ABSTRACT
Excessive fluoride ion (F-) in the environment can affect health and even endanger life when ingested by the human body. However, most fluoride probes have the disadvantages of low sensitivity and long detection time. Herein, fluorescent probe 3a is successfully synthesized by linking two acetylenyltrimethylsilyl groups at both ends of the fluorinated benzothiadiazole core. After the addition of F- to 3a, the emission at 436 nm is significantly quenched and slightly blue-shifted. It is confirmed by electrospray ionization high-resolution mass spectrometry (ESI-HRMS) and density functional theory calculations (DFT) that these changes are due to the F- triggered Si-C bond cleavage and the subsequent inactivation of intramolecular charge transfer (ICT). The detection limit and response time of probe 3a for F- are 10-8 mol/L and 25 s, respectively. Importantly, fluorescent material 3a can be processed into portable test tools for the visual detection of fluoride ion.
ABSTRACT
This study investigates the adaptive strategies of the Alashan Ground Squirrel (Spermophilus alashanicus) in response to habitat changes, as rodents are sensitive indicators of ecosystem changes. Despite its ecological importance, the genome and microbiome of this species have not been thoroughly studied. This research fills this gap by presenting the first comprehensive metagenomic and transcriptomic datasets of the species. Transcriptomic data was collected from five tissue types, including heart, liver, cecum, muscle, and blood, resulting in the assembly of 72,156 unigenes. Metagenomic sequencing identified predominant bacterial groups such as Firmicutes, Bacteroidetes, Verrucomicrobia, Urovircota, and Proteobacteria. Our workflow involved RNA and DNA extraction, library preparation, assembly, and annotation, yielding valuable insights into gene discovery, microbial composition, and further genome and microbial function studies. In conclusion, our findings have significant implications for understanding the adaptive mechanisms of this species in response to environmental changes.
Subject(s)
Metagenomics , Sciuridae , Transcriptome , Animals , Bacteria/genetics , Bacteria/classification , Ecosystem , Metagenome , Microbiota , Sciuridae/genetics , MongoliaABSTRACT
Chemical oxidation processes are widely used for the remediation of organically contaminated soils, but their potential impact on variable-valence and toxic metals such as chromium (Cr) is often overlooked. In this study, we investigated the risk of Cr(â ¢) oxidation in soils during the remediation of 2-chlorophenol (2-CP) contaminated soils using four different processes: Potassium permanganate (KMnO4), Modified Fenton (Fe2+/H2O2), Alkali-activated persulfate (S2O82-/OH-), and Fe2+-activated persulfate (S2O82-/Fe2+). Our results indicated that the KMnO4, Fe2+/H2O2, and S2O82-/Fe2+ processes progressively oxidized Cr(III) to Cr(â ¥) during the 2-CP degradation. The KMnO4 process likely involved direct electron transfer, while the Fe2+/H2O2 and S2O82-/Fe2+ processes primarily relied on HO⢠and/or SO4â¢- for the Cr(III) oxidation. Notably, after 4 h of 2-CP degradation, the Cr(VI) content in the KMnO4 process surpassed China's 3.0 mg kg-1 risk screening threshold for Class I construction sites, and further exceeded the 5.7 mg kg-1 limit for Class II construction sites after 8 h. Conversely, the S2O82-/OH- process exhibited negligible oxidation of Cr(III), maintaining a low oxidation ratio of 0.13%, as highly alkaline conditions induced Cr(III) precipitation, reducing its exposure to free radicals. Cr(III) oxidation ratio was directly proportional to oxidant dosage, whereas the Fe2+/H2O2 process showed a different trend, influenced by the concentration of reductants. This study provides insights into the selection and optimization of chemical oxidation processes for soil remediation, emphasizing the imperative for thorough risk evaluation of Cr(III) oxidation before their application.
Subject(s)
Chlorophenols , Chromium , Environmental Restoration and Remediation , Oxidation-Reduction , Soil Pollutants , Soil , Chromium/chemistry , Soil Pollutants/chemistry , Chlorophenols/chemistry , Soil/chemistry , Hydrogen Peroxide/chemistry , Potassium Permanganate/chemistryABSTRACT
Background: A phenomenon known as legacy effect was observed that poor glycemic control at early stage of patients with newly-diagnosed type 2 diabetes (T2D) increases the risk of subsequent cardiovascular diseases (CVD). Early use of some novel anti-hyperglycemic agents, such as sodium-glucose transport protein 2 inhibitors (SGLT-2i), may attenuate this effect, but the evidence is limited. Methods: Two retrospective cohorts of newly diagnosed T2D patients from 2010-2023 were assembled using the Yinzhou Regional Health Care Database (YRHCD) with different definitions of the early exposure period - the 1-year exposure cohort and 2-year exposure cohort, which were comprised of subjects who had HbA1c measurement data within 1 year and 2 years after their T2D diagnosis, respectively. Using Cox proportional hazards models, we examined the association between high HbA1c level (HbA1c>7%) during the early exposure period and the risk of subsequent CVD. This analysis was performed in the overall cohort and three subpopulations with different treatments during the early exposure period, including patients initiating SGLT-2i or glucagon-like peptide-1 receptor agonists (GLP-1RA), patients using dipeptidyl peptidase-4 inhibitors (DPP-4i), and patients without using SGLT-2i, GLP-1RA, and DPP-4i. Besides, subgroup analyses were performed by stratifying patients into age <55 and ≥55 years. Results: A total of 21,477 and 22,493 patients with newly diagnosed T2D were included in the two final cohorts. Compared with patients with mean HbA1c ≤ 7% during the early exposure period, those with HbA1c>7% had higher risks of incident CVD, with a HR of 1.165 (95%CI, 1.056-1.285) and 1.143 (95%CI, 1.044-1.252) in 1-year and 2-year exposure period cohort. Compared to non-users, in patients initiating SGLT-2i/GLP-1RA within 1 or 2 years after T2D diagnosis, higher HbA1c level at baseline was not associated with CVD in both two cohorts. In subgroup analyses, results were generally consistent with the main analysis. Conclusions: Poor glycemic control in the early stage of T2D increased later CVD risk in Chinese adults with newly diagnosed T2D. Compared to non-users, this association was smaller and non-significant in patients receiving SGLT-2i/GLP-1RA during the early stage of T2D, indicating early use of these drugs may have the potential to mitigate legacy effects of hyperglycemia.
Subject(s)
Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Glucagon-Like Peptide-1 Receptor , Hyperglycemia , Sodium-Glucose Transporter 2 Inhibitors , Humans , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Female , Male , Middle Aged , Glucagon-Like Peptide-1 Receptor/agonists , Retrospective Studies , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Hyperglycemia/epidemiology , Hyperglycemia/chemically induced , Aged , Cardiovascular Diseases/epidemiology , Blood Glucose/metabolism , Blood Glucose/analysis , Blood Glucose/drug effects , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Hypoglycemic Agents/therapeutic use , Adult , Follow-Up Studies , Glycemic Control , Glucagon-Like Peptide-1 Receptor AgonistsABSTRACT
BACKGROUND: Whether health inequalities of disease burden and medical utilization exist by ethnicity in Asian breast cancer (BC) patients remains unclear. The authors aim to measure ethnic disparities in disease burden and utilization among Mongolian and Han female BC patients in China. MATERIALS AND METHODS: Based on data extracted from Inner Mongolia Regional Health Information Platform, a retrospective cohort study was established during 2012-2021. Disease burden including incidence, 5-year prevalence, mortality, survival rate, and medical cost were analyzed and compared between Han and Mongolian patients. RESULTS: A total of 34 878 female patients [mean (SD) age, 52.34 (10.93) years] were included among 18.19 million Chinese, and 4315 (12.03%) participants were Mongolian. Age-standardized rates of incidence are 32.68 (95% CI: 20.39-44.98) per 100 000. Higher age-specific incidence and 5-year prevalence were observed in Mongolian than in Han. The cost of BC annually per capita was significantly lower for Mongolian than Han [$1948.43 (590.11-4 776.42) vs. $2227.35 (686.65-5929.59), P <0.001]. Mongolian females showed higher all-cause mortality [30.92 (95% CI: 28.15-33.89) vs. 27.78 (95% CI: 26.77-28.83) per 1000, P =0.036] and BC-specific mortality [18.78 (95% CI: 16.64-21.13) vs. 15.22 (95% CI: 14.47-16.00) per 1000, P =0.002] than Han females. After adjusting covariates, Mongolian were associated with increased all-cause mortality [HR, 1.21, (95% CI: 1.09-1.34); P <0.001] and BC-specific mortality [HR, 1.31, (95% CI: 1.14-1.49); P <0.001]. CONCLUSION: The findings of this cohort study highlight a higher level of disease burden with unmet medical demand in Mongolian patients, suggesting that more practical efforts should be made for the minority. Further research is needed to explore the concrete mechanisms of the disparities as well as eliminate health disproportion.
Subject(s)
Breast Neoplasms , Cost of Illness , Humans , Female , Breast Neoplasms/mortality , Breast Neoplasms/epidemiology , Retrospective Studies , Middle Aged , China/epidemiology , Adult , Aged , Incidence , Prevalence , Mongolia/epidemiology , Patient Acceptance of Health Care/statistics & numerical dataABSTRACT
The effects of excessive fructose intake on the development and progression of metabolic disorders have received widespread attention. However, the deleterious effects of fructose on the development of hepatic metabolic disease in adolescents and its potential mechanisms are not fully understood. In this study, we investigated the effects of isocaloric fructose-rich diets on the liver of adolescent mice. The results showed that fructose-rich diets had no effect on the development of obesity in the adolescent mice, but did induce hepatic lipid accumulation. Besides, we found that fructose-rich diets promoted hepatic inflammatory responses and oxidative stress in adolescent mice, which may be associated with activation of the NLRP3 inflammasome and inhibition of the Nrf2 pathway. Furthermore, our results showed that fructose-rich diets caused disturbances in hepatic lipid metabolism and bile acid metabolism, as well as endoplasmic reticulum stress and autophagy dysfunction. Finally, we found that the intestinal barrier function was impaired in the mice fed fructose-rich diets. In conclusion, our study demonstrates that dietary high fructose induces hepatic metabolic disorders in adolescent mice. These findings provide a theoretical foundation for fully understanding the effects of high fructose intake on the development of hepatic metabolic diseases during adolescence.
Subject(s)
Autophagy , Bile Acids and Salts , Fructose , Lipid Metabolism , Liver , Mice, Inbred C57BL , Oxidative Stress , Animals , Fructose/adverse effects , Bile Acids and Salts/metabolism , Male , Liver/metabolism , Liver/drug effects , Oxidative Stress/drug effects , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Mice , Fatty Liver/metabolism , Fatty Liver/etiology , Endoplasmic Reticulum Stress/drug effects , NF-E2-Related Factor 2/metabolism , Inflammasomes/metabolismABSTRACT
The lethality, chemoresistance and metastatic characteristics of cancers are associated with phenotypically plastic cancer stem cells (CSCs). How the non-cell autonomous signalling pathways and cell-autonomous transcriptional machinery orchestrate the stem cell-like characteristics of CSCs is still poorly understood. Here we use a quantitative proteomic approach for identifying secreted proteins of CSCs in pancreatic cancer. We uncover that the cell-autonomous E2F1/4-pRb/RBL2 axis balances non-cell-autonomous signalling in healthy ductal cells but becomes deregulated upon KRAS mutation. E2F1 and E2F4 induce whereas pRb/RBL2 reduce WNT ligand expression (e.g. WNT7A, WNT7B, WNT10A, WNT4) thereby regulating self-renewal, chemoresistance and invasiveness of CSCs in both PDAC and breast cancer, and fibroblast proliferation. Screening for epigenetic enzymes identifies GCN5 as a regulator of CSCs that deposits H3K9ac onto WNT promoters and enhancers. Collectively, paracrine signalling pathways are controlled by the E2F-GCN5-RB axis in diverse cancers and this could be a therapeutic target for eliminating CSCs.
Subject(s)
E2F1 Transcription Factor , E2F4 Transcription Factor , Neoplastic Stem Cells , Pancreatic Neoplasms , Paracrine Communication , Humans , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , E2F1 Transcription Factor/metabolism , E2F1 Transcription Factor/genetics , Cell Line, Tumor , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/genetics , E2F4 Transcription Factor/metabolism , E2F4 Transcription Factor/genetics , Animals , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/genetics , Carcinoma, Pancreatic Ductal/metabolism , Wnt Proteins/metabolism , Wnt Proteins/genetics , Retinoblastoma Protein/metabolism , Retinoblastoma Protein/genetics , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/pathology , p300-CBP Transcription Factors/metabolism , p300-CBP Transcription Factors/genetics , Gene Expression Regulation, Neoplastic , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Female , Cell Proliferation , Mice , Signal Transduction , Drug Resistance, Neoplasm/geneticsABSTRACT
Chlorpyrifos (CHP) is an inexpensive highly effective organophosphate insecticide used worldwide. The unguided and excessive use of CHP by farmers has led to its significant accumulation in crops as well as contamination of water sources, causing health problems for humans and animals. Therefore, this study evaluated the toxicological effects of exposure to the environmental pollutant CHP at low, medium, and high (2.5, 5, and 10 mg·kg-1 BW) levels on rat liver by examining antioxidant levels, inflammation, and apoptosis based on the no observed adverse effect levels (NOAEL) (1 mg·kg-1 BW) and the CHP dose that does not cause any visual symptoms (5 mg·kg-1 BW). Furthermore, the involvement of the JAK/STAT and MAPK pathways in CHP-induced toxic effects was identified. The relationship between the expression levels of key proteins (p-JAK/JAK, p-STAT/STAT, p-JNK/JNK, p-P38/P38, and p-ERK/ERK) in the pathways and changes in the expression of markers associated with inflammation [inflammatory factors (IL-1ß, IL-6, IL-10, TNF-α), chemokines (GCLC and GCLM), and inflammatory signaling pathways (NF-кB, TLR2, TLR4, NLRP3, ASC, MyD88, IFN-γ, and iNOS)] and apoptosis [Bad, Bax, Bcl-2, Caspase3, Caspase9, and the cleavage substrate of Caspase PARP1] were also determined. The results suggest that CHP exposure disrupts liver function and activates the JAK/STAT and MAPK pathways via oxidative stress, exacerbating inflammation and apoptosis. Meanwhile, the JAK/STAT and MAPK pathways are involved in CHP-induced hepatotoxicity. These findings provide a novel direction for effective prevention and amelioration of health problems caused by CHP abuse in agriculture and households.
Subject(s)
Chlorpyrifos , Environmental Pollutants , Insecticides , Janus Kinases , Liver , MAP Kinase Signaling System , Chlorpyrifos/toxicity , Animals , Rats , Liver/drug effects , Janus Kinases/metabolism , Environmental Pollutants/toxicity , Insecticides/toxicity , MAP Kinase Signaling System/drug effects , STAT Transcription Factors/metabolism , Male , Apoptosis/drug effects , Signal Transduction/drug effectsABSTRACT
A novel carbon catalyst was created based on plant metallurgy strategy for organic pollutants removal. Plants rich in CeO2 NPs in water were used as carbon precursors and pyrolyzed with urea to obtain Ce/N co-doped carbon catalysts, which were used in the degradation of sulfamethoxazole (SMX) by active peroxymonosulfate (PMS). The results showed that the Ce/N @BC/PMS system achieved to 94.5% degradation of SMX in 40 min at a rate constant of 0.0602 cm-1. The activation center of PMS is widely dispersed Ce oxide nanocrystals, and CeO2 NPs promote the formation of oxygen centered PFR with enhanced catalytic ability and longer half-life. In addition, N-doping facilitates the transfer of π-electrons within the sp2 carbon of biochar, increasing active sites and thus improving PMS activation efficiency. The degradation process was contributed to by both radical and non-radical activation mechanisms including 1O2 and direct electron transfer, with O2â¢- serving as 1O2's precursor. Through the DFT calculations, LC-MS and toxicological analyses, the degradation pathway of pollutants and the toxicity changes throughout the entire degradation process were further revealed, indicating that the degradation of SMX could effectively reduce ecological toxicity.
Subject(s)
Environmental Pollutants , Sulfamethoxazole , Sulfamethoxazole/chemistry , Peroxides/chemistry , OxygenABSTRACT
Protection of the Critically Endangered East Asian Pangolin species is hampered by the vulnerability of captive individuals to infection. Studies have previously shown the pangolin to have a unique pseudogenisation of many immunity genes (including IFNE, IFIH1, cGAS, STING, TLR5, and TLR11), and we suspected that these losses could account for this vulnerability. Here we used RNA-Seq data to show the effect of these gene losses on the transcriptional response to a viral skin infection in a deceased pangolin. This virus is very closely related to the one causing the current COVID-19 pandemic in the human population (SARS-CoV2), and we found the most upregulated pathway was the same one previously identified in the lungs of SARS-CoV2-infected humans. As predicted, we found that the pathways downstream of the lost genes were not upregulated. For example, the pseudogenised interferon epsilon (IFNE) is known to be particularly important in epithelial immunity, and we show that interferon-related responses were not upregulated in the infected pangolin skin. We suggest that the pangolin's innate gene pseudogenisation is indeed likely to be responsible for the animal's vulnerability to infection.
Subject(s)
Pandemics , Pangolins , Animals , Humans , RNA, Viral , RNA-Seq , Endangered Species , InterferonsABSTRACT
In this study, we developed a novel self-catalytic oxidation system involving peroxymonosulfate (PMS) and permanganate (KMnO4), named as CUPP, to efficiently mineralize sulfamethoxazole (SMX) in groundwater. It was found that amorphous MnO2 derived from the in situ reduction of KMnO4 can directly adsorb HSO5-, a complex hydroxyl group, mediate the internal disproportionation reaction of HSO5- with the manganese complex, and effectively activate PMS, thereby promoting the oxidation of SMX and its degradation intermediates through sulfonate radiation. Furthermore, by using electron spin resonance (EPR), HPLC/MS full scan, and response surface methodology, the coexistence of HOË, SO4-Ë, O2-Ë, 1O2, and active chlorine (Cl2, HOCl) in the CUPP system was confirmed. A total of 24 intermediate products were detected, and four possible degradation pathways were identified for SMX. In addition, it was found that the CUPP system has a strong impact resistance to pH variations, groundwater anions, and natural organic matter stress. Undoubtedly, the CUPP system presents an innovative approach for the degradation of various emerging organic pollutants in groundwater.
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The development of accurate and interpretable models for predicting reaction constants of organic compounds with hydroxyl radicals is vital for advancing quantitative structure-activity relationships (QSAR) in pollutant degradation. Methods like molecular descriptors, molecular fingerprinting, and group contribution methods have limitations, as traditional machine learning struggles to capture all intramolecular information simultaneously. To address this, we established an integrated graph neural network (GNN) with approximately 12 million learnable parameters. GNN represents atoms as nodes and chemical bonds as edges, thus transforming molecules into a graph structures, effectively capturing microscopic properties while depicting atom connectivity in non-Euclidean space. Our datasets comprise 1401 pollutants to develop an integrated GNN model with Bayesian optimization, the model achieves root mean square errors of 0.165, 0.172, and 0.189 on the training, validation, and test datasets, respectively. Furthermore, we assess molecular structure similarity using molecular fingerprint to enhance the model's applicability. Afterwards, we propose a gradient weight mapping method for model explainability, uncovering the key functional groups in chemical reactions in artificial intelligence perspective, which would boost chemistry through artificial intelligence extreme arithmetic power.
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Background: Recently, heart failure (HF) and inflammatory bowel disease (IBD) have been considered to be related diseases with increasing incidence rates; both diseases are related to immunity. This study aims to analyze and identify immune-related gene (IRG) markers of HF and IBD through bioinformatics and machine learning (ML) methods and to explore their immune infiltration characteristics. Methods: This study used gene expressiondata (GSE120895, GSE21610, GSE4183) from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs) and compare them with IRGs from the ImmPort database to obtain differentially expressed immune-related genes (DIRGs). Functional enrichment analysis of IRGs was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, three machine models and protein-protein interactions (PPIs) were established to identify diagnostic biomarkers. The receiver operating characteristic (ROC) curves were applied to evaluate the diagnostic value of the candidate biomarkersin the validation set (GSE1145, GSE36807) and obtain their correlations with immune cells through the Spearman algorithm. Finally, the CIBERSORT algorithm was used to evaluate the immune cell infiltration of the two diseases. Results: Thirty-four DIRGs were screened and GO and KEGG analysis results showed that these genes are mainly related to inflammatory and immune responses. CCL2, CXCR2 and S100A9 were identified as biomarkers.The immune correlation results indicated in both diseases that CCL2 is positively correlated with mast cell activation, CXCR2 is positively correlated with neutrophils and S100A9 is positively correlated with neutrophils and mast cell activation. Analysis of immune characteristics showed that macrophages M2, macrophages M0 and neutrophils were present in both diseases. Conclusions: CCL2, CXCR2 and S100A9 are promising biomarkers that will become potential immunogenetic biomarkers for diagnosing comorbidities of HF and IBD. macrophages M2, macrophages M0, neutrophil-mediated inflammation and immune regulation play important roles in the development of HF and IBD and may become diagnostic and therapeutic targets.
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Microplastic-derived dissolved organic matter(MPDOM) during the aging process could be complexed with organic pollutants, heavy metals, and other contaminants and thus affect their migration and transformation. In this study, two types of microplastics, polyethylene terephthalate(PET) and polystyrene(PS), were selected to investigate the spectral properties of MPDOM and their effect on the complexation between MPDOM and sulfadiazine(SDZ)/copper ion(Cu2+) using the fluorescence quenching method, various spectroscopic analysis techniques, and the Ryan-Weber quenching model. The results of UV-vis absorption spectroscopy analysis showed that the molecular weight of the two MPDOMs decreased; the aromaticity and humification increased; and the carboxyl, carbonyl, hydroxyl, and ester substituents on aromatic rings increased after aging. The fluorescence quenching process between MPDOM and SDZ/Cu2+ was static quenching. After quenching, the aromaticity and humification of the two MPDOMs were similar, and the molecular weights were comparable. Combined with three-dimensional fluorescence spectra and parallel factor analysis, two humic-like components and one protein-like component were identified. In addition, the protein-like components of MPDOM reacted preferentially with SDZ and were more sensitive to Cu2+. The results of the Ryan-Weber quenching model revealed that the binding ability of humic-like components to PET-DOM was higher in both SDZ and Cu2+ quenching systems, but the binding ability of MPDOM in the SDZ quenching system was generally stronger than that in the Cu2+ system.
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Background: The Malayan pangolin (Manis javanica) is a placental mammal and is listed as Critically Endangered on the IUCN Red List of Threatened Species. Most previous attempts to breed pangolins in captivity have met with little success because of dietary issues, infections, and other complications, although a previous study reported breeding pangolins in captivity to the third generation. In our previous pangolin genome sequencing data analysis, we obtained a considerable amount of bacterial DNA from a pregnant female Malayan pangolin (named "UM3"), which was likely infected by Paraburkholderia fungorum-an agent of biodegradation and bioremediation in agriculture. Methodology: Here, we further confirmed and characterized this bacterial species using PCR, histological staining, whole-genome sequencing, and bioinformatics approaches. PCR assays with in-house designed primer sets and 16S universal primers showed clear positive bands in the cerebrum, cerebellum, lung, and blood of UM3 suggesting that UM3 might have developed septicaemia. Histological staining showed the presence of Gram-negative rod-shaped bacteria in the pangolin brain and lungs, indicating the colonization of the bacteria in these two organs. In addition, PCR screening of UM3's fetal tissues revealed the presence of P. fungorum in the gastrocnemius muscle, but not in other tissues that we examined. We also sequenced and reconstructed the genome of pangolin P. fungorum, which has a genome size of 7.7 Mbps. Conclusion: Our study is the first to present detailed evidence of the presence of P. fungorum in a pangolin and her fetus (although preliminary results were presented in our previous article). Here, we raise the concern that P. fungorum may potentially infect humans, especially YOPI (young, old, pregnant, and immunocompromised) people. Therefore, caution should be exercised when using this bacterial species as biodegradation or bioremediation agents in agriculture.
Subject(s)
Mammals , Pangolins , Humans , Pregnancy , Animals , Female , Pangolins/genetics , Mammals/genetics , Placenta , Eutheria/genetics , Sequence AnalysisABSTRACT
Cervical cancer is the fourth most common cancer in women, with a high disease burden worldwide. Human papillomavirus (HPV) vaccination reduces HPV-related infection and associated cervical lesions and cancers. Few studies have explored HPV vaccination impact in real-world settings in China. This study aims to monitor HPV vaccine uptake and its effects on HPV-related diseases, evaluating vaccine effectiveness in a real-world context and complementing clinical trial results. Electronic health records (EHRs) from 2010 to 2020 from the Yinzhou Regional Health Information Platform (YRHIP) will be queried/extracted to identify and monitor HPV vaccine uptake in females aged 9-45 years, and HPV-related screening and prevalence (i.e., cervical HPV infection, cervical intraepithelial neoplasia [CIN] grades 1-3, and cervical cancer) in a cohort of females aged 9-70 years. Cervical cancer screening guidelines and expert consultation will be used for intra-database validation, to determine the best algorithm for identifying HPV-related disease. Pre-launch (2010-2016) and post-launch (2018-2020) periods are predefined. A time trend analysis will be performed to describe the vaccination impact on disease prevalence and, if prerequisite conditions are met, vaccine effectiveness will be computed using logistic regression, adjusting for age, calendar year, history of screening and HPV infection. Cohort study design, outcomes validation, data linkage, and multi-step statistical analyses could provide valuable experience for designing other real-world studies in the future. The study outcomes can help inform policy-makers about uptake and HPV vaccination policy in girls and women in Yinzhou District, and provide insights on progress toward achieving goals set by the World Health Organization.
Subject(s)
Papillomavirus Infections , Papillomavirus Vaccines , Uterine Cervical Neoplasms , Humans , Female , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/prevention & control , Human Papillomavirus Viruses , Papillomavirus Infections/epidemiology , Papillomavirus Infections/prevention & control , Papillomavirus Infections/complications , Cohort Studies , Electronic Health Records , Motion Pictures , Early Detection of Cancer , Vaccination , China/epidemiologyABSTRACT
Pancreatic cancer (PC), one of the most aggressive and life-threatening human malignancies, is known for its resistance to cytotoxic therapies. This is increasingly ascribed to the subpopulation of undifferentiated cells, known as pancreatic cancer stem cells (PCSCs), which display greater evolutionary fitness than other tumor cells to evade the cytotoxic effects of chemotherapy. PCSCs are crucial for tumor relapse as they possess 'stem cell-like' features that are characterized by self-renewal and differentiation. However, the molecular mechanisms that maintain the unique characteristics of PCSCs are poorly understood. Here, we identify the histone methyltransferase KMT2A as a physical binding partner of an RNA polymerase-associated PHF5A-PHF14-HMG20A-RAI1 protein subcomplex and an epigenetic regulator of PCSC properties and functions. Targeting the protein subcomplex in PCSCs with a KMT2A-WDR5 inhibitor attenuates their self-renewal capacity, cell viability, and in vivo tumorigenicity.
Subject(s)
Pancreas , Pancreatic Neoplasms , Humans , Neoplastic Stem Cells , Pancreatic Neoplasms/genetics , Research Personnel , Histone Methyltransferases , High Mobility Group Proteins , Trans-Activators , RNA-Binding Proteins , Intracellular Signaling Peptides and ProteinsABSTRACT
As a flexible electricity pricing mechanism, critical peak pricing (CPP) is one of the important means of demand response under the electricity market. The existing CPP research does not take into account the carbon emission problem of units and weakens the difference between the use of terminal loads on critical peak days and non-critical peak days in the establishment of electricity price model, so this paper studies the feedback mechanism of CPP on coal consumption of power generation side units and proposes a dynamic CPP mechanism that takes into account terminal consumption satisfaction and coal consumption of power generation side units. Firstly, the influence mechanism of CPP on the power generation side is studied. Secondly, the consumer psychology theory is used to construct a user demand response model under critical peak days and non-critical peak days. Then, based on the difference in load usage of end users on critical peak days and non-critical peak days, a multi-objective CPP optimization model that considers the benefits of coal consumption and end user electricity expenditure on the power generation side is constructed. Finally, three scenarios were established to analyze the sensitivity of the user demand response model parameters, terminal satisfaction constraints, prices, and rate restrictions on CPP pricing, load improvement, and unit coal consumption reduction and verify the model's effectiveness. The results show that the proposed CPP optimization model has a significant effect on load improvement and carbon emission reduction; the user response gradient, terminal satisfaction, prices, and rate restrictions have a greater influence on the model optimization results, while the threshold and saturation values have little influence on the model optimization results.
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Chlorpyrifos (CPF) is an organophosphorus pesticide that is widely used in agricultural production and residential environments worldwide. In this study, we determined the harmful effects and toxicological mechanism of CPF in porcine trophectoderm (pTr) cells and the placenta of female mice during pregnancy. The findings revealed that CPF significantly decreased cell viability and increased intracellular lactate dehydrogenase (LDH) release in pTr cells. Similarly, CPF induced reproductive toxicity in pregnant maternal mice, including decreased maternal, fetal, and placental weights. Moreover, following CPF treatment, pTr cells and the placenta of female mice showed significant apoptosis. JC-1 staining and flow cytometry analysis also revealed that the mitochondrial membrane potential (MMP) of pTr cells treated with CPF was significantly depolarized. Additionally, CPF can induce an increase in reactive oxygen species (ROS) and barrier dysfunction in pTr cells and the placenta of female mice. We further verified that CPF-induced mitochondrial apoptosis is mediated by the MAPK signaling pathway, as shown by using of small molecular inhibitors of related proteins. Also, CPF-induced oxidative stress, barrier dysfunction, and mitochondrial apoptosis in pTr cells were alleviated by U0126, an inhibitor of the ERK/MAPK signaling pathway. These findings suggested that exposure to CPF in early pregnancy might be a potential risk fator affecting placental formation and function in humans and animals.
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As a natural aldehyde organic compound, cinnamaldehyde (CA) is one of the main components of cinnamon essential oil with multiple bioactivities. In this study, we investigated the protective effects of CA on zearalenone (ZEA)-induced apoptosis, barrier dysfunction and mucin reduction, as well as underlying mechanisms in LS174T cells. In the present study, cells pre-treated with or without CA for 24 h were left untreated or subjected to ZEA for indicated time points Our results showed that 10 µM CA significantly prevented ZEA-induced cell viability decline, reversed ZEA-induced increase of the LDH level, cell cycle disruption and apoptosis in LS174T cells. Periodic acid-schiff (PAS) staining analysis showed that CA significantly alleviated the reduction of mucin secretion in LS174T cells caused by ZEA exposure. Western blot analysis showed that CA significantly reversed ZEA-induced reduction of the expression of mucin 2 (MUC2) and tight junction (TJ) proteins (claudin-1, claudin-3, ZO-1 and ZO-2) in LS174T cells. Notably, CA can significantly reduce the upregulation of the main effector of MAPK and NF-κB signaling pathways in LS174T cells. Further study showed that CA protects cells against ZEA-induced cellular damage through JNK/NF-κB signaling pathway in LS174T cells. Supplementation with CA might be an potential strategy to alleviate the damaging effect of ZEA on epithelial cells.