Global trends and hotspots of ChatGPT in medical research: a bibliometric and visualized study.

Objective: With the rapid advancement of Chat Generative Pre-Trained Transformer (ChatGPT) in medical research, our study aimed to identify global trends and focal points in this domain. Method: All publications on ChatGPT in medical research were retrieved from the Web of Science Core Collection (WoSCC) by Clarivate Analytics from January 1, 2023, to January 31, 2024. The research trends and focal points were visualized and analyzed using VOSviewer and CiteSpace. Results: A total of 1,239 publications were collected and analyzed. The USA contributed the largest number of publications (458, 37.145%) with the highest total citation frequencies (2,461) and the largest H-index. Harvard University contributed the highest number of publications (33) among all full-time institutions. The Cureus Journal of Medical Science published the most ChatGPT-related research (127, 10.30%). Additionally, Wiwanitkit V contributed the majority of publications in this field (20). "Artificial Intelligence (AI) and Machine Learning (ML)," "Education and Training," "Healthcare Applications," and "Data Analysis and Technology" emerged as the primary clusters of keywords. These areas are predicted to remain hotspots in future research in this field. Conclusion: Overall, this study signifies the interdisciplinary nature of ChatGPT research in medicine, encompassing AI and ML technologies, education and training initiatives, diverse healthcare applications, and data analysis and technology advancements. These areas are expected to remain at the forefront of future research, driving continued innovation and progress in the field of ChatGPT in medical research.

PARP1-DOT1L transcription axis drives acquired resistance to PARP inhibitor in ovarian cancer.

BACKGROUND: Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients. METHODS: This study analyzed the expression of DOT1L in PARPi-resistant cell lines compared to sensitive ones and correlated it with clinical outcomes in OC patients. Comprehensive in vitro and in vivo functional experiments were conducted using cellular and mouse models. Molecular investigations, including RNA sequencing, chromatin immunoprecipitation (ChIP) and Cleavage Under Targets and Tagmentation (CUT&Tag) assays, were employed to unravel the molecular mechanisms of DOT1L-mediated PARPi resistance. RESULTS: Our investigation revealed a robust correlation between DOT1L expression and clinical PARPi resistance in non-BRCA mutated OC cells. Upregulated DOT1L expression in PARPi-resistant tissues was associated with diminished survival in OC patients. Mechanistically, we identified that PARP1 directly binds to the DOT1L gene promoter, promoting transcription independently of its enzyme activity. PARP1 trapping induced by PARPi treatment amplified this binding, enhancing DOT1L transcription and contributing to drug resistance. Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. Furthermore, we discovered that combining a DOT1L inhibitor with PARPi demonstrated a synergistic effect in both cell line-derived xenograft mouse models (CDXs) and patient-derived organoids (PDOs). CONCLUSIONS: Our results demonstrate that DOT1L is an independent prognostic marker for OC patients. The PARP1-DOT1L/H3K79me2-PLCG2/ABCB1 axis is identified as a pivotal contributor to PARPi resistance. Targeted inhibition of DOT1L emerges as a promising therapeutic strategy for enhancing PARPi treatment outcomes in OC patients.

Structural Identification of Impurities in Pioglitazone Hydrochloride Preparations by 2D-UHPLC-Q-Exactive Orbitrap HRMS and Their Toxicity Prediction.

Pharmaceutical companies and regulatory agencies have more and more concerns for impurities in pharmaceuticals and their toxicity. In this work, heart-cutting two-dimensional ultrahigh-performance liquid chromatography (2D-UHPLC) in combination with high-resolution mass spectrometry (HRMS) was used, setting HRMS as positive mode of electrospray ionization to identify five impurities in pioglitazone hydrochloride preparations. With the heart-cutting 2D-UHPLC and online desalting technique, the structures of five impurities were deduced in an analysis of MSn data. And three of them, Impurity-2, Impurity-3, and Impurity-5, have never been reported before. The fragmentation patterns of five impurities were proposed on a basis of accurate mass and fragment ions in this study. Since the toxicity of impurities is relevant to their structures, toxicology of all five impurities was predicted by three software tools, and the result showed that these compounds have good safety profile.

Investigation on the synthesis of 24-(R)-hydroxycholesterol.

A facile and novel strategy has been developed for synthesis of 24-(R)-hydroxycholesterol, a key intermediate of tacalcitol, starting from 24-dehydrocholesterol in seven steps with 48.2% overall yield and high diastereomer ratio. Photocatalytic oxidation of olefins by employing inexpensive Rose Bengal as photosensitizer and air as the sole oxidant for the preparation of Δ5,25-3ß-Hydroxycholestadiene-24-one-3-acetate is the key step in this synthetic route. This developed strategy features mild conditions, satisfied total yield and excellent stereoselectivity (24-R/S = 97.7:2.3), providing a novel access to the 24-(R)-hydroxycholesterol.

Photoredox-Catalyzed Tandem Radical Cyclization/Hydroxylation for the Synthesis of 4-Hydroxyalkyl-3,3-difluoro-γ-lactams.

The photoredox-catalyzed radical difluoroalkylation/cyclization/hydroxylation cascade reaction of various 2-bromo-2,2-difluoro-N-arylacetamides containing unactivated alkene moieties has been developed, providing green and efficient access to various 4-hydroxyalkyl-3,3-difluoro-γ-lactams. Control experiments confirmed a radical process, and inexpensive air acted as the sole hydroxy resource. In addition, the highlights of this protocol include good tolerance for a variety functional groups, lower photocatalyst loading, and ease of operation.

Identification of Gene Modules and Hub Genes Associated with Sporisorium scitamineum Infection Using Weighted Gene Co-Expression Network Analysis.

Sporisorium scitamineum is a biotrophic fungus responsible for sugarcane smut disease. To investigate the key genes involved in S. scitamineum infection, we conducted RNA sequencing of sugarcane sprouts inoculated with S. scitamineum teliospores. A weighted gene co-expression network analysis (WGCNA) showed that two co-expressed gene modules, MEdarkturquoise and MEpurple-containing 66 and 208 genes, respectively-were associated with S. scitamineum infection. The genes in these two modules were further studied using Gene Ontology (GO) enrichment analysis, pathogen-host interaction (PHI) database BLASTp, and small secreted cysteine-rich proteins (SCRPs) prediction. The top ten hub genes in each module were identified using the Cytohubba plugin. The GO enrichment analysis found that endoplasmic reticulum-related and catabolism-related genes were expressed during S. scitamineum infection. A total of 83 genes had homologs in the PHI database, 62 of which correlated with pathogen virulence. A total of 21 proteins had the characteristics of small secreted cysteine-rich proteins (SCRPs), a common source of fungal effectors. The top ten hub genes in each module were identified, and seven were annotated as Mig1-Mig1 protein, glycosyl hydrolase, beta-N-acetylglucosaminidase, secreted chorismate mutase, collagen, mRNA export factor, and pleckstrin homology domain protein, while the remaining three were unknown. Two SCRPs-SPSC_06609 and SPSC_04676-and three proteins-SPSC_01958, SPSC_02155, and SPSC_00940-identified in the PHI database were also among the top ten hub genes in the MEdarkturquoise and MEpurple modules, suggesting that they may play important roles in S. scitamineum infection. A S. scitamineum infection model was postulated based on current findings. These findings help to deepen the current understanding of early events in S. scitamineum infection.

Manipulating time-dependent size distribution of sulfur quantum dots and their fluorescence sensing for ascorbic acid.

Unlike the previous commonly used strong alkaline solvent sodium hydroxide, we employ an eco-friendly solvent, ethanol, as a solvent for the preparation of ultra-small-sized sulfur quantum dots (SQDs). Ethanol can disperse bulk sulfur and allow sufficient transfer of large-sized sulfur to smaller-sized SQDs through a one-pot synthesis approach. The SQDs obtained from ethanol as the solvent displays superior photoluminescence properties to those in water and sodium hydroxide. By delicately controlling the reaction conditions, including the amount of bulk sulfur, the reaction time, and the proportion of sulfur to oxidizing reagent, highly blue emissive SQDs with a photoluminescence quantum yield (PLQY) of 7.04% with ultra-high stability for several months can be successfully prepared. Furthermore, we found out that the SQDs display a dynamic photoluminescence properties and varied particle sizes as the reaction time increases, which is possibly realized via the etching-aggregation process. Morevoer, the fluorescence of SQDs-72 can be effectively quenched by CoOOH nanosheets and recovered upon addition of ascorbic acid (AA) by consuming CoOOH nanosheets through the redox reaction, leading to fluorescence recovery. Therefore, a fluorescence "off-on" nanosensor for the detection of AA with a limit of detection (LOD) of 0.85 µM was constructed.

Overexpression of Sugarcane ScDIR Genes Enhances Drought Tolerance in Nicotiana benthamiana.

Dirigent proteins (DIRs) are known to function in lignin biogenesis and to be involved in stress resistance in plants. However, the sugarcane DIRs have not been functionally characterized. In this study, we investigated the DIR-protein-encoding genes in Saccharum spp. (ScDIR) by screening collections of sugarcane databases, monitoring the responses of these genes to drought stress by real-time quantitative PCR, and identifying their heterologous expression in tobacco. Of the 64 ScDIRs identified, four belonging to the DIR-b/d (ScDIR5 and ScDIR11) and DIR-c (ScDIR7 and ScDIR40) subfamilies showed a significant transcriptional response when subjected to drought stress. ScDIR5, ScDIR7, and ScDIR11 are localized in the cell membrane, whereas ScDIR40 is found in the cell wall. The overexpression of these ScDIR genes in tobacco generally increased the drought tolerance of the transgenic lines, with ScDIR7 conferring the highest degree of drought tolerance. The characterization of the physiological and biochemical indicators (superoxide dismutase, catalase, malondialdehyde, and H2O2) confirmed that the ScDIR-overexpressing lines outperformed the wild type. These results demonstrated that specific ScDIRs in sugarcane respond and contribute to tolerance of drought stress, shedding light on potential means of improving drought tolerance in this crop.

Male-specific long non-coding RNA testis-specific transcript, Y-linked 15 promotes gastric cancer cell growth by regulating Wnt family member 1/ß-catenin signaling by sponging microRNA let-7a-5p.

The present study is aimed to investigate the regulatory effects and related mechanism of long non-coding RNA testis-specific transcript, Y-linked 15 (TTTY15) in gastric carcinoma (GC) cell proliferation, migration, invasion, apoptosis and epithelial-mesenchymal transition (EMT). TTTY15 expression in GC tissue samples and cells was detected by quantitative real-time PCR (qRT-PCR), and the correlation between TTTY15 expression and GC clinicopathological indicators was analyzed. Cell counting kit-8 (CCK-8), BrdU, flow cytometry and Transwell assays were performed for detecting GC cell proliferation, migration, invasion and apoptosis. Western blot was performed for detecting the expressions of EMT-associated proteins (N-cadherin and E-cadherin), Wnt family member 1 (Wnt1) protein and ß-catenin protein. Bioinformatics analysis was conducted to predict, and RNA immunoprecipitation (RIP) assay and dual-luciferase reporter gene assay were performed to verify the targeted relationships of microRNA let-7a-5p (let-7a-5p) with TTTY15 and Wnt1 mRNA 3'UTR. It was found that TTTY15 expression was significantly up-regulated in GC tissues and cells, and was associated with advanced TNM stage and poor tumor differentiation. TTTY15 overexpression promoted GC cell proliferation, migration and invasion, the expressions of N-cadherin, Wnt1 and ß-catenin protein, and inhibited the apoptosis and E-cadherin expression, while knocking down TTTY15 had the opposite effects. TTTY15 directly targeted let-7a-5p and negatively regulated its expression. Wnt1 was the target gene of let-7a-5p, and TTTY15 could indirectly and positively regulate Wnt1 expression. In conclusion, TTTY15 promotes GC progression, by regulating the let-7a-5p/Wnt1 axis to activate the Wnt/ß-catenin pathway.

A Plant-Derived Alkanol Induces Teliospore Germination in Sporisorium scitamineum.

Sugarcane smut caused by the basidiomycetes fungus Sporisorium scitamineum is a devastating disease for the sugarcane industry worldwide. As the initial step, the smut teliospores germinate on sugarcane buds, and subsequently, the mycelium infects the bud tissues. However, chemical signals that induce spore germination are still unknown. By comparison of the behavior of the teliospores on the buds of both resistant and susceptible varieties, we found that spore germination rates were significantly lower on the buds of resistant cultivars ZZ1, ZZ6, and ZZ9 than on the susceptible varieties GT42 and ROC22. It was found that the levels of hexacosanol and octacosanol were higher on the buds of smut-susceptible varieties than on the smut-resistant varieties. These observations were extended to the smut-resistant and smut-susceptible sub-genetic populations derived from the cross of ROC25 and YZ89-7. In artificial surface assays, we found that hexacosanol and octacosanol promoted smut teliospore germination. Transcriptome analysis of smut teliospores under the induction by octacosanol revealed that genes in the MAPK signaling pathway and fatty acid metabolism were significantly differentially expressed. Overall, our results provide evidence that alkanol plays important roles in smut teliospore germination and thus could be used as a potential marker for smut resistance in sugarcane breeding programs.

The combination of ursolic acid and empagliflozin relieves diabetic nephropathy by reducing inflammation, oxidative stress and renal fibrosis.

Studies have shown that ursolic acid (UA) and empagliflozin (EM) exert therapeutic effects in the treatment of diabetic nephropathy (DN), but both drugs have disadvantages. This study explores the effect of combining these drugs compared to that of either monotherapy. A diabetic rat model was established by feeding a high-fat diet (HFD) with high-sugar content and administering a low dose of streptozotocin (STZ) via intraperitoneal injection. UA (50 mg/kg/day, po), EM (10 mg/kg/day, po) or both were administered for 8 weeks. The development of DN was determined by observing increases in urine protein, serum creatinine, urea nitrogen, and uric acid and abnormal changes in kidney morphology. UA and EM either alone or in combination can alleviate the increases in blood glucose, glycosylated haemoglobin, blood lipid levels, inflammatory factors (TNF-α, IL-1ß, IL-6), oxidation factors (SOD, MDA, GSH, CAT, NO), renal fibrosis and pro-fibrosis factors (FN, E-cad, MMP-9, TIMP-1, SMA-α, TGF-ß1, SMAD, MAPK). The treatments could also ameliorate DN by preventing the abnormal proliferation of glomerular mesangial cells under high-glucose conditions, aberrant apoptosis and excessive production of reactive oxygen species (ROS). In addition, UA reduces the increase in LDL-L, reverses abnormal bladder morphology and mitigates the increase in colony count caused by EM, and the combination treatment can overcome the disadvantages of the slow hypoglycaemic effect of UA. In short, UA combined with empagliflozin is more effective than either monotherapy in the treatment of DN and can cancel the adverse effects of each other. The protective effect of this regimen on the kidney may be related to reducing inflammation, oxidative stress and renal fibrosis.

BRD4 inhibition sensitizes cervical cancer to radiotherapy by attenuating DNA repair.

Cisplatin-based chemoradiotherapy is the recommended treatment for local advanced cervical cancer, but radioresistance remains one of the most important and unresolved clinical problems. Investigations have revealed aberrant epigenetic modifications as one of the chief culprits for the development of radioresistance. Here, we attempt to identify a radiosensitizer from an epigenetic drug synergy screen and explore the underlying mechanism. We integrated epigenetic inhibitors and radiotherapy in cervical cancer cell lines to identify potential radiosensitizers. We further verified the sensitization effect of the drug and the function of its target gene both in vitro and in vivo. Finally, we validated the clinical significance of its target gene in clinical cervical cancer specimens. We identified JQ1, a BRD4 inhibitor, as a potent radiosensitizer. Functional assays demonstrated that repressing BRD4 activity led to significant radiosensitization and potentiation of DNA damage in cervical cancer cell lines. By using RNA-seq to determine JQ1-mediated changes in transcription, we identified RAD51AP1 as a major BRD4 target gene involved in radiosensitivity. A dual-luciferase reporter assay and ChIP-qPCR showed that BRD4 binds to the promoter region of RAD51AP1 and promotes its transcription, whereas this activity was attenuated by BRD4 inhibition. The in vivo experiments also suggested a synergy between BRD4 inhibition and radiotherapy. High BRD4 expression was found to be related to a worse prognosis and radiation resistance. BRD4 inhibition sensitizes cervical cancer to radiotherapy by inhibiting RAD51AP1 transcription. The combination of JQ1 with radiotherapy merits further evaluation as a therapeutic strategy for improving local control in cervical cancer.

FBW7 suppresses ovarian cancer development by targeting the N6-methyladenosine binding protein YTHDF2.

BACKGROUND: The tumor suppressor FBW7 is the substrate recognition component of the SCF E3-ubiquitin ligase complex that mediates proteolytic degradation of various oncogenic proteins. However, the role of FBW7 in ovarian cancer progression remains inadequately understood. METHODS: IP-MASS, co-IP, immunohistochemistry, and western blotting were used to identify the potential substrate of FBW7 in ovarian cancer. The biological effects of FBW7 were investigated using in vitro and in vivo models. LC/MS was used to detect the m6A levels in ovarian cancer tissues. MeRIP-Seq and RNA-Seq were used to assess the downstream targets of YTHDF2. RESULTS: We unveil that FBW7 is markedly down-regulated in ovarian cancer tissues and its high expression is associated with favorable prognosis and elevated m6A modification levels. Consistently, ectopic FBW7 inhibits ovarian cancer cell survival and proliferation in vitro and in vivo, while ablation of FBW7 empowers propagation of ovarian cancer cells. In addition, the m6A reader protein, YTHDF2, is identified as a novel substrate for FBW7. FBW7 counteracts the tumor-promoting effect of YTHDF2 by inducing proteasomal degradation of the latter in ovarian cancer. Furthermore, YTHDF2 globally regulates the turnover of m6A-modified mRNAs, including the pro-apoptotic gene BMF. CONCLUSIONS: Our study has demonstrated that FBW7 suppresses tumor growth and progression via antagonizing YTHDF2-mediated BMF mRNA decay in ovarian cancer.

The RNA-Binding Protein CELF2 Inhibits Ovarian Cancer Progression by Stabilizing FAM198B.

An increasing number of studies have clarified the functional roles of RNA-binding proteins (RBPs) in driving post-transcriptional mechanisms of cancer progression. In this study, we integrated data from the RBP database and Gene Expression Omnibus (GEO) data with RNA sequencing (RNA-seq) data from 10 ovarian cancer tissues and 8 normal ovarian tissues and identified an RBP, CUGBP- and ETR-3-like family 2 (CELF2). We found that CELF2 expression was downregulated in ovarian cancer and positively correlated with the overall survival (OS) and progression-free survival (PFS) of patients with ovarian cancer. Altered CELF2 expression led to changes in the proliferation, migration, and invasion of ovarian cancer cells in vitro and in vivo. CELF2 expression increased the stability of its target, FAM198B, by binding to AU/U-rich elements (AREs) in the 3' untranslated region (3' UTR). FAM198B knockdown restored the CELF2-mediated suppression of proliferation and migration. We also found that CELF2/FAM198B may repress ovarian cancer progression by inhibiting the mitogen-activated protein kinase/extracellular-regulated protein kinase (MAPK/ERK) signaling pathway. Finally, a curcumin-induced increase in CELF2 expression resulted in increased ovarian cancer cell sensitivity to cisplatin. Our study elucidated a novel mechanism by which the CELF2/FAM198B axis regulates proliferation and metastasis in ovarian cancer, providing novel, potential therapeutic targets for ovarian cancer.

Hepatoprotective effect of gentiopicroside in combination with leflunomide and/or methotrexate in arthritic rats.

AIMS: This study aimed to examine whether gentiopicroside (GPS) could exert hepatoprotective effects on leflunomide (LEF)- and/or methotrexate (MTX)-treated arthritic rats through anti-inflammatory and antioxidant pathways. MAIN METHODS: We observed the external symptoms of joints, analysed serum indicators, measured haematological parameters and mRNA levels, and performed HE staining. KEY FINDINGS: LEF and/or MTX combined with GPS ameliorated oxidative stress by increasing the mRNA levels of the antioxidant gene Nrf2, GCLC, HO-1, and NQO1, increasing the antioxidant enzymes superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT), reducing the oxidant substance malondialdehyde (MDA), reducing the inflammatory response by decreasing the mRNA levels of NF-κB, tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6), and inhibiting the secretion of the pro-inflammatory cytokines TNFα, IL-6, IL-1ß and reducing C-reactive protein (CRP), as well as alleviating the external symptoms of arthritis. SIGNIFICANCE: These results show that GPS plays an antioxidant and anti-inflammatory role in LEF- and/or MTX-treated arthritic rats by affecting the Nrf2 and NF-κB signalling pathways, thus exerting hepatoprotective effects.

A Population-Based Study on Liver Metastases in Women With Newly Diagnosed Ovarian Cancer.

Aim: The purpose of this study was to analyze the incidence, clinical characteristics, prognostic factors and survival of ovarian cancer patients with liver metastases upon initial diagnosis. Methods: Patients with ovarian cancer liver metastases upon initial diagnosis between 2010 and 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression was performed to identify the predictors of the presence of liver metastases in newly diagnosed ovarian cancer patients. Overall survival (OS) was assessed using the Kaplan-Meier method and log-rank test. Univariate and multivariate Cox regression was conducted to determine the independent prognostic factors for OS. Results: A total of 1,744 ovarian cancer patients with liver metastases was identified from the SEER database, accounting for 6.7% of the entire ovarian cancer patients. As to the unique distant organ provided by SEER, liver was the most common metastatic site of ovarian cancer (4.65%). Age, race, laterality, histology, pathological grade, extrahepatic sites, stage of tumor were the predictors of the presence with liver metastases revealed by multivariable logistic regression model. Median OS for the patients with liver metastases at initial diagnosis of ovarian cancer was 16.0 months. Multivariate Cox regression model confirmed race, histology, extrahepatic metastatic sites, surgery and marital status were independent prognostic factors for OS. Conclusion: The study provided population-based estimates of the incidence and prognosis of newly diagnosed ovary cancer patients with liver metastases, which could be potentially used for the risk assessment and individualized treatment.

MALAT1 overexpression promotes the growth of colon cancer by repressing ß-catenin degradation.

Colon cancer is one of the most common types of cancer and more than 80% of colon cancer cases are associated with Wnt-ß-catenin signaling activation. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a multi-functional long non-coding RNA that is overexpressed in many types of cancers, including colon cancer. In this study, MALAT1 and ß-catenin were found to be overexpressed in tumor samples from 62 patients with colon cancer. A positive correlation was identified between MALAT1 levels and ß-catenin protein levels in tumors. MALAT1 was found to upregulate ß-catenin protein levels in HCT116 and LOVO cells without changing the mRNA expression levels. ß-catenin degradation was confirmed to be upregulated in MALAT1-knockdown cells and inhibited in cells overexpressing MALAT1 overexpressing. MALAT1 was then identified as a negative regulator of GSK-3ß; it did so via promotion of H3K27 trimethylation of the promoter region. In conclusion, MALAT1 is an oncogene in colon cancer, which inhibits ß-catenin degradation by upregulating H3K27 trimethylation and repressing GSK-3ß expression.

Clinical features and survival of pregnancy-associated breast cancer: a retrospective study of 203 cases in China.

BACKGROUND: Pregnancy-associated breast cancer (PABC) is an aggressive disease, and since Chinese authority began to encourage childbearing in 2015, the incidence of PABC has increased. This study investigated the characteristics and survival of PABC patients. METHODS: Patients with PABC who underwent surgery at Fudan University, Shanghai Cancer Center between 2005 and 2018 were enrolled. Data concerning the tumor characteristics, maternal state (whether first or non-first pregnancy) and survival outcome were recorded. Pearson Chi-square tests were used to compare the characteristics of the tumors, and Kaplan-Meier methods were used to perform the survival analysis. RESULTS: Overall, 203 PABC patients were recruited. Since 2015, 65.5% of non-first pregnant women were diagnosed with breast cancer, it's 5.7 fold of the incidence of PABC in non-first pregnant women. No significant differences in tumor characteristics were observed between the patients who were in their first pregnancy and those in non-first pregnancy. Among the entire PABC population, luminal B breast cancer accounted for the largest proportion (38.4%), followed by triple-negative breast cancer (TNBC, 30.0%). The distribution of the molecular subtypes of PABC and non-PABC differed (P < 0.001) as follows: in the PABC patients, Luminal B 38.4%, Triple negative breast cancer (TNBC) 30.1%, Human Epidermal Growth Factor Receptor 2 (HER-2) overexpression 15.8%, and Luminal A 10.8%; in the non-PABC patients, Luminal A 50.9%, Luminal B 20.1%, TNBC 17.4%, and HER-2 overexpression 8.0%. The 3-year disease free survival (DFS) of all PABC patients was 80.3%. The 3-year DFS of the patients in the first-pregnancy group was 78.4%, and that of the patients in the non-first-pregnancy group was 83.7% (P = 0.325). CONCLUSIONS: Our study proved that the proportion of women who developed PABC during the second or third pregnancy was extremely high relative to the newborn populations. The patients in the PABC population tended to present more luminal B and TNBC breast cancer than the non-PABC patients.

Circ0004390 promotes cell proliferation through sponging miR-198 in ovarian cancer.

Circular RNAs (circRNAs) are a novel class of non-coding RNAs which play important roles in human diseases and tumor progression. However, the function of circRNAs in ovarian cancer remains to be uncovered. Here we found a large amount of circRNAs that are differentially expressed in ovarian cancer tissues compared with normal ovarian tissues. We further identified one circRNA derived from the LPAR3 gene and termed Circ0004390, which was frequently upregulated in ovarian cancer tissues. The knockdown of Circ0004390 can significantly reduce the proliferation of ovarian cancer cells. We further demonstrated that Circ0004390 may promote cell proliferation by acting as a sponge for the miR-198 family to regulated the MET expression in ovarian cancer cells. The level of Circ0004390 was closely related with overall survival of ovarian cancer patients. Our findings suggested that Circ0004390 regulated ovarian cancer proliferation by miR-198/MET axis, which might provide a potential target for the treatment of ovarian cancer.

Organic matter protection by kaolinite over bio-decomposition as suggested by lignin and solvent-extractable lipid molecular markers.

The formation of organo-mineral complexes is essential in organic matter (OM) stabilization. However, limited studies have been conducted to systematically examine the mineral influence on the decomposition of plant residuals at a molecular level. In this study, pine needles and chestnut leaves were mixed with kaolinite at the weight ratio of 5:1. The controls were plant tissues without kaolinite. All the samples were incubated in the laboratory for one year. Molecular markers, including lignin-derived phenols (e.g. Vanilly units, syringyl units and cinnamyl units) and solvent-extractable lipids (e.g. n-alkanoic acid, n-alkanols and n-alkanes), were analyzed. The concentrations of lignin-derived phenols and lipid compounds were higher in the presence of kaolinite than without kaolinite. Lower degradation indexes, such as (Ad/Al)V (ratio of vanillic acid to vanillin) and CPI (carbon preference index of n-alkanoic acid and n-alkanes), were found in the kaolinite system. These results indicate that kaolinite reduced the OM decomposition. The addition of kaolinite also stabilized some carbohydrates from plants. Furthermore, the degradation of OM led to the generation of persistent free radicals, indicated by electron paramagnetic resonance (EPR) signals. The EPR signals were higher with than without kaolinite. We hypothesize that the adsorption of semiquinone or quinone radicals on kaolinite may limit their reaction with other OM moieties and thus extended their lifetimes. In addition to embedding OM in soil aggregates, our results provide direct evidence of another mineral protective mechanism of soil OM.