Age, sex, and APOE gene-specific associations between dynapenic obesity and dementia in a large cohort.

OBJECTIVE: To investigate the associations between dynapenic obesity and the risk of dementia, and the modifying effects of age, sex, and the APOE gene, using a large population-based cohort. METHODS: 279,884 participants aged 55 and above from the UK Biobank were included. The participants were classified into four categories based on body mass index and hand grip strength: healthy, obesity, dynapenia, and dynapenic obesity. The incident dementia was identified based on linked hospital records and death register data. Cox proportional hazards regression models were used to estimate the associations, followed by age-, sex-, and apolipoprotein E (APOE) gene-stratified analyses. RESULTS: During the median follow-up of 12.4 years, 5,170 (1.8%) participants developed dementia. Compared with the healthy group, participants with dynapenic obesity had 67% higher dementia risk (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.44-1.94). Compared with the healthy group, higher risks of dementia in participants with dynapenic obesity were respectively observed in male (HR: 2.03, 95% CI: 1.65-2.50), younger (<65 years, HR: 1.97, 95% CI: 1.55-2.50), and non-ε4-carrier (HR: 1.97, 95% CI: 1.60-2.44) (all P for interaction <0.05). In participants under 65 years and non-ε4-carrier, those with dynapenic obesity had the highest risk of dementia (HR: 2.63, 95% CI: 1.91-3.62), compared with the healthy group (P for second order interaction = 0.026). CONCLUSIONS: Dynapenic obesity is associated with increased risks of dementia, especially in participants under 65 years and non-ε4-carrier, suggesting the importance of managing dynapenic obesity in the prevention of cognition-related disorders.

Near-infrared fluorescent probe for ultrasensitive detection of organophosphorus pesticides and visualization of their interaction with butyrylcholinesterase in living cells.

The toxicity of organophosphorus pesticides (OPs) can catastrophically cause liver cell damage and inhibit the catalytic activity of cholinesterase. We designed and synthesized a near-infrared fluorescent probe HP-LZB with large Stokes shift which can specifically identify and detect butyrylcholinesterase (BChE) and visually explore the interaction between OPs and endogenous BChE in living cells. Fluorescence was turned on when HP-LZB was hydrolyzed into HP-LZ in the presence of BChE, and OPs could inhibit BChE's activity resulting in a decrease of fluorescence. Six OPs including three oxon pesticides (paraoxon, chlorpyrifos oxon and diazoxon) and their corresponding thion pesticides (parathion, chlorpyrifos and diazinon) were investigated. Both in vitro and cell experiments indicated that only oxon pesticides could inhibit BChE's activity. The limits of detection (LODs) of paraoxon, chlorpyrifos oxon and diazoxon were as low as 0.295, 0.007 and 0.011 ng mL-1 respectively and the recovery of OPs residue in vegetable samples was satisfactory. Thion pesticides themselves could hardly inhibit the activity of BChE and are only toxic when they are converted to their corresponding oxon form in the metabolic process. However, in this work, thion pesticides were found not be oxidized into their oxon forms in living HepG2 cells due to the lack of cytochrome P450 in hepatoma HepG2 cell lines. Therefore, this probe has great application potential in effectively monitoring OPs in real plant samples and visually exploring the interaction between OPs and BChE in living cells.

Ecological drivers of nesting behavior in a subtropical city: An observational study on spotted doves.

Due to rapid homogenization in habitat types as a result of urbanization, some urban birds adapt their nesting strategies to changes in local habitat characteristics. Bird nesting decisions might have been mainly linked to resource constraints and ensuring reproductive success. In this study, we examined patterns of nesting behavior by spotted doves (Spilopelia chinensis) in a rapidly urbanizing area of Nanchang, China using ArcGIS 10.8, satellite tracking, camera traps, and field survey. To explore the mechanisms underlying nesting behavior in urban habitats, we assessed the correlations between nest reuse and reproductive success, and between nest reuse and nest predation. From December 2018 to December 2021, a total of 302 breeding nests were surveyed. The results revealed that the nest reuse rate was 38.08% (n = 115). Nests closer to trunk, with lower nest position and higher large-scale urbanization score tended to have higher reuse rate. In addition, nests with the higher the nest height and percent of canopy cover, and the lower small-scale urbanization score were more likely to reproduce successfully, and the reused nests also reproduce more successfully. The reproductive success associated with nest reuse was significantly higher than that associated with new nests (χ 2 = 8.461, p = .004). High degree of urbanization promoted nest reuse of spotted doves (large-scale urbanization score, z = 2.094, p = .036), which apparently enhanced their reproductive success (nest reuse, z = 2.737, p = .006). In conclusion, a nest structure with good permeability is the material basis for the nest reuse in spotted dove, while the relatively low risk of predation in urban habitat and the scarcity of nest site resources due to urbanization increase the tendency of birds to reuse old nests, which is associated with their reproductive success and evolutionary fitness.

Sodium chloride promotes macrophage pyroptosis and aggravates rheumatoid arthritis by activating SGK1 through GABA receptors Slc6a12.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and the production of autoantibodies. Previous studies have indicated an association between high-salt diets (HSD) and an increased risk of RA, yet the underlying mechanisms remain unclear. Macrophage pyroptosis, a pro-inflammatory form of cell death, plays a pivotal role in RA. In this study, we demonstrate that HSD exacerbates the severity of arthritis in collagen-induced arthritis (CIA) mice, correlating with macrophage infiltration and inflammatory lesions. Given the significant alterations observed in macrophages from CIA mice subjected to HSD, we specifically investigate the impact of HSD on macrophage responses in the inflammatory milieu of RA. In our in vitro experiments, pretreatment with NaCl enhances LPS-induced pyroptosis in RAW.264.7 and THP-1 cells through the p38 MAPK/NF-κB signaling pathway. Subsequent experiments reveal that Slc6a12 inhibitors and SGK1 silencing inhibit sodium-induced activation of macrophage pyroptosis and the p38 MAPK/NF-κB signaling pathway, whereas overexpression of the SGK1 gene counteracts the effect of sodium on macrophages. In conclusion, our findings verified that high salt intake promotes the progression of RA and provided a detailed elucidation of the activation of macrophage pyroptosis induced by sodium transportation through the Slc6a12 channel.

Effects of 3-(4-Hydroxy-3-methoxyphenyl)propionic Acid on Enhancing Grip Strength and Inhibiting Protein Catabolism Induced by Exhaustive Exercise.

3-(4-Hydroxy-3-methoxyphenyl)propionic acid (HMPA), also known as dihydroferulic acid, is a hydroxycinnamic acid derivative that can be derived from the microbial transformation of dietary polyphenols or naturally obtained from fermented foods. Although numerous studies have documented its antioxidant and anti-obesity effects, the effect of HMPA on muscle function remains unknown. This study investigated the effects of HMPA on muscle strength and exercise endurance capacity. Mice were orally administered low and high doses of HMPA for 14 days and subjected to grip force and treadmill exhaustion tests to evaluate muscle function. Our results showed that HMPA-administered groups significantly enhanced absolute grip strength (p = 0.0256) and relative grip strength (p = 0.0209), and low-dose HMPA decreased the plasma level of blood urea nitrogen after exercise (p = 0.0183), but HMPA did not affect endurance performance. Low-dose HMPA administration increased Myf5 expression in sedentary mice (p = 0.0106), suggesting that low-dose HMPA may promote muscle development. Additionally, HMPA improved hepatic glucose and lipid metabolism, and inhibited muscular lipid metabolism and protein catabolism, as indicated by changes in mRNA expression levels of related genes. These findings suggest that HMPA may be a promising dietary supplement for muscle health and performance.

High-Throughput Proteomics Enabled by a Fully Automated Dual-Trap and Dual-Column LC-MS.

This Technical Note describes a dual-column liquid chromatography system coupled to mass spectrometry (LC-MS) for high-throughput bottom-up proteomic analysis. This system made full use of two 2-position 10-port valves and a binary pump with an integrated loading pump of a commercial LC instrument to provide successive operation of two parallel subsystems. Each subsystem consisted of a set of trap columns and an analytical column. A T-junction union was used to split the mobile phase from the loading pump into two parts. This allowed one set of columns to be washed and equilibrated, followed by the injection of the next sample, while the previous sample was eluting and being analyzed on the other set of columns, thereby greatly increasing the analysis throughput. This approach showed high reproducibility for the analysis of HeLa tryptic digests with average relative standard deviation (RSD) values of 1.75%, 6.90%, and 5.19% for the identification number of proteins, peptides, and peptide-spectrum matches (PSMs), respectively, across 10 consecutive runs. The capacity for peptide and protein identification, as well as proteome depth, of the dual-column LC system was comparable to a conventional single-column system. Due to its simple equipment requirements and set up process, this method should be highly accessible for other laboratories.

Identification and seasonal variation of specific particulate bound (halogenated) polycyclic aromatic hydrocarbons in air from different metal industrial parks in Northwest China.

During the process of industrial heating, a large amount of polycyclic aromatic hydrocarbons (PAHs) and their halogenated compounds (Cl/Br-PAHs) can be formed. However, there is still limited understanding of the chemicals from different metal smelting industrial parks. This study evaluated the seasonal variations, composition profiles, and source allocations of the atmospheric particulate-bound PAHs and Cl/Br-PAHs in different metal industrial parks in a typical industrial city in northwest China. The results showed that the main PAHs produced by metal smelting were low molecular weight isomers, and the concentrations of Cl-PAHs were lower compared to Br-PAHs. The main Br-PAHs were 1-Br-Pyr and 4-Br-Pyr, while 9-Cl-Fle, 1-Cl-Pyr, and 6-Cl-BaP were the dominated Cl-PAH isomers. No significant difference was found in the concentrations among the sites, whereas the levels of the target chemicals were higher during cold months compared to warm months. The main source of PAHs was coal combustion and gasoline vehicle emission during metal smelting, and that of Cl/Br-PAHs was also industrial coal burning. In addition to the primary source, the secondary chlorination of parent PAHs was also a significant source of Cl-PAHs in the production of high purity aluminum. This study suggests that Cl-PAHs and Br-PAHs may behave differently in the atmosphere.

Aptamer molecular gate functionalized mesoporous SiO2@MB controlled-release system for pollutant detection using Ti(â ¢) self-doped TiO2 NTs as active photoanode coupled with electrostatic modulation.

Atrazine (ATZ) is a widely used herbicide that can cause serious harm to organisms and ecosystems. An immobilization-free photoelectrochemical (PEC) aptasensor has been herein developed for ATZ based on aptamer molecular gate functionalized mesoporous SiO2@MB controlled release system. Compared with traditional immobilization-based sensors, immobilization-free sensors (IFSs) avoid the modification of the recognition element on the electrode surface. Mesoporous SiO2 with large surface area and good biocompatibility can be used as nanocontainers to stably encapsulate the signal shuttle molecule methylene blue (MB). The bifunctional aptamer (APT) is used not only as the recognition element for ATZ but also as the signal switch to block or release MB. In the presence of ATZ, the specific recognition between ATZ and APT will cause the detachment of APT from the surface of SiO2, thus the molecular gate will open and release MB. Due to pH modulation, the positively charged MB can reach the surface of the negatively charged Ti(III) self-doped TiO2 NTs (Ti(III)-TiO2 NTs) electrode to act as an electron donor, which increases the photocurrent. The immobilization-free aptasensor has shown ultrasensitive detection of ATZ with a wide linear range from 1.0 pM to 100.0 nM and a low detection limit of 0.1 pM. In addition, the sensor has excellent selectivity, stability and anti-interference ability, and has been used in real water sample analysis successfully. This strategy has provided a new idea for the design of advanced immobilization-free PEC sensors for environmental pollutant detection.

Hippo-YAP/TAZ-ROS signaling axis regulates metaflammation induced by SelenoM deficiency in high-fat diet-derived obesity.

INTRODUCTION: Metabolic inflammation (metaflammation) in obesity is primarily initiated by proinflammatory macrophage infiltration into adipose tissue. SelenoM contributes to the modulation of antioxidative stress and inflammation in multiple pathological processes; however, its roles in metaflammation and the proinflammatory macrophage (M1)-like state in adipose tissue have not been determined. OBJECTIVES: We hypothesize that SelenoM could effectively regulate metaflammation via the Hippo-YAP/TAZ-ROS signaling axis in obesity derived from a high-fat diet. METHODS: Morphological changes in adipose tissue were examined by hematoxylin-eosin (H&E) staining and fluorescence microscopy. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to evaluate the impact of SelenoM deficiency on blood glucose levels. RNA-Seq analysis, LC-MS analysis, Mass spectrometry analysis and western blotting were performed to detect the levels of genes and proteins related to glycolipid metabolism in adipose tissue. RESULTS: Herein, we evaluated the inflammatory features and metabolic microenvironment of mice with SelenoM-deficient adipose tissues by multi-omics analyses. The deletion of SelenoM resulted in glycolipid metabolic disturbances and insulin resistance, thereby accelerating weight gain, adiposity, and hyperglycemia. Mice lacking SelenoM in white adipocytes developed severe adipocyte hypertrophy via impaired lipolysis. SelenoM deficiency aggravated the generation of ROS by reducing equivalents (NADPH and glutathione) in adipocytes, thereby promoting inflammatory cytokine production and the M1-proinflammatory reaction, which was related to a change in nuclear factor kappa-B (NF-κB) levels in macrophages. Mechanistically, SelenoM deficiency promoted metaflammation via Hippo-YAP/TAZ-ROS-mediated transcriptional regulation by targeting large tumor suppressor 2 (LATS2). Moreover, supplementation with N-acetyl cysteine (NAC) to reduce excessive oxidative stress partially rescued adipocyte inflammatory responses and macrophage M1 activation. CONCLUSION: Our data indicate that SelenoM ameliorates metaflammation mainly via the Hippo-YAP/TAZ-ROS signaling axis in obesity. The identification of SelenoM as a key regulator of metaflammation presents opportunities for the development of novel therapeutic interventions targeting adipose tissue dysfunction in obesity.

Enhanced Label-Free Photoelectrochemical Strategy for Pollutant Detection: Using Surface Oxygen Vacancies-Enriched BiVO4 Photoanode.

Label-free photoelectrochemical sensors have the advantages of high sensitivity and a simple electrode structure. However, its performance is greatly limited due to the photoactive materials' weak photoactivity and poor stability. Herein, a robust homogeneous photoelectrochemical (PEC) aptasensor has been constructed for atrazine (ATZ) based on photoetching (PE) surface oxygen vacancies (Ov)-enriched Bismuth vanadate (BiVO4) (PE-BVO). The surface of the Ov improves the carrier separation ability of BiVO4, thus providing a superior signal substrate for the sensor. A thiol molecular layer self-assembled on PE-BVO acts as a blocker, while 2D graphene acts as a signal-on probe after release from the aptamer-graphene complex. The fabricated sensor has a wide linear detection range of 0.5 pM to 10.0 nM and a low detection limit of 0.34 pM (S/N = 3) for ATZ. In addition, it can efficiently work in a wide pH range (3-13) and high ionic strength (∼6 M Na+), which provides promising opportunities for detecting environmental pollutants under complex conditions.

A graphene oxide-assisted protein immobilization paper-tip immunosensor with smartphone and naked eye readout for the detection of okadaic acid.

BACKGROUND: Okadaic acid (OA), as a diarrhetic shellfish poisoning, can increase the risk of acute carcinogenic or teratogenic effects for the ingestion of OA contaminated shellfish. At present, much effort has been made to graft immunoassay onto a paper substrate to make paper-based sensors for rapid and simple detection of shellfish toxin. However, the complicated washing steps and low protein fixation efficiency on the paper substrate need to be further addressed. RESULTS: A novel paper-tip immunosensor for detecting OA was developed combined with smartphone and naked eye readout. The trapezoid paper tip was consisted of quantitative and qualitative detection zones. To improve the OA antigen immobilization efficiency on the paper substrate, graphene oxide (GO)-assisted protein immobilization method was introduced. Meanwhile, Au nanoparticles composite probe combined with the lateral flow washing was developed to simplify the washing step. The OA antigen-immobilized zone, as the detection zone Ⅰ, was used for quantitative assay by smartphone imaging. The paper-tip front, as the detection zone Ⅱ, which could qualitatively differentiate OA pollution level within 45 min using the naked eye. The competitive immunoassay on the paper tip exhibited a wide linear range for detecting OA (0.02-50 ng∙mL-1) with low detection limit of 0.02 ng∙mL-1. The recovery of OA in spiked shellfish samples was in the range of 90.3 %-113.%. SIGNIFICANCE: These results demonstrated that the proposed paper-tip immunosensor could provide a simple, low-cost and high-sensitivity test for OA detection without the need for additional large-scale equipment or expertise. We anticipate that this paper-tip immunosensor will be a flexible and versatile tool for on-site detecting the pollution of marine products.

Ratiometric fluorescence imaging of lysosomal NO in living cells and mice brains with Alzheimer's disease.

We report an integrated ratiometric lysosomal nitric oxide (NO) nanoprobe based on engineered semiconducting polymer dots (Pdots), LyNO-Pdots, which consist of a newly designed NO-responsive dye, a fluorescent conjugated polymer and two functional polymers. The developed probe LyNO-Pdots exhibit high specificity and stability, good photostability and favorable blood-brain barrier (BBB) penetration ability. The LyNO-Pdots are successfully applied to ratiometric imaging of lysosomal NO variations in brain-derived endothelial cells, brain tissues and mice brains with Alzheimer's disease (AD). The results demonstrate that the NO content in the brains of AD mice is considerably higher than that in normal mice.

Epigenomic signatures of sarcomatoid differentiation to guide the treatment of renal cell carcinoma.

Renal cell carcinoma with sarcomatoid differentiation (sRCC) is associated with poor survival and a heightened response to immune checkpoint inhibitors (ICIs). Two major barriers to improving outcomes for sRCC are the limited understanding of its gene regulatory programs and the low diagnostic yield of tumor biopsies due to spatial heterogeneity. Herein, we characterized the epigenomic landscape of sRCC by profiling 107 epigenomic libraries from tissue and plasma samples from 50 patients with RCC and healthy volunteers. By profiling histone modifications and DNA methylation, we identified highly recurrent epigenomic reprogramming enriched in sRCC. Furthermore, CRISPRa experiments implicated the transcription factor FOSL1 in activating sRCC-associated gene regulatory programs, and FOSL1 expression was associated with the response to ICIs in RCC in two randomized clinical trials. Finally, we established a blood-based diagnostic approach using detectable sRCC epigenomic signatures in patient plasma, providing a framework for discovering epigenomic correlates of tumor histology via liquid biopsy.

From mechanism to application: Decrypting light-regulated denitrifying microbiome through geometric deep learning.

Regulation on denitrifying microbiomes is crucial for sustainable industrial biotechnology and ecological nitrogen cycling. The holistic genetic profiles of microbiomes can be provided by meta-omics. However, precise decryption and further applications of highly complex microbiomes and corresponding meta-omics data sets remain great challenges. Here, we combined optogenetics and geometric deep learning to form a discover-model-learn-advance (DMLA) cycle for denitrification microbiome encryption and regulation. Graph neural networks (GNNs) exhibited superior performance in integrating biological knowledge and identifying coexpression gene panels, which could be utilized to predict unknown phenotypes, elucidate molecular biology mechanisms, and advance biotechnologies. Through the DMLA cycle, we discovered the wavelength-divergent secretion system and nitrate-superoxide coregulation, realizing increasing extracellular protein production by 83.8% and facilitating nitrate removal with 99.9% enhancement. Our study showcased the potential of GNNs-empowered optogenetic approaches for regulating denitrification and accelerating the mechanistic discovery of microbiomes for in-depth research and versatile applications.

Protective effect of Lactiplantibacillus plantarum CCFM8661 against heavy metal mixture-induced liver and kidney injury in mice.

Human health and the ecological balance are both gravely threatened by heavy metal pollution brought on by global industrialization. Probiotics are thought to represent a novel class of medicinal products for reducing heavy metal toxicity. Though simultaneous poisoning of numerous heavy metals is more prevalent, the majority of current studies on probiotics in the treatment of heavy metal poisoning concentrate on a single heavy metal. Thus, a mouse damage model was created in this investigation using five heavy metals (Pb, Cd, Hg, Cr, and As), and Lactiplantibacillus plantarum CCFM8661 was utilized as an intervention therapy. The oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT), antioxidant capacity (T-AOC), and malondialdehyde (MDA), were evaluated in the blood, liver, and kidney tissues of mice throughout the experiment by tracking changes in body weight. Additionally, the amounts of five heavy metals were measured in the liver and kidney tissues. The alleviation of tissue damage and the detoxifying activity of L. plantarum CCFM8661 in mice with combined heavy metal intoxication were assessed by histopathological examination of liver and kidney tissues. Results revealed that during the test period, L. plantarum CCFM8661 significantly reduced the content of MDA and the contents of Pb, Cd, Hg, Cr, and As in liver and kidney tissues, while also significantly increasing weight gain and the activities of SOD, CAT, and T-AOC in mouse blood, liver, and kidney tissues compared to the model group. Mouse liver and kidney tissue damage from combined heavy metal exposure was considerably lessened by L. plantarum CCFM8661 when compared to the model group, according to H&E staining. This study demonstrates that L. plantarum CCFM8661 may be utilized as a useful intervention for the treatment of combined heavy metal poisoning by efficiently reducing the harm that heavy metals do to the body and maintaining bodily health.

Discovery of Selective Proteolysis-Targeting Chimera Degraders Targeting PTP1B as Long-Term Hypoglycemic Agents.

PTP1B, a promising target for insulin sensitizers in type 2 diabetes treatment, can be effectively degraded using proteolysis-targeting chimera (PROTAC). This approach offers potential for long-acting antidiabetic agents. We report potent bifunctional PROTACs targeting PTP1B through the E3 ubiquitin ligase cereblon. Western blot analysis showed significant PTP1B degradation by PROTACs at concentrations from 5 nM to 5 µM after 48 h. Evaluation of five highly potent PROTACs revealed compound 75 with a longer PEG linker (23 atoms), displaying remarkable degradation activity after 48 and 72 h, with DC50 values of 250 nM and 50 nM, respectively. Compound 75 induced selective degradation of PTP1B, requiring engagement with both the target protein and CRBN E3 ligase, in a ubiquitination and proteasome-dependent manner. It significantly reduced blood glucose AUC0-2h to 29% in an oral glucose tolerance test and activated the IRS-1/PI3K/Akt signaling pathway in HepG2 cells, showing promise for long-term antidiabetic therapy.

DNA polymerase delta governs parental histone transfer to DNA replication lagging strand.

Chromatin replication is intricately intertwined with the recycling of parental histones to the newly duplicated DNA strands for faithful genetic and epigenetic inheritance. The transfer of parental histones occurs through two distinct pathways: leading strand deposition, mediated by the DNA polymerase ε subunits Dpb3/Dpb4, and lagging strand deposition, facilitated by the MCM helicase subunit Mcm2. However, the mechanism of the facilitation of Mcm2 transferring parental histones to the lagging strand while moving along the leading strand remains unclear. Here, we show that the deletion of Pol32, a nonessential subunit of major lagging-strand DNA polymerase δ, results in a predominant transfer of parental histone H3-H4 to the leading strand during replication. Biochemical analyses further demonstrate that Pol32 can bind histone H3-H4 both in vivo and in vitro. The interaction of Pol32 with parental histone H3-H4 is disrupted through the mutation of the histone H3-H4 binding domain within Mcm2. Our findings identify the DNA polymerase δ subunit Pol32 as a critical histone chaperone downstream of Mcm2, mediating the transfer of parental histones to the lagging strand during DNA replication.

Synthesis and Neuroprotective Evaluation of Substituted Indanone/Benzofuranone and Piperidine Hybrids.

Based on the neuroprotection of butylphthalide and donepezil, a series of indanone/benzofuranone and piperidine hybrids were designed and synthesized for assessment of their neuroprotective activities, aiming to enhance the bioavailability and therapeutic efficacy of natural phthalide analogues. Within this study, it was observed that most indanone derivatives bearing 1-methylpiperidine in the tail segment demonstrated superior neuroprotective effects on the oxygen glucose deprivation/reperfusion (OGD/R)-induced rat primary neuronal cell injury model in vitro compared to benzofuranone compounds. Among the synthesized compounds, 11 (4, 14, 15, 22, 26, 35, 36, 37, 48, 49, and 52) displayed robust cell viabilities in the OGD/R model, along with favorable blood-brain barrier permeability as confirmed by the parallel artificial membrane permeability assay. Notably, compound 4 showed significant neuronal cell viabilities within the concentration range of 3.125 to 100 µM, without inducing cytotoxicity. Further results from in vivo middle cerebral artery occlusion/R experiments revealed that 4 effectively ameliorated ischemia-reperfusion injury, reducing the infarct volume to 18.45% at a dose of 40 mg/kg. This outcome suggested a superior neuroprotective effect compared to edaravone at 20 mg/kg, further highlighting the potential therapeutic efficacy of compound 4 in addressing neurological disorders.

Effect of substrate material and abutment geometry on the accuracy of intraoral scanning: An in vitro study.

STATEMENT OF PROBLEM: Digital scanning is gradually replacing conventional impression making, but consensus on how tooth preparation influences the accuracy of intraoral scanning is lacking. PURPOSE: The purpose of this in vitro study was to evaluate the effect of substrate material and abutment geometry on the accuracy of digital casts obtained by intraoral scanning. MATERIAL AND METHODS: The height and total occlusal convergence (TOC) angle were measured in 5 different groups that contained 5 specimens of different materials: natural tooth, cobalt chromium alloy, titanium, zirconium dioxide ceramic, and resin. The specimens were scanned with an industrial scanner to obtain reference data. Each specimen was placed in a maxillary standard dentition model that was assembled in a head simulator. Each dentition model was scanned 10 times with an intraoral scanner (IOS) under operatory lighting conditions to acquire intraoral scanning files for each specimen. All data were imported into a metrology software program and processed. A total of 10 trueness deviations, the mean superimposition results between IOS scanning data and reference data, and precision deviations, the mean superimposition results between IOS scanning data in pairs, were recorded. Two-way analysis of variance (ANOVA) and Tukey multiple comparison test were used to analyze the accuracy of intraoral scanning in relation to the height or TOC angle of the abutment (α=.05). The total means of each substrate material were compared with the Kruskal-Wallis test and Dunn test for multiple comparisons. RESULTS: The accuracy of scanning images was related to material and abutment geometry (P<.05). Bias was larger as abutment height increased with most substrates. Larger TOC angles increased the accuracy of the digital scans. The trueness deviation of translucent materials and the precision deviation of reflective materials were generally larger. CONCLUSIONS: Substrate material and abutment geometry influence the accuracy of intraoral scanning. The accuracy of IOS generally tended to improve with decreasing height and increasing TOC angle and was affected by different substrates.