Modeling of Microplastics Migration in Soil and Groundwater: Insights into Dispersion and Particle Property Effects.

Migration of microplastics (MPs) in soil-groundwater systems plays a pivotal role in determining its concentration in aquifers and future threats to the terrestrial environment, including human health. However, existing models employing an advection-dispersion equation are insufficient to incorporate the holistic mechanism of MP migration. Therefore, to bridge the gap associated with MP migration in soil-groundwater systems, a dispersion-drag force coupled model incorporating a drag force on MPs along with dispersion is developed and validated through existing laboratory and field-scale experiments. The inclusion of the MP dispersion notably increased the global maximum particle velocity (vmaxp) of MPs, resulting in a higher concentration of MPs in the aquifer, which is also established by sensitivity analysis of MP dispersion. Additionally, increasing irrigation flux and irrigation areas significantly accelerates MP migration downward from soil to deep saturated aquifers. Intriguingly, vmaxp of MPs exhibited a nonlinear relationship with MPs' sizes smaller than 20 µm reaching the highest value (=1.64 × 10-5 m/s) at a particle size of 8 µm, while a decreasing trend was identified for particle sizes ranging from 20 to 100 µm because of the hindered effect by porous media and the weaker effect of the drag force. Moreover, distinct behaviors were observed among different plastic types, with poly(vinyl chloride), characterized by the highest density, displaying the lowest vmaxp and minimal flux entering groundwater. Furthermore, the presence of a heterogeneous structure with lower hydraulic conductivity facilitated MP dispersion and promoted their migration in saturated aquifers. The findings shed light on effective strategies to mitigate the impact of MPs in aquifers, contributing valuable insights to the broader scientific fraternity.

A novel correction method for modelling parameter-driven autocorrelated time series with count outcome.

BACKGROUND: Count time series (e.g., daily deaths) are a very common type of data in environmental health research. The series is generally autocorrelated, while the widely used generalized linear model is based on the assumption of independent outcomes. None of the existing methods for modelling parameter-driven count time series can obtain consistent and reliable standard error of parameter estimates, causing potential inflation of type I error rate. METHODS: We proposed a new maximum significant ρ correction (MSRC) method that utilizes information of significant autocorrelation coefficient ρ estimate within 5 orders by moment estimation. A Monte Carlo simulation was conducted to evaluate and compare the finite sample performance of the MSRC and classical unbiased correction (UB-corrected) method. We demonstrated a real-data analysis for assessing the effect of drunk driving regulations on the incidence of road traffic injuries (RTIs) using MSRC in Shenzhen, China. Moreover, there is no previous paper assessing the time-varying intervention effect and considering autocorrelation based on daily data of RTIs. RESULTS: Both methods had a small bias in the regression coefficients. The autocorrelation coefficient estimated by UB-corrected is slightly underestimated at high autocorrelation (≥ 0.6), leading to the inflation of the type I error rate. The new method well controlled the type I error rate when the sample size reached 340. Moreover, the power of MSRC increased with increasing sample size and effect size and decreasing nuisance parameters, and it approached UB-corrected when ρ was small (≤ 0.4), but became more reliable as autocorrelation increased further. The daily data of RTIs exhibited significant autocorrelation after controlling for potential confounding, and therefore the MSRC was preferable to the UB-corrected. The intervention contributed to a decrease in the incidence of RTIs by 8.34% (95% CI, -5.69-20.51%), 45.07% (95% CI, 25.86-59.30%) and 42.94% (95% CI, 9.56-64.00%) at 1, 3 and 5 years after the implementation of the intervention, respectively. CONCLUSIONS: The proposed MSRC method provides a reliable and consistent approach for modelling parameter-driven time series with autocorrelated count data. It offers improved estimation compared to existing methods. The strict drunk driving regulations can reduce the risk of RTIs.

A systematic scoping review of epidemiological studies on the association between organophosphate flame retardants and neurotoxicity.

Organophosphate flame retardants (OPFRs) are increasingly and widely used as substitutes for brominated flame retardants in daily life. The chemical structure of OPFRs is very similar to that of organophosphorus pesticides, leading to concerns about their neurotoxicity. A few epidemiological studies have been published with inconsistent results on this topic, and a systematic scoping review is needed to provide an overview or map of the current evidence on the relationship of OPFRs with neurodevelopmental toxicity. Therefore, MEDLINE (accessed through PubMed), Web of Science, and CNKI (Chinese National Knowledge Infrastructure) were systematically searched for articles published in the last two decades. Nine eligible articles were included in the present systematic scoping review for adherence to the predefined PECOS (population, exposure, comparison, outcome, study design) statement. Six studies were conducted in the USA, and the remaining three studies were conducted in Austria, Norway and China. A total of 2 581 children (1 203 females and 1 378 males) were included. Half of the included studies focused on the adverse effects of OPFR exposure on cognition in children, while others primarily focused on the behaviors of children. In summary, the current evidence suggests inverse associations between early-life exposure to OPFRs and the childhood intelligence quotient and internalizing behavior and positive relationships of OPFR exposure with externalizing behavior. However, some differences in the timing of sample collection for exposure measurements, in the individual OPFR metabolites available, in the neurodevelopmental scales for outcome measurement, and in the statistical methods used to analyze the data are noted. In addition, further studies are warranted to evaluate some important issues, such as sex differences in the association, exposure-sensitive periods, and cumulative exposure risk assessment.

Administration of zoledronic acid alleviates osteoporosis in HIV patients by suppressing osteoclastogenesis via regulating RANKL expression.

BACKGROUND: Osteoporosis is a common phenomenon in HIV patients on tenofovir treatment, but its underlying mechanisms remain to be explored. METHODS: Quantitative real-time PCR was performed to analyze the expression of miR-302, miR-101, miR-145 and osteoclast-specific genes in the serum of HIV patients treated with tenofovir and ZOL. ELISA was used to evaluate the expression of RANKL, SMAD3 and PRKACB in the serum of these patients. Luciferase assay was carried out to explore the inhibitory effects of miR-302, miR-101 and miR-145 on the expression of PRKACB, RANKL and SMAD3, respectively. Western blot was used to examine the expression of genes involved in NF­κB and JNK signaling pathways. RESULTS: ZOL treatment significantly suppressed the expression of CTx and osteocalcin in HIV patients treated with tenofovir. The BMD loss of HIV patients treated with tenofovir was effectively hindered by ZOL treatment. Mechanistically, the expression of miR-302, miR-101, miR-145, RANKL, SMAD3 and PRKACB in the serum was remarkably activated by ZOL treatment. Luciferase assays showed that miR-302, miR-101 and miR-145 effectively suppressed the expression of PRKACB, RANKL and SMAD3, respectively, through binding to their 3' UTR. Furthermore, ZOL treatment notably restored the normal expression of osteoclast­specific genes while activating NF­κB and JNK signaling pathways. CONCLUSION: The findings of this study demonstrated that administration of ZOL suppressed the expression of RANKL via modulating signaling pathways of miR-101-3p/RANKL, miR-302/PRKACB/RANKL and miR-145/SMAD3/RANKL. Furthermore, down-regulated expression of RANKL by ZOL treatment alleviated osteoporosis in HIV-positive subjects treated with tenofovir.

Generation of vector beams of Bell-like states by manipulating vector vortex modes with plasmonic metasurfaces.

Metasurfaces with orthogonal nano-slit pairs arranged on spirals are proposed to generate vector beams (VBs) of Bell-like states and slanted polarizations. The design of the metasurfaces is based on the theoretically derived parameter condition for manipulation of the two vector vortex modes, which is satisfied by matching the three parameters of rotation order m, the spiral order n, and incident polarization helicity σ. The linear polarization states of the VBs are controlled by the initial orientation angle φ0 of slit pairs. VBs of satisfying quality are experimentally obtained, with the analytical and simulated results validated.

Management of Gout-associated MSU crystals-induced NLRP3 inflammasome activation by procyanidin B2: targeting IL-1ß and Cathepsin B in macrophages.

Gout, the most prevalent inflammatory arthritis worldwide, released interleukin-1ß (IL-1ß) and Cathepsin B inflammatory mediators that constitute the hallmark of the disease. Herein we aimed to investigate whether procyanidin B2 (PCB2), a natural dietary compound, can suppress MSU crystals-stimulated gouty inflammation. Treated with lipopolysaccharide (LPS) plus MSU, both mouse peritoneal macrophages (MPM) and mouse bone marrow-derived macrophages (BMDM) released a large amount of mature IL-1ß compared to those treated with MSU or LPS alone, while IL-1ß release was blocked by TLR4 and its downstream effector inhibitors. In two mouse models of gout, oral administration of PCB2 suppressed MSU crystals-induced increasing expression of IL-1ß, Cathepsin B and NLRP3 in the air pouch skin and paws, accompanied with the downregulation prostaglandin E2 (PGE2) in pouch exudates. Inflammatory immune cell infiltration including macrophages and neutrophils were significantly blocked by PCB2 in air pouch skin and paws of mice gout groups. PCB2 also suppressed the release of IL-1ß and Cathepsin B induced by MSU plus LPS in MPM. Our results suggest that the inhibitory effects of PCB2 on NLRP3 inflammasome may alleviate inflammatory response in gout, and this might be a promising anti-inflammatory mechanism of PCB2 against the inflammation in gout.

Total saponins of Bolbostemma paniculatum (maxim.) Franquet exert antitumor activity against MDA-MB-231 human breast cancer cells via inhibiting PI3K/Akt/mTOR pathway.

BACKGROUND: The aim of the present study was to examine the effects of the Bolbostemma paniculatum (Maxim.) Franquet (BP) active compound, BP total saponins (BPTS), on MDA-MB-231 cells, and investigate the underlying mechanism regarding BPTS-mediated attenuation of the PI3K/Akt/mTOR pathway. METHODS: The effect of BPTS on cytotoxicity, induction of apoptosis and migration on MDA-MB-231 cells at three different concentrations was investigated. A CCK-8 assay, wound-healing assay and flow cytometry were used to demonstrate the effects of BPTS. Additionally, expression of the primary members of the PI3K/Akt/mTOR signaling pathway was assessed using western blotting. To verify the underlying mechanisms, a PI3K inhibitor and an mTOR inhibitor were used. RESULTS: BPTS inhibited proliferation of MDA-MB-231 cells with an IC50 value of 10 µg/mL at 48 h. BPTS inhibited migration of MDA-MB-231 cells, and the western blot results demonstrated that BPTS reduced p-PI3K, p-Akt and p-mTOR protein expression levels in MDA-MB-231 cells. Additionally, the results were confirmed using a PI3K inhibitor and an mTOR inhibitor. BPTS decreased proliferation and migration of MDA-MB-231 cells possibly through inhibiting the PI3K/Akt/mTOR signaling pathway. CONCLUSIONS: The results highlight the therapeutic potential of BPTS for treating patients with triple-negative breast cancer.

Generation of a plasmonic radially polarized vector beam with linearly polarized illumination.

Polarization state of a wave field can be manipulated through the plasmonic metasurface consisting of orthogonal nanoslit pairs; the output polarization angle is independent of the incident linearly polarized light and is highly dependent on the orientations of nanoslit pairs. We combine the Archimedes spiral with the nanoslit pairs to compensate for the Pancharatnam-Berry (PB) phase induced by the orientation of nanoslits, as well as achieve the radially polarized vector beam (RPVB) under the illuminations of different linearly polarized lights. Experiments are performed to successfully realize the RPVB, and the results are in excellent agreement with the numerical simulations.

ProtTrans and multi-window scanning convolutional neural networks for the prediction of protein-peptide interaction sites.

This study delves into the prediction of protein-peptide interactions using advanced machine learning techniques, comparing models such as sequence-based, standard CNNs, and traditional classifiers. Leveraging pre-trained language models and multi-view window scanning CNNs, our approach yields significant improvements, with ProtTrans standing out based on 2.1 billion protein sequences and 393 billion amino acids. The integrated model demonstrates remarkable performance, achieving an AUC of 0.856 and 0.823 on the PepBCL Set_1 and Set_2 datasets, respectively. Additionally, it attains a Precision of 0.564 in PepBCL Set 1 and 0.527 in PepBCL Set 2, surpassing the performance of previous methods. Beyond this, we explore the application of this model in cancer therapy, particularly in identifying peptide interactions for selective targeting of cancer cells, and other fields. The findings of this study contribute to bioinformatics, providing valuable insights for drug discovery and therapeutic development.

Casting NETs on Psoriasis: The modulation of inflammatory feedback targeting IL-36/IL-36R axis.

NETosis happens when neutrophils are activated and neutrophil extracellular traps (NETs) are formed synchronously, which is a hallmark of psoriasis. However, the specific trigger that drives NET formation and the distinct contents and interaction with interleukin-36 receptor (IL-36R) of NETs remain to be further elucidated. This work identified NET formation driven by toll-like receptor (TLR) 3 ligand (especially polyinosinic-polycytidylic acid (Poly(I:C)) were enhanced by purinergic receptor P2X ligand-gated ion channel 7 receptor (P2X7R) ligands (especially adenosine 5'-triphosphate (ATP)). NET formation was accompanied by the secretion of inflammatory cytokines and characterized by IL-1ß decoration. NET formation blockade decreased expressions of inflammatory cytokines and chemokines, which consequently improved inflammatory responses. Additionally, imiquimod (IMQ)-induced psoriasiform symptoms including neutrophilic infiltration tended to be time-sensitive. Mouse primary keratinocytes and mice deficient in Il1rl2, which encodes IL-36R, mitigated inflammatory responses and NET formation, thereby delaying the pathophysiology of psoriasis. Together, the findings provided the therapeutic potential for IL-36 targeting NET inhibitors in psoriasis treatment.

NETs contribute to psoriasiform skin inflammation: A novel therapeutic approach targeting IL-36 cytokines by a small molecule tetrahydroxystilbene glucoside.

BACKGROUND: Psoriasis, a chronic immune-mediated skin disease with pathological features such as aberrant differentiation of keratinocytes, dermal-epidermal inflammation, and angiogenesis. 2,3,5,4'-Tetrahydroxy stilbene 2-Ο-ß-d-glucoside (2354Glu) is a natural small molecule polyhydrostilbenes isolated from Polygonum multiglorum Thunb. The regulation of IL-36 subfamily has led to new pharmacologic strategies to reverse psoriasiform dermatitis. PURPOSE: Here we investigated the therapeutic potential of 2354Glu and elucidated the underlying mechanism in psoriasis. METHODS: The effects of 2354Glu on IL-36 signaling were assessed by psoriasiform in vivo, in vitro and ex vivo model. The in vivo mice model of psoriasis-like skin inflammation was established by applying imiquimod (IMQ), and the in vitro and ex vitro models were established by stimulating mouse primary keratinocyte, human keratinocytes cells (HaCaT) and ex vivo skin tissue isolated from the mice back with Polyinosine-polycytidylic acid (Poly(I:C)), IMQ, IL-36γ and Lipopolysaccharide (LPS) respectively. Moreover, NETs formation was inhibited by Cl-amidine to evaluate the effect of NETs in psoriatic mouse model. The effects of 2354Glu on skin inflammation were assessed by western blot, H&E, immunohistochemistry, immunofluorescence, enzyme-linked immunosorbent assay and real-time quantitative PCR. RESULTS: In Poly(I:C)-stimulated keratinocytes, the secretion of IL-36 was inhibited after treatment with 2354Glu, similar to the effects of TLR3, P2X7R and caspase-1 inhibitors. In aldara (imiquimod)-induced mice, 2354Glu (100 and 25 mg/kg) improved immune cell infiltration and hyperkeratosis in psoriasis by directly targeting IL-36 in keratinocytes through P2X7R-caspase-1. When treatment with 2354Glu (25 mg/kg) was insufficient to inhibit IL-36γ, NETs reduced pathological features and IL-36 signaling by interacting with keratinocytes to combat psoriasis like inflammation. CONCLUSION: These results indicated that NETs had a beneficial effect on psoriasiform dermatitis. 2354Glu alleviates psoriasis by directly targeting IL-36/P2X7R axis and NET formation, providing a potential candidate for the treatment of psoriasis.

A therapeutic strategy of parthenolide in improving imiquimod-induced psoriasis-like skin inflammation targeting IL-36/NETs through skin transdermal therapeutic system.

BACKGROUND: Psoriasis is an inflammatory skin disease that occurs repeatedly over time. The natural product of sesquiterpene lactones, Parthenolide (Par), is isolated from Tanacetum parthenium L. (feverfew) which has significant effects on anti-inflammatory. The therapeutic effect of the medication itself is crucial, but different routes of administration of the same drug can also produce different effects. PURPOSE: The aim of our research sought to investigate the ameliorating effects of Par in psoriasis-like skin inflammation and its related mechanism of action. RESULTS: In the IMQ-induced model, intragastric administration of Par reduced the Psoriasis Area and Severity Index (PASI) score, improved skin erythema, scaling, and other symptoms. And Par decreased the expression of Ki67, keratin14, keratin16 and keratin17, and increased the expression of keratin1. Par could reduce IL-36 protein expressions, meanwhile the expression of Il1b, Cxcl1 and Cxcl2 mRNA were also decreased. Par regulated the expression levels of F4/80, MPO and NE. However, skin transdermal administration of Par was more effective. Similarly, Par attenuated IL-36γ, IL-1ß and caspase-1 activated by Poly(I:C) in in vitro and ex vivo. In addition, Par also reduced NE, PR3, and Cathepsin G levels in explant skin tissues. CONCLUSION: Par ameliorated psoriasis-like skin inflammation in both in vivo and in vitro, especially after treatment with transdermal drug delivery, possibly by inhibiting neutrophil extracellular traps and thus by interfering IL-36 signaling pathway. It indicated that Par provides a new research strategy for the treatment of psoriasis-like skin inflammation and is expected to be a promising drug.

Association study between SNP rs150689919 in the DNA demethylation gene, TET1, and Parkinson's disease in Chinese Han population.

BACKGROUND: Recent studies suggest that epigenetic factors may play an important role in the pathogenesis of Parkinson's disease (PD). In our previous work, we sequenced the exomes of sixteen patients from eight Chinese PD families using whole exome sequencing technology, consequently three patients from different pedigrees were found sharing the variant c.1460C > T (rs150689919) in the coding region of the Tet methyl cytosine dioxygenase 1 (TET1) gene. METHODS: In order to evaluate the possible association between sporadic PD and the single nucleotide polymorphism (SNP) rs150689919 in TET1, a case-control cohort study was conducted in 514 sporadic PD patients and 529 normal controls. Genotyping was determined by PCR and direct sequencing. Statistical significance was analyzed by the Chi-squared test. RESULTS: There was no statistical significance in TET1 rs150689919 genotype or allele frequencies between the PD cases and healthy controls, even after being stratified by gender and age at onset. CONCLUSIONS: Our findings suggest that rs150689919 in TET1 may not be associated with PD in Chinese population. However, due to the limited data in this study, replication studies in larger sample and other populations are required.

The correlation between a Th1/Th2 cytokines imbalance and vitamin D level in patients with early chronic obstructive pulmonary disease (COPD), based on screening results.

Objective: This study explored the correlation between a Th1/Th2 cytokines imbalance and 25-hydroxy-vitamin D (vit D) level in early chronic obstructive pulmonary disease (COPD), provided experimental rationales for the role of vit D in the prevention and control of COPD, and elucidated the potential anti-inflammatory mechanism involved. Methods: This study was based on the results of the "Screening and Early Diagnosis of COPD" public health project conducted through Shenzhen Municipal Qianhai Shekou Free Trade Zone Hospital. Patients with early COPD were selected as study participants. A prospective, randomized, and controlled method was employed for assigning eligible participants into three groups, i.e., a COPD lung function (LF) I, COPD LF II, and a healthy group, respectively (n = 40 each). The serum content of tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), interleukin 4 (IL-4), and IL-6 were measured by enzyme-linked immunosorbent assay, and the ratio of IFN-γ/IL-4 treated as a marker for Th1/Th2. The serum concentration of 25-hydroxyl-vit D (25 [OH]D) was quantified by a chemiluminescence assay. Statistical processing was performed, and the correlations between changes in the above parameters with vit D level and LF parameters were examined. Results: There were differences in FEV1pred%, FEV1/FVC, IFN-γ, IL-4, IL-6 and IFN-γ/IL-4 between the healthy group, the COPD LF I group and the COPD LF II group (p < 0.05). In early COPD, Th1/Th2 cytokines was positively correlated with forced expiratory volume/expected value (FEV1pred%) (r = 0.485, p < 0.001) and forced expiratory volume/forced vital capacity (FEV1/FVC) (r = 0.273, p = 0.018); Th1/Th2 cytokines levels positively correlated with vit D level (r = 0.27, p = 0.02), and 25(OH)D level positively correlated with FEV1pred% (r = 0.695, p < 0.001). Conclusion: Vitamin D deficiency was ubiquitous in patients with early COPD. It was positively correlated with the FEV1pred% and FEV1/FVC LF parameters. Accordingly, this study provides experimental rationales for the role of vit D in the prevention and control of COPD and the potential anti-inflammatory mechanisms involved.

Potential skin health promoting benefits of costunolide: a therapeutic strategy to improve skin inflammation in imiquimod-induced psoriasis.

Psoriasis is a recurrent inflammatory skin disease. IL-36-related cytokines are overexpressed in psoriasis, but the mechanism is not yet clear. Costunolide (Cos) is a sesquiterpenoid compound derived from the root of the traditional Chinese medicine Aucklandia lappa Decne. This study aimed to explore the mechanism of Cos on improving psoriasis-like skin inflammation. An in vivo model was established by applying imiquimod treatment to the back skin of mice, and an in vitro model was established by using polyinosinic-polycytidylic acid (Poly(I:C)) stimulated-mouse primary dermal fibroblasts to induce inflammation. The results showed that Cos improved the pathological changes of psoriasis-like skin inflammation. In addition, Cos could inhibit epidermal damage and inflammation-related expression and improve the occurrence of skin-related inflammation in both in vivo and in vitro experiments. The improvement of psoriasis-like skin inflammatory response might be through the P2X7R/IL-36 signaling pathway. Collectively, Cos has an inhibitory effect on the expression of psoriasis-like skin inflammation. This showed that Cos has potential skin health promoting benefits by preventing psoriasis-like skin inflammation.

[Simultaneous determination of seven quaternary ammonium compounds in frozen food by ultra performance liquid chromatography-tandem mass spectrometry combined with modified QuEChERS method].

Quaternary ammonium compounds (QACs) are a class of cationic surfactants that can be used as the main active ingredient of disinfectants. The increased use of QACs is concerning as exposure from inhalation or ingestion to these compounds that has been associated with adverse effects on the reproductive and respiratory systems. Humans are exposed to QACs primarily by food consumption and inhalation of air. QAC residues pose significant threats to public health. Given the importance of assessing potential residue levels for QACs in food, therefore, a method was developed for the simultaneous detection of six common QACs and one emerging QAC (Ephemora) in frozen food by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) coupled with the modified QuEChERS method. The main factors governing the response, recovery, and sensitivity of the method, including extraction solvents, types and dosages of adsorbents, apparatus conditions, and mobile phases, were optimized in the course of sample pretreatment and instrument analysis. QAC residues in frozen food were extracted using 20 mL methanol-water (90∶10, containing 0.5% formic acid) for 20 min by the vortex shock method. The mixture was ultrasonicated for 10 min and centrifuged at 10000 r/min for 10 min. A 1-mL aliquot of the supernatant was transferred to a new tube and purified using 100 mg of PSA adsorbents. After mixing and centrifugation at 10000 r/min for 5 min, the purified solution was analyzed. Target analytes were separated on an ACQUITY UPLC BEH C8 chromatographic column (50 mm×2.1 mm, 1.7 µm) at a column temperature of 40 ℃ and a flow rate of 0.3 mL/min. The injection volume was 1 µL. Gradient elution was performed using methanol and 5 mmol/L ammonium acetate solution as the mobile phases. Multiple reaction monitoring (MRM) was conducted in the positive electrospray ionization (ESI+) mode. The matrix-matched external standard method was used to quantify seven QACs. The optimized chromatography-based method completely separated the seven analytes. Good linear relationships were obtained for the seven QACs in the range of 0.1-100.0 ng/mL. The correlation coefficient (r2) ranged from 0.9971 to 0.9983. The limits of detection and limits of quantification ranged from 0.5 to 1.0 µg/kg and 1.5 to 3.0 µg/kg, respectively. Accuracy and precision were determined by spiking salmon and chicken samples with 3.0, 10.0, and 100.0 µg/kg of analytes, in compliance with the current legislation, with six replicates per determination. The average recoveries of the seven QACs ranged from 65.4% to 101%. The relative standard deviations (RSDs) were between 0.64% and 16.8%. Matrix effects of the analytes were between -27.5% and 33.4% in salmon and chicken samples after purifying using PSA. The developed method was applied to the determination of seven QACs in rural samples. QACs were detected in only one sample; the level did not exceed European Food Safety Authority specified residue limit standards. The detection method has high sensitivity, good selectivity and stability, and the results are accurate and reliable. It is suitable for the simultaneous rapid determination of seven QAC residues in frozen food. The results provide valuable information for future risk assessment studies targeting this class of compounds.

[Strategies for exome sequence data analysis for discovering genes underlying autosomal recessive disorders].

Introduced in 2009, whole-exome sequencing (WES) is a technology in which target capture methods are used to enrich sequences of coding regions of genes from fragmented total genomic DNA, which is followed by high-throughput sequencing of the captured fragments. As reported, WES has been successfully applied for discovering genes underlying several Mendelian diseases, especially autosomal recessive types. In this review, authors have summarized the main computational strategies which have been applied to identify novel autosomal recessive diseases genes using whole-exome data.

Construction of Low-Carbon Ferry-A Case of Jingning, China.

As the Chinese government has pledged to reach its carbon peak by 2030 and carbon neutrality by 2060, it is necessary to investigate how regional sustainable development can be achieved. This paper used a 'bottom-up' model to calculate the ferry carbon emissions in Jingning, China, and proposed four measures to reduce carbon emissions, including renewing ferryboats, planting water-level-fluctuating zones, greening the ferries, and installing solar energy. Quantitative analyses were conducted to calculate the possible emissions reduction from 2021 to 2025, with the results indicating that the total emissions could be reduced by 392.67 t. Finally, a new low-carbon ferry concept is proposed, based on simultaneous carbon emission reduction and carbon sink enhancement. This study provided a theoretical and decision-making reference for the operation of green, beautiful, and low-carbon ferries.

Novel High-Temperature-Resistant Phosphates: Thermal Ablation Behavior of La-Al System Phosphates at 2000 °C.

The saturation-free and directionless cross-linking and interpenetration processes between La3+ and [(H2PO4)2Al(HPO4)]-plasma in La-Al phosphate by mixing Al(OH)3, CrO3, and H2O2 dissolved in H3PO4 and La2O3 as a curing accelerator, as well as the thermal stability of the La-Al phosphate bulk materials and the evolutions of the phase composition and morphology at different temperatures were studied using thermogravimetric/differential scanning calorimetry under different temperatures in a muffle furnace. The La-Al phosphates showed good thermal stability, and the thermal weight loss rate of the materials decreased from 18% before heat treatment to ∼2% after heat treatment. In addition, the La-Al phosphate bulk material showed excellent resistance to ablation when subjected to ablation by an oxyacetylene flame at 2000 °C for 30 s. It evolved into a dense LaPO4 and AlPO4 high-temperature phase layer on the sample surface, which prevented further ablation damage to the sample and significantly improved the temperature resistance of the La-Al phosphate bulk material.

Inhibition of HMGB1/TLR4 Signaling Pathway by Digitoflavone: A Potential Therapeutic Role in Alcohol-Associated Liver Disease.

Digitoflavone (DG) is a natural flavonoid abundant in many fruits, vegetables, and medicinal plants. We investigated whether DG inhibits lipid accumulation and inflammatory responses in alcoholic liver disease (ALD) in vivo and in vitro. The mouse ALD model was established by chronically feeding male C57BL/6 mice an ethanol-containing Lieber-DeCarli liquid diet. In vitro, mouse peritoneal macrophages (MPMs) and mouse bone marrow-derived macrophages (BMDMs) were stimulated with LPS/ATP, whereas HepG2 cells and mouse primary hepatocytes were treated with ethanol. DG reduced the serum levels of transaminase and serum and hepatic levels of triglycerides and malondialdehyde in ALD mice. DG downregulated SREBP1 and its target genes and upregulated PPARα and its target genes in the liver of mice with ALD. DG inhibited TLR4-mediated NLRP3 inflammasome activation, consequently reversing the inflammatory response, including the production of HMGB1, IL-1ß, and IL-36γ, as well as the infiltration of macrophages and neutrophils. DG blocked NLRP3/ASC/caspase-1 inflammasome activation and HMGB1 release in LPS/ATP-stimulated MPMs. When Tlr4 was knocked in LPS/ATP-stimulated BMDMs, HMGB1 production and release were blocked, and NLRP3-mediated cleavage and release of IL-1ß was suppressed in Hmgb1-silenced BMDMs. DG amplified these inhibitory effects in Tlr4 or Hmgb1 knockdown BMDMs. In ethanol-exposed hepatocytes, DG reduced lipogenesis and promoted lipid oxidation by inhibiting the HMGB1-TLR4 signaling pathway while suppressing the inflammatory response induced by ethanol exposure. Our data demonstrated that DG inhibited the occurrence of lipid accumulation and the inflammatory response via the HMGB1-TLR4 axis, underscoring a promising approach and utility of DG for the treatment of ALD.