Low Concentration Group Research Articles

Silicon supplementation improves biomass and direct defense of ryegrass: A multi-omics study

Silicon (Si) has the potential to promote plant yield and improve their insect resistance, but the direct defense mechanisms associated with the effects of Si on forage grasses and its regulation are not known. In this study, the conditions of silica fertilization nutrition (1 and 3 mmol L−1 recorded as low concentration (LC) and high concentration (HC) groups, respectively) were changed during the seed germination period, which did not significantly affect the seed germination of ryegrass. However, the shoot biomass and insect resistance of ryegrass were significantly increased in the HC group. Comparison of the transcriptional results from RNA-seq assays revealed that the accumulation of ryegrass biomass may be closely related to the silicon intervention in photosynthesis, and the metabolic synthesis of lignin, carbohydrates, and hemicellulose. There was an additive effect of silicon concentration on the regulatory effects of ryegrass at the transcriptional level. Meanwhile, 98 and 1291 differentially expressed genes were assigned to the metabolic process in the LC and HC groups, respectively. Metabolomic results combined with LC-MS analysis showed that Si initiated a direct defense network in ryegrass with Phenylpropanoid biosynthesis as the backbone, and Flavonoid, Flavone and flavonol, and Isoflavonoid biosynthesis as important branches. The relative content of phenolics was significantly up-regulated, especially in the HC group, and most of these phenolics were potent SOS substances, closely related to the physiological disturbances suffered by Spodoptera frugiperda, with inhibitory effects on larval body weight. The above results confirm that silicon promotes an increase in ryegrass yield while initiating its direct defense network against insects, and that silicon is an effective supplement in improving ryegrass yield and insect resistance.

Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer Brachionus plicatilis.

This present study was conducted to provide evidence and an explanation for the apoptosis that occurs in the marine rotifer Brachionus plicatilis when facing 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) stress. Metabolomics analysis showed that aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, and arginine biosynthesis were the top three sensitive pathways to BDE-47 exposure, which resulted in the reduction in the amino acid pool level. Pyrimidine metabolism and purine metabolism pathways were also significantly influenced, and the purine and pyrimidine content were obviously reduced in the low (0.02 mg/L) and middle (0.1 mg/L) concentration groups while increased in the high (0.5 mg/L) concentration group, evidencing the disorder of nucleotide synthesis and decomposition in B. plicatilis. The biochemical detection of the key enzymes in purine metabolism and pyrimidine metabolism showed the downregulation of Glutamine Synthetase (GS) protein expression and the elevation of Xanthine Oxidase (XOD) activity, which suggested the impaired DNA repair and ROS overproduction. The content of DNA damage biomarker (8-OHdG) increased in treatment groups, and the p53 signaling pathway was found to be activated, as indicated by the elevation of the p53 protein expression and Bax/Bcl-2 ratio. The ROS scavenger (N-acetyl-L-cysteine, NAC) addition effectively alleviated not only ROS overproduction but also DNA damage as well as the activation of apoptosis. The combined results backed up the speculation that purine metabolism and pyrimidine metabolism alteration play a pivotal role in BDE-47-induced ROS overproduction and DNA damage, and the consequent activation of the p53 signaling pathway led to the observed apoptosis in B. plicatilis.

Topical Drug Delivery of Concentrated Cabazitaxel in an α-Tocopherol and DMSO Solution.

Topical chemotherapy approaches are relevant for certain skin cancer treatments. This study observes that cabazitaxel (CTX), a broad-spectrum second-generation taxane cytotoxic agent, can be dissolved in α-tocopherol at high concentrations exceeding 100mgmL-1 . 2D nuclear magnetic resonance (NMR) analysis and molecular dynamics (MD) are used to study this phenomenon. The addition of 30% dimethyl sulfoxide (DMSO) to the α-tocopherol/CTX solution improves its working viscosity and enhances CTX permeation through human skin in vitro (over 5µgcm-2 within 24h), while no detectable drug permeates when CTX is dissolved in α-tocopherol alone. In a transepidermal water loss assay, the barrier impairment induced by CTX in 30% DMSO in α-tocopherol, but not in pure DMSO, is reversible 8h after the formulation removal from the skin surface. Antitumor efficacy of the topical CTX formulation is evaluated in nude mice bearing A431 human squamous carcinoma skin cancer xenografts. With topical application of concentrated CTX solutions (75mgmL-1 ), tumor growth is significantly suppressed compared to lower concentration groups (0, 25, or 50mgmL-1 CTX). Taken together, these findings show that topical delivery of CTX using a DMSO and α-tocopherol solvent warrants further study as a treatment for skin malignancies.

Long-term influence of chloroxylenol on anaerobic microbial community: Performance, microbial interaction, and antibiotic resistance gene behaviors

The use of antibacterial and disinfection products is increasing in recent years. Para-chloro-meta-xylenol (PCMX), a widely used antimicrobial agent, has been detected in various environments. Herein, the impacts of PCMX with long-term exposure on anaerobic sequencing batch reactors were investigated. The high concentration (50 mg/L, GH group) PCMX severely inhibited the nutrient removal process, and the low concentration group (0.5 mg/L, GL group) slightly affected the removal efficiency which was recovered after 120 days of adaptation compared to the control group (0 mg/L, GC group). Cell viability tests indicated that PCMX inactivated the microbes. A significant reduction in bacterial α-diversity was observed in the GH but not the GL group. The microbial communities were shifted upon PCMX exposure, among which Olsenella, Novosphingobium, and Saccharibacteria genera incertae Sedis became the predominant genera in the GH groups. Network analyses showed that PCMX significantly reduced the complexity and interactions of the microbial communities, consistent with the negative impacts on bioreactor performance. Real-time PCR analysis indicated that PCMX affected the behavior of antibiotic resistance genes (ARGs), and the relationship between ARGs and bacterial genera gradually became complicated after long-term exposure. Most detected ARGs decreased on Day 60 but increased on Day 120 especially in the GL group, implying the potential risk of environment-relevant concentration of PCMX in the ecosystems. This study provides new insights into the understanding of the impacts and risks of PCMX on wastewater treatment processes.

Serum lipids concentration on prognosis of high-grade glioma.

To investigate the effect of serum lipids concentration on the prognosis of high-grade glioma patients undergoing postoperative radiotherapy. Retrospective analysis of the patients with high-grade glioma who received postoperative Intensity Modulated Radiotherapy between 13 May 2013 and 12 September 2018 was performed. The patients were grouped according to the average values of serum total cholesterol, LDL, and HDL concentration in peripheral blood (before surgery, 6months after therapy). Cox proportional hazards model was performed to determine whether the total cholesterol concentration, LDL concentration, and HDL concentration in peripheral blood before therapy and their changes after therapy were factors influencing the prognosis. The results of COX regression analysis showed that the independent prognostic factors of high-grade glioma patients were pathological grade, the extent of resection, serum cholesterol concentration pre-surgery, and the change of LDL concentration from pre-surgery to post-therapy. The prognosis of patients with high serum total cholesterol concentration before therapy was worse than those of patients with low total cholesterol concentration. The 5-year survival rate and the median survival time of patients with high serum total cholesterol concentration before therapy were 4.9% and 23.6months, but the low cholesterol concentration group were 19.6% and 24.5months, respectively. Besides, the average serum LDL concentration in high-grade glioma patients gradually increased after therapy. The 5-year survival rate of patients and the median survival time with elevated LDL concentration after therapy is 11.8% and 20.4months, but the reduced LDL concentration group was 16.7% and 28.4months, respectively. The total cholesterol and LDL concentration increased significantly after therapy in Grade IV patients while Grade III patients did not. The cholesterol concentration before therapy and LDL concentration change from pre-surgery to post-therapy are the factors that affect the prognosis of high-grade glioma patients who have undergone postoperative radiotherapy. In the final analysis, the high serum cholesterol pre-surgery and the increased in serum LDL concentration from pre-surgery to post-therapy were associated with worse survival of patients.

The effect of EDTA solution on corneal endothelial cells in rabbits

Corneal disease threatens vision globally. Among corneal diseases, calcific band keratopathy has severe effects on vision owing to its unique location. Currently, ethylene diamine tetraacetic acid (EDTA) chelation remains the most important treatment. However, only the safety of low-dose topical EDTA eye drops is well established in humans. Therefore, the purpose of this study was to determine the safe dose range of EDTA for calcific band keratopathy surgery and its toxic effects on rabbit eyes. Rabbits were administered different doses of EDTA solutions (0.50, 0.20, 0.10, 0.05, and 0.01 M) for twenty minutes. In day seven, the rabbits were euthanized and pathological examination was performed for cornea. We found severe corneal edema in 0.50 M group, while milder edema in lower-concentration treated groups. Followed by corneal thickness measurement, the measured values increase to the peak in post-operative three day (0.20 M group) or one day (lower-concentration groups), then decreased. Groups comparison shown significant difference between BSS control group and higher concentration groups (0.20 M and 0.10 M) (P < 0.001) in observation period, but no significance was observed between low concentration and control group in the day seven after surgery (P > 0.05). Confocal microscopy examination suggested, the number of corneal endothelial cells significantly decreased from 3428.6 ± 180.3 cells/mm2 to 2808 ± 80.6 cells/mm2 in the 0.50 M group, while the lower-concentration groups showed lesser toxic effects on corneal endothelial cells. Finally, our histological examination demonstrated inflammation in each experimental group and dose-dependent, compared with control group. Our study found 0.05 M and 0.01 M EDTA solutions had no obvious toxic effect on the corneal endothelium compared with higher concentration. However, further study of EDTA side effect by clinical trials, and therapeutic effect observation with different concentration are necessary.

RNAseq analysis of the drug jian-yan-ling (JYL) using both in vivo and in vitro models

Ethnopharmacological relevanceJian-yan-ling (JYL) is a drug used in traditional Chinese medicine (TCM) prescriptions for the treatment of tumors after radiotherapy and chemotherapy, to effectively alleviate leukocytopenia. However, the genetic mechanisms underlying the function of JYL remain unclear. Aim of the studyThis study aimed to explore the RNA changes and potential biological processes related to the anti-aging or life-extending effects of JYL treatments. Materials and methodsIn vivo treatments were performed using Canton-S Drosophila corresponding to three groups: control, low-concentration (low-conc.), and high-concentration (high-conc.) groups. The low-conc. And the high-conc. Groups were treated with 4 mg/mL JYL and 8 mg/mL JYL, respectively. Thirty Drosophila eggs were placed in each vial, and the third instar larvae and adults 7 and 21 days post-eclosion were collected for RNA sequencing, irrespective of the gender.In vitro treatments were conducted using humanized immune cell lines HL60 and Jurkat, which were divided into 3 groups: control (0 μg/mL JYL), low-concentration (40 μg/mL JYL), and high-concentration (80 μg/mL JYL). The cells were collected after 48 h of each JYL drug treatment. Both the Drosophila and cell samples were analyzed using RNA sequencing. ResultsThe in vivo experiments revealed 74 upregulated genes in the low-concentration group, and CG13078 was a commonly downregulated differential gene, which is involved in ascorbate iron reductase activity. Further analysis of the co-expression map identified the key genes: regulatory particle non-ATPase (RPN), regulatory particle triple-A ATPase (RPT), and tripeptidyl-peptidase II (TPP II). For the in vitro experiments, 19 co-differential genes were compared between different concentrations of the HL 60 cell line, of which three genes were upregulated: LOC107987457 (phostensin-like gene), HSPA1A (heat shock protein family A member 1 A), and H2AC19 (H2A clustered histone 19). In the HL 60 cell line, JYL activated proteasome-related functions. In the Jurkat cell line, there were no common differential genes despite the presence of a dosage-dependent trend. ConclusionsThe RNA-seq results showed that the traditional Chinese medicine JYL has longevity and anti-aging effects, indicating that further investigation is required.

Effect of rhizosphere microorganisms on aflatoxin contamination of maize

The continued large consumption of maize makes it one of the most important food crops worldwide. However, the yield and quality of maize are greatly affected by global warming, and mycotoxin pollution keeps increasing. The effect of environmental factors, especially rhizosphere microorganisms, on mycotoxin pollution of maize is not completely clear, so we carried out relevant studies. In this study, we found that microbial communities inhabiting the maize rhizosphere, which consists of soil particles firmly attached to roots, as well as the soil, have a significant influence on the aflatoxin pollution of maize. The ecoregion and soil properties also had considerable effects on the microbial structure and diversity. The bacterial communities from the rhizosphere soil were profiled using a high-throughput next-generation sequencing method. The ecoregion and soil properties had considerable effects on the microbial structure and diversity. A comparison of the aflatoxin high concentration group with the low concentration group found that bacteria of the phylum Gemmatimonadetes and order Burkholderiales were significantly more abundant in the high concentration samples. Furthermore, these bacteria were significantly correlated with aflatoxin contamination and could aggravate its contamination of maize. The results of these analyses showed that seeding location could cause significant shifts in the root microbiota of maize, and the bacteria enriched in high aflatoxin contamination area soils should attract special concern. These findings will support strategies for improving maize yield and aflatoxin contamination control.

Optimal concentration of Lugol's solution for detecting early esophageal carcinoma: A randomized controlled trial.

Lugol chromoendoscopy is the standard technique to detect an esophageal squamous cell carcinoma (ESCC). However, a high concentration of Lugol's solution can induce mucosal injury and adverse events. We aimed to investigate the optimal concentration of Lugol's solution to reduce mucosal injury and adverse events without degrading image quality. This was a two-phase double-blind randomized controlled trial. In phase I, 200 eligible patients underwent esophagogastroduodenoscopy and then were randomly (1:1:1:1:1) sprayed with 1.2%, 1.0%, 0.8%, 0.6%, or 0.4% Lugol's solution. Image quality, gastric mucosal injury, adverse events, and operation satisfaction were compared to investigate the minimal effective concentration. In phase II, 42 cases of endoscopic mucosectomy for early ESCC were included. The patients were randomly assigned (1:1) to the minimal effective (0.6%) or conventional (1.2%) concentration of Lugol's solution for further comparison of the effectiveness. In phase I, the gastric mucosal injury was significantly reduced in 0.6% group (P<0.05). Furthermore, there was no statistical significance in image quality between 0.6% and higher concentrations of Lugol's solution (P>0.05, respectively). It also showed that the operation satisfaction decreased in 1.2% group compared with the lower concentration groups (P<0.05). In phase II, the complete resection rate was 100% in both groups, while 0.6% Lugol's solution showed higher operation satisfaction (W=554.500, P=0.005). The study indicates that 0.6% might be the optimal concentration of Lugol's solution for early detection and delineation of ESCC, considering minimal mucosal injury and satisfied image. The registry of clinical trials: ClinicalTrials.gov (NCT03180944).

Design, Synthesis and Biological Evaluation of Multi-Target Anti-Cancer Agent PYR26.

This study investigates the synthesis of a new compound, PYR26, and the multi-target mechanism of PYR26 inhibiting the proliferation of HepG2 human hepatocellular carcinoma cells. PYR26 significantly inhibits the growth of HepG2 cells (p < 0.0001) and this inhibition has a concentration effect. There was no significant change in ROS release from HepG2 cells after PYR26 treatment. The mRNA expressions of CDK4, c-Met and Bak genes in HepG2 cells were significantly inhibited (p < 0.05), while mRNA expression of pro-apoptotic factors such as caspase-3 and Cyt c was significantly increased (p < 0.01). The expression of PI3K, CDK4 and pERK proteins decreased. The expression level of caspase-3 protein was increased. PI3K is a kind of intracellular phosphatidylinositol kinase. PI3K signaling pathway is involved in signal transduction of a variety of growth factors, cytokines and extracellular matrix and plays an important role in preventing cell apoptosis, promoting cell survival and influencing cell glucose metabolism. CDK4 is a catalytic subunit of the protein kinase complex and is important for G1 phase progression of the cell cycle. PERK refers to phosphorylated activated ERK, which is translocated from cytoplasm to the nucleus after activation, and then participates in various biological reactions such as cell proliferation and differentiation, cell morphology maintenance, cytoskeleton construction, cell apoptosis and cell canceration. Compared with the model group and the positive control group, the tumor volume of the nude mice in the low-concentration PYR26 group, the medium-concentration group and the high-concentration group was smaller, and the organ volume was smaller than that in the model group and the positive control group. The tumor inhibition rates of low-concentration group PYR26, medium-concentration group and high-concentration group reached 50.46%, 80.66% and 74.59%, respectively. The results showed that PYR26 inhibited the proliferation of HepG2 cells and induced apoptosis of HepG2 cells by down-regulating c-Met, CDK4 and Bak, up-regulating the mRNA expression of caspase-3 and Cyt c genes, down-regulating PI3K, pERK and CDK4 proteins and up-regulating the protein level of caspase-3. In a certain range, with the increase in PYR26 concentration, the tumor growth was slower and the tumor volume was smaller. Preliminary results showed that PYR26 also had an inhibitory effect on the tumors of Hepa1-6 tumor-bearing mice. These results suggest that PYR26 has an inhibitory effect on the growth of liver cancer cells, therefore it has potential to be developed into a new anti-liver cancer drug.

Norvancomycin plasma concentration monitoring in hemodialysis patients with end stage kidney disease: A retrospective cohort study

Blood concentration monitoring plays an important role in the rational use of norvancomycin. However, the reference interval for the norvancomycin plasma concentration in the treatment of infections in hemodialysis patients with end stage kidney disease is undefined. To determine the safe and effective interval for the norvancomycin plasma trough concentration, 39 patients treated with hemodialysis and norvancomycin were analyzed retrospectively. The norvancomycin plasma concentration before hemodialysis was tested as the trough concentration. The associations of the norvancomycin trough concentration with efficacy and adverse reactions were evaluated. No norvancomycin concentration above 20μg/mL was detected. The trough concentration, but not the dose, had a significant effect on the anti-infectious efficacy. Compared with the low norvancomycin trough concentration group (<9.30μg/mL), the high concentration group (9.30-20.0μg/mL) had improved efficacy (OR=15.45, p<0.01) with similar side effects (OR=0.5417, p=0.4069). It is beneficial to maintain the norvancomycin trough concentration at 9.30-20.0μg/mL to achieve a good anti-infectious effect in hemodialysis patients with end stage kidney disease. Plasma concentration monitoring provides a data basis for the individual treatment of infections with norvancomycin in hemodialysis patients.

Transcriptomic analysis of the effect of deferoxamine exposure on the growth, photosynthetic activity and iron transfer of Microcystis aeruginosa

Deferoxamine (DFB) is a trihydroxamic acid siderophore that chelates with iron (Fe) to form iron-siderophore complexes. The existence of siderophores in nature changes the form of iron and affects the absorption and utilization of iron by organisms. However, the relationship between siderophores and the growth of Cyanobacteria is largely unknown. In this study, the cellular and transcriptomic responses to the addition of DFB were investigated. A high concentration of DFB (12 mg/L) significantly inhibited the growth of Cyanobacteria cells, reduced photosynthetic activity, and induced the production of peroxidase, with the highest inhibition rate of algal growth of 74.82%. These indexes were also affected for the low (3 mg/L) and medium concentration (6 mg/L) groups, but this difference is closely related to the growth stage of Cyanobacteria cells. This may be due to competition between the cell-associated iron-binding part/system and the extracellular Fe (Ⅲ)-DFB ligand. Transcriptome results showed that most of the genes involved in iron uptake and transport were down-regulated, and only the fur gene encoding the iron uptake regulator protein was significantly up-regulated. Most genes related to photosynthesis, glycolysis, and fatty acid metabolism were also down-regulated, while the obvious up-regulation of a few genes may be a complex regulation in response to the down-regulation of most genes. These findings will provide important insights into the effects of siderophores on iron bioavailability in algae.

Key Targets and Molecular Mechanisms of the Fat-soluble Components of Ginseng for Lung Cancer Treatment

Objective: To analyze the regulatory effects and key targets of the fat-soluble components of ginseng in lung cancer. Methods: Gas chromatography–mass spectrometry and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform were used to analyze and identify the fat-soluble components of ginseng. Network pharmacology was used to analyze the therapeutic targets of the fat-soluble components of ginseng in lung cancer and screen key proteins. In vitro assays were conducted to verify the effects of the active fat-soluble components of ginseng on proliferation and apoptosis in lung cancer cells and to verify the regulation of key proteins. Results: Ten active fat-soluble components of ginseng were screened for follow-up. Network pharmacology showed 33 overlapping targets between the active fat-soluble components of ginseng and lung cancer, and functional enrichment of the targets showed involvement of response to nitrogen, hormone response, membrane raft, and positive regulation of external stimulus. Pathway enrichment analysis showed vascular endothelial growth factor (VEGF) signaling, adipocyte lipolysis regulation, chronic myelogenous leukemia, endocrine resistance, and NSCLC-related pathways. A protein-protein interaction network was constructed, and the top 10 targets were selected in accordance with their scores. Ultimately, five target genes (EGFR, KDR, MAPK3, PTPN11, and CTNNB1) were selected in combination with literature mining for subsequent experimental verification. Proliferation assays showed that the growth of lung cancer cells was significantly decreased in a concentration-dependent manner in the fat-soluble components of ginseng intervention group compared with controls. Flow cytometry showed that active fat-soluble components of ginseng promoted apoptosis in a concentration-dependent manner in lung cancer cells. Western blot and quantitative real-time PCR showed that levels of the five key proteins and mRNAs were significantly decreased in the intervention group; furthermore, histone protein and mRNA levels were significantly higher in the high-concentration intervention group compared with the low-concentration group. Conclusion: The active fat-soluble components of ginseng inhibited the growth of lung cancer cells and promoted apoptosis. The underlying regulatory mechanisms may be related to signaling pathways involving EGFR, KDR, MAPK3, PTPN11, and CTNNB1.

Response of bacterial communities (Marivita, Marinobacter, and Oceanicaulis) in the phycosphere to the growth of Phaeodactylum tricornutum in different inorganic nitrogen sources

IntroductionIn marine ecosystems, microbial communities are important drivers of material circulation and energy flow. The complex interactions between phytoplankton and bacterial communities constitute one of the most crucial ecological relationships in the marine environment. Inorganic nitrogen can affect the type of relationship between algae and bacteria. However, the quantitative relationship between the bacterial communities, inorganic nitrogen, and phytoplankton remains unclear.MethodsUnder laboratory conditions, we altered the forms (nitrate and ammonium) and amounts of nitrogen sources to study the dynamics of bacterial biomass, diversity, and community structure in the phycosphere of the marine model species Phaeodactylum tricornutum. The bacterial community structure during P. tricornutum growth was analyzed using Illumina HiSeq sequencing of 16S rDNA amplicons.ResultsThe results indicated that inorganic nitrogen concentration was the main factor promoting P. tricornutum biomass growth. The change in the algal biomass would significantly increase the phycosphere bacterial biomass. The bacterial biomass in the algal-bacteria co-culture system was 1.5 ~ 5 times that of the conditional control groups without microalgae under the same culture conditions. The variation of P. tricornutum biomass also affected the bacterial communities in the phycosphere. When P. tricornutum was in the exponential phase (96 ~ 192 h), the bacterial community structure differed between the high- and low-concentration groups. The difference in the bacterial communities over time in the high-concentration groups was more prominent than in the low-concentration groups. Under high-concentration groups (HA and HN), the relative abundance of Marivita and Marinobacter, engaged in the transformation of aquatic inorganic nitrogen, gradually decreased with time. However, the relative abundance of Oceanicaulis, closely related to algal growth, gradually increased with time.DiscussionThe above phenomena might be related to the change in P. tricornutum biomass. Our results explain when and how the phycosphere bacterial communities responded to algal biomass variations. The study provides a foundation for the quantitative relationship among nutrients, microalgae, and bacteria in this system.

Effect of PFOA exposure on diminished ovarian reserve and its metabolism

Owing to its difficulty in degrading and ease of accumulation in the body, perfluorooctanoic acid (PFOA) has a detrimental effect on reproduction. This study aimed to examine the effect of PFOA concentration in follicular fluid during ovulation stimulation on embryo quality and the impact of PFOA exposure on the metabolic components of follicular fluid. This was a single-center prospective study that included 25 patients with diminished ovarian reserve (DOR), 25 with normal ovarian reserve (NOR), and 25 with polycystic ovary syndrome (PCOS). Follicular fluid samples were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry. We demonstrated that the PFOA levels of follicular fluid in the DOR group were higher than those in the NOR group and PCOS group (P < 0.05). PFOA concentration in the PCOS group was negatively correlated with high-quality embryos (P < 0.05). To gain more insight into the impact of PFOA on the metabolic composition of follicular fluid, we classified the DOR group based on the PFOA concentration, for which metabolomic analysis was performed. In the high-concentration PFOA group, there was an increase and a decrease in three and nine metabolites, respectively, compared to that in the low-concentration group. These results suggest that PFOA may alter the metabolic composition of follicular fluid, thus, affecting ovarian reserve function.

Correlation study of male semen parameters and embryo aneuploidy in preimplantation genetic testing for aneuploidy.

The purpose of this study was to evaluate the influence of abnormal semen parameters on embryo aneuploidy based on single nucleotide polymorphism microarray (SNP array). A total of 464 blastocysts from 103 PGT-A cycles were analyzed. The embryo quality and embryo aneuploidy rates were compared between different groups which divided by male semen parameters (sperm concentration, motility, morphology, and DFI) according the WHO criteria (2021). The total blastocysts chromosome aneuploidy rate was 42.3% (191/452). In the teratozoospermia group, the good-quality embryo and blastocyst formation rate were lower than the normal group(44.4% vs 60.7%, P <0.01; 33.3% vs 43.5%, P<0.05), The good-quality embryo rate in normal DFI group was significantly higher than high-DFI group (59.0% vs 48.4%, P < 0.05). The blastocyst aneuploidy rate in low sperm concentration group, and high DFI group was no differences between with that in normal sperm concentration and DFI group (47.7% vs 37.8% and 44.7% vs 37.8%, P>0.05). The aneuploid rate of blastocyst in teratozoospermic and asthenozoospermia group was significantly higher than that of normal morphology and motility group (50.0% vs 34.0% and 46.7% vs 33.7%, P<0.05). Our study revealed that sperm DFI were positively correlated with blastocyst aneuploidy rate, while sperm motility and sperm morphology rate were negatively correlated with blastocyst aneuploidy rate. Abnormal semen parameters may affect embryo quality and increase the aneuploidy rate of blastocyst chromosomes, suggesting that in clinical practice of assisted reproduction patients with abnormal semen parameters can be treated in advance to improve sperm quality, so as to reduce the impact on embryo quality and achieve a better pregnancy outcome.

Relationship Between Osimertinib Concentration and Clinical Response in Japanese Patients With Non-small Cell Lung Cancer.

Osimertinib is the first-line treatment for patients with advanced epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). The present study aimed to determine the previously unclarified association of osimertinib plasma trough concentrations with efficacy, adverse events, and genetic polymorphisms in Japanese patients with NSCLC harboring EGFR mutations. In this prospective study, blood samples of 25 patients who received osimertinib were collected to measure plasma osimertinib concentrations and to genotypically characterize ATP-binding cassette subfamily B member 1 and ATP-binding cassette subfamily G member 2 polymorphisms. Plasma osimertinib concentrations were analyzed using validated multiple reaction monitoring mode-based liquid chromatography-tandem mass spectrometry. Osimertinib concentration necessary to achieve optimal median progression-free survival (PFS) was determined using receiver operating characteristic curve analysis. PFS and overall survival were analyzed using the Kaplan-Meier method, and between-group differences were compared using the log-rank test. Plasma osimertinib concentrations between different patient groups were compared using the Mann-Whitney U-test. Patients were divided into high and low concentration groups based on a plasma osimertinib cut-off concentration of 211 ng/ml. Median PFS was longer in the high trough concentration group than that in the low trough concentration group (46.3 vs. 16.8 months, p=0.029). Plasma osimertinib concentrations adjusted for dose and body weight did not differ between the patients with and without variant polymorphisms. Monitoring plasma trough concentrations during maintenance might improve osimertinib treatment efficacy in patients with NSCLC harboring EGFR mutations.

Effects of phthalates on human chorionic trophoblast cells and mouse embryonic development

Phthalate exposure is associated with reproductive health, but the mechanism is unclear. This study used human chorionic trophoblast epithelial cells (HTR8/Svneo cells) and mouse embryos as objects aims to explore the effects of phthalate plasticizers on germ cells and fertility and the possible signalling pathways. In the present study, high concentrations of MEHP for 24 h significantly inhibited the proliferation and viability of HTR8/SVneo cells. Compared with the negative control (NC) group, the MEHP medium and high concentration groups promoted the apoptosis of HTR8/SVneo cells and inhibited the cell cycle, HTR8/SVneo cells were blocked in G1/G0 phase and could not enter S phase, and cell meiosis was inhibited. Western blot experiments showed that there was no difference in the protein expression of wnt inhibitory factor 1 (WIF1) and β-catenin in HTR8/SVneo cells between the MEHP exposure groups and the NC groups. In vitro embryo culture experiments found that there was no difference in blastocyst formation rate among groups after exposure to DEHP for 2 h. Immunofluorescence showed that the expression of WIF1 decreased in the low concentration group, and there was no difference in the medium and high concentration groups, while the expression of β-catenin was increased in both the low concentration group and the high concentration group. Our data suggest that exposure to phthalate plasticizers can affect the viability, cell cycle and apoptosis of trophoblast cells, resulting in abnormal expression of the embryonic WIF1/β-catenin signalling pathway and impaired fertility.

Diagnostic and prognostic value of plasma cell-free DNA combined with VEGF-C in laryngeal squamous cell carcinoma

BackgroundCirculating cell-free DNA (cfDNA) and vascular endothelial growth factor-C (VEGF-C) can be utilized to detect cancer and predict its prognosis. However, their potential application in laryngeal squamous cell carcinoma (LSCC) is unclear. PurposeThis study aimed to identify the diagnostic and prognostic value of cfDNA and VEGF-C in LSCC patients. MethodsThe plasma cfDNA of 148 LSCC patients and 43 non-tumor patients were isolated. Quantitative real-time PCR (qRT-PCR) was performed to assess long and short DNA fragments in plasma by amplifying the ALU repeats. ALU-qPCR results (ALU247/ALU115) were used to calculate cfDNA integrity index. Vascular endothelial growth factor-C (VEGF-C) level was detected by ELISA assay. Correlation between cfDNA and clinical features was analyzed. For detecting the sensitivity and specificity of cfDNA and VEGF-C alone or in combination for diagnosing LSCC, receiver operator characteristic (ROC) was established. For evaluating the overall survival (OS) of LSCC, Kaplan-Meier curves were established. ResultsLSCC patients had significantly higher levels of plasma cfDNA (ALU115, ALU247, and cfDNA integrity index) and VEGF-C than those without cancer (p < 0.05), showing area under the curve (AUC) values of 0.79, 0.74, 0.62 and 0.80, when cutoff value was correspondingly defined at 2.14 ng/mL, 1.39 ng/mL, 0.73 and 412.90 pg/mL, respectively. The AUC for distinguishing LSCC patients from non-tumor patients by plasma cfDNA combined with VEGF-C was 0.89 (95% CI: 0.83–0.94). A significant correlation was found between plasma cfDNA levels and Ki-67, tumor size, pT stage, and smoking history (p < 0.05). Based on survival analysis, low VEGF-C concentration groups had longer OS than those with high VEGF-C concentration (p = 0.02). ConclusionIndicators such as plasma cfDNA and VEGF-C may be used to diagnose and monitor LSCC for its noninvasiveness and rapid accessibility.

Associations between welding fume exposure and neurological function in Japanese male welders and non-welders.

There are some studies reporting the association between (manganese [Mn]) exposure to welding fume and neurological dysfunction. This study examined the relationship between Mn exposure and neurological behavior in Japanese male welders and non-welders using biological samples, which to date has not been assessed in Japan. A total of 94 male welders and 95 male non-welders who worked in the same factories were recruited. The blood and urine samples were obtained from all the participants to measure Mn exposure levels. Neurological function tests were also conducted with all participants. The sampling of the breathing air zone using a personal sampler was measured for welders only. The odds ratios (ORs) for the Working Memory Index (WMI) scores were significantly higher among all participants in the low blood Mn concentration group than those in the high blood Mn concentration group (OR, 2.77; 95% confidence interval [CI], 1.24, 6.19; P=.013). The association of WMI scores and blood Mn levels in welders had the highest OR (OR, 3.73; 95% CI, 1.04, 13.38; P=.043). Although not statistically significant, a mild relationship between WMI scores and blood Mn levels was observed in non-welders (OR, 2.09; 95% CI, 0.63, 6.94; P=.227). The results revealed a significant positive relationship between blood Mn and neurological dysfunction in welders. Furthermore, non-welders at the same factories may be secondarily exposed to welding fumes. Further research is needed to clarify this possibility.