A new antibacterial with anti-inflammatory properties promotes wound healing through inhibiting cGAS/STING/NF-κB/IRF3 pathway.

Benzothiazole-urea hybrid 8l was found to be a potent anti-bacterial agent against methicillin-resistant Staphylococcus aureus (MRSA2858) (MIC = 0.78 µM, Eur J Med Chem. 2022,236:114333). Herein, 8l was further evaluated to remedy the MRSA-infected scald with bacterial infection and severe inflammation. In scalded skin model with MRSA infection, 8l not only effectively reduced bacterial load, but also decreased pro-inflammatory cytokines secretion and promoted collagen deposition to effectively reverse the progression of wound infection and inflammation by blocking cGAS/STING/NF-κB/IRF3 signaling pathway. In vitro model of RAW264.7 cells verified that 8l can inhibit MRSA-induced inflammation via regulating this pathway. All in all, dual anti-bacterial and anti-inflammatory agent 8l could heal MRSA-infected refractory scald by regulating cGAS/STING/NF-κB/IRF3 pathway.

Cannabidiol suppresses silica-induced pulmonary inflammation and fibrosis through regulating NLRP3/TGF-ß1/Smad2/3 pathway.

Silica-induced pulmonary fibrosis is an irreversible and progressive lung disease with limited treatments available. In this work, FDA-approved cannabidiol (CBD) was studied for its potential medical use in silicosis. In silicosis female C57BL/6 mice model, oral CBD or pirfenidone (PFD) on day 1 after intratracheal drip silica (150 mg/mL) and continued for 42 days. Lung inflammatory and fibrotic changes were studied using ELISA kits, H&E staining and Masson staining. Osteopontion (OPN) and α-smooth muscle actin (α-SMA) expression in lung tissues was determined using immunohistochemical staining. The results indicated that CBD attenuated silica-induced pulmonary inflammation and fibrosis. Human myeloid leukemia mononuclear cells (THP-1) were treated with silica (200 µg/mL) to induce cell damage, then CBD (10 µM, 20 µM) and PFD (100 µM) were incubated. In vitro experiments showed that CBD can effectively reduce the expression of NLRP3 inflammasome in THP-1 cells and subsequently block silica-stimulated transformation of fibromuscular-myofibroblast transition (FMT) by culturing human embryonic lung fibroblasts (MRC-5) in conditioned medium of THP-1 cells. Therefore, CBD exhibited the potential therapy for silicosis through inhibiting the silica-induced pulmonary inflammation and fibrosis via the NLRP3/TGF-ß1/Smad2/3 signaling pathway.

GAMG ameliorates silica-induced pulmonary inflammation and fibrosis via the regulation of EMT and NLRP3/TGF-ß1/Smad signaling pathway.

Silicosis is an occupational disease caused by exposure to silica characterized by pulmonary inflammation and fibrosis, for which there is a lack of effective drugs. Glycyrrhetinic acid 3-O-ß-D-glucuronide (GAMG) can treat silicosis due to its anti-inflammatory and anti-fibrotic properties. Here, the effect of therapeutic interventions of GAMG was evaluated in early-stage and advanced silicosis mouse models. GAMG significantly improved fibrotic pathological changes and collagen deposition in the lungs, alleviated lung inflammation in the BALF, reduced the expression of TNF-α, IL-6, NLRP3, TGF-ß1, vimentin, Col-Ⅰ, N-cadherin, and inhibited epithelial-mesenchymal transition (EMT), thereby ameliorating pulmonary fibrosis. Moreover, the dose of 100 mg/kg GAMG can effectively prevent early-stage silicosis, while that of 200 mg/kg was recommended for advanced silicosis. In vitro and in vivo study verified that GAMG can suppress EMT through the NLRP3/TGF-ß1/Smad2/3 signaling pathway. Therefore, GAMG could be a promising preventive (early-stage silicosis) and therapeutic (advanced silicosis) strategy, which provides a new idea for formulating prevention and treatment strategies.

Nitenpyram in tea: Eco-friendly detection methodology and residue behavior.

Studies on nitenpyram determination and behavior within tea remain limited despite its widespread use as a neonicotinoid. An organic-saving analytical approach tailored for the detection of nitenpyram in tea was established. Nitenpyram was extracted by boiling water and cleaned up by Cleanert PCX solid-phase. The average recoveries were 75.1-94.5 %, with relative standard deviations (RSDs) of 0.7-8.6 % for saving 34.5-88.6 % organic solvent. The limits of quantification (LOQs) were 0.002 mg·kg-1 in fresh tea shoots, 0.005 mg·kg-1 in made tea, and 0.001 mg·L-1 in tea brew, satisfying the current minimum Maximum Residue Limit (MRL). Nitenpyram dissipated rapidly with half-lives of 1.2-1.4 days at the recommended dosage (27 g a.i. ha-1) in two locations. Remarkably, 20-110 % of nitenpyram was leached out from made tea in different brewing modes. This work provides insights into nitenpyram's rational application in tea cultivation and offers considerations to institutions tasked with unestablished MRLs in tea.

Design and construction of light-regulated gene transcription and protein translation systems in yeast P. Pastoris.

INTRODUCTION: P. pastoris is a common host for effective biosynthesis of heterologous proteins as well as small molecules. Accurate regulation of gene transcription and protein synthesis is necessary to coordinate synthetic gene circuits and optimize cellular energy distribution. Traditional methanol or other inducible promoters, natural or engineered, have defects in either fermentation safety or expression capacity. The utilization of chemical inducers typically adds complexity to the product purification process, but there is no other well-controlled protein synthesis system than promoters yet. OBJECTIVE: The study aimed to address the aforementioned challenges by constructing light-regulated gene transcription and protein translation systems with excellent expression capacity and light sensitivity. METHODS: Trans-acting factors were designed by linking the N. crassa blue-light sensor WC-1 with the activation domain of endogenous transcription factors. Light inducible or repressive promoters were then constructed through chimeric design of cis-elements (light-responsive elements, LREs) and endogenous promoters. Various configurations of trans-acting factor/LRE pairs, along with different LRE positions and copy numbers were tested for optimal promoter performance. In addition to transcription, a light-repressive translation system was constructed through the "rare codon brake" design. Rare codons were deliberately utilized to serve as brakes during protein synthesis, which were switched on and off through the light-regulated changes in the expression of the corresponding pLRE-tRNA. RESULTS: As demonstrated with GFP, the light-inducible promoter 4pLRE-cPAOX1 was 70 % stronger than the constitutive promoter PGAP, with L/D ratio = 77. The light-repressive promoter PGAP-pLRE was strictly suppressed by light, with expression capacity comparable with PGAP in darkness. As for the light-repressive translation system, the "triple brake" design successfully eliminated leakage and achieved light repression on protein synthesis without any impact on mRNA expression. CONCLUSION: The newly designed light-regulated transcription and translation systems offer innovative tools that optimize the application of P. pastoris in biotechnology and synthetic biology.

Arsenic exposure at environmentally relevant levels induced metabolic toxicity in development mice: Mechanistic insights from integrated transcriptome and metabolome.

Emerging evidence has linked arsenic exposure and metabolic homeostasis, but the mechanism is incompletely understood, especially at relatively low concentrations. In this study, we used a mouse model to evaluate the health impacts and metabolic toxicity of arsenic exposure in drinking water at environmentally relevant levels (0.25 and 1.0 ppm). Our results indicated that arsenic damaged intestinal barrier and induced arsenic accumulation, oxidative stress, and pathological changes in the liver and illum. Interestingly, arsenic increased the hepatic triglyceride (TG) and total cholesterol (TC), while reduced serum TG and TC levels. The liver transcriptome found that arsenic exposure caused transcriptome perturbation and promoted hepatic lipid accumulation by regulating the exogenous fatty acids degradation and apolipoproteins related genes. The serum metabolomics identified 74 and 88 differential metabolites in 0.25 and 1.0 ppm, respectively. The KEGG disease and subcellular location analysis indicated that arsenic induced liver and intestinal diseases, and the mitochondrion might be the target organelle for arsenic-induced toxicity. Co-enrichment of transcriptome and metabolome identified 24 metabolites and 9 genes as metabolic toxicity biomarkers. Moreover, 40 male (20 nonalcoholic fatty liver disease (NAFLD) cases and 20 healthy controls) was further selected to validate our findings. Importantly, the significantly changed L-palmitoylcarnitine, 3-hydroxybutyric acid, 2-hydroxycaproic acid and 6 genes of Hadha, Acadl, Aldh3a2, Cpt1a, Cpt2, and Acox1 were found in the NAFLD cases. The results from integrated multi-omics and chemical-protein network analysis indicated that L-palmitoylcarnitine played a critical role in metabolic toxicity by regulating mitochondrial fatty acids ß-oxidation genes (Cpt1a, Cpt2). In conclusion, these findings provided new clues for the metabolic toxicity of arsenic exposure at environmentally relevant levels, which involved in the late-life NAFLD development. Our results also contribute to understanding the human responses and phenotypic changes to this hazardous material exposure in the environment.

Construction of ecological network in Qujing city based on MSPA and MCR models.

With the rapid advancement of urbanization and industrialization, ecological patches within cities and towns are fragmented and ecological corridors are cut off, regional ecological security is threatened and sustainable development is hindered. Building an ecological network that conforms to regional realities can connect fragmented patches, protect biodiversity and regional characteristics, and provide scientific reference for regional ecological protection and ecological network planning. By taking Qilin District, the main urban area of Qujing City as an example, and using geospatial data as the main data source, based on morphological spatial pattern analysis (MSPA) and minimum cumulative resistance (MCR), this study identified ecological source areas, extracted ecological corridors, and build & optimize ecological networks. (1) All landscape types are identified based on MSPA, the proportion of core area was the highest among all landscape types, which was 80.69%, combined with the connectivity evaluation, 14 important ecological source areas were selected. (2) 91 potential ecological corridors were extracted through MCR and gravity models, there were 16 important ones. (3) The network connectivity analysis method is used to calculate the α, ß, and γ indexes of the ecological network before optimization, which were 2.36, 6.5, and 2.53, while after optimization, α, ß and γ indices were 3.8, 9.5 and 3.5, respectively. The combined application of MSPA-MCR model and ecological network connectivity analysis evaluation is conducive to improving the structure and functionality of ecological network.

Inhibiting Peptidoglycan Hydrolase Alleviates MRSA Pneumonia Through Autolysin-Mediated MDP-NOD2 Pathway.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a cause of staph infection that is difficult to treat because of resistance to some antibiotics. A recent study indicated that diarylurea ZJ-2 is a novel antibacterial agent against multi-drug resistant Enterococcus faecium. In this work, we refined the bactericidal mechanism of ZJ-2 as a peptidoglycan (PG) hydrolase by affecting AtlA-mediated PG homeostasis. Methods: A wild-type strain (WT) and a mutant strain (ΔatlA) were used to investigate the effects of ZJ-2 on the cell wall, PG, and autolysin regulatory system by antimicrobial susceptibility testing, hemolytic toxin assay, microanalysis, autolysis assay, qRT-PCR, ELISA and mouse model of pneumonia. Results: The results revealed that ZJ-2 down-regulated the expression of genes related to peptidoglycan hydrolase (PGH) (sprX, walR, atlA, and lytM), and reduced the levels of PG, muramyl dipeptide (MDP), cytokines, and hemolytic toxin, while ΔatlA interfered with the genes regulation and PG homeostasis. In the mouse MRSA pneumonia model, the same trend was observed in the nucleotide oligomerization domain protein 2 (NOD2) and relative proinflammatory factors. Conclusion: ZJ-2 may act as a novel inhibitor of PG hydrolyse, disrupting autolysin-mediated PG homeostasis, and reducing inflammation by down-regulating the MDP-NOD2 pathway.

Portable ratiometric fluorescence detection of Cu2+and thiram.

Food contaminants pose a danger to human health, but rapid, sensitive and reliable food safety detection methods can offer a solution to this problem. In this study, an optical fiber ratiometric fluorescence sensing system based on carbon dots (CDs) and o-phenylenediamine (OPD) was constructed. The ratiometric fluorescence response of Cu2+and thiram was carried out by the fluorescence resonance energy transfer (FRET) between CDs and 2,3-diaminophenazine (ox-OPD, oxidized state o-phenylenediamine). The oxidation of OPD by Cu2+resulted in the formation of ox-OPD, which quenched the fluorescence of CDs and exhibited a new emission peak at 573 nm. The formation of a [dithiocarbamate-Cu2+] (DTC-Cu2+) complex by reacting thiram with Cu2+, inhibits the OPD oxidation reaction triggered by Cu2+, thus turning off the fluorescence signal of OPD-Cu2+. The as-established detection system presented excellent sensitivity and selectivity for the detection of Cu2+and thiram in the ranges of 1 ∼ 100µM and 5 ∼ 50µM, respectively. The lowest detection limits were 0.392µM for Cu2+and 0.522µM for thiram. Furthermore, actual sample analysis indicated that the sensor had the potential for Cu2+and thiram assays in real sample analysis.

Gut microbiota deficiency aggravates arsenic-induced toxicity by affecting bioaccumulation and biotransformation in C57BL/6J mice.

Gut microbiome can influence the arsenic metabolism in mammals. Confusingly, gut microbiome was found to both mitigate and exacerbate arsenic toxicity. In this study, the role of gut microbiota in arsenic bioaccumulation, biotransformation, and organ toxicity in C57BL/6J mice was investigated. Gut microbiota deficiency model was established by antibiotics (Ab) cocktail AVNM. Conventional and gut microbiota deficiency mice were exposed to NaAsO2 for 4 weeks. Comparing with Ab-treated mice, the total arsenic (tAs) in the tissues was significantly reduced in conventional mice, which was opposed to the results of those in feces. Interestingly, dimethyl arsenite (DMA) was the most abundant metabolite in the feces of Ab-treated mice, while arsenic acid (AsV) had the highest proportion in the feces of conventional mice with approximately 16-fold than that in Ab-treated mice, indicating the critical role of gut microbiota in metabolizing arsenious acid (AsIII) to AsV. Additionally, the liver and kidney in Ab-treated mice showed more severe pathological changes and apoptosis. The significant increased level of ionized calcium-binding adapter molecule 1 (IBA-1) was also found in the brains of Ab-treated mice. Our results indicated that gut microbiota protected the host from arsenic-induced toxicity in liver, kidney, and brain by reducing the arsenic accumulation.

Synergistic effect of cannabidiol with dasatinib on lung cancer by SRC/PI3K/AKT signal pathway.

Dasatinib-related resistance frequently occurs and may lead to the failure of chemotherapy; thus, dose interruptions are necessary. Cannabidiol (CBD) has potential for integration with orthodox cancer care. In this study, we explored the combination effect of CBD and dasatinib on A549 cells. CBD in combination with dasatinib could induce significant synergistic apoptosis in vitro (ZIP > 10) and in vivo. The combination of CBD and low-dose dasatinib exhibited antiproliferative and proapoptotic effects through up-regulation of caspase-3 and Bax, and down-regulation of Bcl-2 in A549 cells. The xenograft mouse model suggested that the combination was more efficient and safer. In short, CBD and low-dose dasatinib exhibited a synergistic effect on anticancer by targeting the SRC/PI3K/AKT signaling pathway, suggesting a potential therapeutic option for the treatment of lung cancer.

Associations of arsenic exposure and arsenic metabolism with the risk of non-alcoholic fatty liver disease.

Growing evidences supported that arsenic exposure contributes to non-alcoholic fatty liver disease (NAFLD) risk, but findings were still inconsistent. Additionally, once absorbed, arsenic is methylated into monomethyl and dimethyl arsenicals. However, no studies investigated the association of arsenic metabolism with NAFLD. Our objectives were to evaluate the associations of arsenic exposure and arsenic metabolism with NAFLD prevalence. We conducted a case-control study with 1790 participants derived from Dongfeng-Tongji cohort and measured arsenic species (arsenite, arsenate, monomethylarsonate [MMA], dimethylarsinate [DMA], and arsenobetaine) in urine. Arsenic exposure (∑As) was defined as the sum of inorganic arsenic (iAs), MMA, and DMA. Arsenic metabolism was evaluated as the proportions of inorganic-related species (iAs%, MMA%, and DMA%) and methylation efficiency ratios (primary methylation index [PMI], secondary methylation index [SMI]). NAFLD was diagnosed by liver ultrasound. Logistic regression was used to evaluate the associations. The median of ∑As was 13.24 µg/g creatinine. The ∑As showed positive and nonlinear association with moderate/severe NAFLD (OR: per log-SD = 1.33, 95% CI: [1.03,1.71]; Pfor nonlinearity = 0.021). The iAs% (OR: per SD = 1.16, 95% CI: [1.03,1.30]) and SMI (OR: per log-SD = 1.16, 95% CI: [1.03,1.31]) showed positive while MMA% (OR: per SD = 0.80, 95% CI: [0.70,0.91]) and PMI (OR: per log-SD = 0.86, 95% CI: [0.77,0.96]) showed inverse associations with NAFLD. Moreover, the ORs (95% CI) of NAFLD for each 5% increase in iAs% was 1.36 (1.17,1.58) when MMA% decreased and 1.07 (1.01,1.13) when DMA% decreased; and for each 5% increase in MMA%, it was 0.74 (0.63,0.86) and 0.79 (0.69,0.91) when iAs% and DMA% decreased, respectively. The results suggest that inorganic arsenic exposure is positively associated with NAFLD risk and arsenic methylation efficiency plays a role in the NAFLD. The findings provide clues to explore potential interventions for the prevention of NAFLD. Prospective studies are needed to validate our findings.

Epigenome-wide perspective of cadmium-associated DNA methylation and its mediation role in the associations of cadmium with lipid levels and dyslipidemia risk.

BACKGROUND: Studies demonstrated the associations of cadmium (Cd) with lipid levels and dyslipidemia risk, but the mechanisms involved need further exploration. OBJECTIVES: We aimed to explore the role of DNA methylation (DNAM) in the relationship of Cd with lipid levels and dyslipidemia risk. METHODS: Urinary cadmium levels (UCd) were measured by inductively coupled plasma mass spectrometry, serum high-density lipoprotein (HDL), total cholesterol, triglyceride, and low-density lipoprotein were measured with kits, and DNAM was measured using the Infinium MethylationEPIC BeadChip. Robust linear regressions were conducted for epigenome-wide association study. Multivariate linear and logistic regressions were performed to explore the associations of UCd with lipid levels and dyslipidemia risk, respectively. Mediation analyses were conducted to explore potential mediating role of DNAM in the associations of Cd with lipid levels and dyslipidemia risk. RESULTS: UCd was negatively associated with HDL levels (p = 0.01) and positively associated with dyslipidemia (p < 0.01). There were 92/11 DMPs/DMRs (FDR<0.05) associated with UCd. Cd-associated DNAM and pathways were connected with cardiometabolic diseases and immunity. Cg07829377 (LINC01060) mediated 42.05%/22.88% of the UCd-HDL/UCd-dyslipidemia associations (p = 0.02 and 0.01, respectively). CONCLUSIONS: Cadmium caused site-specific DNAM alterations and the associations of UCd with lipid levels and dyslipidemia risk may be partially mediated by DNAM.

Gas-Source Comparison and Hydrocarbon Generation and Expulsion Histories of the Main Source Rocks of the Middle Jurassic Shaximiao Formation, Western Sichuan Basin.

With the discovery and exploration of tight sandstone gas reservoirs in the Sichuan Basin, the Middle Jurassic Shaximiao Formation has gradually become the focus of exploration. However, the gas source of the Shaximiao Formation in the Western Sichuan Basin is still controversial, and research on the hydrocarbon generation and expulsion histories of the primary source rocks lags behind, which restricts the study of tight sandstone gas reservoir dynamics within the Shaximiao Formation in the Western Sichuan Basin and further affects the oil and gas exploration process. This paper, utilizing geochemical parameters, including 82 natural gas components and 68 carbon isotopes, conducted an investigation into the origin identification of natural gas and gas-source comparisons within the Shaximiao Formation in the Western Sichuan Basin. By utilizing basin modeling technology, we reconstructed the histories of hydrocarbon generation and expulsion of the primary source rocks and identified the potential exploration areas. The findings indicate that the natural gas within the Shaximiao Formation in the Western Sichuan Basin is characterized by a typical high-maturity wet gas-dry gas reservoir. It is a thermogenic coal-type gas produced by kerogen cracking, and the gas source is primarily type-III kerogen. The main source of natural gas is the coal-measure source rock of the Upper Triassic Xujiahe 5 Formation, which has mainly experienced two stages of increasing maturity, characterized by "two stages of gas generation and one stage of gas expulsion". The hydrocarbon generation and expulsion histories for the source rocks within the Xujiahe 5 Formation is shown as follows: the source rocks of the Xujiahe 5 Formation reached the hydrocarbon generation threshold by the end of the Early Jurassic and peaked in hydrocarbon generation by the end of the Late Jurassic, and then the natural gas migrated to the paleostructural highs of the Shaximiao Formation to form the paleo-gas reservoir. From the end of the Early Cretaceous, the paleo-gas reservoir underwent adjustments and transformations to evolve into the present-day gas reservoir. The source rocks exhibit substantial potential for the forming of large-medium and extralarge gas fields, with favorable exploration zones concentrated in the southern and central portions of the study area. The research findings can provide a scientific foundation for the next exploration and deployment of natural gas resources within the Shaximiao Formation in the Western Sichuan Basin.

[Discussion of Application Status and Key Attentions on Registration for Ossicular Replacement Prosthesis].

The ossicular replacement prosthesis should have good biocompatibility, stability, easy to install, and excellent sound transmission capacity. In this study, the characteristics of ideal materials for the ossicular replacement prosthesis were analyzed by searching the types of materials used in clinical practice and comparing the advantages and disadvantages of various materials and structures. At the same time, in combination with the current evaluation requirements and evaluation experience, the focus of the performance research project of ossicular replacement prosthesis in the process of registration is discussed to clarify the performance evaluation requirements of these products, so as to provide reference for the future work of manufacturers and regulators. The performance evaluation of ossicular replacement prosthesis focuses on its mechanical properties, fixation stability, sound transmission characteristics, biological characteristics, and magnetic resonance compatibility.

MULTI-TASK DEEP LEARNING AND UNCERTAINTY ESTIMATION FOR PET HEAD MOTION CORRECTION.

Head motion occurring during brain positron emission tomography images acquisition leads to a decrease in image quality and induces quantification errors. We have previously introduced a Deep Learning Head Motion Correction (DL-HMC) method based on supervised learning of gold-standard Polaris Vicra motion tracking device and showed the potential of this method. In this study, we upgrade our network to a multi-task architecture in order to include image appearance prediction in the learning process. This multi-task Deep Learning Head Motion Correction (mtDL-HMC) model was trained on 21 subjects and showed enhanced motion prediction performance compared to our previous DL-HMC method on both quantitative and qualitative results for 5 testing subjects. We also evaluate the trustworthiness of network predictions by performing Monte Carlo Dropout at inference on testing subjects. We discard the data associated with a great motion prediction uncertainty and show that this does not harm the quality of reconstructed images, and can even improve it.

Exploration of street space architectural color measurement based on street view big data and deep learning-A case study of Jiefang North Road Street in Tianjin.

Urban space architectural color is the first feature to be perceived in a complex vision beyond shape, texture and material, and plays an important role in the expression of urban territory, humanity and style. However, because of the difficulty of color measurement, the study of architectural color in street space has been difficult to achieve large-scale and fine development. The measurement of architectural color in urban space has received attention from many disciplines. With the development and promotion of information technology, the maturity of street view big data and deep learning technology has provided ideas for the research of street architectural color measurement. Based on this background, this study explores a highly efficient and large-scale method for determining architectural colors in urban space based on deep learning technology and street view big data, with street space architectural colors as the research object. We conducted empirical research in Jiefang North Road, Tianjin. We introduced the SegNet deep learning algorithm to semantically segment the street view images, extract the architectural elements and optimize the edges of the architecture. Based on K-Means clustering model, we identified the colors of the architectural elements in the street view. The accuracy of the building color measurement results was cross-sectionally verified by means of a questionnaire survey. The validation results show that the method is feasible for the study of architectural colors in street space. Finally, the overall coordination, sequence continuity, and primary and secondary hierarchy of architectural colors of Jiefang North Road in Tianjin were analyzed. The results show that the measurement model can realize the intuitive expression of architectural color information, and also can assist designers in the analysis of architectural color in street space with the guidance of color characteristics. The method helps managers, planners and even the general public to summarize the characteristics of color and dig out problems, and is of great significance in the assessment and transformation of the color quality of the street space environment.

Markerless head motion tracking and event-by-event correction in brain PET.

Objective.Head motion correction (MC) is an essential process in brain positron emission tomography (PET) imaging. We have used the Polaris Vicra, an optical hardware-based motion tracking (HMT) device, for PET head MC. However, this requires attachment of a marker to the subject's head. Markerless HMT (MLMT) methods are more convenient for clinical translation than HMT with external markers. In this study, we validated the United Imaging Healthcare motion tracking (UMT) MLMT system using phantom and human point source studies, and tested its effectiveness on eight18F-FPEB and four11C-LSN3172176 human studies, with frame-based region of interest (ROI) analysis. We also proposed an evaluation metric, registration quality (RQ), and compared it to a data-driven evaluation method, motion-corrected centroid-of-distribution (MCCOD).Approach.UMT utilized a stereovision camera with infrared structured light to capture the subject's real-time 3D facial surface. Each point cloud, acquired at up to 30 Hz, was registered to the reference cloud using a rigid-body iterative closest point registration algorithm.Main results.In the phantom point source study, UMT exhibited superior reconstruction results than the Vicra with higher spatial resolution (0.35 ± 0.27 mm) and smaller residual displacements (0.12 ± 0.10 mm). In the human point source study, UMT achieved comparable performance as Vicra on spatial resolution with lower noise. Moreover, UMT achieved comparable ROI values as Vicra for all the human studies, with negligible mean standard uptake value differences, while no MC results showed significant negative bias. TheRQevaluation metric demonstrated the effectiveness of UMT and yielded comparable results to MCCOD.Significance.We performed an initial validation of a commercial MLMT system against the Vicra. Generally, UMT achieved comparable motion-tracking results in all studies and the effectiveness of UMT-based MC was demonstrated.

Association of urinary arsenic metabolism with type 2 diabetes and glucose homeostasis: Cross-sectional and longitudinal associations.

BACKGROUND: Previous researches have assessed the relationships of urinary arsenic metabolism with type 2 diabetes (T2D) and glucose-insulin homeostasis, but the results were controversial, and potential mechanisms remain largely unclear. OBJECTIVES: This study aimed to investigate the cross-sectional and longitudinal associations of urinary arsenic metabolism with T2D prevalence and glucose changes in relatively higher arsenic exposure, and further to evaluate the underlying roles of oxidative damage in these relationships. METHODS: We included 796 participants at baseline, among them 509 participants were followed up after 2 years. Logistic regression model and leave-one-out approach were applied to evaluate the associations of arsenic metabolism with T2D prevalence. Linear mixed model was conducted to estimate the relationship of arsenic metabolism with glycemic changes over two years. The associations between arsenic metabolism and indicators of oxidative stress were assessed with a linear regression model. We further performed mediation analysis to investigate the role of oxidative stress in the associations of arsenic metabolism with 2-year change of glucose levels. RESULTS: Higher urinary MMA% increased T2D prevalence and baseline glucose levels. MMA% was positively associated with 2-year change of glucose levels. Moreover, we observed significant dose-response relationship between MMA% and 8-hydroxy-2-deoxyguanosine (8-OHdG). However, the mediating role of 8-OHdG in the association of MMA% and 2-year change of glucose levels was not observed in this population. CONCLUSIONS: In this population exposure to relatively higher arsenic levels, higher MMA% contributed to increased T2D prevalence and glucose homeostasis disorder. Arsenic metabolism also affected oxidative stress levels, especially 8-OHdG. Further studies are required to investigate the potential mechanisms.

Associations of essential trace elements with epigenetic aging indicators and the potential mediating role of inflammation.

BACKGROUND: Essential trace elements (ETEs) play essential roles in vital functions, but their effects on epigenetic aging remain poorly understood. OBJECTIVES: This study aimed to investigate the associations of ETEs with four epigenetic aging indicators and assess the potential mediating role of inflammation. METHODS: We recruited 93 individuals from hospitals between October 2018 and August 2019. Plasma levels of cobalt, copper, iron, manganese, molybdenum, selenium, and zinc were measured by ICP-MS, and leukocyte DNA methylation levels were measured using Illumina MethylationEPIC beadchip. Linear regression was used to estimate the association between seven plasma ETEs and epigenetic aging indicators. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to evaluate the effect of ETEs mixtures. Inflammatory status was assessed using four systemic inflammation indices (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII)) and three cytokines (IL-4, IL-6, and IL-13). Mediation analysis was performed to explore the role of inflammation in the above associations. RESULTS: Plasma Se levels were significantly negatively associated with DunedinPACE, whereas Cu levels were significantly positively associated with it. Both WQS regression and BKMR models suggested that Se and Cu dominate the effect of the ETEs mixture. MLR and interleukin 6 were significantly and positively associated with DunedinPACE. Further mediation analysis indicated that inflammation partially mediated the association between ETEs and DunedinPACE. DISCUSSION: Plasma Se and Cu levels are closely associated to epigenetic aging, and inflammation might be a potential mechanism underlying this relationship. These findings contribute to the prevention of health hazards associated with population aging.