BACKGROUND: We aimed to evaluate the interaction between colorectal adenoma risks among asymptomatic individuals in terms of metabolic health status and obesity, and examine the normal waist-to-hip ratio (WHR) in adults with colorectal adenoma risk. METHODS: A cross-sectional, retrospective study was conducted at MacKay Memorial Hospital involving 16,996 participants who underwent bidirectional gastrointestinal endoscopy between 2013 and 2023. The study recorded important clinicopathological characteristics, including age, body mass index and WHR, Framingham Risk Score (FRS), blood glucose level, and Helicobacter pylori (H. pylori) infection status. RESULTS: Multivariate logistic regression analysis demonstrated that elevated hemoglobin A1C (HbA1c), increased FRS, positive H. pylori infection, and WHR ≥ 0.9 are independent risk factors for colorectal adenoma. In examining the interaction between FRS and WHR using multivariate logistic regression to evaluate adenoma risk, the OR for the interaction term was 0.95, indicating a decline in adenoma risk when considering the interaction between these two factors. Incorporating HbA1c into the analysis, evaluating the interaction between FRS and WHR still demonstrated a statistically significant impact on adenoma risk (OR 0.96, p < 0.001). Participants with WHR < 0.9, elevated FRS, positive H. pylori infection, and increased HbA1c levels were associated with a higher risk of colorectal adenoma formation. Remarkably, the increased risk of adenoma due to rising HbA1c levels was statistically significant only for those with a WHR < 0.9. CONCLUSIONS: An increase in FRS and HbA1c or a positive H. pylori infection still warrants vigilance for colorectal adenoma risk when WHR is 0.9. These factors interacted with each other and were found to have a minimal decline in adenoma risk when considering the interaction between WHR and FRS.
Introduction: In urban traffic management, the timely detection of road faults plays a crucial role in improving traffic efficiency and safety. However, conventional methods often fail to fully leverage the information from road topology and traffic data. Methods: To address this issue, we propose an innovative detection system that combines Artificial Neural Networks (ANNs), specifically Graph Convolutional Networks (GCN), Bidirectional Gated Recurrent Units (BiGRU), and self-attention mechanisms. Our approach begins by representing the road topology as a graph and utilizing GCN to model it. This allows us to learn the relationships between roads and capture their structural dependencies. By doing so, we can effectively incorporate the spatial information provided by the road network. Next, we employ BiGRU to model the historical traffic data, enabling us to capture the temporal dynamics and patterns in the traffic flow. The BiGRU architecture allows for bidirectional processing, which aids in understanding the traffic conditions based on both past and future information. This temporal modeling enhances our system's ability to handle time-varying traffic patterns. To further enhance the feature representations, we leverage self-attention mechanisms. By combining the hidden states of the BiGRU with self-attention, we can assign importance weights to different temporal features, focusing on the most relevant information. This attention mechanism helps to extract salient features from the traffic data. Subsequently, we merge the features learned by GCN from the road topology and BiGRU from the traffic data. This fusion of spatial and temporal information provides a comprehensive representation of the road status. Results and discussions: By employing a Multilayer Perceptron (MLP) as a classifier, we can effectively determine whether a road is experiencing a fault. The MLP model is trained using labeled road fault data through supervised learning, optimizing its performance for fault detection. Experimental evaluations of our system demonstrate excellent performance in road fault detection. Compared to traditional methods, our system achieves more accurate fault detection, thereby improving the efficiency of urban traffic management. This is of significant importance for city administrators, as they can promptly identify road faults and take appropriate measures for repair and traffic diversion.
The high use of plastic wraps leads to significant environmental pollution. In this study, the surface structure and microbial community evolution of commercially available plastic wraps [polyethylene (PE), polyvinyl chloride (PVC), polyvinylidene chloride (PVDC), and polylactic acid (PLA)] in constructed wetlands (CWs) were investigated. The results indicated that all plastic wraps gradually decreased in molecular weight, crystallinity, melting, and crystallization temperatures, whereas a gradual increase was observed in the surface roughness, polymer dispersity index (PDI), carbonyl index (CI) and Shannon index of microorganisms colonizing the CWs. The aging rate of the plastic wrap was in the order: PLAâ¯>â¯PVCâ¯>â¯PEâ¯>â¯PVDC, at the same site in the CWs, and it was in the order: soil surface > plant roots > subsoil, for the same plastic wrap. The diversity of microorganisms colonizing the same plastic wrap was in the order: plant roots > subsoil > soil surface. The Shannon indices of microorganisms on plastic wraps were lower than those in the soil, indicating that the diversity of microorganisms colonizing plastic wraps is limited. Additionally, the microbial community structure on the plastic surface was co-differentiated by the plastic type, placement position in the CWs, and aging time. Significantly different microbial community structures were found on the PVC and PVDC wrap surfaces, revealing that the chlorine in plastics limits microbial diversity. Unclassified members of Rhizobiaceae and Pseudomonadaceae were the dominant genera on the surface of the plastic wraps, suggesting that they may be the microorganisms involved in plastic degradation processes. The study provides valuable perspectives to facilitate a comprehensive understanding of the migration, fate, and environmental risks associated with microplastics (MPs) in wetlands.
Spider silk is a promising material with great potential in biomedical applications due to its incredible mechanical properties and resistance to degradation of commercially available bacterial strains. However, little is known about the bacterial communities that may inhabit spider webs and how these microorganisms interact with spider silk. In this study, we exposed two exopolysaccharide-secreting bacteria, isolated from webs of an orb spider, to major ampullate (MA) silk from host spiders. The naturally occurring lipid and glycoprotein surface layers of MA silk were experimentally removed to further probe the interaction between bacteria and silk. Extensibility of major ampullate silk produced by Triconephila clavata that was exposed to either Microbacterium sp. or Novosphigobium sp. was significantly higher than that of silk that was not exposed to bacteria (differed by 58.7%). This strain-enhancing effect was not observed when the lipid and glycoprotein surface layers of MA silks were removed. The presence of exopolysaccharides was detected through NMR from MA silks exposed to these two bacteria but not from those without exposure. Here we report for the first time that exopolysaccharide-secreting bacteria inhabiting spider webs can enhance extensibility of host MA silks and silk surface layers play a vital role in mediating such effects.
Silk , Spiders , Animals , Spiders/microbiology , Spiders/metabolism , Silk/metabolism , Bacteria/metabolism , Polysaccharides, Bacterial/metabolism
Metals are recognized as important factors related to breast cancer (BC) risk. Homologous recombination repair (HRR) genes might modify the toxicity of metals by influencing the distribution and metabolism of metal compounds. This study aims to investigate the modification effects of single nucleotide polymorphisms (SNPs) in HRR genes on the associations between urinary metals and BC risk. A total of 685 BC cases and 741 controls were recruited from October 2009 to December 2012. Twenty-one metals were analyzed in urine samples using inductively coupled plasma mass spectrometry (ICP-MS), and three SNPs (LIG3 rs1052536, RFC1 rs6829064, and RAD54L rs17102086) were genotyped. We identified significant interactions between four metals and two SNPs on the risk of BC. For LIG3 rs1052536 C/T variant, participants with CT/TT genotypes exposed to higher cobalt (Co) levels had higher BC risk compared to those with CC genotype (Pinteraction = 0.048). For RAD54L rs17102086 T/C variant, participants with TT genotype who were exposed to higher levels of zinc (Zn), Co, arsenic (As), and strontium (Sr) had more pronounced BC risk than the CC/TC genotypes (all Pinteraction < 0.05). This study showed compelling evidence for the interaction between genetic variants within the HRR system and urinary metals on BC risk. Our findings highlight the need to consider genetic makeup when evaluating the carcinogenic or protective potential of metals.
BACKGROUND: Temporomandibular disorders (TMD) is the leading cause of pain and disability among frequently occurring facial pain and the second leading cause of musculoskeletal conditions. AIM: We examined whether acupuncture could alleviate pain intensity in patients with temporomandibular disorders (TMD). DESIGN AND METHODS: Sixty participants with TMD were randomly assigned (ratio 1:1) to receive three acupuncture or sham acupuncture sessions weekly for 4 weeks. The primary outcome was the change in the mean weekly pain intensity from baseline to week 4. Secondary and exploratory outcomes included proportion of participants with ≥30% or ≥ 50% reduction in pain intensity, change in jaw opening and movement, graded chronic pain scale, jaw functional limitations scale-20-item, Depression, Anxiety and Stress Scales-21, Pittsburgh sleep quality index at week 4 and 8, and the pressure pain threshold and surface electromyography at week 4. RESULTS AND CONCLUSION: The acupuncture group showed significantly reduced pain intensity compared to the sham group at week 4 (-1.49, 95% confidence interval [CI]: -2.32 to -0.65; P < 0.001) and week 8 (-1.23, 95% CI: -2.11 to -0.54; P = 0.001). Acupuncture's effectiveness surpassed sham's at 4 weeks and lasted 8 weeks. Participants in the acupuncture group experienced significantly greater improvements in the 30% and 50% response rate, jaw opening and movement, GCPS, JFLS-20, DASS-21 and PSQI than those in the sham acupuncture group. There were no significant between-group differences in PPT and sEMG. In summary, acupuncture provided marked pain relief and improvement in physical and emotional function for patients with TMD compared with sham acupuncture.
BACKGROUND: C-X-C motif chemokine ligand 1 (CXCL1) and epithelial growth factor (EGF) are highly secreted by oral squamous cell carcinoma (OSCC) cells and tumor-associated macrophages, respectively. Recent studies have shown that there is intricate "cross-talk" between OSCC cells and macrophages. However, the underlying mechanisms are still poorly elucidated. METHODS: The expression of CXCL1 was detected by immunohistochemistry in OSCC clinical samples. CXCL1 levels were evaluated by RTâPCR and ELISA in an OSCC cell line and a normal epithelial cell line. The expression of EGF was determined by RTâPCR and ELISA. The effect of EGF on the proliferation of OSCC cells was evaluated by CCK-8 and colony formation assays. The effect of EGF on the migration and invasion ability and epithelial-mesenchymal transition (EMT) of OSCC cells was determined by wound healing, Transwell, RTâPCR, Western blot and immunofluorescence assays. The polarization of macrophages was evaluated by RTâPCR and flow cytometry. Western blotting was used to study the molecular mechanism in OSCC. RESULTS: The expression of C-X-C motif chemokine ligand 1 (CXCL1) was higher in the OSCC cell line (Cal27) than in immortalized human keratinocytes (Hacat cells). CXCL1 derived from Cal27 cells upregulates the expression of epithelial growth factor (EGF) in macrophages. Paracrine stimulation mediated by EGF further facilitates the epithelial-mesenchymal transition (EMT) of Cal27 cells and initiates the upregulation of CXCL1 in a positive feedback-manner. Mechanistically, EGF signaling-induced OSCC cell invasion and migration can be ascribed to the activation of NF-κB signaling mediated by the epithelial growth factor receptor (EGFR), as determined by western blotting. CONCLUSIONS: OSCC cell-derived CXCL1 can stimulate the M2 polarization of macrophages and the secretion of EGF. Moreover, EGF significantly activates NF-κB signaling and promotes the migration and invasion of OSCC cells in a paracrine manner. A positive feedback loop between OSCC cells and macrophages was formed, contributing to the promotion of OSCC progression.
OBJECTIVE: Given the scarcity of studies analyzing the clinical predictors of pediatric septic cases that would progress to septic shock, this study aimed to determine strong predictors for pediatric emergency department (PED) patients with sepsis at risk for septic shock and mortality. METHODS: We conducted chart reviews of patients with ≥ 2 age-adjusted quick Sequential Organ Failure Assessment score (qSOFA) criteria to recognize patients with an infectious disease in two tertiary PEDs between January 1, 2021, and April 30, 2022. The age range of included patients was 1 month to 18 years. The primary outcome was development of septic shock within 48 h of PED attendance. The secondary outcome was sepsis-related 28-day mortality. Initial important variables in the PED and hemodynamics with the highest and lowest values during the first 24 h of admission were also analyzed. RESULTS: Overall, 417 patients were admitted because of sepsis and met the eligibility criteria for the study. Forty-nine cases progressed to septic shock within 48 h after admission and 368 were discharged without progression. General demographics, laboratory data, and hemodynamics were analyzed by multivariate analysis. Only the minimum diastolic blood pressure/systolic blood pressure ratio (D/S ratio) during the first 24 h after admission remained as an independent predictor of progression to septic shock and 28-day mortality. The best cutoff values of the D/S ratio for predicting septic shock and 28-day mortality were 0.52 and 0.47, respectively. CONCLUSIONS: The D/S ratio is a practical bedside scoring system in the PED and had good discriminative ability in predicting the progression of septic shock and in-hospital mortality in PED patients. Further validation is essential in other settings.
Blood Pressure , Emergency Service, Hospital , Sepsis , Shock, Septic , Humans , Male , Female , Child , Shock, Septic/mortality , Shock, Septic/diagnosis , Shock, Septic/physiopathology , Child, Preschool , Infant , Adolescent , Sepsis/mortality , Sepsis/diagnosis , Sepsis/complications , Sepsis/physiopathology , Retrospective Studies , Organ Dysfunction Scores , Disease Progression , Fever , Hospital Mortality
Background: Previous studies have shown that endoplasmic reticulum stress (ERS) -induced apoptosis is involved in the pathogenesis of dilated cardiomyopathy (DCM). However, the molecular mechanism involved has not been fully characterized. Results: In total, eight genes were obtained at the intersection of 1,068 differentially expressed genes (DEGs) from differential expression analysis between DCM and healthy control (HC) samples, 320 module genes from weighted gene co-expression network analysis (WGCNA), and 2,009 endoplasmic reticulum stress (ERGs). These eight genes were found to be associated with immunity and angiogenesis. Four of these genes were related to apoptosis. The upregulation of MX1 may represent an autocompensatory response to DCM caused by a virus that inhibits viral RNA and DNA synthesis, while acting as an autoimmune antigen and inducing apoptosis. The upregulation of TESPA1 would lead to the dysfunction of calcium release from the endoplasmic reticulum. The upregulation of THBS4 would affect macrophage differentiation and apoptosis, consistent with inflammation and fibrosis of cardiomyocytes in DCM. The downregulation of MYH6 would lead to dysfunction of the sarcomere, further explaining cardiac remodeling in DCM. Moreover, the expression of genes affecting the immune micro-environment was significantly altered, including TGF-ß family member. Analysis of the co-expression and competitive endogenous RNA (ceRNA) network identified XIST, which competitively binds seven target microRNAs (miRNAs) and regulates MX1 and THBS4 expression. Finally, bisphenol A and valproic acid were found to target MX1, MYH6, and THBS4. Conclusion: We have identified four ERS-related genes (MX1, MYH6, TESPA1, and THBS4) that are dysregulated in DCM and related to apoptosis. This finding should help deepen understanding of the role of endoplasmic reticulum stress-induced apoptosis in the development of DCM.
BACKGROUND: Carbon-based nanozymes have recently received enormous concern, however, there is still a huge challenge for inexpensive and large-scale synthesis of magnetic carbon-based "Two-in-One" mimics with both peroxidase (POD)-like and laccase-like activities, especially their potential applications in multi-mode sensing of antibiotics and neurotransmitters in biofluids. Although some progresses have been made in this field, the feasibility of biomass-derived carbon materials with both POD-like and laccase-like activities by polyatomic doping strategy is still unclear. In addition, multi-mode sensing platform can provide a more reliable result because of the self-validation, self-correction and mutual agreement. Nevertheless, the use of magnetic carbon-based nanozyme sensors for the multi-mode detection of antibiotics and neurotransmitters have not been investigated. RESULTS: We herein report a shrimp shell-derived N, O-codoped porous carbon confined magnetic CuFe2O4 nanosphere with outstanding laccase-like and POD-like activities for triple-mode sensing of antibiotic d-penicillamine (D-PA) and chloramphenicol (CPL), as well as colorimetric detection of neurotransmitters in biofluids. The magnetic CuFe2O4/N, O-codoped porous carbon (MCNPC) armored mimetics was successfully fabricated using a combined in-situ coordination and high-temperature crystallization method. The synthesized MCNPC composite with superior POD-like activity can be used for colorimetric/temperature/smartphone-based triple-mode detection of D-PA and CPL in goat serum. Importantly, the MCNPC nanozyme can also be used for colorimetric analysis of dopamine and epinephrine in human urine. SIGNIFICANCE: This work not only offered a novel strategy to large-scale, cheap synthesize magnetic carbon-based "Two-in-One" armored mimetics, but also established the highly sensitive and selective platforms for triple-mode monitoring D-PA and CPL, as well as colorimetric analysis of neurotransmitters in biofluids without any tanglesome sample pretreatment.
Anti-Bacterial Agents , Carbon , Copper , Neurotransmitter Agents , Carbon/chemistry , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/urine , Anti-Bacterial Agents/blood , Neurotransmitter Agents/urine , Neurotransmitter Agents/analysis , Neurotransmitter Agents/blood , Porosity , Copper/chemistry , Humans , Nanospheres/chemistry , Colorimetry/methods , Ferric Compounds/chemistry , Biomimetic Materials/chemistry , Animals , Biosensing Techniques/methods , Chloramphenicol/analysis , Chloramphenicol/urine , Limit of Detection
Background: Cancer has the highest mortality rate among gynecological cancers and poses a serious threat to women's lives. However, the treatment options for ovarian cancer are still limited, and exploring effective targeted biomarkers is particularly important for predicting and treating ovarian cancer. Therefore, it is necessary to explore the molecular mechanisms of the occurrence and development of ovarian cancer. Methods: This investigation encompassed the analysis of gene expression profiles, measurement of transcription levels of potential target genes in peripheral blood samples from ovarian cancer patients and characterization of the ovarian cancer-related secretory protein sphingomyelin phosphodiesterase acid-like 3B (SMPDL3B). Through bioinformatics analysis, potential target genes were identified, and their association with overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients was assessed utilizing relevant databases. Subsequently, differences in target gene expression in ovarian cancer tissue samples were validated through protein blotting and quantitative real-time PCR (qRT-qPCR). Cell proliferation assays using the cell count kit-8 (CCK-8) method, as well as transwell chamber assay and pre coated matrix gel chamber assay were employed to elucidate the role of SMPDL3B in ovarian cancer cell migration and invasion. Results: This study revealed a substantial upregulation of SMPDL3B in the serum of ovarian cancer patients, correlating with an unfavorable prognosis. High SMPDL3B expression was linked not only to increased proliferation of ovarian cancer cells, but also enhanced migration and invasion. Remarkably, the knockdown the human alkaline ceramidase 2 (ACER2) gene in cancer cells with heightened SMPDL3B expression significantly inhibited cell proliferation, migration, and invasion induced by SMPDL3B activation (P<0.05), highlighting the functional interplay between ACER2 and SMPDL3B in ovarian cancer. Conclusions: In summary, this study proposes SMPDL3B as a prognostic marker for ovarian cancer, with implications for potential therapeutic intervention targeting the ACER2-SMPDL3B axis.
The most prevalent glycoprotein on the influenza virus envelope is called hemagglutinin (HA), yet little is known about its involvement in the pathophysiology and etiology of severe influenza pneumonia. Here, after stimulating human bronchial epithelial cells (16-HBE) and mice with HA of H1N1 for 12â¯h, we investigated the proliferation, migration, inflammatory cytokines expression, and apoptosis in 16-HBE and the pathological damage in mouse lung tissue. The expression of inflammatory cytokines plasminogen activator inhibitor 1(PAI-1), urokinase-type (uPA) and tissue-type (tPA) plasminogen activators, and apoptosis were all enhanced by HA, which also prevented the proliferation and migration of bronchial epithelial cells. HA enhanced up-regulated PAI-1, uPA, and tPA protein expression within mouse lung tissue and caused lung injury. In conclusion, HA alone, but not the whole H1N1 virus, induces lung tissue injury by inhibiting cell proliferation and migration, while promoting the expression of inflammatory cytokines and apoptosis.
Introduction Given that PD-L1 is a crucial immune checkpoint in regulating T cell responses, the aim of this study was to explore the impact of PD-L1 gene polymorphism and its interaction with cooking with solid fuel on susceptibility to tuberculosis (TB) in Chinese Han populations. Methods A total of 503 TB patients and 494 healthy controls were enrolled in this case-control study. Mass spectrometry (MS) technology was applied to genotype rs2297136 and rs4143815 of PD-L1 genes. The associations between SNPs and TB were assessed using unconditional logistic regression analysis. Marginal structural linear odds models were used to estimate the gene-environment interactions. Results Compared with genotype CC, genotypes GG and CG + GG at rs4143815 locus were significantly associated with susceptibility to TB (OR: 3.074 and 1.506, respectively, P<0.05). However, no statistical association was found between rs2297136 SNP and TB risk. Moreover, the relative excess risk of interaction (RERI) between rs4143815 of the PD-L1 gene and cooking with solid fuel was 2.365 (95% CI 1.922,2.809), suggesting positive interactions with TB susceptibility. Conclusion The rs4143815 polymorphism of the PD-L1 gene was associated with susceptibility to TB in Chinese Han populations. There were significantly positive interactions between rs4143815 and cooking with solid fuel.
Muscarinic acetylcholine receptors (mAChRs) play a significant role in the pathophysiology of schizophrenia. Although activating mAChRs holds potential in addressing the full range of schizophrenia symptoms, clinical application of many non-selective mAChR agonists in cognitive deficits, positive and negative symptoms is hindered by peripheral side effects (gastrointestinal disturbances and cardiovascular effects) and dosage restrictions. Ligands binding to the allosteric sites of mAChRs, particularly the M1 and M4 subtypes, demonstrate activity in improving cognitive function and amelioration of positive and negative symptoms associated with schizophrenia, enhancing our understanding of schizophrenia. The article aims to critically examine current design concepts and clinical advancements in synthesizing and designing small molecules targeting M1/M4, providing theoretical insights and empirical support for future research in this field.
Antipsychotic Agents , Receptor, Muscarinic M1 , Schizophrenia , Antipsychotic Agents/pharmacology , Antipsychotic Agents/chemistry , Antipsychotic Agents/therapeutic use , Molecular Structure , Receptor, Muscarinic M1/metabolism , Receptor, Muscarinic M1/agonists , Receptor, Muscarinic M1/antagonists & inhibitors , Receptor, Muscarinic M4/metabolism , Receptor, Muscarinic M4/antagonists & inhibitors , Schizophrenia/drug therapy , Schizophrenia/metabolism
To investigate the effect of Jiedu Xiaozheng Yin (JXY) on the polarization of macrophages in colitis-associated colon cancer (CAC). An orthotopic model of CAC was established to monitor changes in the pathological state of mice. Colon length, number of colon tumors were recorded, and indices for liver, spleen, and thymus were calculated. Hematoxylin and eosin (H&E) staining was employed to observe intestinal mucosal injury and tumor formation. Immunohistochemistry (IHC) staining was utilized to investigate the effect of JXY on M1 and M2 polarization of macrophages in the colonic mucosa of CAC mice. For in vitro experiments, RT-qPCR (Reverse Transcription-quantitative PCR) and flow cytometry were used to observe the effect of JXY on various M1-related molecules such as IL-1ß, TNF-α, iNOS, CD80, CD86, and its phagocytic function as well as M2-related molecules including Arg-1, CD206, and IL-10. Subsequently, after antagonizing the TLR4 pathway with antagonists (TAK242, PDTC, KG501, SR11302, LY294002), the expression of IL-6, TNF-α, iNOS, and IL-1ß mRNA were detected by RT-qPCR. In vivo experiments, the results showed that JXY improved the pathological condition of mice in general. And JXY treatment decreased the shortening of colon length and number of tumors as compared to non-treated CAC mice. Additionally, JXY treatment improved the lesions in the colonic tissue and induced a polarization of intestinal mucosal macrophages towards the M1 phenotype, while inhibiting polarization towards the M2 phenotype. In vitro experiments further confirmed that JXY treatment promoted the activation of macrophages towards the M1 phenotype, leading to increased expression of IL-1ß, TNF-α, iNOS, CD80, CD86, as well as enhanced phagocytic function. JXY treatment concomitantly inhibited the expression of M2-phenotype related molecules Arginase-1 (Arg-1), CD206, and IL-10. Furthermore, JXY inhibited M1-related molecules such as IL-6, TNF-α, iNOS, and IL-1ß after antagonizing the TLR4 pathway. Obviously, JXY could exhibit inhibitory effects on the development of colon tumors in mice with CAC by promoting M1 polarization through TLR4-mediated signaling and impeding M2 polarization of macrophages.
Colitis-Associated Neoplasms , Drugs, Chinese Herbal , Macrophages , Animals , Mice , Colitis-Associated Neoplasms/drug therapy , Colitis-Associated Neoplasms/metabolism , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Interleukin-10/metabolism , Interleukin-6/metabolism , Macrophages/drug effects , Macrophages/metabolism , Phenotype , Toll-Like Receptor 4/drug effects , Toll-Like Receptor 4/metabolism , Tumor Necrosis Factor-alpha/metabolism
The chemical and optical properties of secondary organic aerosols (SOA) have been widely studied through environmental chamber experiments, and some of the results have been parametrized in atmospheric models to help understand their radiative effects and climate influence. While most chamber studies investigate the aerosol formed from a single volatile organic compound (VOC), the potential interactions between reactive intermediates derived from VOC mixtures are not well understood. In this study, we investigated the SOA formed from pure and mixtures of anthropogenic (phenol and 1-methylnaphthalene) and/or biogenic (longifolene) VOCs using continuous-flow, high-NOx photooxidation chamber experiments to better mimic ambient conditions. SOA optical properties, including single scattering albedo (SSA), mass absorption coefficient (MAC), and refractive index (RI) at 375 nm, and chemical composition, including the formation of oxygenated organic compounds, organic-nitrogen compounds (including organonitrates and nitro-organics), and the molecular structure of the major chromophores, were explored. Additionally, the imaginary refractive index values of SOA in the multi-VOC system were predicted using a linear-combination assumption and compared with the measured values. When two VOCs were oxidized simultaneously, we found evidence for changes in SOA chemical composition compared to SOA formed from single-VOC systems, and this change led to nonlinear effects on SOA optical properties. The nonlinear effects were found to vary between different systems.
BACKGROUND: Sequencing the mitochondrial genome has been increasingly important for the investigation of primary mitochondrial diseases (PMD) and mitochondrial genetics. To overcome the limitations originating from PCR-based mtDNA enrichment, we set out to develop and evaluate a PCR-independent approach in this study, named Pime-Seq (PCR-independent mtDNA enrichment and next generation Sequencing). RESULTS: By using the optimized mtDNA enrichment procedure, the mtDNA reads ratio reached 88.0 ± 7.9% in the sequencing library when applied on human PBMC samples. We found the variants called by Pime-Seq were highly consistent among technical repeats. To evaluate the accuracy and reliability of this method, we compared Pime-Seq with lrPCR based NGS by performing both methods simultaneously on 45 samples, yielding 1677 concordant variants, as well as 146 discordant variants with low-level heteroplasmic fraction, in which Pime-Seq showed higher reliability. Furthermore, we applied Pime-Seq on 4 samples of PMD patients retrospectively, and successfully detected all the pathogenic mtDNA variants. In addition, we performed a prospective study on 192 apparently healthy pregnant women during prenatal screening, in which Pime-Seq identified pathogenic mtDNA variants in 4 samples, providing extra information for better health monitoring in these cases. CONCLUSIONS: Pime-Seq can obtain highly enriched mtDNA in a PCR-independent manner for high quality and reliable mtDNA deep-sequencing, which provides us an effective and promising tool for detecting mtDNA variants for both clinical and research purposes.
DNA, Mitochondrial , High-Throughput Nucleotide Sequencing , Mitochondrial Diseases , Polymerase Chain Reaction , Humans , DNA, Mitochondrial/genetics , High-Throughput Nucleotide Sequencing/methods , Female , Polymerase Chain Reaction/methods , Mitochondrial Diseases/genetics , Mitochondrial Diseases/diagnosis , Pregnancy , Reproducibility of Results , Male , Adult
Endometriosis diagnosis is usually delayed. The gold standard for diagnosing endometriosis is laparoscopy, which is invasive and accompanied by several risks. Currently, there are no effective non-invasive biomarkers for diagnosing endometriosis. Here, we investigated whether metabolites whose levels are altered in patients with endometriosis hold potential as diagnostic biomarkers for the disease. This case-control study involved 32 patients with endometriosis and 29 patients with other benign gynecological disease. The diagnosis of all patients was confirmed through postoperative histopathological examination, and the patients were divided into two groups: an endometriosis group (EM) and a control group. Fasting blood was collected and used for non-targeted metabolomic-based detection. The data were processed through principal component analysis, orthogonal partial least squares discriminant analysis, and significance analysis of microarrays. A univariate receiver operating characteristic curve was used to evaluate the diagnostic value of the metabolites. The metabolite profiles of patients with endometriosis were markedly different compared with those of the controls. In addition, several metabolic pathways, including biosynthesis of unsaturated fatty acids, arginine biosynthesis, and glutathione metabolism, were altered. Ornithine and medorinone showed better potential as biomarkers for endometriosis diagnosis than CA125. We analyzed the altered metabolic profiles in patients with endometriosis and found ornithine and medorinone as potential non-invasive biomarkers for endometriosis diagnosis, whereas the combined ornithine-medorinone diagnosis is more valuable. These findings may help advance research on non-invasive diagnostic biomarkers for endometriosis. Further research with an improved study design and a larger cohort should be performed to confirm the diagnostic potential and clinical application of these biomarkers.
Manipulating surface charge, electric field, and plasma afterglow in a non-equilibrium plasma is critical to control plasma-surface interaction for plasma catalysis and manufacturing. Here, we show enhancements of surface charge, electric field during breakdown, and afterglow by ferroelectric barrier discharge. The results show that the ferroelectrics manifest spontaneous electric polarization to increase the surface charge by two orders of magnitude compared to discharge with an alumina barrier. Time-resolved in-situ electric field measurements reveal that the fast polarization of ferroelectrics enhances the electric field during the breakdown in streamer discharge and doubles the electric field compared to the dielectric barrier discharge. Moreover, due to the existence of surface charge, the ferroelectric electrode extends the afterglow time and makes discharge sustained longer when alternating the external electric field polarity. The present results show that ferroelectric barrier discharge offers a promising technique to tune plasma properties for efficient plasma catalysis and electrified manufacturing.
