Single-cell and spatial transcriptome sequencing uncover a platinum-resistant cluster overexpressed TACSTD2 in high-grade serous ovarian cancer.

Purpose: Platinum-based chemotherapy is effective but limited by resistance in high-grade serous ovarian cancer (HGSOC). Single-cell RNA sequencing (scRNA-seq) can reveal tumour cell heterogeneity and subclonal differentiation. We aimed to analyze resistance mechanisms and potential targets in HGSOC using scRNA-seq. Methods: We performed 10× genomics scRNA-seq sequencing on tumour tissues from 3 platinum-sensitive and 3 platinum-resistant HGSOC patients. We analyzed cell subcluster communication networks and spatial distribution using cellchat. We performed RNA-seq analysis on TACSTD2, a representative resistance gene in the E0 subcluster, to explore its molecular mechanism. Results: Epithelial cells, characterized by distinct chemotherapy resistance traits and highest gene copy number variations, revealed a specific cisplatin-resistant cluster (E0) associated with poor prognosis. E0 exhibited malignant features related to resistance, fostering growth through communication with fibroblasts and endothelial cells. Spatially, E0 promoted fibroblasts to protect tumour cells and impede immune cells infiltration. Furthermore, TACSTD2 was identified as a representative gene of the E0 subcluster, elucidating its role in platinum resistance through the Rap1/PI3K/AKT pathway. Conclusions: Our study reveals a platinum-resistant epithelial cell subcluster E0 and its association with TACSTD2 in HGSOC, uncovers new insights and evidence for the platinum resistance mechanism, and provides new ideas and targets for the development of therapeutic strategies against TACSTD2+ epithelial cancer cells.

Markovnikov Hydrochlorination of Unactivated Alkenes with FeCl3 via a HAT/XAT Sequence.

Hydrochlorination of alkenes is a practical strategy for accessing organic chlorides. Herein, we report the hydrochlorination of unactivated alkenes via a hydrogen atom transfer/halogen atom transfer process using earth-abundant and biocompatible FeCl3 as a chlorine source under extraordinarily mild reaction conditions. The protocol is easy to operate with notable features such as excellent chemoselectivity, remarkable efficiency, a broad substrate scope, and good functional group tolerance. Importantly, the synthetic utility is highlighted by scaled-up reactions, late-stage derivatizations of products, and the modification of sulfonamides.

Coated cysteamine, a potential feed additive for ruminants - An updated review.

For sustainable development, better performance, and less gas pollution during rumen fermentation, there is a need to find a green and safe feed additive for ruminants. Cysteamine (CS) is a biological compound naturally produced in mammalian cells. It is widely used as a growth promoter in ruminants because of its ability to control hormone secretions. It mainly controls the circulating concentration of somatostatin and enhances growth hormone production, leading to improved growth performance. CS modulates the rumen fermentation process in a way beneficial for the animals and environment, leading to less methane production and nutrients loss. Another beneficial effect of using CS is that it improves the availability of nutrients to the animals and enhances their absorption. CS also works as an antioxidant and protects the cells from oxidative damage. In addition, CS has no adverse effects on bacterial and fungal alpha diversity in ruminants. Dietary supplementation of CS enhances the population of beneficial microorganisms. Still, no data is available on the use of CS on reproductive performance in ruminants, so there is a need to evaluate the effects of using CS in breeding animals for an extended period. In this review, the action mode of CS was updated according to recently published data to highlight the beneficial effects of using CS in ruminants.

Single-cell transcriptomics identify TNFRSF1B as a novel T-cell exhaustion marker for ovarian cancer.

BACKGROUND: Ovarian cancer (OC) patients routinely show poor immunotherapeutic response due to the complex tumour microenvironment (TME). It is urgent to explore new immunotherapeutic markers. METHODS: Through the single-cell RNA sequencing (scRNA-seq) analyses on high-grade serous OC (HGSOC), moderate severity borderline tumour and matched normal ovary, we identified a novel exhausted T cells subpopulation that related to poor prognosis in OC. Histological staining, multiple immunofluorescences, and flow cytometry were applied to validate some results from scRNA-seq. Furthermore, a tumour-bearing mice model was constructed to investigate the effects of TNFRSF1B treatment on tumour growth in vivo. RESULTS: Highly immunosuppressive TME in HGSOC is displayed compared to moderate severity borderline tumour and matched normal ovary. Subsequently, a novel exhausted subpopulation of CD8+ TNFRSF1B+ T cells is identified, which is associated with poor survival. In vitro experiments demonstrate that TNFRSF1B is specifically upregulated on activated CD8+ T cells and suppressed interferon-γ secretion. The expression of TNFRSF1B on CD8+ T cells is closely related to OC clinical malignancy and is a marker of poor prognosis through 140 OC patients' verification. In addition, the blockade of TNFRSF1B inhibits tumour growth via profoundly remodeling the immune microenvironment in the OC mouse model. CONCLUSIONS: Our transcriptomic results analyzed by scRNA-seq delineate a high-resolution snapshot of the entire tumour ecosystem of OC TME. The major applications of our findings were an exhausted subpopulation of CD8+ TNFRSF1B+ T cells for predicting OC patient prognosis and the potential therapeutic value of TNFRSF1B. These findings demonstrated the clinical value of TNFRSF1B as a potential immunotherapy target and extended our understanding of factors contributing to immunotherapy failure in OC.

Targeting oncogenic KRAS in non-small cell lung cancer with EGFR aptamer-conjugated multifunctional RNA nanoparticles.

KRAS mutations are one of the most common oncogenic driver mutations in human cancers, including non-small cell lung cancer (NSCLC), and have established roles in cancer pathogenesis and therapeutic resistance. The development of effective inhibitors of mutant KRAS represents a significant challenge. Three-way junction (3WJ)-based multi-functional RNA nanoparticles have the potential to serve as an effective in vivo siRNA delivery platform with the ability to enhance tumor targeting specificity and visualize biodistribution through an imaging moiety. Herein, we assembled novel EGFRapt-3WJ-siKRASG12C mutation targeted nanoparticles to target EGFR-expressing human NSCLC harboring a KRASG12C mutation to silence KRASG12C expression in a tumor cell-specific fashion. We found that EGFRapt-3WJ-siKRASG12C nanoparticles potently depleted cellular KRASG12C expression, resulting in attenuation of downstream MAPK pathway signaling, cell proliferation, migration/invasion ability, and sensitized NSCLC cells to chemoradiotherapy. In vivo, these nanoparticles induced tumor growth inhibition in KRASG12C NSCLC tumor xenografts. Together, this study suggests that the 3WJ pRNA-based platform has the potential to suppress mutant KRAS activity for the treatment of KRAS-driven human cancers, and warrants further development for clinical translation.

Influence of probiotic supplementation on the growth performance, plasma variables, and ruminal bacterial community of growth-retarded lamb.

Introduction: Growth-retarded lambs would reduce the economic incomes of sheep farming. Nutritional interventions are supposed to promote gastrointestinal health and the compensatory growth of growth-retarded lambs. This study evaluated the effects of probiotic supplementation on the growth performance, plasma characteristics and ruminal bacterial community of growth-retarded lambs. Methods: Twenty-four 50-days old male Hu lambs, including 8 healthy lambs (13.2 ± 1.17 kg) and 16 growth-retarded lambs (9.46 ± 0.81 kg), were used in this study. The 8 healthy lambs were fed the basal diet and considered the positive control (GN), and the other 16 growth-retarded lambs were randomly assigned into 2 groups (basal diet without probiotic [negative control, GR] and basal diet supplementation with 1 g/kg concentrate feed probiotic [GRP]), with each group having 4 replicate pens. The feeding trial lasted for 60 days with 7 days for adaptation. Results: The results showed that dietary supplementation with probiotic increased (p < 0.05) the average daily gain and dry matter intake of growth-retarded lambs. For growth-retarded lambs, supplementation with probiotic increased (p < 0.05) the activities of superoxide dismutase and glutathione peroxidase, as well as the concentrations of growth hormone and immunoglobulin G. Furthermore, the highest (p < 0.05) concentrations of interleukin-6, interferon-gamma and tumor necrosis factor alpha were observed in the GR group. The concentrations of total volatile fatty acids and acetate in growth-retarded lambs were increased by probiotic supplementation (p < 0.05). The relative abundances of Ruminococcus, Succiniclasticum and Acidaminococcus were lower (p < 0.05) in growth-retarded lambs. However, probiotic supplementation increased (p < 0.05) the relative abundances of these three genera. Discussion: These results indicate that dietary supplementation with probiotic are promising strategies for improving the growth performance of growth-retarded lambs by enhancing immunity and altering the ruminal microbiota.

Single-cell transcriptomics in ovarian cancer identify a metastasis-associated cell cluster overexpressed RAB13.

BACKGROUND: Metastasis, the leading cause of cancer-related death in patients diagnosed with ovarian cancer (OC), is a complex process that involves multiple biological effects. With the continuous development of sequencing technology, single-cell sequence has emerged as a promising strategy to understand the pathogenesis of ovarian cancer. METHODS: Through integrating 10 × single-cell data from 12 samples, we developed a single-cell map of primary and metastatic OC. By copy-number variations analysis, pseudotime analysis, enrichment analysis, and cell-cell communication analysis, we explored the heterogeneity among OC cells. We performed differential expression analysis and high dimensional weighted gene co-expression network analysis to identify the hub genes of C4. The effects of RAB13 on OC cell lines were validated in vitro. RESULTS: We discovered a cell subcluster, referred to as C4, that is closely associated with metastasis and poor prognosis in OC. This subcluster correlated with an epithelial-mesenchymal transition (EMT) and angiogenesis signature and RAB13 was identified as the key marker of it. Downregulation of RAB13 resulted in a reduction of OC cells migration and invasion. Additionally, we predicted several potential drugs that might inhibit RAB13. CONCLUSIONS: Our study has identified a cell subcluster that is closely linked to metastasis in OC, and we have also identified RAB13 as its hub gene that has great potential to become a new therapeutic target for OC.

Convergent synthesis of triarylamines via Ni-catalyzed dual C(sp2)-H amination from benzamides with benzohydroxamic acids.

An unprecedented method of nickel-catalyzed dual C(sp2)-H amination of N-quinolylbenzamides with benzohydroxamic acids is developed to access triarylamines in one pot. For the first time, broad-spectrum hydroxylamine is employed as an amino source for C-H amination, featuring good chemo-selectivity and functional group tolerance. Furthermore, the catalytic system could be further extended to N-(pivaloyloxy)benzamide, dioxazolone, isocyanate and aniline for C-H amination.

Integrating single-cell RNA sequencing and prognostic model revealed the carcinogenicity and clinical significance of FAM83D in ovarian cancer.

Background: Ovarian cancer (OC) is a fatal gynecological tumor with high mortality and poor prognosis. Yet, its molecular mechanism is still not fully explored, and early prognostic markers are still missing. In this study, we assessed carcinogenicity and clinical significance of family with sequence similarity 83 member D (FAM83D) in ovarian cancer by integrating single-cell RNA sequencing (scRNA-seq) and a prognostic model. Methods: A 10x scRNA-seq analysis was performed on cells from normal ovary and high-grade serous ovarian cancer (HGSOC) tissue. The prognostic model was constructed by Lasso-Cox regression analysis. The biological function of FAM83D on cell growth, invasion, migration, and drug sensitivity was examined in vitro in OC cell lines. Luciferase reporter assay was performed for binding analysis between FAM83D and microRNA-138-5p (miR-138-5p). Results: Our integrative analysis identified a subset of malignant epithelial cells (C1) with epithelial-mesenchymal transition (EMT) and potential hyperproliferation gene signature. A FAM83D+ malignant epithelial subcluster (FAM83D+ MEC) was associated with cell cycle regulation, apoptosis, DNA repair, and EMT activation. FAM83D resulted as a viable prognostic marker in a prognostic model that efficiently predict the overall survival of OC patients. FAM83D downregulation in SKOV3 and A2780 cells increased cisplatin sensitivity, reducing OC cell proliferation, migration, and invasion. MiR-138-5p was identified to regulate FAM83D's carcinogenic effect in OC cells. Conclusions: Our findings highlight the importance of miR-138 -5p/FAM83D/EMT signaling and may provide new insights into therapeutic strategies for OC.

Effects of Dietary Coated Lysozyme on the Growth Performance, Antioxidant Activity, Immunity and Gut Health of Weaned Piglets.

The purpose of this study was to evaluate the effects of dietary coated lysozyme on growth performance, serum biochemical indexes, antioxidant activity, digestive enzyme activity, intestinal permeability, and the cecal microbiota in weaned piglets. In total, 144 weaned Large White × Landrace piglets were divided into six treatment groups, with 3 replicates and 8 piglets per replicate: CN, a basal diet; CL-L, CL-M, and CL-H, basal diet supplemented with 100, 150, 500 mg/kg coated lysozyme; UL, basal diet supplemented with 150 mg/kg lysozyme; and Abs, basal diet supplemented with 150 mg/kg guitaromycin for 6 weeks. Compared with the CN and UL diets, dietary CL-H inclusion increased the average daily gain (ADG) and decreased the feed/gain (F/G) ratio of piglets (p < 0.05). The addition of 500 mg/kg coated lysozyme to the diet significantly increased the total protein (TP) and globulin (Glob) plasma levels of weaned piglets (p < 0.05). Supplementation with 500 mg/kg coated lysozyme significantly increased the serum IgM concentration and increased lipase activity in the duodenum (p < 0.05). The addition of coated lysozyme and lysozyme significantly decreased the malondialdehyde (MDA) content, while the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) levels all increased (p < 0.05). High-throughput sequencing results showed that CL-H treatment effectively improved the intestinal microbiome. The relative abundance of Terrisporobacter in the CL-H and CL-M groups was significantly lower than that in the other groups (p < 0.05). LEfSe analysis results showed that the relative abundance of Coprococcus_3 was higher in the CL-M treatment group. The marker species added to the CL-H treatment group was Anaerofilum. In summary, as a potential substitute for feed antibiotics, lysozyme is directly used as a dietary additive, which is inefficient. Therefore, we used palm oil as the main coating material to coat lysozyme. Lysozyme after coating can more effectively improve the growth performance of piglets by improving the intestinal flora, improving the activity of digestive enzymes, reducing the damage to intestinal permeability and oxidative stress in piglets caused by weaning stress, and improving the immunity of piglets.

Inhibition of Chitosan with Different Molecular Weights on Barley-Borne Fusarium graminearum during Barley Malting Process for Improving Malt Quality.

There are many Fusarium graminearum contaminations in barley that are often associated with malt and beer quality issues. Thus, it is important to find a biological antifungal agent to prevent the growth of F. graminearum during malting. Minimum inhibition concentration (MIC) of chitosan for mycelial growth and spore germination of F. graminearum was 2.6 g/L and 1.6 g/L, respectively, indicating that the F. graminearum strain was highly sensitive toward chitosan. Chitosan with a molecular weight of 102.7 kDa was added at 0.5 g/kg during the first steeping stage, resulting in the maximum inhibition rate of F. graminearm in barley. The biomass of F. graminearm and deoxynivalenol content in the infected barley at the end of germination with 0.5 g/kg chitosan treatment were decreased by 50.7% and 70.5%, respectively, when compared with the infected barley without chitosan. Chitosan could remove the negative effects of F. graminearm infection on barley germination and malt quality, which makes the application of chitosan during the steeping process as a potential antifungal agent in the malting process to protect from F. graminearum infection.

Single-cell RNA-seq highlights a specific carcinoembryonic cluster in ovarian cancer.

Expounding the heterogeneity for ovarian cancer (OC) with the cognition in developmental biology might be helpful to search for robust prognostic markers and effective treatments. In the present study, we employed single-cell RNA-seq with ovarian cancers, normal ovary, and embryo tissue to explore their heterogeneity. Then the differentiation process of clusters was explored; the pivotal cluster and markers were identified. Furthermore, the consensus clustering algorithm was used to explore the different clinical phenotypes in OC. At last, a prognostic model was construct and used to assess the prognosis for OCs. As a result, eight diverse clusters were identified, and the similarity existed in some clusters between embryo and tumours based on their gene expression. Meaningfully, a subtype of malignant epithelial cluster, PEG10+ EME, was associated with poor survival and was an intermediate stage of embryo to tumour. PEG10 was a CSC marker and might influence CSC self-renewal and promote cisplatin resistance via NOTCH pathway. Utilising specific gene profiles of PEG10+ EME based on public data sets, four phenotypes with different survival and clinical response to anti-PD-1/PD-L1 immunotherapy were identified. These insights allowed for the investigation of single-cell transcriptome of OCs and embryo, which advanced our current understanding of OC pathogenesis and resulted in promising therapeutic strategies.

Single-cell analysis revealed that IL4I1 promoted ovarian cancer progression.

BACKGROUND: Ovarian cancer was one of the leading causes of female deaths. Patients with OC were essentially incurable and portends a poor prognosis, presumably because of profound genetic heterogeneity limiting reproducible prognostic classifications. METHODS: We comprehensively analyzed an ovarian cancer single-cell RNA sequencing dataset, GSE118828, and identified nine major cell types. Relationship between the clusters was explored with CellPhoneDB. A malignant epithelial cluster was confirmed using pseudotime analysis, CNV and GSVA. Furthermore, we constructed the prediction model (i.e., RiskScore) consisted of 10 prognosis-specific genes from 2397 malignant epithelial genes using the LASSO Cox regression algorithm based on public datasets. Then, the prognostic value of Riskscore was assessed with Kaplan-Meier survival analysis and time-dependent ROC curves. At last, a series of in-vitro assays were conducted to explore the roles of IL4I1, an important gene in Riskscore, in OC progression. RESULTS: We found that macrophages possessed the most interaction pairs with other clusters, and M2-like TAMs were the dominant type of macrophages. C0 was identified as the malignant epithelial cluster. Patients with a lower RiskScore had a greater OS (log-rank P < 0.01). In training set, the AUC of RiskScore was 0.666, 0.743 and 0.809 in 1-year, 3-year and 5-year survival, respectively. This was also validated in another two cohorts. Moreover, downregulation of IL4I1 inhibited OC cells proliferation, migration and invasion. CONCLUSIONS: Our work provide novel insights into our understanding of the heterogeneity among OCs, and would help elucidate the biology of OC and provide clinical guidance in prognosis for OC patients.

Single-Cell RNA-Sequencing Portraying Functional Diversity and Clinical Implications of IFI6 in Ovarian Cancer.

Ovarian cancer (OC) is one of the most lethal gynecologic malignancies. Most patients die of metastasis due to a lack of other treatments aimed at improving the prognosis of OC patients. In the present study, we use multiple methods to identify prognostic S1 as the dominant subtype in OC, possessing the most ligand-receptor pairs with other cell types. Based on markers of S1, the consensus clustering algorithm is used to explore the clinical treatment subtype in OC. As a result, we identify two clusters associated with distinct survival and drug response. Notably, IFI6 contributes to the cluster classification and seems to be a vital gene in OC carcinogenesis. Functional enrichment analysis demonstrates that its functions involve G2M and cisplatin resistance, and downregulation of IFI6 suppresses proliferation capabilities and significantly potentiates cisplatin-induced apoptosis of OC cells in vitro. To explore possible mechanisms of IFI6 influencing OC proliferation and cisplatin resistance, GSEA is conducted and shows that IFI6 is positively correlated with the NF-κB pathway, which is validated by RT-qPCR. Significantly, we develop a prognostic model including IFI6, RiskScore, which is an independent prognostic factor and presents encouraging prognostic values. Our findings provide novel insights into elucidating the biology of OC based on single-cell RNA-sequencing. Moreover, this approach is potentially helpful for personalized anti-cancer strategies and predicting outcomes in the setting of OC.

Cytoplasmic Localization Isoform of Cyclin Y Enhanced the Metastatic Ability of Lung Cancer via Regulating Tropomyosin 4.

Cyclin Y (CCNY) is a novel cyclin and highly conserved in metazoan species. Previous studies from our and other laboratory indicate that CCNY play a crucial role in tumor progression. There are two CCNY isoform which has different subcellular distributions, with cytoplasmic isoform (CCNYc) and membrane distribution isoform (CCNYm). However, the expression and function of CCNY isoforms is still unclear. We firstly found CCNYc was expressed in natural lung cancer tissue and cells through the subcellular distribution. Co-IP and immunofluorescence showed that both CCNYm and CCNYc could interact with PFTK1. Further studies illustrated that CCNYc but not CCNYm enhanced cell migration and invasion activity both in vivo and vitro. The function of CCNYc could be inhibited by suppression of PFTK1 expression. In addition, our data indicated that tropomyosin 4 (TPM4), a kind of actin-binding proteins, was down-regulated by suppression of CCNY. F-actin assembly could be controlled by CCNYc as well as PFTK1 and TPM4. As a result, CCNY was mainly expressed in lung cancer. CCNYc could promote cell motility and invasion. It indicated that CCNYc/PFTK1 complex could promote cell metastasis by regulating the formation of F-actin via TPM4.

Non-Small-Cell Lung Cancer Regression by siRNA Delivered Through Exosomes That Display EGFR RNA Aptamer.

Lung cancer is the second most common cancer in both men and women and is the leading cause of cancer death in the United States. The development of drug resistance to commonly used chemotherapeutics in non-small-cell lung cancer (NSCLC) poses significant health risks and there is a dire need to improve patient outcomes. In this study, we report the use of RNA nanotechnology to display ligand on exosome that was loaded with small interfering RNA (siRNA) for NSCLC regression in animal trials. Cholesterol was used to anchor the ligand targeting epidermal growth factor receptor on exosomes that were loaded with siRNA to silence the antiapoptotic factor survivin. The cytosolic delivery of siRNA overcame the problem of endosome trapping, leading to potent gene knockdown, chemotherapy sensitization, and tumor regression, thus achieving a favorable IC50 of 20 nmol/kg siRNA encapsulated by exosome particles in the in vivo gene knockdown assessment.

Identification of potential markers for differentiating epithelial ovarian cancer from ovarian low malignant potential tumors through integrated bioinformatics analysis.

BACKGROUND: Epithelial ovarian cancer (EOC), as a lethal malignancy in women, is often diagnosed as advanced stages. In contrast, intermediating between benign and malignant tumors, ovarian low malignant potential (LMP) tumors show a good prognosis. However, the differential diagnosis of the two diseases is not ideal, resulting in delays or unnecessary therapies. Therefore, unveiling the molecular differences between LMP and EOC may contribute to differential diagnosis and novel therapeutic and preventive policies development for EOC. METHODS: In this study, three microarray data (GSE9899, GSE57477 and GSE27651) were used to explore the differentially expressed genes (DEGs) between LMP and EOC samples. Then, 5 genes were screened by protein-protein interaction (PPI) network, receiver operating characteristic (ROC), survival and Pearson correlation analysis. Meanwhile, chemical-core gene network construction was performed to identify the potential drugs or risk factors for EOC based on 5 core genes. Finally, we also identified the potential function of the 5 genes for EOC through pathway analysis. RESULTS: Two hundred thirty-four DEGs were successfully screened, including 81 up-regulated genes and 153 down-regulated genes. Then, 5 core genes (CCNB1, KIF20A, ASPM, AURKA, and KIF23) were identified through PPI network analysis, ROC analysis, survival and Pearson correlation analysis, which show better diagnostic efficiency and higher prognostic value for EOC. Furthermore, NetworkAnalyst was used to identify top 15 chemicals that link with the 5 core genes. Among them, 11 chemicals were potential drugs and 4 chemicals were risk factors for EOC. Finally, we found that all 5 core genes mainly regulate EOC development via the cell cycle pathway by the bioinformatic analysis. CONCLUSION: Based on an integrated bioinformatic analysis, we identified potential biomarkers, risk factors and drugs for EOC, which may help to provide new ideas for EOC diagnosis, condition appraisal, prevention and treatment in future.

International trends in ovarian cancer incidence from 1973 to 2012.

PURPOSE: Ovarian cancer is the 7th leading cancer diagnosis and the 8th leading cause of cancer death in women worldwide. We conducted this study to investigate the incidence of ovarian cancer internationally. METHODS: The trends in ovarian cancer incidence were analyzed through the latest data of CI5 over the 40-year period from 21 populations in 4 continents using Joinpoint analysis, ASRs and proportions of different histological subtypes in those populations were also analyzed using volume XI of CI5. RESULTS: ASRs of ovarian cancer were from 7.0 to 11.6 per 100,000 in non-Asia populations during 2008-2012. In Asia, the ASR in Israel (Jews) were the highest, up to 8.1 per 100,000 in the same period. The international trends from 1973 to 2012 showed that ASRs of ovarian cancer were decreasing in 8 of 21 selected populations, whereas ASRs in Slovakia, Spain (Navarra) and China (Shanghai) were increasing. Meanwhile, there are certain differences in the main pathological classification patterns within different regions. In Asia, China (Hong Kong) and Japan both have a higher ASRs and proportions for clear cell and endometrioid carcinomas, while Japan has the highest ASRs and proportions for mucinous carcinomas. CONCLUSION: Although the reasons for those trends were not entirely clear, environmental, reproductive and genetic factors were likely to have led to these patterns. Meanwhile, more attention and further study should be given to the etiological factors of histology-specific ovarian cancer.

An efficient and facile strategy for trifluoromethylation and perfluoroalkylation of isoquinolines and heteroarenes.

An effective and regioselective strategy for trifluoromethylation and perfluoroalkylation of isoquinolines and heteroarenes was developed. By combination of TMSCnF2n+1 (n = 1, 2, 3) with PIFA, the method achieved the corresponding perfluoroalkylated products with broad functional group tolerance.

TOP2A Promotes Tumorigenesis of High-grade Serous Ovarian Cancer by Regulating the TGF-ß/Smad Pathway.

Background: High-grade serous ovarian cancer (HGS) is the most aggressive form of ovarian cancer due to its rapid spread, insidious onset, and early dissemination throughout the abdominal cavity. However, the molecular pathogenesis of HGS remains unclear. This study aimed to identify key pathogenic genes and explore the underlying molecular mechanisms of HGS using bioinformatics analysis and biological experiments. Methods: Two datasets were downloaded from the Gene Expression Omnibus databases to find differentially expressed genes (DEGs) between HGS and normal tissue samples. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were applied to investigate the primary functions of the DEGs. The protein-protein interaction network of the DEGs was constructed, and the interactions of various genes were ranked. Results: Topoisomerase IIα (TOP2A) was identified as the hub gene associated with survival and mutation. Gene Set Enrichment Analysis and Gene Set Variation Analysis were conducted to predict the potential biological functions of TOP2A. Furthermore, the TOP2A expression level was significantly up-regulated in HGS cell lines, SKOV3 and HEY. Moreover, the proliferation, migration, and invasion capacities of SKOV3 and HEY cells were strongly suppressed after TOP2A knockdown. In addition, the levels of phosphorylated Smad2 and Smad3, the key members of the transforming growth factor-ß (TGF-ß)/Smad pathway that regulate HGS tumorigenesis, strongly decreased after knockdown of TOP2A. Conclusions: This study identified that TOP2A was up-regulated in HGS, and it accelerated HGS progression via the TGF-ß/Smad pathway. The findings provided a blueprint for TOP2A serving as a therapeutic target and a treatment response prediction biomarker for HGS.