Knowledge mapping and research trends of exosomes in pancreatic cancer: a bibliometric analysis and review (2013-2023).

Objective: This review aims to provide a quantitative and qualitative bibliometric analysis of literature from 2013 to 2023 on the role of exosomes in PC, with the goal of identifying current trends and predicting future hotspots. Methods: We retrieved relevant publications concerning exosomes in PC, published between 2013 and 2023, from the Web of Science Core Collection. Bibliometric analyses were conducted using VOSviewer(1.6.19), CiteSpace(6.2.R4), and Microsoft Excel (2019). Results: A total of 624 papers were analyzed, authored by 4017 researchers from 55 countries/regions and 855 institutions, published in 258 academic journals. China (n=285, 34.42%) and the United States (n=183, 24.87%) were the most frequent contributors and collaborated closely. However, publications from China had a relatively low average number of citations (41.45 times per paper). The output of Shanghai Jiao Tong University ranked first, with 28 papers (accounting for 4.5% of the total publications). Cancers (n=31, 4.9%); published the most papers in this field. Researcher Margot Zoeller published the most papers (n=12) on this topic. Research hotspots mainly focused on the mechanisms of exosomes in PC onset and progression, the role of exosomes in PC early diagnosis and prognosis, exosomes promote the development of PC chemoresistance, and potential applications of exosomes as drug carriers for PC therapies. We observed a shift in research trends, from mechanistic studies toward clinical trials, suggesting that clinical applications will be the focus of future attention. Emerging topics were pancreatic stellate cells, diagnostic biomarkers, mesenchymal stem cells, extracellular vesicles. Conclusion: Our scientometric and visual analysis provides a comprehensive overview of the literature on the role of exosomes in PC published during 2013-2023. This review identifies the frontiers and future directions in this area over the past decade, and is expected to provide a useful reference for researchers in this field.

Key factors capturing the willingness to use automated vehicles for travel in China.

With the continuous advancement of technology, automated vehicle technology is progressively maturing. It is crucial to comprehend the factors influencing individuals' intention to utilize automated vehicles. This study examined user willingness to adopt automated vehicles. By incorporating age and educational background as random parameters, an ordered Probit model with random parameters was constructed to analyze the influential factors affecting respondents' adoption of automated vehicles. We devised and conducted an online questionnaire survey, yielding 2105 valid questionnaires. The findings reveal significant positive correlations between positive social trust, perceived ease of use, perceived usefulness, low levels of perceived risk, and the acceptance of automated vehicles. Additionally, our study identifies extraversion and openness as strong mediators in shaping individuals' intentions to use automated vehicles. Furthermore, prior experience with assisted driving negatively impacts people's inclination toward embracing automated vehicles. Our research also provides insights for promoting the adoption of automated vehicles: favorable media coverage and a reasonable division of responsibilities can enhance individuals' intentions to adopt this technology.

Effect of beta-cypermethrin on the reproductive capacity of female mice in advanced age.

The aim of the present study was to investigate whether exposure to pesticides beta-cypermethrin (ß-CYP) harms the reproductive capacity of advanced-age female mice. The results evidenced that peri-implantation ß-CYP exposure significantly reduced the number of fetuses per advanced-age female in the first litter, and the number and weight of implantation sites. The levels of decidualization markers were significantly reduced in ß-CYP-administered advanced-age mice. Lower expression of Pcna, Cdk6, Foxo1, Ki67, and p62 protein and mRNA was found in the decidua of ß-CYP-treated advanced-age mice. The levels of Bax, cleaved caspase-3, Lc3a/b, Atg, mTOR, and p-mTOR protein, and the ratio of p-mTOR/mTOR protein expression were clearly downregulated by peri-implantation ß-CYP exposure. These results indicated that peri-implantation ß-CYP exposure may elevate the decline in reproductive capacity of early pregnant mice in advanced age.

Toxicity mechanism of peri-implantation pesticide beta-cypermethrin exposure on endometrial remodeling in early pregnant mice.

Beta-cypermethrin (ß-CYP) is a universally used pyrethroid pesticide with adverse effects on human health. ß-CYP may impair endometrial remodeling in mice; however, the mechanism remains largely unknown. Endometrial remodeling plays a vital role in embryonic development and the maintenance of pregnancy. Therefore, we explored the mechanism by which peri-implantation ß-CYP administration reduces uterine remodeling in pregnant mice. The C57BL/6 J pregnant mice were administered a dose of 20 mg/kg.bw. d ß-CYP via oral gavage once daily from day 1 of gestation (GD1) to GD7. Molecular markers of endometrial remodeling, stromal cell proliferation, cell cycle regulation, and the PI3K/Akt/mTOR signaling pathway were evaluated in the decidual tissue of the uterus on GD7. An in vivo pseudopregnancy mouse model, a pregnant mouse model treated with an mTOR activator and an mTOR inhibitor and an in vitro decidualization model of mouse endometrial stromal cells were used to confirm ß-CYP-induced defective endometrial remodeling and the key molecules expression of PI3K/Akt/mTOR signaling pathway. The results showed that ß-CYP decreased the expression of the endometrial remodeling markers MMP9 and LIF in the uterine decidua. Peri-implantation ß-CYP treatment markedly downregulated the expression of endometrial proliferation markers PCNA and Ki67 and decreased decidua thickness. Correspondingly, peri-implantation ß-CYP exposure upregulated the expression of FOXO1, P57 and p-4E-BP1 in the decidua. Further experiments showed ß-CYP significantly inhibited key molecules in the PI3K/Akt/mTOR pathway: PI3K, p-Akt/Akt, p-mTOR, and p-P70S6K in the uterine decidua. Additional experiments showed that aberrant endometrial remodeling induced by ß-CYP was aggravated by rapamycin (an mTOR inhibitor) and partially reversed by MHY1485 (an mTOR agonist). In summary, our results indicated that a reduction in the PI3K/Akt/mTOR pathway may enhance defective endometrial remodeling by downregulating the proliferation and differentiation of endometrial stromal cells in early pregnant mice exposed to ß-CYP. Our study elucidates the mechanism of defective endometrial remodeling induced by peri-implantation ß-CYP exposure.

Early pregnancy exposure to beta-cypermethrin compromises endometrial decidualisation in mice via downregulation of cyclin D3, CDK4/6, and p21.

Beta-cypermethrin (ß-CYP) is a highly effective broad-spectrum insecticide that can potentially affect female reproduction. However, little is known about the effect of ß-CYP on uterine decidualisation, which is a vital process by which the uterus provides a suitable microenvironment for pregnancy maintenance. Therefore, we focused on the effect and mechanism of ß-CYP on endometrial decidualisation during early pregnancy in mice. The results indicated that the expression levels of HOXA10, BMP2, and IGFBP1 was significantly downregulated in the decidual tissue and primary endometrial stromal cells of pregnant and pseudopregnant mice following ß-CYP treatment. Serum E2 concentration was significantly increased, whereas P4 concentration and oestrogen receptor (ERα) and progesterone receptor (PRA) expression were significantly downregulated following ß-CYP exposure. The number of polyploid decidual cells was lower in the ß-CYP-treated group. Furthermore, ß-CYP significantly downregulated the protein expression levels of CDK4 and CDK6, and the mRNA expression levels of cyclin D3 and p21. The number of foetuses per female in the first litter was markedly reduced following exposure to ß-CYP. In summary, early pregnancy exposure to ß-CYP may result in defective endometrial decidualisation via compromised proliferation of uterine stromal cells and reduced expressions of cyclin D3, CDK4/6, and p21 in mice.

miR-21a inhibits decidual cell apoptosis by targeting Pdcd4.

Decidualization of endometrial stromal cells (ESCs) accompanied with embryo implantation is a key process in mammalian reproduction. Evidence suggests that maintenance of decidual cells function is essential. As a critical part in post-transcriptional gene regulation, microRNAs (miRNAs/miR) have been confirmed to be involved in decidualization. However, whether microRNAs regulate decidual cells function has not been reported. Aiming to clarify the role and potential mechanism of miRNAs in decidual cells, artificial induced decidualization model in mice was established. There are 94 differentially expressed miRNAs (≥two-fold change) between decidualized and non-decidualized tissues, including 60 upregulated and 34 downregulated miRNAs. Of the differentially expressed miRNAs, mmu-miR-21a is up-regulated. RT-qPCR also confirmed the up-regulation of mmu-miR-21a following decidualization in vivo and in vitro, and bioinformatic analysis and luciferase activity assay revealed Pdcd4 to be the target gene of mmu-miR-21a. Inhibition of mmu-miR-21a restrained secretory function of decidual cells induced by mESCs, accompanied with increase of Pdcd4 expression and resulted in the increase of cell apoptosis. In addition, we also determined the expression of hsa-miR-21 and Pdcd4 in human proliferative endometrial tissues and decidua tissues. hsa-miR-21 showed higher expression in human decidua tissues compared with proliferative endometrial tissues, while expression of Pdcd4 was contrary to that of hsa-miR-21. Similarly, cell apoptosis increased significantly in human endometrial stromal cell line in response to inhibition of hsa-miR-21. Collectively, we conclude that mmu-miR-21a/hsa-miR-21 may play a key role in regulating the function of decidual cells by inhibiting cell apoptosis through targeting Pdcd4.

Beta-cypermethrin exposure affects female reproduction by enhancing oxidative stress in mice uterine tissue.

This study aimed to investigate the toxicity mechanism of beta-cypermethrin (beta-CYP) on fertility in female mice. Eighty female mice were randomly assigned to four groups of 20 mice each: one control group and three beta-CYP-treated groups. The control group was administered corn oil only, while the three beta-CYP-treated groups were given corn oil containing 1.38, 2.76, and 5.52 mg/kg bw.d beta-CYP for 180 days through intragastric administration. The results found that the 2.76 and 5.52 mg/kg bw.d beta-CYP significantly decreased the rate of successful pregnancy (p < 0.05). The concentrations of biomarkers related to oxidative stress were significantly elevated, while the concentrations of the endogenic enzymatic antioxidants were significantly decreased by the beta-CYP exposure (all p < 0.05). The expression levels of inflammatory-related molecules and the DNA-protein crosslink coefficient in mice uteri were significantly increased after beta-CYP exposure (all p < 0.05). The concentration of 8-hydroxy-2-deoxyguanosine was significantly increased in the 5.52 mg/kg bw.d beta-CYP group (p < 0.05). These results suggested that beta-CYP exposure significantly decreased female reproduction by enhancing oxidative stress in uterine tissue, which led to the increased inflammatory response and oxidative DNA damage in uterine tissue.

A meta-analytic review of the association between two common SNPs in miRNAs and lung cancer susceptibility.

BACKGROUND: MicroRNAs (miRNAs) are involved in many biological processes, including tumor suppression. Multiple studies have shown an association between the miRNA-196a2 rs11614913 and miRNA-146a rs2910164 polymorphisms and cancer risk. However, the implications of the reported data are debatable and inconclusive. MATERIALS AND METHODS: Relevant articles were retrieved from the PubMed, EMBASE, China National Knowledge Infrastructure, and WanFang databases from January 1, 2007, to April 30, 2017. Studies were assessed based on designated inclusion and exclusion criteria, and data were manually extracted from relevant studies by two investigators. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to explore the association between two single-nucleotide polymorphisms (SNPs) in miRNAs and lung cancer susceptibility. RESULTS: Nine eligible articles were included, consisting of 3,101 cancer cases and 3,234 controls for miRNA-196a2 rs11614913, and 3,483 cases and 3,578 controls for miRNA-146a rs2910164. For studies evaluating miRNA-196a2 rs11614913, significant associations with lung cancer risk were discovered. Overall, the pooled analysis showed that miRNA-196a2 rs11614913 was associated with a decreased cancer risk (CC vs TT: OR = 1.25, 95% CI: 1.09-1.44; CT vs TT: OR = 1.26, 95% CI: 1.03-1.53). For miRNA-146a rs2910164, only the CC genotype was found to be associated with high lung cancer risk (OR = 1.30, 95% CI: 1.13-1.49). Subgroup analyses based on ethnicity, source of control group, and country indicated that there were strong associations between miRNA-146a rs2910164 and cancer risk. CONCLUSION: The results indicated that lung cancer risk was significantly associated with miRNA-196a2 rs11614913 and miRNA-146a rs2910164. These two common SNPs in miRNAs may be potential biomarkers of lung cancer.

Exposure to beta-cypermethrin impairs the reproductive function of female mice.

This study aimed to investigate the effects of beta-cypermethrin (ß-CYP) on female reproductive function and examine the morphology of the uterine endometrium and follicular development. The results found that the rate of successful pregnancy in the ß-CYP-treated groups significantly decreased. The levels of serum E2 and FSH were significantly increased in the ß-CYP-treated groups. The concentrations of serum P and LH were significantly decreased in the ß-CYP-treated groups. The uterine endometrium was damaged and the endometrial pinopode was markedly inhibited. In addition, the total number of follicles of all types was significantly lower in the medium- and high-dose ß-CYP-treated groups. These results suggest that ß-CYP significantly affected the reproductive function of female mice. ß-CYP may have significantly decreased the fertility of female mice by disturbing the reproductive hormone concentrations and inhibiting the development of the endometrium and the endometrial pinopode.

Expression and function of Pdcd4 in mouse endometrium during early pregnancy.

Embryo implantation is a complex process involving synchronised crosstalk between a receptive endometrium and functional blastocysts. Apoptosis plays an important role in this process as well as in the maintenance of pregnancy. In this study, we analysed the expression pattern of programmed cell death 4 (Pdcd4), a gene associated with apoptosis in the mouse endometrium, during early pregnancy and pseudopregnancy by real-time quantitative polymerase chain reaction, in situ hybridisation, Western blotting and immunohistochemistry. The results showed that Pdcd4 was increased along with days of pregnancy and significantly reduced at implantation sites (IS) from day 5 of pregnancy (D5). The level of Pdcd4 at IS was substantially lower than that at interimplantation sites (IIS) on D6 and D7. In addition, Pdcd4 expression in the endometrium was reduced in response to artificially induced decidualisation in vivo and in vitro Downregulation of Pdcd4 gene expression in cultured primary stromal cells promoted decidualisation, while upregulation inhibited the decidualisation process by increasing apoptosis. These results demonstrate that Pdcd4 is involved in stromal cell decidualisation by mediating apoptosis and therefore plays a role in embryo implantation in mice.

Effect of beta-cypermethrin exposure on embryo implantation in mice.

The aim of this study was to investigate the effect of ß-CP on embryo implantation in mice. Forty female mice were randomly assigned to four groups of 10 mice each: one control group and three ß-CP treated groups. The control group was administered corn oil only, while the three ß-CP-treated groups were given corn oil containing 5, 10, and 20 mg/kg bw d ß-CP for 3 months through intragastric administration. The results indicated that the administration of ß-CP decreased the rate of embryo implantation (all p < 0.05), E2 level in the serum, and the expression of Homeobox A10 (HoxA10) protein. In addition, ß-CP significantly increased ERa and PRA protein expression levels. These results suggest that ß-CP can disrupt the balance of E2 and P, influence ERa and PRA expression and their downstream-related molecule Hoxa10, and decrease embryo implantation.

The differential expression of microRNAs between implantation sites and interimplantation sites in early pregnancy in mice and their potential functions.

Embryo implantation is a complex process that involves synchronized crosstalk between a receptive endometrium and a functional blastocyst. It can take place only during the window of implantation, a period when a series of changes in gene expression occur in the endometrium to accept the embryo. As modulators of gene expression, microRNAs (miRNAs) have been identified as regulators of embryo implantation. To better understand how miRNAs regulate implantation and the related molecular mechanisms, we compared the expression profiles of miRNAs and messenger RNAs between implantation sites (IMs) and inter-IMs in the endometrium of pregnant mice on day 5 by microarrays. The results showed that compared with inter-IMs, 30 miRNAs were upregulated and 42 miRNAs (>2-fold) were downregulated at the IMs. By combining the results of the microarray experiments, we found that 20 upregulated pathways and 14 downregulated pathways might be subject to miRNA regulation at IMs. We also found that some miRNAs and their targets may play a key role in implantation.

The toxicity mechanism of sodium fluoride on fertility in female rats.

Recognition of the harmful effects of sodium fluoride (NaF) on human reproduction is increasing, especially as it relates to female reproduction. However, the mechanism by which NaF interferes with female reproduction is unclear. The aims of the present study were to investigate the effects of fluoride exposure on female fertility and to elucidate the mechanisms underlying these effects. Female Sprague-Dawley rats were divided into three groups: one control group and two NaF-treated groups (100 and 200 mg/L in the drinking water for 12 weeks). Several parameters were evaluated, including: (i) fluoride concentrations; (ii) estrogen (E2) and progesterone (P) concentrations; (iii) estrogen receptor alpha protein (ERα); (iv) progesterone receptor (PgR) protein; (v) follicle-stimulating hormone receptor (FSHR) and luteinizing hormone receptor (LHR) protein. The results indicated that administration of NaF lead to significant decreases in E2 and P levels in the serum and in the expression of FSHR protein. In addition, fluoride exposure significantly increased Erα and PgR protein expression levels and LHR protein expression. These results suggest that the reproductive hormone reduction and the abnormalities of related receptor proteins expression are important factors underlying the decreased fertility observed in female rats that have been exposed to NaF.

Effects of sodium fluoride on reproductive function in female rats.

The aim of this study was to investigate the effects of sodium fluoride (NaF) on female reproductive function and examine the morphology of the ovaries and uteri of rats exposed to NaF. Eighty female Sprague-Dawley (SD) rats were divided randomly into four groups of 20: one control group and three NaF treated groups. The three NaF treated groups received 100, 150, and 200 ppm, respectively, of NaF for 6 months via their drinking water, while the control group (GC) received distilled water. The levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), progesterone (P) and estradiol (E2) were measured using an enzyme-linked immunosorbent assay. Pathomorphological evaluation of the uteri and ovaries was conducted after staining with hematoxylin-eosin and immunohistochemistry. The rate of successful pregnancy in the NaF-treated groups declined in a dose-dependent manner. The concentration of reproductive hormones was significantly lower in the three NaF-treated groups, and the endometrium was damaged. The maturation of follicles was inhibited. In addition, the total number of follicles of all types was significantly lower in the NaF-treated groups. These results suggest that female reproductive function is inhibited by NaF and that exposure to NaF causes ovarian and uterine structural damage. NaF may thus significantly reduce the fertility of female rats.

Facile and economical synthesis of an electrochromic copolymer for black based on electropolymerization of thiophene and 3,4-ethylenedioxythiophene.

We report the facile and economical synthesis of an electrochromic copolymer for black based on electrochemical copolymerization of thiophene and 3, 4-ethylenedioxythiophene in boron trifluoride diethyl etherate. The resultant copolymer presents multicolor electrochromism with reversible color change between drab color and blue black. Furthermore, in the polar state the resultant copolymer shows strong and broad absorption in the whole visible region and then exhibits black color. The copolymer presents a transmittance variation of 25% at 522 nm, and corresponding response times for bleaching and coloration are 4.2 and 3.3 s, respectively. Good electrochemical stability can be achieved by the copolymer film, which retains 87% of its original electroactivity after 2000 cycles.

Ultrathin and broadband high impedance surface absorbers based on metamaterial substrates.

An ultrathin and simultaneously broadband high impedance surface absorber based on a metamaterial (MM) substrate is presented at microwave frequencies. The MM substrate is designed using metallic split ring resonators (SRRs) vertically embedded into a dielectric slab. Both the simulated and experimental results display two absorption peaks and an expanded absorption bandwidth of less than -10 dB compared to conventional ultrathin absorbers. By analyzing the field distributions and the substrate impedance characteristics, it is found that this feature is mainly related to the LC resonance of the substrate caused by the embedded SRRs. Our results demonstrate the great feasibility of broadening the absorption bandwidth of the ultrathin high impedance surface absorbers by the MMs incorporation.

Broadband metamaterial absorber based on coupling resistive frequency selective surface.

We report the design, fabrication, and measurement of a broadband metamaterial absorber, which consists of lossy frequency selective surface (FSS) and a metallic ground plane separated by a dielectric layer. The compact single unit cell of the FSS contains crisscross and fractal square patch which couple with each other. Both qualitative analysis by equivalent circuit and accurate numeric calculation show that the coupling between the crisscross and the fractal square patch can enhance the bandwidth with the reflectivity below -10dB in the frequency range of 2-18GHz by producing a third absorption null. In the end, the designed absorber was realized by experiment.