Determination of 16 ultraviolet-absorbing compounds in marine invertebrates by using LC-USI-MS/MS coupled with QuEChERS.

In this study, we examined multiple endocrine-disrupting ultraviolet-absorbing compounds (UVACs) in marine invertebrates used in personal care products and packaging. Modified QuEChERS and liquid chromatography UniSpray ionization tandem mass spectrometry were used to identify 16 UVACs in marine invertebrates. Matrix-matched calibration curves revealed high linearity (r ≥ 0.9929), with limits of detection and quantification of 0.006-1.000 and 0.020-3.000 ng/g w.w., respectively. In oysters, intraday and interday analyses revealed acceptable accuracy (93%-120%) and precision (≤18%), except for benzophenone (BP) and ethylhexyl 4-(dimethylamino) benzoate. Analysis of 100 marine invertebrate samples revealed detection frequencies of 100%, 98%, 89%, 64%, and 100% for BP, 4-hydroxybenzophenone, 4-methylbenzophenone, 4-methylbenzylidene camphor, and benzophenone-3 (BP-3), respectively. BP and BP-3 were detected at concentrations of 4.40-27.39 and < 0.020-0.560 ng/g w.w., respectively, indicating their widespread presence. Overall, our proposed method successfully detected UVACs in marine invertebrates, raising concerns regarding their potential environmental and health effects.

The Systemic Immune-Inflammation Index as an Independent Predictor of Survival in Patients with Locally Advanced Esophageal Squamous Cell Carcinoma Undergoing Neoadjuvant Radiotherapy.

Purpose: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) scheduled for neoadjuvant radiotherapy still have a poor prognosis. This study was to explore the prognostic value of the pretreatment systemic immune-inflammation index (SII) in patients with locally advanced ESCC after neoadjuvant radiotherapy (NRT). Materials and Methods: Eighty-two consecutive patients with ESCC scheduled for neoadjuvant radiotherapy between 2011 and 2017 were enrolled in this study. SII values (SII = platelet × neutrophil/lymphocyte), prognostic nutritional index values (PNI = albumin concentration (g/L) + 5 × total lymphocyte count (109/L)), platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR) were retrospectively collected and calculated before treatment. The Cut-off Finder application was applied to find out the cut-off points of the SII, NLR, PNI and PLR. A regression model was used to examine prognostic factors for overall survival (OS) rates. Results: The median follow-up was 44 months (3 to 83). Sixty patients (73.17%) underwent surgery as scheduled. This study found that factors improving OS were a lower SII (≤916.6 × 109/L) (P=0.040) and neoadjuvant chemoradiotherapy (NCRT) (P=0.034). The patients with a lower SII and NCRT had a better OS (P< 0.001). Moreover, additionally, a higher SII was associated with a lower resectability rate (P=0.035). Conclusion: The SII can predict resectability in ESCC patients following neoadjuvant radiotherapy. Both the SII and neoadjuvant chemoradiotherapy appear to influence OS.

Probabilistic risk assessment of dietary exposure to benzophenone derivatives in cereals in Taiwan.

Benzophenone (BP) and BP derivatives (BPDs) are widely used as ultraviolet (UV) stabilizers in food packaging materials and as photoinitiators in UV-curable inks for printing on food-contact materials. However, our knowledge regarding the sources and risks of dietary exposure to BP and BPDs in cereals remains limited, which prompted us to conduct this study. We measured the levels of BP and nine BPDs-BP-1, BP-2, BP-3, BP-8, 2-hydroxybenzophenone, 4-hydroxybenzophenone, 4-methylbenzophenone (4-MBP), methyl-2-benzoylbenzoate, and 4-benzoylbiphenyl-in three types of cereals (rice flour, oatmeal, and cornflakes; 180 samples in total). A Bayesian Markov-chain Monte Carlo (MC) simulation approach was used for deriving the posterior distributions of BP and BPD residues. This approach helped in addressing the uncertainty in probabilistic distribution for the sampled data under the detection limit. Through an MC simulation, we calculated the daily exposure levels of dietary BP and BPDs and corresponding health risks. The results revealed the ubiquitous presence of BP, BP-3, and 4-MBP in cereals. Older adults (aged >65 years) had the highest (97.5 percentile) lifetime carcinogenic risk for BP exposure through cereals (9.41 × 10-7), whereas children aged 0-3 years had the highest (97.5 percentile) hazard indices for BPD exposure through cereals (2.5 × 10-2). Nevertheless, across age groups, the lifetime carcinogenic risks of BP exposure through cereals were acceptable, and the hazard indices for BPD exposure through cereals were <1. Therefore, BPD exposure through cereals may not be a health concern for individuals in Taiwan.

Prenatal and childhood neonicotinoid exposure and neurodevelopment: A study in a young Taiwanese cohort.

Neonicotinoid insecticides (NEOs) dominate the global pesticide market because of their low cost and effectiveness. However, epidemiological studies regarding the potential adverse health effects of exposure to NEOs before birth and in early childhood are limited. Therefore, this study investigated the associations between NEO exposure before birth and during early childhood and neurodevelopment. A total of 273 mother-child pairs were enrolled in this study. Mothers provided urine samples in the third trimester and breast milk during the first and third months of lactation. Their children provided urine samples and were evaluated for neurodevelopment by using the Bayley Scales of Infant and Toddler Development, Third Edition at 2-3 years (N = 96) and the Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) at 4-6 years (N = 63). The sum of the concentrations of seven NEOs (ΣNEOs) and the relative potency factor of NEOs, based on comparison with imidacloprid (IMIRPF), were used to assess total exposure to NEOs. Multivariate linear regression analyses were conducted to assess the associations between prenatal and childhood exposure to NEOs and neurodevelopment. The results of the analysis revealed that clothianidin (CLO) and thiamethoxam were the most common NEOs to which children in the Taipei metropolitan area were exposed and that exposure concentrations were high in the Taipei metropolitan area. Imidacloprid was the most frequently detected NEO during the postnatal period. Additionally, exposure to NEOs through breast milk was low. Exposure to CLO, ΣNEOs, and IMIRPF in boys aged 4-6 years was negatively correlated with WPPSI-IV Fluid Reasoning Index. The results of this study indicate that exposure during the third trimester to NEOs does not affect neurodevelopment but that childhood exposure to NEOs may, especially for boys. Further studies with larger sample sizes are required to confirm the sex-specific associations between NEO exposure and neurodevelopment.

Comparisons of pharmacokinetics and tissue distribution of six major bioactive components of the herbal pair Alpinia officinarum-Cyperus rotundus in normal and primary dysmenorrhea rats.

The Liangfu formula, as described in 'Liangfang Jiye', is well-known for its efficacy in treating stomach pain, abdominal pain, and dysmenorrhea. This research aimed to investigate the pharmacokinetics and tissue distribution of 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone (DPHA), Galangin, Kaempferide, 5-Hydroxy-1,7-diphenyl-3-heptanone (DPHC), α-Cyperone, and Nootkatone in vivo using an LC-MS/MS method. The method successfully separated the six active components and internal standards (Chrysin and Yakuchinone-A) on an XB-C18 column with a mobile phase of 0.2 ‰ formic acid water-acetonitrile. It demonstrated good linearity with a correlation coefficient (r2) ≥ 0.9911 and a lower limit of quantification (LLOQ) of 5-80 ng/mL for the different components. Precision, accuracy, matrix effects, and recovery rates were within acceptable ranges. Pharmacokinetic analysis revealed significant differences in parameters between primary dysmenorrhea (PD) and normal rats (especially AUC, Tmax, and CLz/F). Tissue distribution showed that the six active components of the herbal pair Alpinia officinarum Hance-Cyperus rotundus L. (HPAC) extract was primarily distributed in the liver, lung, and kidney. This study offers valuable insights into the potential mechanisms of action and drug development for treating PD.

Short-term changes in serum miRNA levels and patient-reported clinical outcomes in myasthenia gravis.

INTRODUCTION/AIMS: The circulating microRNAs (miRNAs) miR-150-5p, miR-30e-5p, and miR-21-5p have been suggested as potential biomarkers for myasthenia gravis (MG); however, the relationships between short-term natural changes of the miRNAs and patient-reported MG outcome scores have not been well-studied. We assessed the short-term fluctuations in miRNA levels and patient-reported outcome measures in MG. METHODS: This prospective cohort study included 39 MG patients with regular follow-ups and unchanged medications at the Neurology outpatient clinic at Uppsala University Hospital. Patients had weekly follow-up visits for 1 month, at which blood samples were drawn, and scores from MG activities of daily living (MG-ADL), MG quality-of-life-15 (MG-QoL15), and Fatigue Severity Scale (FSS) were assessed. Serum levels of miRNA miR-150-5p, miR-30e-5p, and miR-21-5p were analyzed using quantitative real-time PCR. RESULTS: Intra-individual levels of miR-30e-5p and miR-150-5p were stable, whereas a significant reduction in miR-21-5p was observed from week 1 to week 2 (p = .0024) and from week 2 to week 3 (p < .0001). There were intra-individual differences over a short time in MG-ADL, with higher scores in female patients (p = .0281) and a significant reduction from the first to the second weeks (p = .0281), whereas MG-QoL15 and FSS scores were stable. DISCUSSION: The suggested MG biomarkers miR-30e-5p and miR-150-5p were more stable than miR-21-5p over a short time, indicating their short-term stability as biomarkers. Prospective multi-center studies with longer periods of follow-up and matched controls are needed to validate these miRNAs as biomarkers in MG.

Based on Immune Microenvironment and Genomic Status, Exploring Immunotherapy in Advanced Hidradenocarcinoma: A Retrospective Analysis.

There are no standard treatment guidelines for hidradenocarcinoma, and the immune microenvironment and genomic data are very limited. Thus, in this study the immune microenvironment and genomic indicators in hidradenocarcinoma was investigated, and immunotherapy for hidradenocarcinoma was initially explored. Forty-seven hidradenocarcinoma patients were retrospectively collected. Immunohistochemical staining was performed to identify CD3/CD8+ T cells and programmed death ligand-1 expression. In total, 89.4% and 10.6% of samples had Immunoscores of 0-25% and 25-70%. Tumour proportion score distribution was as follows: tumour proportion score < 1% in 72.4%, 1-5% in 17.0%, and > 5% in 10.6%. Combined positive score distribution was as follows: combined positive score < 1 in 63.8%, 1-5 in 14.9%, and > 5 in 21.3%. Next-generation sequencing revealed that TP53 (33%), PI3KCA (22%), and ERBB3 (22%) were the most frequently mutated genes. The PI3K-Akt signalling pathway, growth, and MAPK signalling pathways were significantly enriched. Five patients had a low TMB (< 10 muts/Mb), and 9 patients had MSS. Three patients treated with immune combined with chemotherapy achieved significant tumour regression, and the progression-free survival was 28.8 months. In conclusion, the hidradenocarcinoma immune microenvironment tends to be noninflammatory. Evidence-based targets for targeted therapy are lacking. Immunotherapy combined with chemotherapy may be better for most advanced hidradenocarcinoma patients with a noninflammatory microenvironment.

Safety evaluation of single-sperm cryopreservation technique applied in intracytoplasmic sperm injection.

Intracytoplasmic sperm injection (ICSI) is a technique that directly injects a single sperm into the cytoplasm of mature oocytes. Here, we explored the safety of single-sperm cryopreservation applied in ICSI. This retrospective study enrolled 186 couples undergoing ICSI-assisted pregnancy. Subjects were allocated to the fresh sperm (group A)/single-sperm cryopreservation (group B) groups based on sperm type, with their clinical baseline/pathological data documented. We used ICSI-compliant sperm for subsequent in vitro fertilization and followed up on all subjects. The recovery rate/cryosurvival rate/sperm motility of both groups, the pregnancy/outcome of women receiving embryo transfer, and the delivery mode/neonatal-related information of women with successful deliveries were recorded. The clinical pregnancy rate, cumulative clinical pregnancy rate, abortion rate, ectopic pregnancy rate, premature delivery rate, live birth delivery rate, neonatal birth defect rate, and average birth weight were analyzed. The two groups showed no significant differences in age, body mass index, ovulation induction regimen, sex hormone [anti-Müllerian hormone (AMH)/follicle-stimulating hormone (FSH)/luteinizing hormone (LH)] levels, or oocyte retrieval cycles. The sperm recovery rate (51.72%-100.00%) and resuscitation rate (62.09% ± 16.67%) in group B were higher; the sperm motility in the two groups demonstrated no significant difference and met the ICSI requirements. Group B exhibited an increased fertilization rate, decreased abortion rate, and increased safety versus group A. Compared with fresh sperm, the application of single-sperm cryopreservation in ICSI sensibly improved the fertilization rate and reduced the abortion rate, showing higher safety.

Concentrations, compositional profiles, and health risks of benzophenones among the Taiwanese population based on analysis of 23 daily consumed foods.

In this study, we analyzed the occurrence and distribution of 11 benzophenone-type ultraviolet filters (BPs) in 893 food samples spanning 7 food categories in Taiwan. We conducted a Monte Carlo simulation to determine the carcinogenic and noncarcinogenic risks of BPs. The results indicated that cornflakes had the highest mean level of BPs (103 ng/g), followed by bread (101 ng/g) and pastries (59 ng/g). BP was the most prevalent category, followed by 4-methylbenzophenone (4-MBP), 2-hydroxybenzophenone, and benzophenone-3. Estimation of the lifetime cancer risk (LTCR) of BP (average life expectancy of 80 years) placed them in the 50th and 97.5th percentiles [P50 (P97.5)] LTCR of 1.9 × 10-7 (5.7 × 10-6), indicating that BP in food poses a low renal hazard to the Taiwanese population. The noncarcinogenic risk of BPs was evaluated using a hazard quotient and combined margin of exposure (MOET), revealing a P50 (P97.5) hazard index of < 1 for BP, 4-MBP, and methyl-2-benzoylbenzoate. Although the P50 MOET values for all age groups were within the moderate range of concern, with a more conservative extreme (P2.5), the MOET values for the 0-3, 3-6, and 6-12 age groups fell below 100, indicating a high concern for renal degeneration and hyperplasia.

Tissue Inhibitor of Metalloproteinase 3: Unravelling Its Biological Function and Significance in Oncology.

Tissue inhibitor of metalloproteinases-3 (TIMP3) is vital in regulating several biological processes. TIMP3 exerts antitumour effects via matrix metalloproteinase (MMP)-dependent and MMP-independent pathways. Due to promoter methylation and miRNA binding, TIMP3 expression has been observed to decrease in various cancers. Consequently, the migration and invasion of cancer cells increases. Conflicting results have reported that expression levels of TIMP3 in primary and advanced cancers are higher than those in healthy tissues. Therefore, the role of TIMP3 in cancer biology and progression needs to be elucidated. This review provides an overview of TIMP3, from its biological function to its effects on various cancers. Moreover, gynaecological cancers are discussed in detail. TIMP3 has been associated with cervical adenocarcinoma as well as cancer development in serous ovarian cancer and breast cancer metastasis. However, the relationship between TIMP3 and endometrial cancers remains unclear. TIMP3 may be a useful biomarker for gynaecological cancers and is a potential target for future cancer therapy.

Prenatal to preschool exposure of nonylphenol and bisphenol A exposure and neurodevelopment in young children.

BACKGROUND: Nonylphenol (NP) and bisphenol A (BPA) are produced in large quantities worldwide as multipurpose agents. However, studies on relations between NP and BPA exposure and childhood neurodevelopment are few, and the results are inconsistent. This study aimed to investigate associations between prenatal and early childhood NP and BPA exposure and neurodevelopment in mother-child pairs. METHODS: Pregnant women at 27-38 weeks' gestation were recruited, as were children 2-3 years of age (n = 94) and 4-6 years of age (n = 56) years. Urine was collected to assess NP and BPA exposure. Bayley Scales of Infant and Toddler Development (3rd edition; Bayley-III), Wechsler Preschool and Primary Scale of Intelligence (4th edition), and the Full Scale Intelligence Quotient (WPPSI-IV-FSIQ) were used to assess the neurodevelopment of the children. RESULTS: The detection rate and concentration of NP and BPA in the urine of children 4-6 years old were higher than in those 2-3 years old. Children were divided into a high concentration group (3rd tertile) and a reference group (1st and 2nd tertiles) based on natural log-transformed urine concentration of NP and BPA. Girls' Bayley-III motor scores in the high concentration group were higher than those of the BPA reference group of urine of mothers (ß = 6.85, 95% confidence interval [CI]: 1.58-12.13). Boys' FSIQ in the higher concentration group were significantly lower than those in children 2-3 years old in the NP reference group (ß = -11.29, 95% CI: -18.62 to -3.96) (all, p < 0.05). CONCLUSIONS: Prenatal and childhood exposure to NP and BPA may have different effects on the neurodevelopment of young children, and there are no consistent effects between boys and girls.

Clinical features and prognosis of cardiac metastatic tumors.

BACKGROUND: This study aimed to explore the clinical features and prognosis of cardiac metastatic tumors. In addition, whether continuing antitumor therapy after the development of cardiac metastases can benefit patients and the response of cardiac metastases were investigated. METHODS: A retrospective analysis was conducted on patients with malignancies who were admitted to Fujian Cancer Hospital and Fujian Provincial Hospital from January 2007 to September 2022, and the follow-up period ended in March 2023. Clinical data were gathered, treatment efficacy was evaluated, and survival analysis was performed. RESULTS: After the patients developed cardiac metastasis, the overall 30-day, 3-month, 6-month, and 12-month survival rates were 85.00%, 59.00%, 51.00% and 38.00%, respectively. With continued treatment, the average survival time was 27.33 months (95% confidence interval [CI]: 16.88-37.79), which exceeded the 6.6 months (95% confidence interval [CI]: 0.03-13.69) observed for patients who withdrew from treatment (P < 0.001). The responses of cardiac metastases corresponded to the responses of the primary tumors. Patients with a cardiac response had a median survival time of 55.60 months, which exceeded the 13.40 months observed for those without a cardiac response. However, there was no significant difference (P = 0.375). CONCLUSIONS: In conclusion, continuing antitumor therapy after the development of cardiac metastases can significantly prolong patient survival. Cardiac metastases and primary tumors respond consistently to antitumor treatment. The risk of death due to heart failure in cancer patients with cardiac metastases needs to be further investigated.

Dietary risk assessment of benzophenone derivatives using bread consumption estimates in a Taiwanese population.

Listed as endocrine-disrupting chemicals, benzophenone (BP) and its nine analogues (BPs) are an emerging group of contaminants. The migration of BPs from ultraviolet inks to food has been investigated in many studies; however, few studies have investigated BPs in foods and the risks of human exposure to BPs. We validated a trace and multi-residue method for simultaneously determining 10 BPs, including BP, BP-1, BP-2, BP-3, BP-8, 4-MBP, 2-OHBP, 4-OHBP, M2BB, and PBZ. Eighty-one bread samples were analyzed using stable isotope labeling and ultrahigh-performance liquid chromatography-electrospray ionization tandem mass spectrometry with solid-liquid extraction. We determined the estimated daily intake of BPs, non-cancer risks, and lifetime cancer risks (LTCRs) from daily bread consumption for seven age groups using a Monte Carlo simulation. The method demonstrated robust linearity (R2 ≥ 0.991), low limits of detection (0.04-2 ng/g), and satisfactory precision. The intra- and interday relative standard deviation ranges were 0.6%-9% and 3%-20%, respectively. BP, 4-MBP, 2-OHBP, BP-1, and BP-3 were detected in 97%, 67%, 59%, 24%, and 23% of the samples, respectively. 2-OHBP had the highest mean (range) value of 18.3 (

The downregulation of miR-509-3p expression by collagen type XI alpha 1-regulated hypermethylation facilitates cancer progression and chemoresistance via the DNA methyltransferase 1/Small ubiquitin-like modifier-3 axis in ovarian cancer cells.

BACKGROUND: MicroRNAs are a group of small non-coding RNAs that are involved in development and diseases such as cancer. Previously, we demonstrated that miR-335 is crucial for preventing collagen type XI alpha 1 (COL11A1)-mediated epithelial ovarian cancer (EOC) progression and chemoresistance. Here, we examined the role of miR-509-3p in EOC. METHODS: The patients with EOC who underwent primary cytoreductive surgery and postoperative platinum-based chemotherapy were recruited. Their clinic-pathologic characteristics were collected, and disease-related survivals were determined. The COL11A1 and miR-509-3p mRNA expression levels of 161 ovarian tumors were determined by real-time reverse transcription-polymerase chain reaction. Additionally, miR-509-3p hypermethylation was evaluated by sequencing in these tumors. The A2780CP70 and OVCAR-8 cells transfected with miR-509-3p mimic, while the A2780 and OVCAR-3 cells transfected with miR-509-3p inhibitor. The A2780CP70 cells transfected with a small interference RNA of COL11A1, and the A2780 cells transfected with a COL11A1 expression plasmid. Site-directed mutagenesis, luciferase, and chromatin immunoprecipitation assays were performed in this study. RESULTS: Low miR-509-3p levels were correlated with disease progression, a poor survival, and high COL11A1 expression levels. In vivo studies reinforced these findings and indicated that the occurrence of invasive EOC cell phenotypes and resistance to cisplatin are decreased by miR-509-3p. The miR-509-3p promoter region (p278) is important for miR-509-3p transcription regulation via methylation. The miR-509-3p hypermethylation frequency was significantly higher in EOC tumors with a low miR-509-3p expression than in those with a high miR-509-3p expression. The patients with miR-509-3p hypermethylation had a significantly shorter overall survival (OS) than those without miR-509-3p hypermethylation. Mechanistic studies further indicated that miR-509-3p transcription was downregulated by COL11A1 through a DNA methyltransferase 1 (DNMT1) stability increase. Moreover, miR-509-3p targets small ubiquitin-like modifier (SUMO)-3 to regulate EOC cell growth, invasiveness, and chemosensitivity. CONCLUSION: The miR-509-3p/DNMT1/SUMO-3 axis may be an ovarian cancer treatment target.

Assessment of various conditions for the simultaneous determination of US EPA and EU priority PAHs in coffee samples and their PAHs consumption risk.

The optimal conditions for simultaneous determination of the U.S. Environmental Protection Agency (US EPA) and European Union (EU) priority polycyclic aromatic hydrocarbons (PAHs) in coffee beans and coffee brews were developed. The QuEChERS (quick, easy, cheap, effective, rugged and safe) technology combined with high performance liquid chromatography - temperature-controlled fluorescence detection and gas chromatography - tandem mass spectrometry were used in the investigation. PAHs could be determined in commercially available green coffee beans (possibly caused by environmental contamination), and their PAHs content increased with the degree of roasting. Coffee beans brewed with the coffee machine released more PAHs into their brews than those brewed with the drip bag. The PAHs consumption risk of the brewed coffee samples was not high due to their low PAH level. Nevertheless, the methods of roasting and brewing and the amount of drinking could still be considered to reduce the intake of PAHs.

The Downregulation of miR-509-3p Expression by Collagen Type XI Alpha 1-Regulated Hypermethylation Facilitates Cancer Progression and Chemoresistance via the DNA Methyltransferase 1/Small Ubiquitin-like Modifier-3 Axis in Ovarian Cancer Cells.

Background MicroRNAs are a group of small non-coding RNAs that are involved in development and diseases such as cancer. Previously, we demonstrated that miR-335 is crucial for preventing collagen type XI alpha 1 (COL11A1)-mediated epithelial ovarian cancer (EOC) progression and chemoresistance. Here, we examined the role of miR-509-3p in EOC. Methods The patients with EOC who underwent primary cytoreductive surgery and postoperative platinum-based chemotherapy were recruited. Their clinic-pathologic characteristics were collected, and disease-related survivals were determined. The COL11A1 and miR-509-3p mRNA expression levels of 161 ovarian tumors were determined by real-time reverse transcription-polymerase chain reaction. Additionally, miR-509-3p hypermethylation was evaluated by sequencing in these tumors. The A2780CP70 and OVCAR-8 cells transfected with miR-509-3p mimic, while the A2780 and OVCAR-3 cells transfected with miR-509-3p inhibitor. The A2780CP70 cells transfected with a small interference RNA of COL11A1, and the A2780 cells transfected with a COL11A1 expression plasmid. Site-directed mutagenesis, luciferase, and chromatin immunoprecipitation assays were performed in this study. Results Low miR-509-3p levels were correlated with disease progression, a poor survival, and high COL11A1 expression levels. In vivo studies reinforced these findings and indicated that the occurrence of invasive EOC cell phenotypes and resistance to cisplatin are decreased by miR-509-3p. The miR-509-3p promoter region (p278) is important for miR-509-3p transcription regulation via methylation. The miR-509-3p hypermethylation frequency was significantly higher in EOC tumors with a low miR-509-3p expression than in those with a high miR-509-3p expression. The patients with miR-509-3p hypermethylation had a significantly shorter overall survival (OS) than those without miR-509-3p hypermethylation. Mechanistic studies further indicated that miR-509-3p transcription was downregulated by COL11A1 through a DNA methyltransferase 1 (DNMT1) phosphorylation and stability increase. Moreover, miR-509-3p targets small ubiquitin-like modifier (SUMO)-3 to regulate EOC cell growth, invasiveness, and chemosensitivity. Conclusion The miR-509-3p/DNMT1/SUMO-3 axis may be an ovarian cancer treatment target.

Reduction in Nitrogen Rate and Improvement of Nitrogen Use Efficiency without Loss of Peanut Yield by Regional Mean Optimal Rate of Chemical Fertilizer Based on a Multi-Site Field Experiment in the North China Plain.

It is important to quantify nutrient requirements and optimize fertilization to improve peanut yield and fertilizer use efficiency. In this study, a multi-site field trial was conducted from 2020 to 2021 in the North China Plain to estimate nitrogen (N), phosphorus (P), and potassium (K) uptake and requirements of peanuts, and to evaluate the effects of fertilization recommendations from the regional mean optimal rate (RMOR) on dry matter, pod yield, nutrient uptake, and fertilizer use efficiency. Results show that compared with farmer practice fertilization (FP), optimal fertilization (OPT) based on the RMOR increased peanut dry matter by 6.6% and pod yield by 10.9%. The average uptake rates of N, P, and K were 214.3, 23.3, and 78.4 kg/ha, respectively, with 76.0% N harvest index, 59.8% P harvest index, and 41.4% K harvest index. The OPT treatment increased N, P, and K uptake by 19.3%, 7.3%, and 11.0% compared with FP, respectively. However, the average of yield, nutrition uptake, and harvest indexes of N, P, and K were not significantly affected by fertilization. The peanut required 42.0 kg N, 4.6 kg P, and 15.3 kg K to produce 1000 kg of pods. The OPT treatment significantly improved the N partial factor productivity and N uptake efficiency but decreased the K partial factor productivity and K uptake efficiency. The present study demonstrates that fertilizer recommendations from RMOR improve N use efficiency, and reduce N and P fertilizer application without yield loss in regions with smallholder farmers, and the corresponding estimation of nutrient requirements helps to make peanut fertilization recommendations.

Effect of icariin on the H2O2-induced proliferation of mouse airway smooth muscle cells through miR-138-5p regulating SIRT1/AMPK/PGC-1α axis.

Icariin exerts antioxidative and anti-inflammatory effects and is used in the treatment of bronchial asthma. However, the specific modes of action are uncertain. In this study, we investigated whether icariin could modulate the silencing information regulator 2-related enzyme 1 (SIRT1)/adenosine monophosphate-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma co-activator 1α (PGC-1α) axis by regulating miR-138-5p during H2O2-induced proliferation of mouse airway smooth muscle cells (ASMCs). Primary BALB/c mouse ASMCs were cultured using the tissue block adherence method and were induced with hydrogen peroxide (H2O2; 200 µmol/L) to establish a bronchial asthma ASMC proliferation model. With the aid of Western Blot and quantitative real-time polymerase chain reaction (qRT-PCR) in H2O2-induced ASMCs, the expression of miR-138-5p, SIRT1, AMPK, PGC-1α, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1), collagen I, and collagen III protein and mRNA were investigated. The proliferation rate and activities of superoxide dismutase1 (SOD1), reduced glutathione (GSH), malonaldehyde (MDA), and reactive oxygen species (ROS) in ASMCs were determined. The results suggest Compared with the H2O2-induced group, icariin inhibited the miR-138-5p expression; enhanced SIRT1, p-AMPK, and PGC-1α expression; attenuated MDA activity and ROS level; lowered TGF-ß1, collagen I, and collagen III expression levels; and decreased the proliferation of ASMCs induced by H2O2. The dual-luciferase reporter gene assay results showed that SIRT1 is a regulatory target of miR-138-5p.The results suggest that Icariin could improve the H2O2-induced proliferation of ASMCs. The mechanism may be related to the increase of activation of SIRT1/AMPK/PGC-1α axis by suppressing the expression of miR-138-5p. Thus, SIRT1 is the regulatory target of miR-138-5p.

Exposure to bisphenols, parabens and phthalates during pregnancy and postpartum anxiety and depression symptoms: Evidence from women with twin pregnancies.

BACKGROUND: Women are vulnerable to suffer from the common mental disorders like anxiety and depression during the postpartum period. Exposure to bisphenols, parabens, and phthalates has been linked to anxiety and depression symptoms in the general population. However, little is known about their impacts on postpartum women. OBJECTIVE: To evaluate the effects of individual and joint exposure to 11 nonpersistent chemicals during pregnancy on postpartum anxiety and depression. METHODS: Among 278 mothers from the Wuhan Twin Birth Cohort (WTBC), bisphenols, parabens, and phthalate metabolites were measured in maternal urine samples from each trimester. Self-rating Anxiety Scale (SAS) and Edinburgh Postnatal Depression Scale (EPDS) were administrated at early pregnancy and 1 month and 6 months postpartum to determine anxiety and depression symptoms, respectively. Associations between urinary chemical biomarkers (individual or mixtures) and anxiety and depression symptoms were estimated using multiple informant model and quantile-based g-computation. RESULTS: With adjustment for confounders, one quartile increase in the overall chemical mixture (bisphenols, parabens and phthalate metabolites) during the second trimester was associated with 1.03-point (95% CI: 0.07, 1.99, P = 0.036) higher EPDS score at 1 month postpartum, in which bisphenol A (BPA) and bisphenol F (BPF) contributed the most to the positive association. Consistent effects were also observed in the multiple informant models. We found that second-trimester BPA and BPF exposure individually showed the strongest and significant associations with anxiety and depression symptoms, and some of associations differed across trimesters (Ptrimester-int < 0.05). CONCLUSIONS: Second-trimester nonpersistent chemical exposure was associated with increased postpartum anxiety and depression symptoms.

Desmoid-type fibromatosis mimicking uterine fibroid invade the urinary bladder: A case report and literature review.

OBJECTIVE: Desmoid fibromatosis (DF) is a rare, locally aggressive soft tissue tumor. Computed tomography (CT) and magnetic resonance imaging (MRI) play a critical role in the diagnosis of DF and in developing treatment plans. Currently, observation is the primary therapeutic option for a biopsy-confirmed DF. Here, we present a case of a DF that was misdiagnosed as uterine fibroid before surgery. CASE REPORT: A 36-year-old woman presented with urinary frequency and a palpable lower abdominal mass, which was suspected as uterine fibroid based on sonography and CT. During surgery, an abdominal wall mass was found to be densely adherent to the bladder. Permanent pathology revealed that the tumor was desmoid-type fibromatosis. CONCLUSION: Desmoid tumors often occur in the abdomen, abdominal wall, extremities, head, and neck. Abdominal wall DF involving the rectus abdominis muscles is most commonly observed. Conversely, desmoid tumors involving the bladder are less described. The review of similar cases reported since 1985 showed that partial cystectomy was primarily performed for complete resection.