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Air pollution, particularly fine particulate matter with an aerodynamic diameter of ≤ 2.5 µm (PM2.5), has been recognized for its adverse effects on multiple organs beyond the lungs. Among these, the bone began to garner significant attention. This review covers epidemiological, animal and cell studies on PM2.5 exposure and bone health as well as studies on PM2.5-induced diseases with skeletal complications. Emerging evidence from epidemiological studies indicates a positive association between PM2.5 exposure and the incidence of osteoporosis and fractures, along with a negative association with bone mineral density. Experimental studies have demonstrated that PM2.5 can disrupt the metabolic balance between osteoclasts and osteoblasts through inflammatory responses, oxidative stress, and endocrine disruption, thereby triggering bone loss and osteoporosis. Additionally, this review proposes a secondary mechanism by which PM2.5 may impair bone homeostasis via pathological alterations in other organs, offering new perspectives on the complex interactions between environmental pollutants and bone health. In conclusion, this contemporary review underscores the often-overlooked risk factors of PM2.5 in terms of its adverse effects on bone and elucidates the mechanisms of both primary and secondary toxicity. Further attention should be given to exploring the molecular mechanisms of PM2.5-induced bone impairment and developing effective intervention strategies. With global climate change, increasing ozone pollution, emerging pollutants, and multifactorial exposure to environmental factors, these issues are likely to become of greater concern in the near future.
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BACKGROUND: A combination of axitinib and immune checkpoint inhibitors (ICIs) demonstrated promising efficacy in the treatment of advanced renal cell carcinoma (RCC). This study aims to prospectively evaluate the safety, efficacy, and biomarkers of neoadjuvant toripalimab plus axitinib in non-metastatic clear cell RCC. METHODS: This is a single-institution, single-arm phase II clinical trial. Patients with non-metastatic biopsy-proven clear cell RCC (T2-T3N0-1M0) are enrolled. Patients will receive axitinib 5 mg twice daily combined with toripalimab 240 mg every 3 weeks (three cycles) for up to 12 weeks. Patients then will receive partial (PN) or radical nephrectomy (RN) after neoadjuvant therapy. The primary endpoint is objective response rate (ORR). Secondary endpoints include disease-free survival, safety, and perioperative complication rate. Predictive biomarkers are involved in exploratory analysis. RESULTS: A total of 20 patients were enrolled in the study, with 19 of them undergoing surgery. One patient declined surgery. The primary endpoint ORR was 45%. The posterior distribution of πORR had a mean of 0.44 (95% credible intervals: 0.24-0.64), meeting the predefined primary endpoint with an ORR of 32%. Tumor shrinkage was observed in 95% of patients prior to nephrectomy. Furthermore, four patients achieved a pathological complete response. Grade ≥3 adverse events occurred in 25% of patients, including hypertension, hyperglycemia, glutamic pyruvic transaminase/glutamic oxaloacetic transaminase (ALT/AST) increase, and proteinuria. Postoperatively, one grade 4a and eight grade 1-2 complications were noted. In comparison to patients with stable disease, responders exhibited significant differences in immune factors such as Arginase 1(ARG1), Melanoma antigen (MAGEs), Dendritic Cell (DC), TNF Superfamily Member 13 (TNFSF13), Apelin Receptor (APLNR), and C-C Motif Chemokine Ligand 3 Like 1 (CCL3-L1). The limitation of this trial was the small sample size. CONCLUSION: Neoadjuvant toripalimab combined with axitinib shows encouraging activity and acceptable toxicity in locally advanced clear cell RCC and warrants further study. TRIAL REGISTRATION NUMBER: clinicaltrials.gov, NCT04118855.
Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Axitinib , Carcinoma, Renal Cell , Kidney Neoplasms , Neoadjuvant Therapy , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/pathology , Axitinib/therapeutic use , Axitinib/pharmacology , Male , Female , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Middle Aged , Neoadjuvant Therapy/methods , Aged , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adult , Prospective Studies , Nephrectomy/methodsABSTRACT
This paper presents a newly developed high-performance mobile single-photon ionization time-of-flight mass spectrometry (M-SPI-TOFMS) system for on-line analysis and stereoscopic monitoring of complex gas mixtures. The system is designed for stereoscopic imaging to map the distribution of volatile organic compounds (VOCs) and trace their emission sources in urban areas and industrial parks. It mainly consists of a SPI-TOFMS instrument, a customized commercial vehicle, a meteorological five-parameter monitor with GPS, a high-power generator, and an uninterruptible power supply. The SPI technique, using a 118 nm VUV lamp, can ionize compounds with an ionization potential below 10.78 eV. Mass spectra obtained using this technique show the profiles of various VOCs and some inorganic compounds. The VOCs composition information and mobile location data are simultaneously sent to the GIS software. In GIS software, this data is used for real-time stereoscopic imaging of VOC distribution and precise tracking of VOC movement. The system can achieve a spatial data resolution of 0.69 mm at 25 km/h due to the microsecond detection speed of the M-SPI-TOFMS instrument. The laboratory test provides a rapid overview characterization of benzene, toluene, and xylene. The M-SPI-TOFMS has limits of detection and mass resolution of 33.7 pptv and 1060, respectively. Several field applications were carried out using M-SPI-TOFMS at various locations to identify VOC sources near different factories. The M-SPI-TOFMS system has a navigation monitoring speed of 25 km/h with a time resolution of 1 s. The widespread use of this system will provide accurate data to support environmental management departments in formulating VOCs pollution control policies and improving control efficiency.
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Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Both FSH insufficiency (due to genetic or nongenetic factors) and FSH excess (as encountered with ovarian stimulation in assisted reproductive technology [ART]) can cause poor female reproductive outcomes, but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and such threshold is moderately variable among individual follicles between 5 and 10â mIU/mL. FSH at 5, 10, 20, and 30â mIU/mL induced distinct expression patterns of follicle maturation-related genes, follicular transcriptomics, and follicular cAMP levels. RNA sequencing analysis identified FSH-stimulated activation of G proteins and downstream canonical and novel signaling pathways that may critically regulate follicle maturation, including the cAMP/PKA/CREB, PI3K/AKT/FOXO1, and glycolysis pathways. High FSH at 20 and 30â mIU/mL resulted in noncanonical FSH responses, including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health.
Subject(s)
Follicle Stimulating Hormone , Ovarian Follicle , Transcriptome , Animals , Female , Follicle Stimulating Hormone/pharmacology , Mice , Ovarian Follicle/drug effects , Ovarian Follicle/metabolism , Transcriptome/drug effects , Dose-Response Relationship, Drug , Oocytes/drug effects , Oocytes/metabolism , Oogenesis/drug effects , Oogenesis/genetics , Signal Transduction/drug effects , Granulosa Cells/drug effects , Granulosa Cells/metabolism , Cyclic AMP/metabolismABSTRACT
Down-polyethylene film material has been introduced for the first time as an excellent non-frame sound absorber, showing a distinctively outstanding performance. It contains down fiber adjacent to each other without firm connection in between, forming a structure of elastic fiber network. The unique structure has broadband response to sound wave, showing non-synchronous vibration in low and middle frequency and synchronous vibration in middle and high frequency. The broadband resonance in middle and high frequency allows the structure to achieve complete sound absorption in resonance frequency band. Moreover, down-polyethylene film material possesses forced vibration, corresponding sound absorption coefficient has been obtained based on vibration theory. The down-film sound absorption material has the characteristics of light weight, soft, environment-friendly, and has excellent broadband sound absorption performance.
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Flexible nanocomposite dielectrics with inorganic nanofillers exhibit great potential for energy storage devices in advanced microelectronics applications. However, high loading of inorganic nanofillers in the matrix results in an inhomogeneous electric field distribution, thereby hindering the improvement of the energy storage density (Ue) of the dielectrics. Herein, we proposed a strategy that utilized (00l)-oriented barium titanate (BT) single-crystal platelets to fabricate trilayered nanocomposite dielectrics for energy storage applications. The trilayered nanocomposites consisted of two high-permittivity layers of (Ta2O5, Al2O3) codoped TiO2 nanoparticles (Ta-Al@TiO2 nps) dispersed in a poly(vinylidene fluoride) (PVDF) matrix to facilitate large electric displacement and a middle layer of (00l)-oriented BT single-crystal platelets to provide high breakdown strength. Hence, the trilayered PVDF/Ta-Al@TiO2 nps/BT single-crystal platelet nanocomposite film attains an outstanding Ue of 16.9 J cm-3 at 370 kV mm-1, which is â¼625% higher than that of the single-layer PVDF/Ta-Al@TiO2 nps film. Finite element simulation further clarified that the successive inner layer of highly (00l)-oriented BT single-crystal platelets could effectively restrain the propagation of electrical treeing in trilayered nanocomposites. This research offers an effective approach for developing flexible dielectric capacitors with an excellent energy storage performance.
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Optical delay lines have wide applications in terahertz time-domain spectroscopy and optical coherence tomography. In this study, a fast-rotating optical delay line (FRODL) with 24 turntable reflection surfaces was designed. By analyzing the working principle of the FRODL, a mathematical model was established for the nonlinear parameter error of the FRODL delay time. By constructing the polarization Michelson interference system and testing the FRODL structure, the error of actual assembly parameters of the FRODL was approximately 0.015 mm, the actual delay time of the FRODL was greater than 43.5 ps, and the linearity was 99.785%.
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Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXXmut, n = 7) or absence (MEN1/DAXXwild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease's progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.
Subject(s)
Liver Neoplasms , Neuroendocrine Tumors , Pancreatic Neoplasms , Humans , Exome Sequencing , Neuroendocrine Tumors/genetics , Genomics , Liver Neoplasms/genetics , Pancreatic Neoplasms/genetics , Tumor MicroenvironmentABSTRACT
It is well known that extreme heat events happen frequently due to climate change. However, studies examining the direct health impacts of increased temperature and heat waves are lacking. Previous reports revealed that heatstroke induced acute lung injury and pulmonary dysfunction. This study aimed to investigate whether heat exposure induced lung fibrosis and to explore the underlying mechanisms. Male C57BL/6 mice were exposed to an ambient temperature of 39.5 ± 0.5 °C until their core temperature reached the maximum or heat exhaustion state. Lung fibrosis was observed in the lungs of heat-exposed mice, with extensive collagen deposition and the elevated expression of fibrosis molecules, including transforming growth factor-ß1 (TGF-ß1) and Fibronectin (Fn1) (p < 0.05). Moreover, epithelial-mesenchymal transition (EMT) occurred in response to heat exposure, evidenced by E-cadherin, an epithelial marker, which was downregulated, whereas markers of EMT, such as connective tissue growth factor (CTGF) and the zinc finger transcriptional repressor protein Slug, were upregulated in the heat-exposed lung tissues of mice (p < 0.05). Subsequently, cell senescence examination revealed that the levels of both senescence-associated ß-galactosidase (SA-ß-gal) staining and the cell cycle protein kinase inhibitor p21 were significantly elevated (p < 0.05). Mechanistically, the cGAS-STING signaling pathway evoked by DNA damage was activated in response to heat exposure (p < 0.05). In summary, we reported a new finding that heat exposure contributed to the development of early pulmonary fibrosis-like changes through the DNA damage-activated cGAS-STING pathway followed by cellular senescence.
Subject(s)
Pulmonary Fibrosis , Male , Mice , Animals , Pulmonary Fibrosis/metabolism , Hot Temperature , Mice, Inbred C57BL , Lung/pathology , Transforming Growth Factor beta1/metabolism , Epithelial-Mesenchymal Transition/physiology , Cellular Senescence , Nucleotidyltransferases/metabolismABSTRACT
Multi-layer lightweight composite structures are widely used in the field of aviation and aerospace during the processes of manufacturing and use, and, as such, they inevitably produce defects, damage, and other quality problems, creating the need for timely non-destructive testing procedures and the convenient repair or replacement of quality problems related to the material. When using terahertz non-destructive testing technology to detect defects in multi-layer lightweight composite materials, due to the complexity of their structure and defect types, there are many signal characteristics of terahertz waves propagating in the structures, and there is no obvious rule behind them, resulting in a large gap between the recognition results and the actual ones. In this study, we introduced a U-Net-BiLSTM network that combines the strengths of the U-Net and BiLSTM networks. The U-Net network extracts the spatial features of THz signals, while the BiLSTM network captures their temporal features. By optimizing the network structure and various parameters, we obtained a model tailored to THz spectroscopy data. This model was subsequently employed for the identification and quantitative analysis of defects in multi-layer lightweight composite structures using THz non-destructive testing. The proposed U-Net-BiLSTM network achieved an accuracy of 99.45% in typical defect identification, with a comprehensive F1 score of 99.43%, outperforming the CNN, ResNet, U-Net, and BiLSTM networks. By leveraging defect classification and thickness recognition, this study successfully reconstructed three-dimensional THz defect images, thereby realizing quantitative defect detection.
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PURPOSE: To investigate pain hypervigilance in individuals suffering from chronic neck and shoulder pain (CNSP) and its underlying brain mechanism. METHODS: The evaluation of pain vigilance was conducted through the utilization of pain vigilance and awareness questionnaires. Voxel-wise regional homogeneity (ReHo) from 60 CNSP patients and 60 healthy controls (HCs) using resting-state fMRI data. Voxel-wise two-sample T-test was conducted to reveal the ReHo variations between CNSP and HC. Correlation analyses were utilized to reveal the connection between brain abnormalities and medical measurements. Furthermore, a mediation analysis was conducted to elucidate the pathway-linking changes in brain function with medical measurements. RESULTS: Our present study revealed three main findings. Firstly, patients with CSNP demonstrated a heightened vigilance of pain in comparison to healthy adults, a common occurrence among individuals with chronic pain conditions. Secondly, we observed brain abnormalities in various brain regions in CSNP patients, and these alterations were associated with the extent of pain vigilance. Lastly, the pain hypervigilance impact on the severity of pain was found to be controlled by regional neural activity in the anterior cingulate cortex (ACC) in subjects with CSNP. CONCLUSION: Our findings suggested that long-term repetitive nociceptive input caused by chronic pain further aggravates the pain intensity by impairing the vigilance-related pain processing within the anterior cingulate cortex in CNSP patients.
Subject(s)
Chronic Pain , Magnetic Resonance Imaging , Neck Pain , Pain Measurement , Shoulder Pain , Humans , Female , Male , Magnetic Resonance Imaging/methods , Neck Pain/physiopathology , Neck Pain/diagnostic imaging , Shoulder Pain/diagnostic imaging , Shoulder Pain/physiopathology , Chronic Pain/physiopathology , Chronic Pain/diagnostic imaging , Adult , Case-Control Studies , Middle Aged , Brain Mapping/methods , Surveys and Questionnaires , Brain/diagnostic imaging , Brain/physiopathologyABSTRACT
INTRODUCTION: Brain metastasis, with the highest incidence in patients with lung cancer, significantly worsens prognosis and poses challenges to clinical management. To date, how brain metastasis evades immune elimination remains unknown. METHODS: Whole-exome sequencing and RNA sequencing were performed on 30 matched brain metastasis, primary lung adenocarcinoma, and normal tissues. Data from The Cancer Genome Atlas primary lung adenocarcinoma cohort, including multiplex immunofluorescence, were used to support the findings of bioinformatics analysis. RESULTS: Our study highlights the key role of intratumor heterogeneity of genomic alterations in the metastasis process, mainly caused by homologous recombination deficiency or other somatic copy number alteration-associated mutation mechanisms, leading to increased genomic instability and genomic complexity. We further proposed a selection model of brain metastatic evolution in which intratumor heterogeneity drives immune remodeling, leading to immune escape through different mechanisms under local immune pressure. CONCLUSIONS: Our findings provide novel insights into the metastatic process and immune escape mechanisms of brain metastasis and pave the way for precise immunotherapeutic strategies for patients with lung cancer with brain metastasis.
Subject(s)
Adenocarcinoma of Lung , Brain Neoplasms , Lung Neoplasms , Humans , Lung Neoplasms/pathology , Immune Evasion , Mutation , Adenocarcinoma of Lung/genetics , Brain Neoplasms/genetics , Genetic Heterogeneity , Tumor MicroenvironmentABSTRACT
Using the value-added method in the global input-output framework, embedded carbon transfers between economies are measured. Then, the international embedded carbon network (IECN) models are constructed and analyzed to reveal the real pattern of the IECN. Influential factors of the IECN are further explored with Quadratic Assignment Procedure (QAP). The main findings are as follows: first, the IECN has the characteristics of small world and scale-free. Developed economies led by the USA have high centrality indicators and always occupy the core position in the network; the network position of China and India has risen significantly with different network characteristics. Second, the subgroup relationships of the carbon network implied by international trade are becoming more and more complex and diverse, economies' participation in the global carbon chain is gradually increasing, and the number of edge nodes are decreasing. Third, the results of QAP analysis show that in addition to the negative impact of geographical distance on embedded carbon transfers between economies, inter-country trade agreement relations, differences in industrial structure, energy intensity, environmental regulation, economic size, and population size have a positive impact on embedded carbon transfers between economies. These findings can provide important practice implications for the global carbon neutrality.
Subject(s)
Commerce , Internationality , Carbon , Industry , Social Conditions , China , Carbon Dioxide/analysis , Economic DevelopmentABSTRACT
Transparent soil (TS) was specifically designed to support root growth in the presence of air, water, and nutrients and allowed the time-resolved phenotyping of roots in vivo. Nevertheless, it is imperative to further optimize the reagent cost of TS to enable its wider utilization. We substituted the costly Phytagel obtained from Sigma with two more economical alternatives, namely Biodee and Coolaber. TS beads from each brand were prepared using 12 different polymer concentrations and seven distinct crosslinker concentrations. A comprehensive assessment encompassing transparency, mechanical characteristics, particle size, porosity, and stability of TS was undertaken. Compared to the Sigma Phytagel brand, both Biodee and Coolaber significantly reduced the transparency and collapse stress of the TS they produced. Consequently, this led to a significant reduction in the allowable width and height of the growth box, although they could still simultaneously exceed 20 cm and 19 cm. There was no notable difference in porosity and stability among the TS samples prepared using the three Phytagel brands. Therefore, it is feasible to consider replacing the Phytagel brand to reduce TS production costs. This study quantified the differences in TS produced using three Phytagel brands at different prices that will better promote the application of TS to root phenotypes.
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To accurately phenocopy human biology in vitro, researchers have been reducing their dependence on standard, static two-dimensional (2D) cultures and instead are moving towards three-dimensional (3D) and/or multicellular culture techniques. While these culture innovations are becoming more commonplace, there is a growing body of research that illustrates the benefits and even necessity of recapitulating the dynamic flow of nutrients, gas, waste exchange and tissue interactions that occur in vivo. However, cost and engineering complexity are two main factors that hinder the adoption of these technologies and incorporation into standard laboratory workflows. We developed LATTICE, a plug-and-play microfluidic platform able to house up to eight large tissue or organ models that can be cultured individually or in an interconnected fashion. The functionality of the platform to model both healthy and diseased tissue states was demonstrated using 3D cultures of reproductive tissues including murine ovarian tissues and human fallopian tube explants (hFTE). When exogenously exposed to pathological doses of gonadotropins and androgens to mimic the endocrinology of polycystic ovarian syndrome (PCOS), subsequent ovarian follicle development, hormone production and ovulation copied key features of this endocrinopathy. Further, hFTE cilia beating decreased significantly only when experiencing continuous media exchanges. We were then able to endogenously recreate this phenotype on the platform by dynamically co-culturing the PCOS ovary and hFTE. LATTICE was designed to be customizable with flexibility in 3D culture formats and can serve as a powerful automated tool to enable the study of tissue and cellular dynamics in health and disease in all fields of research.
Subject(s)
Polycystic Ovary Syndrome , Female , Animals , Humans , Mice , Polycystic Ovary Syndrome/metabolism , Microfluidics , Coculture TechniquesABSTRACT
There remains a lack of effective and noninvasive methods for the diagnosis and prognosis prediction of epithelial ovarian carcinoma (EOC). Here, we investigated the possibility of serum-derived small extracellular vesicle (sEV) microRNAs (miRNAs) as potential biomarkers for distinguishing between benign and malignant adnexal masses and predicting the prognosis of EOC patients. A serum sEV miRNA model for identifying the EOC (sEVmiR-EOC) was successfully established in the training cohort. Furthermore, the sEVmiR-EOC model was confirmed in the testing cohort and validation cohort, demonstrating robust diagnostic accuracy. The sEVmiR-EOC model showed better performance than carbohydrate antigen 125 (CA125) in discriminating patients with stage I EOC from benign patients. Using EOC samples and follow-up data, we identified miR-141-3p and miR-200c-3p as potential prognostic predictors. Finally, we confirmed the change of the sEVmiR-EOC RiskScore between the preoperative and postoperative samples and found that the sEVmiR-EOC model could predict the prognosis of EOC patients.
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MOTIVATION: Single-cell DNA methylation sequencing can assay DNA methylation at single-cell resolution. However, incomplete coverage compromises related downstream analyses, outlining the importance of imputation techniques. With a rising number of cell samples in recent large datasets, scalable and efficient imputation models are critical to addressing the sparsity for genome-wide analyses. RESULTS: We proposed a novel graph-based deep learning approach to impute methylation matrices based on locus-aware neighboring subgraphs with locus-aware encoding orienting on one cell type. Merely using the CpGs methylation matrix, the obtained GraphCpG outperforms previous methods on datasets containing more than hundreds of cells and achieves competitive performance on smaller datasets, with subgraphs of predicted sites visualized by retrievable bipartite graphs. Besides better imputation performance with increasing cell number, it significantly reduces computation time and demonstrates improvement in downstream analysis. AVAILABILITY AND IMPLEMENTATION: The source code is freely available at https://github.com/yuzhong-deng/graphcpg.git.
Subject(s)
Epigenome , Genome-Wide Association Study , DNA Methylation , Biological Assay , Cell CountSubject(s)
Transcriptome , Vitrification , Female , Humans , Ovulation , Ovarian Follicle , CryopreservationABSTRACT
BACKGROUND: Cyanobacterial harmful algal blooms (CyanoHABs) originate from the excessive growth or bloom of cyanobacteria often referred to as blue-green algae. They have been on the rise globally in both marine and freshwaters in recently years with increasing frequency and severity owing to the rising temperature associated with climate change and increasing anthropogenic eutrophication from agricultural runoff and urbanization. Humans are at a great risk of exposure to toxins released from CyanoHABs through drinking water, food, and recreational activities, making CyanoHAB toxins a new class of contaminants of emerging concern. OBJECTIVES: We investigated the toxic effects and mechanisms of microcystin-LR (MC-LR), the most prevalent CyanoHAB toxin, on the ovary and associated reproductive functions. METHODS: Mouse models with either chronic daily oral or acute intraperitoneal exposure, an engineered three-dimensional ovarian follicle culture system, and human primary ovarian granulosa cells were tested with MC-LR of various dose levels. Single-follicle RNA sequencing, reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, immunohistochemistry (IHC), and benchmark dose modeling were used to examine the effects of MC-LR on follicle maturation, hormone secretion, ovulation, and luteinization. RESULTS: Mice exposed long term to low-dose MC-LR did not exhibit any differences in the kinetics of folliculogenesis, but they had significantly fewer corpora lutea compared with control mice. Superovulation models further showed that mice exposed to MC-LR during the follicle maturation window had significantly fewer ovulated oocytes. IHC results revealed ovarian distribution of MC-LR, and mice exposed to MC-LR had significantly lower expression of key follicle maturation mediators. Mechanistically, in both murine and human granulosa cells exposed to MC-LR, there was reduced protein phosphatase 1 (PP1) activity, disrupted PP1-mediated PI3K/AKT/FOXO1 signaling, and less expression of follicle maturation-related genes. DISCUSSION: Using both in vivo and in vitro murine and human model systems, we provide data suggesting that environmentally relevant exposure to the CyanoHAB toxin MC-LR interfered with gonadotropin-dependent follicle maturation and ovulation. We conclude that MC-LR may pose a nonnegligible risk to women's reproductive health by heightening the probability of irregular menstrual cycles and infertility related to ovulatory disorders. https://doi.org/10.1289/EHP12034.