Proteomic profiling of TBC1 domain family member 21-null sperms reveals the critical roles of TEKT 1 in their tail defects.

BACKGROUND: Approximately 7% of the males exhibit reduced fertility; however, the regulatory genes and pathways involved remain largely unknown. TBC1 domain family member 21 (TBC1D21) contains a conserved RabGAP catalytic domain that induces GDP/GTP exchange to inactivate Rabs by interacting with microtubules. We previously reported that Tbc1d21-null mice exhibit severe sperm tail defects with a disrupted axoneme, and that TBC1D21 interacts with RAB10. However, the pathological mechanisms underlying the Tbc1d21 loss-induced sperm tail defects remain unknown. RESULTS: Murine sperm from wild-type and Tbc1d21-null mice were comparatively analyzed using proteomic assays. Over 1600 proteins were identified, of which 15 were significantly up-regulated in Tbc1d21-null sperm. Notably, several tektin (TEKT) family proteins, belonging to a type of intermediate filament critical for stabilizing the microtubular structure of cilia and flagella, were significantly up-regulated in Tbc1d21-/- sperm. We also found that TBC1D21 interacts with TEKT1. In addition, TEKT1 co-localized with RAB10 during sperm tail formation. Finally, we found Tbc1d21-null sperm exhibited abnormal accumulation of TEKT1 in the midpiece region, accompanied by disrupted axonemal structures. CONCLUSIONS: These results reveal that TBC1D21 modulates TEKTs protein localization in the axonemal transport system during sperm tail formation.

Feature-based maximum entropy for geophysical properties of the seabeda).

The coherent recombination of a direct and seabed reflected path is sensitive to the geophysical properties of the seabed. The concept of feature-based inversion is used in the analysis of acoustic data collected on a vertical line array (VLA) on the New England continental shelf break in about 200 m of water. The analysis approach for the measurements is based on a ray approach in which a direct and bottom reflected path is recombined, resulting in constructive and destructive interference of the acoustic amplitudes with frequency. The acoustic features have the form of prominent nulls of the measured received levels as a function of frequency as a broadband (500-4500 Hz) source passes the closest point of approach to the VLA. The viscous grain shearing (VGS) model is employed to parameterize a two-layer seabed model. The most likely seabed is a sand sediment with a porosity of about 0.42. There is a possibility of a thin (less than 0.5 m) surface layer having a slightly higher porosity between 0.45 and 0.50. Using the estimates for the VGS parameters inferred from the short-range frequency features, a normal mode model is used to predict the received acoustic levels over larger range scales.

Spatially confined CuFe2O4 nanosphere in N/O-codoped porous carbon mimetics for triple-mode sensing of antibiotics and visual detection of neurotransmitters in biofluids.

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.

Endoplasmic reticulum stress-related gene expression causes the progression of dilated cardiomyopathy by inducing apoptosis.

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.

Crosstalk between cancer cells and macrophages promotes OSCC cell migration and invasion through a CXCL1/EGF positive feedback loop.

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 RT‒PCR and ELISA in an OSCC cell line and a normal epithelial cell line. The expression of EGF was determined by RT‒PCR 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, RT‒PCR, Western blot and immunofluorescence assays. The polarization of macrophages was evaluated by RT‒PCR 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.

Effect of acupuncture for temporomandibular disorders: a randomized clinical trial.

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.

Contribution of sphingomyelin phosphodiesterase acid-like 3B to the proliferation, migration, and invasion of ovarian cancer cells.

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.

Genetic predisposition to bone mineral density and their health conditions in East Asians.

Osteoporosis, a condition defined by low bone mineral density (BMD) (typically < -2.5 SD), cause a higher fracture risk and lead to significant economic, social, and clinical impacts. Genome-wide studies mainly in Caucasians have found many genetic links to osteoporosis, fractures, and BMD, with limited research in East Asians. We investigated the genetic aspects of BMD in 86,716 individuals from the Taiwan Biobank and their causal links to health conditions within East Asians. A genome-wide association study (GWAS) was conducted, followed by observational studies, polygenic risk score assessments, and genetic correlation analyses to identify associated health conditions linked to BMD. GWAS and gene-based GWAS studies identified 78 significant SNPs and 75 genes related to BMD, highlighting pathways like Hedgehog, WNT-mediated, and TGF-ß. Our cross-trait linkage disequilibrium score regression analyses for BMD and osteoporosis consistently validated their genetic correlations with body mass index (BMI) and type 2 diabetes (T2D) in East Asians. Higher BMD was linked to lower osteoporosis risk but increased BMI and T2D, whereas osteoporosis linked to lower BMI, waist circumference, HbA1c, and reduced T2D risk. Bidirectional Mendelian randomization (MR) analyses revealed that a higher BMI causally increases BMD in East Asians. However, no direct causal relationships were found between BMD and T2D, or between osteoporosis and either BMI or T2D. This study identified key genetic factors for bone health in Taiwan, and revealed significant health conditions in East Asians, particularly highlighting the genetic interplay between bone health and metabolic traits like T2D and BMI.

We investigated how genetics affect bone health and related conditions like diabetes and obesity in 86,716 East Asians. Previously, most studies focused on Caucasian populations, but our work helps to understand these issues in East Asians. Our findings show that stronger bones are linked to a lower chance of osteoporosis but a higher risk of obesity and type 2 diabetes. On the other hand, those with osteoporosis tend to have lower body weight and a decreased risk of diabetes, illustrating a complex relationship between bone health and body metabolism. Future research will focus on deeper genetic interactions and developing targeted interventions for bone health and related metabolic disorders in East Asians.

Psychomotor symptoms, cognitive impairments and suicidal thoughts after COVID-19 infection: a case report and the possible allostatic mechanism.

Although neuropsychiatric manifestations are common in survivors of coronavirus disease 2019 (COVID-19), the pathophysiology is not yet elucidated. Here we describe the case of a geriatric inpatient who developed postCOVID depression with psychomotor retardation, anxiety, hopelessness, executive function problems, and suicidal ideations. The language problems and cognitive impairments coemerged with the motor problems. We propose a mechanism associated with problems in energy prediction and regulation in which the coronavirus infection, which causes neuroinflammation and viral activity in the nervous system, interferes with the reward pathway and sensory prediction process. Sigma-1 receptor agonists such as sertraline may regulate energy expenditure and, thus, be beneficial to the process. The treatment improvements in our patient included those in the autonomic nervous system, activity, and circadian rhythm.

Associations among global long interspersed nuclear element-1 DNA methylation, metal exposure, and chronic kidney disease.

Long interspersed nuclear element-1 (LINE-1) methylation serves as an indicator of global DNA methylation. This study explored the correlation between LINE-1 methylation and chronic kidney disease (CKD). We also evaluated whether LINE-1 methylation could modify the association between CKD and metal exposure. A total of 213 patients with clinically defined CKD, without hemodialysis and 416 age and sex matched controls were recruited. Levels of LINE-1 methylation, total urinary arsenic, blood lead, blood cadmium, and plasma selenium were assessed. The results reveal a positive association between LINE-1 methylation and CKD, with an odds ratio (OR) of 5.30 (95% confidence interval: 2.81 to 9.99). Total urinary arsenic and blood cadmium concentrations were positively related with LINE-1 methylation. This study was the first to observe that low plasma selenium, high blood cadmium, and high blood lead levels significantly and additively interact with increased LINE-1 methylation to increase the OR of CKD. Additionally, high LINE-1 methylation interacted multiplicatively with low plasma selenium to increase the OR of CKD (p < 0.001). This study highlighted the significant association between LINE-1 hypermethylation and CKD. Furthermore, the results demonstrate that LINE-1 methylation can interact with high blood cadmium or low plasma selenium to affect CKD risk.

Functional metalloenzymes based on myoglobin and neuroglobin that exploit covalent interactions.

Globins, such as myoglobin (Mb) and neuroglobin (Ngb), are ideal protein scaffolds for the design of functional metalloenzymes. To date, numerous approaches have been developed for enzyme design. This review presents a summary of the progress made in the design of functional metalloenzymes based on Mb and Ngb, with a focus on the exploitation of covalent interactions, including coordination bonds and covalent modifications. These include the construction of a metal-binding site, the incorporation of a non-native metal cofactor, the formation of Cys/Tyr-heme covalent links, and the design of disulfide bonds, as well as other Cys-covalent modifications. As exemplified by recent studies from our group and others, the designed metalloenzymes have potential applications in biocatalysis and bioconversions. Furthermore, we discuss the current trends in the design of functional metalloenzymes and highlight the importance of covalent interactions in the design of functional metalloenzymes.

Design of urban road fault detection system based on artificial neural network and deep learning.

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.

Bacteria inhabiting spider webs enhance host silk extensibility.

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.

Ozonolysis of Terpene Flavor Additives in Vaping Emissions: Elevated Production of Reactive Oxygen Species and Oxidative Stress.

The production of e-cigarette aerosols through vaping processes is known to cause the formation of various free radicals and reactive oxygen species (ROS). Despite the well-known oxidative potential and cytotoxicity of fresh vaping emissions, the effects of chemical aging on exhaled vaping aerosols by indoor atmospheric oxidants are yet to be elucidated. Terpenes are commonly found in e-liquids as flavor additives. In the presence of indoor ozone (O3), e-cigarette aerosols that contain terpene flavorings can undergo chemical transformations, further producing ROS and reactive carbonyl species. Here, we simulated the aging process of the e-cigarette emissions in a 2 m3 FEP film chamber with 100 ppbv of O3 exposure for an hour. The aged vaping aerosols, along with fresh aerosols, were collected to detect the presence of ROS. The aged particles exhibited 2- to 11-fold greater oxidative potential, and further analysis showed that these particles formed a greater number of radicals in aqueous conditions. The aging process induced the formation of various alkyl hydroperoxides (ROOH), and through iodometric quantification, we saw that our aged vaping particles contained significantly greater amounts of these hydroperoxides than their fresh counterparts. Bronchial epithelial cells exposed to aged vaping aerosols exhibited an upregulation of the oxidative stress genes, HMOX-1 and GSTP1, indicating the potential for inhalation toxicity. This work highlights the indirect danger of vaping in environments with high ground-level O3, which can chemically transform e-cigarette aerosols into new particles that can induce greater oxidative damage than fresh e-cigarette aerosols. Given that the toxicological characteristics of e-cigarettes are mainly associated with the inhalation of fresh aerosols in current studies, our work may provide a perspective that characterizes vaping exposure under secondhand or thirdhand conditions as a significant health risk.

Cardiac Genetic Test Yields and Genotype-Phenotype Correlations from Large Cohort Investigated by Medical Examiner's Office.

BACKGROUND: Few reports describe the yield of postmortem genetic testing from medical examiners' offices or correlate genetic test results with autopsy-confirmed phenotypes from a large cohort. OBJECTIVES: To report results from cardiomyopathy- and cardiac arrhythmia-associated genetic testing in conjunction with autopsy findings of cases investigated at the United States' largest medical examiner office. METHODS: Postmortem cases tested from 2015 to 2022 with a cardiomyopathy- and cardiac arrhythmia-associated gene panel were reviewed. American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines were used to classify variant pathogenicity. Correlations of pathogenic/likely pathogenic variants (P/LPVs) with cardiac pathology were evaluated. RESULTS: The cohort included 1107 decedents of diverse ages and ethnicities. P/LPVs were detected in 87 (7.9%) cases, with 73 and 14 variants in cardiomyopathy and cardiac arrhythmia genes, respectively. Variants of uncertain significance were detected in 437 (39.5%) cases. The diagnostic yield (percentage of P/LPV) in decedents with cardiomyopathy (26.1%) was significantly higher than those without (P < 0.0001). The diagnostic yield was significantly lower in infants (0.7%) than older age groups (ranging from 1 to 74 years old, 5.7%-25.9%), which had no statistical difference between their yields. The diagnostic yields by cardiac autopsy findings were 54.0% for hypertrophic cardiomyopathy, 47.1% for arrhythmogenic cardiomyopathy, 20.0% for myocardial fibrosis, 19.0% for dilated cardiomyopathy, and 11.3% for myocarditis. Most P/LPVs were in MYBPC3, TTN, PKP2, SCN5A, MYH7, and FLNC. Ten P/LPVs were novel. CONCLUSIONS: Our results support the importance of performing postmortem genetic testing on decedents of all ages with cardiomyopathy, cardiac lesions insufficient to diagnosis a specific cardiomyopathy (e.g., myocardial fibrosis), and myocarditis. Combined postmortem cardiac examination and genetic analysis are advantageous in accurately determining the underlying cause of death and informing effective clinical care of family members.

Correlation gas chromatography and two-dimensional volatility basis methods to predict gas-particle partitioning for e-cigarette aerosols.

E-cigarette aerosols contain a complex mixture of harmful and potentially harmful chemicals. Once released into the environment, they evolve and become new sources of indoor air pollutants that could pose a significant threat to both users and non-users. However, current understanding of the physicochemical properties of e-cigarette aerosol constituents that govern gas-particle partitioning in the atmosphere is limited, making it difficult to estimate the health risks associated with exposure. Here, we used correlation gas chromatography (C-GC) and two-dimensional volatility basis set (2D-VBS) methods to determine the vapor pressures and volatility for commonly reported toxic and irritating e-cigarette aerosol constituents. The vapor pressures of target compounds at 298 K were estimated from the Antoine-type linear relationship between the vapor pressure of reference standards and their retention times. Our C-GC results showed an overall positive correlation (R = 0.84) with estimates using the EPI (Estimation Programs Interface) Suite. The volatility calculated by 2D-VBS correlates well with the calculated vapor pressure from both C-GC (R = 0.82) and EPI Suite (R = 0.85). The volatility distribution also indicated fresh e-cigarette aerosol constituents are mainly more volatile organic compounds. Our case study revealed that low-vapor-pressure compounds (e.g., σ-dodecalactone, γ-decalactone, and maltol) become enriched in the e-cigarette aerosols within 2 hours following vaping emissions. Overall, these findings demonstrate the applicability of the C-GC and 2D-VBS methods for determining the physiochemical properties of e-cigarette aerosol constituents, which can aid in assessing the dynamic chemical composition of e-cigarette aerosols and exposures to vaping emissions in indoor environments.

Causal roles and clinical utility of cardiovascular proteins in colorectal cancer risk: a multi-modal study integrating mendelian randomization, expression profiling, and survival analysis.

PURPOSE: This comprehensive investigation delved into the intricate causal interplay existing between cardiovascular-related plasma proteins and the susceptibility to colorectal cancer, leveraging the robust framework of Mendelian randomization, and employed expression profiling and survival analysis to unravel the latent clinical worth embedded within pertinent gene expressions. METHODS: Protein quantitative trait loci (pQTLs) of 85 cardiovascular proteins were employed as instrumental variables to investigate the causal relationship between proteins and CRC risk using a Mendelian randomization approach. Causal inferences were graded as strong, intermediate or weak based on statistical checks. Drug-target MR examined VEGF receptors for their potential as therapeutic targets for colorectal cancer. Differential expression analysis, diagnostic ROC curves, and survival analyses were performed for identified proteins using RNA-seq data from The Cancer Genome Atlas (TCGA) colorectal cancer cohort. RESULTS: Using cis-pQTLs, LOX-1, VEGF-A and OPG were associated with increased CRC risk (strong evidence), while PTX3, TNF-R2 and MMP-7 were protective (strong evidence). Pan-pQTL analysis found MMP-10 increased risk (intermediate evidence) and ADM increased risk (weak evidence). Drug-target MR found VEGF R1 may be promising therapeutic targets. Differential expression analysis revealed seven genes encoding the identified proteins were dysregulated in tumors. ROC analysis showed five gene expression had high diagnostic accuracy. KM analysis showed four genes had prognostic value. CONCLUSIONS: This large-scale MR study implicates several cardiovascular proteins in CRC susceptibility and progression. Findings highlight roles for VEGF signaling and extracellular matrix regulation. Results nominate specific proteins as potential diagnostic biomarkers or therapeutic targets warranting further investigation.

Conversion from seismic to underwater sound waves along the Louisville Seamount Chain.

The conversion from seismic to ocean-acoustic waves occurs in different places on the bottom of the ocean, often hundreds to thousands of kilometers away from the epicenter. Here, we investigate this conversion process by studying 15 large-magnitude earthquakes that occurred between 2014 and 2022 along the Kermadec Arc in the southwestern Pacific Ocean. To pinpoint the location where seismic-to-acoustic conversion takes places, we analyze hydroacoustic signals recorded by a hydrophone triplet station of the International Monitoring System in the Juan Fernández archipelago. Results from direction-of-arrival and travel-time calculations indicate that the location of the conversion zone largely matches segments of the Louisville Seamount Chain, its lateral extent ranging from approximately 300 to 1800 km, and its location depending on the geometry between earthquake epicenter and the seamounts.

Evaluating a novel online behavioural intervention to encourage cost-conscious strategies among US adults with chronic conditions who are enrolled in a high-deductible health plan: a proof-of-concept pilot study.

OBJECTIVES: Patients with chronic conditions enrolled in high-deductible health plans (HDHPs) face cost-related access barriers and high out-of-pocket spending. Our objectives were to develop a novel behavioural intervention to help HDHP enrollees with chronic conditions use cost-conscious strategies and evaluate the intervention's preliminary effectiveness, acceptability and feasibility. DESIGN: Prospective. SETTING: Online (USA). PARTICIPANTS: 36 US adults enrolled in an HDHP through their employer or an exchange with diabetes, hypertension, asthma, coronary artery disease and/or chronic obstructive pulmonary disease. 31/36 participants completed the study. INTERVENTION: We developed a 5-week intervention consisting of a website with educational modules on discussing costs with clinicians, saving for future healthcare costs, comparing healthcare prices and quality, preparing for appointments, following up after appointments and planning for future healthcare needs; and emails encouraging participants to access each module. OUTCOMES: We conducted a single-arm proof-of-concept pilot study of the intervention. Baseline and postintervention surveys measured primary outcomes of health insurance literacy and confidence in using cost-conscious strategies. 10 participants completed postintervention interviews. RESULTS: 31 (86%) participants completed a baseline and postintervention survey. Mean health insurance literacy scores (20-80 scale) improved from 56.5 to 67.1 (p<0.001). Mean confidence scores (0-10 scale) improved for talking to a healthcare provider about cost (6.1-7.6, p=0.0094), saving for healthcare (5.8-6.6, p=0.068), comparing prices (5.4-6.9, p=0.005) and comparing quality (6.1 to 7.6, p=0.0034). Participants found the website easy to use and helpful for learning about cost-conscious strategies on postintervention interviews. CONCLUSIONS: Our novel behavioural intervention was acceptable to HDHP enrollees with chronic conditions, feasible to deliver and associated with increased health insurance literacy and confidence in using cost-conscious strategies. This intervention should be tested in a definitive randomised controlled trial that is fully powered to evaluate its effects on cost-related access barriers, out-of-pocket spending and health outcomes in this growing patient population.