The Effect of Coenzyme Q10 Supplementation on Bile Acid Metabolism: Insights from Network Pharmacology, Molecular Docking, and Experimental Validation.

SCOPE: Bile acids play a crucial role in lipid absorption and the regulation of lipid, glucose, and energy homeostasis. Coenzyme Q10 (CoQ10), a lipophilic antioxidant, has been recognized for its positive effects on obesity and related glycolipid metabolic disorders. However, the relationship between CoQ10 and bile acids has not yet been evaluated. METHODS AND RESULTS: This study assesses the impact of CoQ10 treatment on bile acid metabolism in mice on a high-fat diet using Ultra-Performance Liquid Chromatography-tandem Mass Spectrometry. CoQ10 reverses the reduction in serum and colonic total bile acid levels and alters the bile acid profile in mice that are caused by a high-fat diet. Seventeen potential targets of CoQ10 in bile acid metabolism are identified by network pharmacology, with six being central to the mechanism. Molecular docking shows a high binding affinity of CoQ10 to five of these key targets. Further analyses indicate that farnesoid X (FXR) receptor and Takeda G-protein coupled receptor 5 (TGR5) may be crucial targets for CoQ10 to regulate bile acid metabolism and exert beneficial effects. CONCLUSION: This study sheds light on the impact of CoQ10 in bile acids metabolism and offers a new perspective on the application of CoQ10 in metabolic health.

Gadd45g insufficiency drives the pathogenesis of myeloproliferative neoplasms.

Despite the identification of driver mutations leading to the initiation of myeloproliferative neoplasms (MPNs), the molecular pathogenesis of MPNs remains incompletely understood. Here, we demonstrate that growth arrest and DNA damage inducible gamma (GADD45g) is expressed at significantly lower levels in patients with MPNs, and JAK2V617F mutation and histone deacetylation contribute to its reduced expression. Downregulation of GADD45g plays a tumor-promoting role in human MPN cells. Gadd45g insufficiency in the murine hematopoietic system alone leads to significantly enhanced growth and self-renewal capacity of myeloid-biased hematopoietic stem cells, and the development of phenotypes resembling MPNs. Mechanistically, the pathogenic role of GADD45g insufficiency is mediated through a cascade of activations of RAC2, PAK1 and PI3K-AKT signaling pathways. These data characterize GADD45g deficiency as a novel pathogenic factor in MPNs.

Effect of Brucea javanica Oil on the Toxicity of ß-Cypermethrin Emulsifiable Concentrate Formulation.

Enhancing the performance of traditional pesticide formulations by improving their leaf surface wetting capabilities is a crucial approach for maximizing the pesticide efficiency. This study develops an emulsifiable concentrate (EC) of 4.5% ß-cypermethrin containing Brucea javanica oil (BJO). The incorporation of BJO aims to improve the leaf-wetting properties of the EC formulation and enhance its insecticidal effectiveness. The droplet size and emulsion characteristics of ß-CYP EC emulsion with varying concentrations of the emulsifier were evaluated, and changes after incorporating BJO were assessed to develop the optimal formulation. A comprehensive comparison was conducted among commercial 4.5% ß-cypermethrin EC (ß-CYP EC-1), 4.5% ß-cypermethrin EC with BJO (ß-CYP EC-2), and 4.5% ß-cypermethrin EC without BJO (ß-CYP EC-3). This comparison encompassed various factors including storage stability, insecticidal activity, cytotoxicity, and wetting performance on cabbage leaves. The results indicated that the ideal emulsifier concentration was 15% emulsifier 0201B. ß-CYP EC-2 demonstrated superior wetting properties on cabbage leaves (the wetting performance of ß-CYP EC-2 emulsion on cabbage leaves is 2.60 times that of the ß-CYP EC-1 emulsion), heightened insecticidal activity against the third larvae of Plutella xylostella [diamondback moth (DBM)] [the insecticidal activity of the ß-CYP EC-2 emulsion against the third larvae of DBM is 1.93 times that of the ß-CYP EC-1 emulsion (12 h)], and more obvious inhibitory effects on the proliferation of DBM embryo cells than the other tested formulations. These findings have significant implications for advancing pest control strategies and promoting sustainable and effective agricultural practices.

Study on the correlation between suicidal ideation and ABI3BP gene、DPYSL2 gene methylation in pediatric bipolar disorder with depressive episode.

Patients with bipolar disorder have a higher risk of suicide than the general population. This study aimed to explore the correlation between suicide and gene methylation, as screened by genome-wide scanning, in children and adolescents with bipolar disorder. A total of 45 children and adolescents with bipolar disorder were divided into a suicidal ideation group (n = 41), a non-suicidal ideation group (n = 4), a low-risk group (n = 12), and a middle-to-high-risk group (n = 33). A pre-experiment was conducted on the suicidal ideation (n = 6) and non-suicidal ideation groups (n = 4). Blood samples were scanned using an Illumina HD 850K microarray, and methylation levels were analysed. Differential methylation sites among the sample groups were screened from the original data, and genes related to suicide were identified. Methylation of the ABI3BP and DPYSL2 genes was detected by pyrophosphate sequencing and statistically analysed. There was a significant difference in age between the low- and middle-risk groups. The results of GO analysis for the suicidal ideation and non-suicidal ideation groups showed that the differential methylation sites were mainly involved in the interferon-γ-mediated signalling pathway, with the main signalling pathways being the inflammatory bowel disease (IBD) pathway and type 1 diabetes mellitus (T1DM) pathway. There were significant differences in the methylation of ABI3BP, HLA-DQB1, HLA-DRB1, AUTS2, SP3, NINJ2, DPYSL2, and other genes between the suicidal and non-suicidal ideation groups. There was also a statistically significant difference in the gene methylation levels between the two groups. However, there was no significant difference in the degree of methylation of the ABI3BP and DPYSL2 genes between the low- and middle-to-high-risk groups. These results suggest that suicidal ideation is correlated with the methylation levels of differentially methylated genes in children with bipolar disorder. However, the severity of suicide risk in paediatric patients with bipolar disorder may not be correlated with the degree of methylation of the ABI3BP and DPYSL2 genes. Therefore, further validation was required.

Twist family BHLH transcription factor 1 is required for the maintenance of leukemia stem cell in MLL-AF9+ acute myeloid leukemia.

Leukemia stem cells (LSC) are a rare population capable of limitless self-renewal and are responsible for the initiation, maintenance, and relapse of leukemia. Elucidation of the mechanisms underlying the regulation of LSC function could provide novel treatment strategies. Here, we show that TWIST1 is extremely highly expressed in the LSC of MLL-AF9+ acute myeloid leukemia (AML), and its upregulation is positively regulated by KDM4C in a H3K9me3 demethylation-dependent manner. We further demonstrate that TWIST1 is essential for the viability, dormancy, and self-renewal capacities of LSC, and that it promotes the initiation and maintenance of MLL-AF9-mediated AML. In addition, TWIST1 directly interacts and collaborates with HOXA9 in inducing AML in mice. Mechanistically, TWIST1 exerts its oncogenic function by activating the WNT5a/RAC1 axis. Collectively, our study uncovers a critical role of TWIST1 in LSC function and provides new mechanistic insights into the pathogenesis of MLL-AF9+ AML.

Serum remnant cholesterol is a potential predictor of liver stiffness in patients with nonalcoholic fatty liver disease.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is associated with dyslipidemia, and the connection between dyslipidemia and remnant cholesterol (RC), a component of triglyceride-rich lipoproteins, remains enigmatic. METHODS: In this cross-sectional study, our primary aim was to investigate the role of RC in the progression of NAFLD and to provide robust evidence of RC's involvement in the pathogenesis of NAFLD. We enrolled 2800 NAFLD patients from the National Health and Nutrition Examination Survey (NHANES). Logistic regression was employed to examine the relationship between serum RC levels and liver stiffness, while receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capability of RC. RESULTS: RC exhibited an independent correlation with the extent of liver stiffness, with odds ratios (OR) of 1.02 for liver steatosis (p = 0.014) and 1.02 for liver fibrosis (p = 0.014). To predict NAFLD, the optimal RC thresholds were 17.25 mg/dL for males and 15.25 mg/dL for females in the case of liver steatosis. For advanced liver fibrosis, the best thresholds were 17.25 mg/dL for males and 16.25 mg/dL for females. CONCLUSIONS: RC demonstrated a positive correlation with the degree of liver stiffness and exhibited superior diagnostic efficacy for liver steatosis and fibrosis compared to other cholesterol indicators.

Elevated serum remnant cholesterol (RC) levels may serve as a potential indicator of metabolic diseases, including nonalcoholic fatty liver disease (NAFLD). The connection between serum RC and NAFLD has been previously undervalued. In our investigation, we examined 2800 NAFLD patients from the National Health and Nutrition Examination Survey (NHANES). Our cross-sectional study has revealed a more distinct relationship between RC and the degree of liver stiffness, especially concerning liver steatosis when compared to other cholesterol indicators. Recognizing RC's significant role in metabolic disorders may lead to innovative approaches for diagnosing and treating NAFLD patients.

Green synthesis of a chlorfenapyr chitosan nanopesticide for maize root application: Reducing environmental pollution and risks to nontarget organisms.

Chlorfenapyr (CHL) is a pyrrole insecticide with a novel structure that is used to control resistant pests. However, its weak systemic activity limits its application to crop roots. Herein, a novel CHL formulation with improved effective utilization rates and suitability for root application is developed to avoid or reduce contamination caused by pesticide spraying. Accordingly, we prepared CHL@CS/CMCS nanoparticle (NP) suspensions with a particle size of approximately 100 nm using chitosan (CS) and carboxymethyl chitosan (CMCS). These suspensions exhibited better thermal stability, adhesion, permeability and systemic activity than a CHL suspension concentrate (CHL-SC). The nanoformulation deposition rate on maize leaves after spraying was 12.28 mg/kg, significantly higher than that of CHL-SC. The nanosuspension was effectively absorbed and transported by roots after irrigation and was suitable for root application. The efficacy was 89.46-92.36 % against Spodoptera frugiperda at 7 d, 7.5-17.5 times higher than that of CHL-SC. Furthermore, the CHL@CS/CMCS nanosuspension was safer for earthworms. These results suggest that chitosan-based nanoformulations improve the efficacy, utilization efficiency and active period of CHL control, providing a new approach for CHL application, reducing pollutant dispersal and the environmental impacts of pesticide application and facilitating sustainable agricultural production.

Different effects of dietary ß-hydroxy-ß-methylbutyrate on composition of fatty acid and free amino acid, and fatty metabolism in the different muscles of broilers.

In the study, 336 broiler chickens were selected to explore dietary effects of different ß-hydroxy-ß-methylbutyrate (HMB) levels (0 (control), 0.05, 0.10, and 0.15%) on the compositions of fatty acids and free amino acids, and lipid metabolism in the different muscles of broilers. In the breast muscle, dietary HMB supplementation hardly affected the free amino acid composition (P > 0.05). Compared to the control group, dietary 0.10 and 0.15% HMB supplementation decreased the content of C18:1n9c and thus the monounsaturated fatty acid (MUFA), and dietary 0.15% HMB supplementation increased the sum of saturated fatty acids (SFA) (P < 0.05). Moreover, compared to the control group, dietary 0.05 and 0.10% HMB increased the mRNA expression of proliferator activated receptor-γ and the activity of fatty acid synthase (FAS), and dietary 0.10% HMB increased the acetyl-CoA carboxylase activity (P < 0.05). In the leg muscle, dietary 0.10 and 0.15% HMB increased the MUFA content and decreased the polyunsaturated fatty acid (PUFA) content, the PUFA to SFA ratio, the mRNA expression of sterol regulatory element binding proteins-1c, and the activities of acyl-CoA oxidase 1 and acetyl-CoA synthetase (P < 0.05). Moreover, dietary 0.10% HMB decreased the activities of hydroxy-3-methylglutaryl-CoA synthase 1 and FAS in comparison to the control group (P < 0.05). Dietary 0.05% HMB decreased the contents of essential amino acids and nonessential amino acids (NEAA), and dietary 0.15% HMB decreased the NEAA content (P < 0.05). In summary, dietary 0.10% HMB supplementation had superior efficiency on lipogenesis in the breast muscle of broilers. However, dietary HMB supplementation, especially at the level of 0.05 and 0.15%, decreased meat nutritional values and the lipogenesis in leg muscles.

Integrated analysis of circRNA, lncRNA, miRNA and mRNA to reveal the ceRNA regulatory network of postnatal skeletal muscle development in Ningxiang pig.

Introduction: The development of skeletal muscle is regulated by regulatory factors of genes and non-coding RNAs (ncRNAs). Methods: The objective of this study was to understand the transformation of muscle fiber type in the longissimus dorsi muscle of male Ningxiang pigs at four different growth stages (30, 90, 150, and 210 days after birth, n = 3) by histological analysis and whole transcriptome sequencing. Additionally, the study investigated the expression patterns of various RNAs involved in muscle fiber transformation and constructed a regulatory network for competing endogenous RNA (ceRNA) that includes circular RNA (circRNA)/long non-coding RNA (lncRNA)-microRNA (miRNA)-messenger RNA (mRNA). Results: Histomorphology analysis showed that the diameter of muscle fiber reached its maximum at 150 days after birth. The slow muscle fiber transformation showed a pattern of initial decrease followed by an increase. 29,963 circRNAs, 2,683 lncRNAs, 986 miRNAs and 22,411 mRNAs with expression level ≥0 were identified by whole transcriptome sequencing. Furthermore, 642 differentially expressed circRNAs (DEc), 505 differentially expressed lncRNAs (DEl), 316 differentially expressed miRNAs (DEmi) and 6,090 differentially expressed mRNAs (DEm) were identified by differential expression analysis. Functions of differentially expressed mRNA were identified by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). GO enrichment analysis indicates that 40 known genes and 6 new genes are associated with skeletal muscle development. Additionally, KEGG analysis shows that these genes regulate skeletal muscle development via MAPK, FoxO, Hedgehog, PI3K-Akt, Notch, VEGF and other signaling pathways. Through protein-protein interaction (PPI) and transcription factor prediction (TFP), the action mode of skeletal muscle-related genes was explored. PPI analysis showed that there were stable interactions among 19 proteins, meanwhile, TFP analysis predicted 22 transcription factors such as HMG20B, MYF6, MYOD1 and MYOG, and 12 of the 19 interacting proteins were transcription factors. The regulatory network of ceRNA related to skeletal muscle development was constructed based on the correlation of various RNA expression levels and the targeted binding characteristics with miRNA. The regulatory network included 31 DEms, 59 miRNAs, 667 circRNAs and 224 lncRNAs. conclusion: Overall, the study revealed the role of ceRNA regulatory network in the transformation of skeletal muscle fiber types in Ningxiang pigs, which contributes to the understanding of ceRNA regulatory network in Ningxiang pigs during the skeletal muscle development period.

Development and Recovery of Liver Injury in Piglets by Incremental Injection of LPS.

This study aimed to explore the effects of the incremental injection of lipopolysaccharide (LPS) on liver histopathology, inflammation, oxidative status, and mitochondrial function in piglets. Forty healthy Duroc × Landrace × Yorkshire castrated boars (21 ± 2 days old, weight 6.84 ± 0.11 kg) were randomly assigned to five groups (n = 8) and then slaughtered on days 0 (group 0, without LPS injection), 1 (group 1), 5 (group 5), 9 (group 9), and 15 (group 15) of LPS injection, respectively. The results showed that, compared to the piglets without LPS injection, LPS injection caused liver injury in the early phase, as manifested by the increased activities of serum liver injury-related parameters (aspartate amino transferase, alanine aminotransferase, alkaline phosphatase, cholinesterase, and total bile acid) on day 1, and impaired liver morphology (disordered hepatic cell cord arrangement, dissolved and vacuolized hepatocytes, karyopycnosis, and inflammatory cell infiltration and congestion) on days 1 and 5. Meanwhile, LPS injection caused liver inflammation, oxidative stress, and mitochondrial dysfunction on days 1 and 5, as reflected by the upregulated mRNA expression of TNF-α, IL-6, IL-1ß, TLR4, MyD88, and NF-κB; increased MPO and MDA content; and impaired mitochondrial morphology. However, these parameters were ameliorated in the later phase (days 9~15). Taken together, our data indicate that the incremental injection of the LPS-induced liver injury of piglets could be self-repaired.

ß-Hydroxy-ß-methyl Butyrate Regulates the Lipid Metabolism, Mitochondrial Function, and Fat Browning of Adipocytes.

A growing number of in vivo studies demonstrated that ß-hydroxy-ß-methyl butyrate (HMB) can serve as a lipid-lowering nutrient. Despite this interesting observation, the use of adipocytes as a model for research is yet to be explored. To ascertain the effects of HMB on the lipid metabolism of adipocytes and elucidate the underlying mechanisms, the 3T3-L1 cell line was employed. Firstly, serial doses of HMB were added to 3T3-L1 preadipocytes to evaluate the effects of HMB on cell proliferation. HMB (50 µM) significantly promoted the proliferation of preadipocytes. Next, we investigated whether HMB could attenuate fat accumulation in adipocytes. The results show that HMB treatment (50 µM) reduced the triglyceride (TG) content. Furthermore, HMB was found to inhibit lipid accumulation by suppressing the expression of lipogenic proteins (C/EBPα and PPARγ) and increasing the expression of lipolysis-related proteins (p-AMPK, p-Sirt1, HSL, and UCP3). We also determined the concentrations of several lipid metabolism-related enzymes and fatty acid composition in adipocytes. The HMB-treated cells showed reduced G6PD, LPL, and ATGL concentrations. Moreover, HMB improved the fatty acid composition in adipocytes, manifested by increases in the contents of n6 and n3 PUFAs. The enhancement of the mitochondrial respiratory function of 3T3-L1 adipocytes was confirmed via Seahorse metabolic assay, which showed that HMB treatment elevated basal mitochondrial respiration, ATP production, H+ leak, maximal respiration, and non-mitochondrial respiration. In addition, HMB enhanced fat browning of adipocytes, and this effect might be associated with the activation of the PRDM16/PGC-1α/UCP1 pathway. Taken together, HMB-induced changes in the lipid metabolism and mitochondrial function may contribute to preventing fat deposition and improving insulin sensitivity.

Intermittent Fasting Alleviates Non-Alcoholic Steatohepatitis by Regulating Bile Acid Metabolism and Promoting Fecal Bile Acid Excretion in High-Fat and High-Cholesterol Diet Fed Mice.

SCOPE: Intermittent fasting (IF) has a protective role across a wide range of chronic disorders, including obesity, diabetes, and cardiovascular disease, but its protection against non-alcoholic steatohepatitis (NASH) is still lacking. This study seeks to investigate how IF alleviates NASH by regulating gut microbiota and bile acids (BAs) composition. METHODS AND RESULTS: Male C57BL/6 mice are fed a high-fat and high-cholesterol (HFHC) diet for 16 weeks to establish a NASH model. Mice then continued HFHC feeding and are treated with or without every other day fasting for 10 weeks. Hepatic pathology is assessed using hematoxylin-eosin staining. Gut microbiota of the cecum are profiled using 16S rDNA gene sequencing and the levels of BAs in serum, colon contents, and feces are measured using ultra-performance liquid chromatography-tandem mass spectrometry. Results indicate that IF significantly decreases murine body weight, insulin resistance, hepatic steatosis, ballooning, and lobular inflammation. IF reshapes the gut microbiota, reduces the accumulation of serum BAs, and increases total colonic and fecal BAs. Moreover, IF increases the expression of cholesterol 7α-hydroxylase 1 in liver, but decreases the expressions of both farnesoid-X-receptor and fibroblast growth factor 15 in the ileum. CONCLUSION: IF alleviates NASH by regulating bile acid metabolism and promoting fecal bile acid excretion.

Protein-Targeted Glycan Editing on Living Cells Disrupts KRAS Signaling.

The frequent mutation of KRAS oncogene in some of the most lethal human cancers has spurred incredible efforts to develop KRAS inhibitors, yet only one covalent inhibitor for the KRASG12C mutant has been approved to date. New venues to interfere with KRAS signaling are desperately needed. Here, we report a "localized oxidation-coupling" strategy to achieve protein-specific glycan editing on living cells for disrupting KRAS signaling. This glycan remodeling method exhibits excellent protein and sugar specificity and is applicable to different donor sugars and cell types. Attachment of mannotriose to the terminal galactose/N-acetyl-D-galactosamine epitopes of integrin αv ß3 , a membrane receptor upstream of KRAS, blocks its binding to galectin-3, suppresses the activation of KRAS and downstream effectors, and mitigates KRAS-driven malignant phenotypes. Our work represents the first successful attempt to interfere with KRAS activity by manipulating membrane receptor glycosylation.

n-3 PUFA Promotes Ferroptosis in PCOS GCs by Inhibiting YAP1 through Activation of the Hippo Pathway.

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by hyperandrogenemia with multiple suspended sinus follicles, thickened cortical tissue, and excessive proliferation of ovarian granulosa cells that severely affects the fertility and quality of life of women. The addition of n-3 PUFA to the diet may slightly reduce body weight and greatly alleviate disturbed blood hormone levels in PCOS mice. We treated KGN as a cell model for n-3 PUFA addition and showed that n-3 PUFA inhibited the proliferation of GCs and promoted ferroptosis in ovarian granulosa cells. We used CCK-8, fluorescence quantitative transmission electron microscopy experiments and ferroptosis marker gene detection and other methods. Furthermore, n-3 PUFA was found to promote YAP1 exocytosis by activating Hippo and weakening the cross-talk between YAP1 and Nrf2 by activating the Hippo signaling pathway. In this study, we found that n-3 PUFA inhibited the over proliferation of granulosa cells in ovarian follicles by activating Hippo, promoting YAP1 exocytosis, weakening the cross-talk between YAP1 and Nrf2, and ultimately activating the ferroptosis sensitivity of ovarian granulosa cells. We demonstrate that n-3 PUFA can alleviate the hormonal and estrous cycle disorder with PCOS by inhibiting the YAP1-Nrf2 crosstalk that suppresses over proliferating ovarian granulosa cells and promotes iron death in GCs. These findings reveal the molecular mechanisms by which n-3 PUFA attenuates PCOS and identify YAP1-Nrf2 as a potential therapeutic target for regulation granulosa cells in PCOS.

Regulation of SIRT1 in Ovarian Function: PCOS Treatment.

The sirtuin family, a group of NAD+-dependent class 3 histone deacetylases (HDACs), was extensively studied initially as a group of longevity genes that are activated in caloric restriction and act in concert with nicotinamide adenine dinucleotides to extend the lifespan. Subsequent studies have found that sirtuins are involved in various physiological processes, including cell proliferation, apoptosis, cell cycle progression, and insulin signaling, and they have been extensively studied as cancer genes. In recent years, it has been found that caloric restriction increases ovarian reserves, suggesting that sirtuins may play a regulatory role in reproductive capacity, and interest in the sirtuin family has continued to increase. The purpose of this paper is to summarize the existing studies and analyze the role and mechanism of SIRT1, a member of the sirtuin family, in regulating ovarian function. Research and review on the positive regulation of SIRT1 in ovarian function and its therapeutic effect on PCOS syndrome.

Estimating the restraint of SARS-CoV-2 spread using a conventional medical air-cleaning device: Based on an experiment in a typical dental clinical setting.

OBJECTIVES: Droplets or aerosols loaded with SARS-CoV-2 can be released during breathing, coughing, or sneezing from COVID-19-infected persons. To investigate whether the most commonly applied air-cleaning device in dental clinics, the oral spray suction machine (OSSM), can provide protection to healthcare providers working in clinics against exposure to bioaerosols during dental treatment. METHOD: In this study, we measured and characterized the temporal and spatial variations in bioaerosol concentration and deposition with and without the use of the OSSM using an experimental design in a dental clinic setting. Serratia marcescens (a bacterium) and ΦX174 phage (a virus) were used as tracers. The air sampling points were sampled using an Anderson six-stage sampler, and the surface-deposition sampling points were sampled using the natural sedimentation method. The Computational Fluid Dynamics method was adopted to simulate and visualize the effect of the OSSM on the concentration spatial distribution. RESULTS: During dental treatment, the peak exposure concentration increased by up to 2-3 orders of magnitude (PFU/m3) for healthcare workers. Meanwhile, OSSM could lower the mean bioaerosol exposure concentration from 58.84 PFU/m3 to 4.10 PFU/m3 for a healthcare worker, thereby inhibiting droplet and airborne transmission. In terms of deposition, OSSM significantly reduced the bioaerosol surface concentration from 28.1 PFU/m3 to 2.5 PFU/m3 for a surface, effectively preventing fomite transmission. CONCLUSION: The use of OSSM showed the potential to restraint the spread of bioaerosols in clinical settings. Our study demonstrates that OSSM use in dental clinics can reduce the exposure concentrations of bioaerosols for healthcare workers during dental treatment and is beneficial for minimizing the risk of infectious diseases such as COVID-19.

Effects of glycosylation on the accumulation and transport of fipronil in earthworm (Eisenia fetida).

In this study, the differences in the accumulation of fipronil (F) and the glycosylated product glucose-fipronil (GTF) in Eisenia fetida within 48 h were investigated, and the reason for these differences was discussed. The accumulation of F and GTF in E. fetida and soil was determined by high-performance liquid chromatography (HPLC) after simple, rapid pretreatment; the mean recoveries of F and GTF were 84.79 ~ 95.83%, and the relative standard deviations were 3.39 ~ 9.21%, indicating that the methods could accurately detect the accumulation of F and GTF in E. fetida and soil. Results showed that the accumulation concentrations of F and GTF in E. fetida increased with exposure time; the concentrations of F in E. fetida were 3.1 ~ 6.2 times higher than those of GTF. In addition, the half-lives of GTF in soil (16.90 ~ 18.24 days) were significantly lower than those of F (24.75 ~ 26.65 days). After the addition of phlorizin, a hexose transport inhibitor, the accumulation of F in E. fetida did not change significantly, but the accumulation of GTF in E. fetida was significantly inhibited. The concentrations of GTF in E. fetida after adding phlorizin were 32.71 ~ 59.07% of those without phlorizin. Overall, our results indicated that the uptake and transport of F and GTF in E. fetida were significantly different; the uptake and transport of GTF was related to monosaccharide transporters, and glycosylation could reduce the bioaccumulation of fipronil to E. fetida and shorten the half-life of fipronil in soil, providing an important reference for the application of glucose-fipronil.

The neural correlates of amplitude of low-frequency fluctuation: a multimodal resting-state MEG and fMRI-EEG study.

The amplitude of low-frequency fluctuation (ALFF) describes the regional intensity of spontaneous blood-oxygen-level-dependent signal in resting-state functional magnetic resonance imaging (fMRI). How the fMRI-ALFF relates to the amplitude in electrophysiological signals remains unclear. We here aimed to investigate the neural correlates of fMRI-ALFF by comparing the spatial difference of amplitude between the eyes-closed (EC) and eyes-open (EO) states from fMRI and magnetoencephalography (MEG), respectively. By synthesizing MEG signal into amplitude-based envelope time course, we first investigated 2 types of amplitude in MEG, meaning the amplitude of neural activities from delta to gamma (i.e. MEG-amplitude) and the amplitude of their low-frequency modulation at the fMRI range (i.e. MEG-ALFF). We observed that the MEG-ALFF in EC was increased at parietal sensors, ranging from alpha to beta; whereas the MEG-amplitude in EC was increased at the occipital sensors in alpha. Source-level analysis revealed that the increased MEG-ALFF in the sensorimotor cortex overlapped with the most reliable EC-EO differences observed in fMRI at slow-3 (0.073-0.198 Hz), and these differences were more significant after global mean standardization. Taken together, our results support that (i) the amplitude at 2 timescales in MEG reflect distinct physiological information and that (ii) the fMRI-ALFF may relate to the ALFF in neural activity.

Pharmacokinetics and bioequivalence of two methylprednisolone tablet formulations in healthy Chinese subjects under fasting and fed conditions.

AIMS: The aims of this study were to evaluate and compare the pharmacokinetic profiles and bioequivalence of two tablet formulations of methylprednisolone (test formulation: Zhejiang Xianju Pharmaceutical Co., Ltd., China; reference formulation: Medrol, Pfizer Italia SRL) in healthy Chinese subjects under fasting and fed conditions. MATERIALS AND METHODS: Subjects were randomly allocated to either the fasting group or the fed group and also to one of two sequences (test-reference or reference-test), according to which they received a single 16-mg dose of the test or reference methylprednisolone tablet in the study periods. Blood samples were collected pre dose and at intervals up to 16 hours after administration. Plasma methylprednisolone concentrations were determined using a validated liquid chromatography tandem mass spectrometry method. The safety of the medications was monitored throughout the study. The primary pharmacokinetic parameters measured were Cmax, AUC0-t, and AUC0-∞. RESULTS: A total of 56 subjects were enrolled, and all completed the study. The 90% confidence intervals for Cmax, AUC0-t, and AUC0-∞, measured under both fasting and fed conditions, fell within the acceptable range for bioequivalence of 80 - 125%. Analysis of variance showed that there were no significant differences in the primary pharmacokinetic parameters (Cmax, AUC0-t, and AUC0-∞) between the test and reference formulation measured under both fasted and fed conditions. No serious or unexpected adverse drug reactions occurred during the study period. CONCLUSION: The test methylprednisolone 16 mg tablet produced in China is bioequivalent to the reference formulation (Medrol) in healthy Chinese subjects measured under both fasting and fed conditions. Both formulations were well tolerated by all study participants.

Development of Intestinal Injury and Restoration of Weaned Piglets under Chronic Immune Stress.

This study aimed to investigate the effects of lipopolysaccharide (LPS)-induced chronic immune stress on intestinal morphology and function, immune system, oxidative status, and mitochondrial function in piglets. Fifty healthy Duroc × Landrace × Yorkshire piglets (21 ± 2 days old, barrow, 6.98 ± 0.14 kg body weight) were selected and randomly allotted to five groups, which were slaughtered at 0 (0 group), 1, 5, 9, and 15 d of LPS injection. The results showed that compared with the piglets without LPS injection, LPS injection significantly impaired the intestinal morphology and permeability at 1, 5, and 9 d, as manifested by the increased serum lactic acid and decreased ratio of villus height to crypt depth (p < 0.05). Moreover, intestinal inflammation and oxidative and mitochondrial injury were caused at 1 d, as manifested by upregulated IL-6 mRNA expression, increased malondialdehyde content, and impaired mitochondrial morphology (p < 0.05). However, these parameters were restored to levels identical to 0 group at 9~15 d, accompanied by significantly increased antioxidant capacity, enhanced protein expression of CD3+ and CD68+, and upregulated mRNA abundance of genes related to mitochondrial biogenesis and functions (p < 0.05). Collectively, these results suggest that the intestinal injury of piglets caused by chronic immune stress could be self-repaired.