma cortisol provides a strategy to diagnose adrenocortical carcinoma during pregnancy.

Local climate zone-based urban land cover classification from multi-seasonal Sentinel-2 images with a recurrent residual network.

The local climate zone (LCZ) scheme was originally proposed to provide an interdisciplinary taxonomy for urban heat island (UHI) studies. In recent years, the scheme has also become a starting point for the development of higher-level products, as the LCZ classes can help provide a generalized understanding of urban structures and land uses. LCZ mapping can therefore theoretically aid in fostering a better understanding of spatio-temporal dynamics of cities on a global scale. However, reliable LCZ maps are not yet available globally. As a first step toward automatic LCZ mapping, this work focuses on LCZ-derived land cover classification, using multi-seasonal Sentinel-2 images. We propose a recurrent residual network (Re-ResNet) architecture that is capable of learning a joint spectral-spatial-temporal feature representation within a unitized framework. To this end, a residual convolutional neural network (ResNet) and a recurrent neural network (RNN) are combined into one end-to-end architecture. The ResNet is able to learn rich spectral-spatial feature representations from single-seasonal imagery, while the RNN can effectively analyze temporal dependencies of multi-seasonal imagery. Cross validations were carried out on a diverse dataset covering seven distinct European cities, and a quantitative analysis of the experimental results revealed that the combined use of the multi-temporal information and Re-ResNet results in an improvement of approximately 7 percent points in overall accuracy. The proposed framework has the potential to produce consistent-quality urban land cover and LCZ maps on a large scale, to support scientific progress in fields such as urban geography and urban climatology.

Effect of monoacylglycerol lipase on the tumor growth in endometrial cancer.

AIM: Abnormal lipid metabolism plays a dual role in tumorigenesis, specifically in the occurrence and development of cancers. Monoacylglycerol lipase (MAGL), a hydrolase that is important for lipid metabolism, plays a vital role in different aspects of tumorigenesis. Many studies have shown that MAGL is highly elevated in a variety of cancers and plays an active role. However, its potential role in supporting endometrial cancer (EC) growth and progression has not yet been explored in depth. METHODS: Immunohistochemistry and quantitative real-time reverse transcription polymerase chain reaction were performed to estimate the protein and messenger RNA (mRNA) levels of MAGL in tumor tissues. Then, JZL184 and small interfering RNA (siRNA) were used to decrease the expression of MAGL in EC cells. The gene and protein expression levels of MAGL were measured using quantitative real-time PCR and western blotting, respectively. Additionally, the effect of MAGL on tumor growth in EC was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide , cell cycle and western blotting assay in vitro. RESULTS: We found that MAGL was overexpressed in EC and was significantly correlated with surgical-pathological stage, myometrial invasion, number of pregnancies and body mass index. The growth and cell cycle progression of tumor cells were significantly impaired in vitro by the pharmacological and siRNA-mediated MAGL inhibition. In addition, MAGL inhibition seemed to repress two target genes, Cyclin D1 and Bcl-2. CONCLUSION: In summary, we have demonstrated that MAGL is involved in EC growth and progression. Our results suggest that targeting MAGL may be a novel and valid treatment for EC.

Squamous cell carcinoma transformation in mature cystic teratoma of the ovary: a systematic review.

BACKGROUND: 0.17-2% of mature cystic teratoma of the ovary (MCTO) undergo malignant transformation, of which 80% are squamous cell carcinoma (SCC) transformation in MCTO. We aim to investigate the clinical characteristics and treatment of SCC transformation in MCTO METHODS: We systematically searched PubMed database and individual patient data about SCC transformation in MCTO were extracted. The published cases were combined with 6 cases of SCC transformation in MCTO from Qilu Hospital, Shandong University. RESULTS: The incidence of SCC transformation in MCTO was 0.3%. A total of 435 cases of SCC transformation in MCTO were enrolled in the analysis. The mean age of diagnosis was 53.5 (range 19-87) years old. The most common clinical manifestations were abdominal pain (47.3%) and abdominal mass (26.0%). StageI,II, III and IV accounted for 50.0, 18.8, 26.8 and 4.4% of all cases, respectively. Patients with stage I had significantly better prognosis than stage II, III and IV patients (P < 0.01). Hysterectomy can improve overall survival (P < 0.01). For patients younger than 45 years old with stageIA orIC, there was no difference in mortality between fertility-sparing and radical surgery (P = 1.00). Adjuvant chemotherapy can improve survival in patients with advanced stage (P = 0.02), and chemotherapy with platinum was related to better prognosis (P = 0.02). CONCLUSION: SCC transformation in MCTO is a rare malignancy mainly occurs in older age. FIGO stage is an independent prognostic factor. Hysterectomy and platinum-based chemotherapy are associated with better survival. Fertility-sparing surgery is feasible for young patients with early stage.