Loop-Mediated Isothermal Amplification for Detecting Gly-4891-Glu and Ile-4734 Multiple Mutations of Ryanodine Receptor in the Fall Armyworm, Spodoptera frugiperda.

The key mutations, such as the Gly-4891-Glu substitution and the Ile-4734 multiple substitutions within the ryanodine receptors (RyR), are linked to diamide resistance in fall armyworm (FAW), Spodoptera frugiperda. In this study, we found that FAW remained sensitive to cyantraniliprole and chlorantraniliprole, while its sensitivity to flubendiamide was reduced. Moreover, a low level of heterozygous mutation at I4743 was observed. To facilitate the detection procedure of these mutations, a simple and efficient loop-mediated isothermal amplification (LAMP) protocol was developed for operation. The reaction for detecting the G4891E and I4743 single or multiple mutations was carried out at 68 °C for 85 min and 68 °C for 85 min or 68 °C for 65 min, respectively. These LAMP reactions can be easily observed via visualization of the color change from pink to yellow. This assay provides a simple, convenient, and effective means of detecting mutations in the RyR of FAW for pest management purposes.

Acoustic Skyrmionic Mode Coupling and Transferring in a Chain of Subwavelength Metastructures.

Skyrmions, a stable topological vectorial textures characteristic with skyrmionic number, hold promise for advanced applications in information storage and transmission. While the dynamic motion control of skyrmions has been realized with various techniques in magnetics and optics, the manipulation of acoustic skyrmion has not been done. Here, the propagation and control of acoustic skyrmion along a chain of metastructures are shown. In coupled acoustic resonators made with Archimedes spiral channel, the skyrmion hybridization is found giving rise to bonding and antibonding skyrmionic modes. Furthermore, it is experimentally observed that the skyrmionic mode of acoustic velocity field distribution can be robustly transferred covering a long distance and almost no distortion of the skyrmion textures in a chain of metastructures, even if a structure defect is introduced in the travel path. The proposed localized acoustic skyrmionic mode coupling and propagating is expected in future applications for manipulating acoustic information storage and transfer.

Season and side-chain length affect the occurrences and behaviors of phthalic acid esters in wastewater treatment plants.

Emerging pollutants (EPs) are prevalent in aquatic environments globally. Researchers strive to understand their occurrence and behavior prior to their release into the environment. In this study, we examined five wastewater treatment plants (WWTPs), collected 50 wastewater samples and 10 sludge samples. We explored the sources and destinations of phthalic acid esters (PAEs) within these WWTPs using mass balance equations. Wastewater treatment diminished the frequency and concentration of PAEs, and decreased the fraction of short-chain PAEs. We confirmed the increased concentration of PAEs post-primary treatment and modified the mass balance equation. Calculations suggest that weaker "the mix" in winter than in summer and stronger sedimentation in winter than in summer resulted in high efficiency of PAEs removal by winter wastewater treatment. The mass flux of biodegradation was influenced by the combination of biodegradation efficiency and the strength of the particular type of PAEs collected, with no seasonal differences. Mass fluxes for sludge sedimentation were mainly influenced by season and were higher in winter than in summer. This study enhances our understanding of emerging pollutants in manual treatment facilities and offers insights for optimizing wastewater treatment methods for water professionals.

Molecular docking and MD simulation studies of 4-thiazol-N-(pyridin-2-yl)pyrimidin-2-amine derivatives as novel inhibitors targeted to CDK2/4/6.

PURPOSE: Nowadays, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have been approved for treating metastatic breast cancer and have achieved inspiring curative effects. But some discoveries have indicated that CDK 4/6 are not the requisite factors in some cell types because CDK2 partly compensates for the inhibition of CDK4/6. Thus, it is urgent to design CDK2/4/6 inhibitors for significantly enhancing their potency. This study aims to explore the mechanism of the binding of CDK2/4/6 kinases and their inhibitors to design novel CDK2/4/6 inhibitors for significantly enhancing their potency in different kinds of cancers. MATERIALS AND METHODS: A series of 72 disparately functionalized 4-substituted N-phenylpyrimidin-2-amine derivatives exhibiting potent inhibitor activities against CDK2, CDK4 and CDK6 were collected to apply to this research. The total set of these derivatives was divided into a training set (54 compounds) and a test set (18 compounds). The derivatives were constructed through the sketch molecule module in SYBYL 6.9 software. A Powell gradient algorithm and Tripos force field were used to calculate the minimal structural energy and the minimized structure was used as the initial conformation for molecular docking. By the means of 3D-QSAR models, partial least squares (PLS) analysis, molecular dynamics (MD) simulations and binding free energy calculations, we can find the relationship between structure and biological activity. RESULTS: In this study, we used molecular docking, 3D-QSAR and molecular dynamics simulation methods to comprehensively analyze the interaction and structure-activity relationships of 72 new CDK2/4/6 inhibitors. We used detailed statistical data to reasonably verify the constructed 3D-QSAR models for three receptors (q2 of CDK2 = 0.714, R2pred = 0.764, q2 = 0.815; R2pred of CDK4 = 0.681, q2 = 0.757; R2pred of CDK6 = 0.674). MD simulations and decomposition energy analysis validated the reasonability of the docking results and identified polar interactions as crucial factors that influence the different bioactivities of the studied inhibitors of CDK2/4/6 receptors, especially the electrostatic interactions of Lys33/35/43 and Asp145/158/163. The nonpolar interaction with Ile10/12/19 was also critical for the differing potencies of the CDK2/4/6 inhibitors. We concluded that the following probably enhanced the bioactivity against CDK2/4/6 kinases: (1) electronegative groups at the N1-position and electropositive and moderate-sized groups at ring E; (2) electrogroups featured at R2; (3) carbon atoms at the X-position or ring C replaced by a benzene ring; and (4) an electrogroup as R4. CONCLUSION: Previous studies, to our knowledge, only utilized a single approach of 3D-QSAR and did not integrate this method with other sophisticated techniques such as molecular dynamics simulations to discover new potential inhibitors of CDK2, CDK4, or CDK6. So we applied the intergenerational technology, such as 3D-QSAR technology, molecular docking simulation techniques, molecular dynamics simulations and MMPBSA19/MMGBSA20-binding free energy calculations to statistically explore the correlations between the structure with biological activities. The constructed 3D-QSAR models of the three receptors were reasonable and confirmed by the excellent statistical data. We hope the results obtained from this work will provide some useful references for the development of novel CDK2/4/6 inhibitors.

Genomic structural variation contributes to evolved changes in gene expression in high-altitude Tibetan sheep.

Tibetan sheep were introduced to the Qinghai Tibet plateau roughly 3,000 B.P., making this species a good model for investigating genetic mechanisms of high-altitude adaptation over a relatively short timescale. Here, we characterize genomic structural variants (SVs) that distinguish Tibetan sheep from closely related, low-altitude Hu sheep, and we examine associated changes in tissue-specific gene expression. We document differentiation between the two sheep breeds in frequencies of SVs associated with genes involved in cardiac function and circulation. In Tibetan sheep, we identified high-frequency SVs in a total of 462 genes, including EPAS1, PAPSS2, and PTPRD. Single-cell RNA-Seq data and luciferase reporter assays revealed that the SVs had cis-acting effects on the expression levels of these three genes in specific tissues and cell types. In Tibetan sheep, we identified a high-frequency chromosomal inversion that exhibited modified chromatin architectures relative to the noninverted allele that predominates in Hu sheep. The inversion harbors several genes with altered expression patterns related to heart protection, brown adipocyte proliferation, angiogenesis, and DNA repair. These findings indicate that SVs represent an important source of genetic variation in gene expression and may have contributed to high-altitude adaptation in Tibetan sheep.

Sublethal effect and detoxifying metabolism of metaflumizone and indoxacarb on the fall armyworm, Spodoptera frugiperda.

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera, Noctuidae), is a highly polyphagous invasive pest that damages various crops. Pesticide control is the most common and effective strategy to control FAW. In this study, we evaluated the toxicity of metaflumizone and indoxacarb against third-instar FAW larvae using the insecticide-incorporated artificial diet method under laboratory conditions. Both metaflumizone and indoxacarb exhibited substantial toxicity against FAW, with LC50 values of 2.43 and 14.66 mg/L at 72 h, respectively. The sublethal effects of metaflumizone and indoxacarb on parental and F1 generation FAW were investigated by exposing third-instar larvae to LC10 and LC30 concentrations of these insecticides. Sublethal exposure to these two insecticides significantly shortened adult longevity, extended pupal developmental times and led to reduced pupal weight, pupation rates, and adult fecundity in the treated parental generation and F1 generation at LC10 or LC30 concentrations, in comparison to the control group. The larval developmental times were shortened in the parental generation but prolonged in the F1 generation, after being treated with sublethal concentrations of metaflumizone. Furthermore, larvae exposed to LC10 or LC30 concentrations of indoxacarb exhibited elevated activity levels of cytochrome P450 monooxygenase and glutathione S-transferase, which coincides with the observed synergistic effect of piperonyl butoxide and diethyl maleate. In conclusion, the high toxicity and negative impact of metaflumizone and indoxacarb on FAW provided significant implications for the rational utilization of insecticides against this pest.

The Challenges in Using eHealth Decision Resources for Surrogate Decision-Making in the Intensive Care Unit.

The mortality rate in intensive care units (ICUs) is notably high, with patients often relying on surrogates for critical medical decisions due to their compromised state. This paper provides a comprehensive overview of eHealth. The challenges of applying eHealth tools, including economic disparities and information inaccuracies are addressed. This study then introduces eHealth literacy and the assessment tools to evaluate users' capability and literacy levels in using eHealth resources. A clinical scenario involving surrogate decision-making is presented. This simulated case involves a patient with a hemorrhagic stroke who has lost consciousness and requires medical procedures such as tracheostomy. However, due to the medical surrogate's lack of familiarity with eHealth devices and limited literacy in using eHealth resources, difficulties arise in assisting the patient in making medical decisions. This scenario highlights challenges related to eHealth literacy and solution strategies are proposed. In conclusion, effective ICU decision-making with eHealth tools requires a careful balance between efficiency with inclusivity. Tailoring communication strategies and providing diverse materials are essential for effective eHealth decision resources in the ICU setting. Health professionals should adopt a patient-centered approach to enhance the decision-making experience, particularly for individuals with limited eHealth literacy.

Long-term outcomes of survivors with influenza A H1N1 virus-induced severe pneumonia and ARDS: a single-center prospective cohort study.

Introduction: Systematic evaluation of long-term outcomes in survivors of H1N1 is still lacking. This study aimed to characterize long-term outcomes of severe H1N1-induced pneumonia and acute respiratory distress syndrome (ARDS). Method: This was a single-center, prospective, cohort study. Survivors were followed up for four times after discharge from intensive care unit (ICU) by lung high-resolution computed tomography (HRCT), pulmonary function assessment, 6-minute walk test (6MWT), and SF-36 instrument. Result: A total of 60 survivors of H1N1-induced pneumonia and ARDS were followed up for four times. The carbon monoxide at single breath (DLCO) of predicted values and the 6MWT results didn't continue improving after 3 months. Health-related quality of life didn't change during the 12 months after ICU discharge. Reticulation or interlobular septal thickening on HRCT did not begin to improve significantly until the 12-month follow-up. The DLCO of predicted values showed negative correlation with the severity degree of primary disease and reticulation or interlobular septal thickening, and a positive correlation with physical functioning. The DLCO of predicted values and reticulation or interlobular septal thickening both correlated with the highest tidal volume during mechanical ventilation. Levels of fibrogenic cytokines had a positive correlation with reticulation or interlobular septal thickening. Conclusion: The improvements in pulmonary function and exercise capacity, imaging, and health-related quality of life had different time phase and impact on each other during 12 months of follow-up. Long-term outcomes of pulmonary fibrosis might be related to the lung injury and excessive lung fibroproliferation at the early stage during ICU admission.

Genomic structural variation is associated with hypoxia adaptation in high-altitude zokors.

Zokors, an Asiatic group of subterranean rodents, originated in lowlands and colonized high-elevational zones following the uplift of the Qinghai-Tibet plateau about 3.6 million years ago. Zokors live at high elevation in subterranean burrows and experience hypobaric hypoxia, including both hypoxia (low oxygen concentration) and hypercapnia (elevated partial pressure of CO2). Here we report a genomic analysis of six zokor species (genus Eospalax) with different elevational ranges to identify structural variants (deletions and inversions) that may have contributed to high-elevation adaptation. Based on an assembly of a chromosome-level genome of the high-elevation species, Eospalax baileyi, we identified 18 large inversions that distinguished this species from congeners native to lower elevations. Small-scale structural variants in the introns of EGLN1, HIF1A, HSF1 and SFTPD of E. baileyi were associated with the upregulated expression of those genes. A rearrangement on chromosome 1 was associated with altered chromatin accessibility, leading to modified gene expression profiles of key genes involved in the physiological response to hypoxia. Multigene families that underwent copy-number expansions in E. baileyi were enriched for autophagy, HIF1 signalling and immune response. E. baileyi show a significantly larger lung mass than those of other Eospalax species. These findings highlight the key role of structural variants underlying hypoxia adaptation of high-elevation species in Eospalax.

Unveiling the Therapeutic Potential of Herba Epimedii: Enhancing Bone Healing Through Cytoskeletal Regulation of RhoA/Rock1 Pathway.

Herba Epimedii is widely used to promote bone healing, and their active ingredients are total flavonoids of Epimedium (TFE). Ras homolog gene family member A / Rho-associated protein kinase (RhoA/Rock), an important pathway regulating the cytoskeleton, has been proven to affect bone formation. However, whether TFE promotes bone healing via this pathway remains unclear. In this study, the therapeutic effects of TFE were estimated using micro-computed tomography and hematoxylin and eosin staining of pathological sections. F-actin in osteoblasts was stained to investigate the protective effects of TFE on the cytoskeleton. Its regulatory effects on the RhoA/Rock1 pathway were explored using RT-qPCR and Western blot analysis. Besides, flow cytometry, alkaline phosphatase and nodule calcification staining were performed to evaluate the effects on osteogenesis. The bone healing in rats was improved, the cytoskeletal damage in osteoblasts was reduced, the RhoA/Rock1 pathway was downregulated, and osteogenesis was enhanced after TFE treatment. Thus, TFE can promote bone formation at least partially by regulating the expression of key genes and proteins in the cytoskeleton. The findings of this study provided evidence for clinical applications and would contribute to a better understanding of Epimedium's mechanisms in treating bone defects.

Short-term effects of exposure to ambient PM2.5 and its components on hospital admissions for threatened and spontaneous abortions: A multicity case-crossover study in China.

BACKGROUND: The adverse effects of short-term exposure to PM2.5 and its components on hospital admissions for threatened and spontaneous abortions (TSAB) are still controversial. METHODS: Data on daily hospitalizations for TSAB and PM2.5 and its components, including sulfate (SO42-), nitrate (NO3-), ammonium salt (NH4+), organic matter (OM), and black carbon (BC), were collected from January 2015 to December 2021 (total 2,557 days) in five cities in China. Case-crossover analyses were conducted to investigate the short-term associations between PM2.5 and its components and TSAB. Additionally, the modification effects by age (<35 and ≥35 years), season (cold and warm seasons), and the "Three-Year Action Plan to Win the Blue Sky Defense War" (before and after implementation) on the above associations were further conducted. RESULTS: For each 10 µg/m3 (1 µg/m3 for BC) increase, the strongest relative risks (95% confidence intervals) of hospitalization for TSAB were 1.011 (1.001-1.021) for PM2.5 in lag02, 1.060 (1.003-1.120) for SO42- in lag02, 1.035 (1.000-1.070) for NO3- in lag02, 1.065 (1.009-1.124) for NH4+ in lag02, 1.047 (1.008-1.088) for OM in lag01 and 1.029 (1.005-1.054) for BC in lag02 (all P <0.05). Furthermore, significant modifying effects of age and the Action Plan were found. The effects of NO3- (lag2), NH4+ (lag2), and BC (lag2) were more pronounced in mothers aged ≥35 years and the effects of PM2.5 (lag4), NO3- (lag4), NH4+ (lag4), OM (lag4), and BC (lag4) was more pronounced in the period before the Action Plan was implemented (all P modification <0.05). CONCLUSION: Short-term exposure to ambient PM2.5 and its components (SO42-, NO3-, NH4+, OM, and BC) was related to increased risks of hospitalization for TSAB. The effects were more pronounced in mothers aged ≥35 years and the period before the Action Plan.

[Preparation and quality evaluation of total flavonoids microemulsion of "Pueraria lobata-Hovenia dulcis"].

The effective components of flavonoids in the "Pueraria lobata-Hovenia dulcis" drug pair have low bioavailability in vivo due to their unstable characteristics. This study used microemulsions with amphoteric carrier properties to solve this problem. The study drew pseudo-ternary phase diagrams through titration compatibility experiments of the oil phase with emulsifiers and co-emulsifiers and screened the prescription composition of blank microemulsions. The study used average particle size and PDI as evaluation indicators, and the central composite design-response surface method(CCD-RSM) was used to optimize the prescription; high-dosage drug-loaded microemulsions were obtained, and their physicochemical properties, appearance, and stability were evaluated. The results showed that when ethyl butyrate was used as the oil phase, polysorbate 80(tween 80) as the surfactant, and anhydrous ethanol as the cosurfactant, the maximum microemulsion area was obtained. When the difference in results was small, K_(m )of 1∶4 was chosen to ensure the safety of the prescription. The prescription composition optimized by the CCD-RSM was ethyl butyrate(16.28%), tween 80(9.59%), and anhydrous ethanol(38.34%). When the dosage reached 3% of the system mass, the total flavonoid microemulsion prepared had a clear and transparent appearance, with average particle size, PDI, and potential of(74.25±1.58)nm, 0.277±0.043, and(-0.08±0.07) mV, respectively. The microemulsion was spherical and evenly distributed under transmission electron microscopy. The centrifugal stability and temperature stability were good, and there was no layering or demulsification phenomenon, which significantly improved the in vitro dissolution of total flavonoids.

Inversion method for soil moisture content based on a distributed fiber optic acoustic sensing system.

The traditional measurement method can't achieve real-time monitoring of soil moisture content (SMC) within a two-dimensional area. To solve the above problems, we propose a rapid SMC monitoring method for two-dimensional area based on distributed acoustic sensing (DAS). DAS demodulates the backward Rayleigh scattering signal containing seismic wave sound velocity information from the active seismic source. The folding ruler approximation is employed to calculate the sound velocity of the soil, which is then inverted to determine the soil moisture content. The experiment measured the soil within a two-dimensional area formed by the seismic source and the acoustic sensing optical cable. The sensing optical cable and the active seismic source are organized into a two-dimensional area and the measurement range is 3 × 10 m with 33 points. The SMC ranges from 15% to 40%. The experiment shows that the absolute error between the measured values obtained by DAS and the water cut meter is 7%. This experiment verifies the feasibility of using the Rayleigh scattering properties to invert SMC and provides a new method for real-time monitoring of SMC in a large area.

The molecular basis of drug selectivity for α5 subunit-containing GABAA receptors.

α5 subunit-containing γ-aminobutyric acid type A (GABAA) receptors represent a promising drug target for neurological and neuropsychiatric disorders. Altered expression and function contributes to neurodevelopmental disorders such as Dup15q and Angelman syndromes, developmental epilepsy and autism. Effective drug action without side effects is dependent on both α5-subtype selectivity and the strength of the positive or negative allosteric modulation (PAM or NAM). Here we solve structures of drugs bound to the α5 subunit. These define the molecular basis of binding and α5 selectivity of the ß-carboline, methyl 6,7-dimethoxy-4-ethyl-ß-carboline-3-carboxylate (DMCM), type II benzodiazepine NAMs, and a series of isoxazole NAMs and PAMs. For the isoxazole series, each molecule appears as an 'upper' and 'lower' moiety in the pocket. Structural data and radioligand binding data reveal a positional displacement of the upper moiety containing the isoxazole between the NAMs and PAMs. Using a hybrid molecule we directly measure the functional contribution of the upper moiety to NAM versus PAM activity. Overall, these structures provide a framework by which to understand distinct modulator binding modes and their basis of α5-subtype selectivity, appreciate structure-activity relationships, and empower future structure-based drug design campaigns.

Molecular properties and biotoxicity of dissolved organic matter leached from microplastic (MP-DOM) during typical hydrothermal treatment of sewage sludge.

Microplastic-derived dissolved organic matter (MP-DOM) is crucial for assessing ecological and environmental impact of microplastics. However, the factors that influence the ecological effects of MP-DOM are yet to be determined. This study investigated the influence of plastic type and leaching conditions (thermal hydrolysis, TH; hydrothermal carbonization, HTC) on the molecular properties and toxicity of MP-DOM using spectroscopy and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). Results revealed that plastic type was the main factor affecting the chemodiversity of MP-DOM, compared to leaching conditions. Polyamide 6 (PA6) dissolved the largest number of DOM due to the presence of heteroatoms, followed by polypropylene (PP) and polyethylene (PE). From TH to HTC processes, the molecular composition of PA-DOM remained constant, with CHNO compounds being dominant, and labile compounds (lipids-like, and protein/amino sugar-like compounds) accounting for >90 % of the total compounds. In polyolefin-sourced DOM, CHO compounds were dominant, and the relative concentration of labile compounds decreased dramatically, resulting in the higher degree of unsaturation and humification than PA-DOM. The mass difference network analysis showed that the main reaction in PA-DOM and PE-DOM was oxidation while in PP-DOM, it was the carboxylic acid reaction. However, plastic type and leaching conditions jointly influenced the toxic effects of MP-DOM. PA-DOM was bioavailable, while polyolefin-sourced DOM leached under HTC treatment exhibited toxicity, with lignin/CRAM-like compounds being the dominant toxic compounds. Notably, the 2-fold higher relative intensity of the toxic compounds and the 6-fold higher abundance of highly unsaturated and phenolic-like compounds in PP-DOMHTC resulted in the higher inhibition rate than PE-DOMHTC. Toxic molecules in PE-DOMHTC mainly directly dissolved from PE polymers, while almost 20 % of toxic molecules in PP-DOMHTC resulted from molecular transformation, where dehydration (-H2O) was the core reaction. These findings offer advanced insights into the management and treatment of MPs in sludge.

Diagnostic and prognostic performance of plasma neurofilament light chain in multiple system atrophy: a cross-sectional and longitudinal study.

BACKGROUND: The longitudinal dynamics of neurofilament light chain (NfL) in multiple system atrophy (MSA) were incompletely illuminated. This study aimed to explore whether the plasma NfL (pNfL) could serve as a potential biomarker of clinical diagnosis and disease progression for MSA. METHODS: We quantified pNfL concentrations in both a large cross-sectional cohort with 214 MSA individuals, 65 PD individuals, and 211 healthy controls (HC), and a longitudinal cohort of 84 MSA patients. Propensity score matching (PSM) was used to balance the age between the three groups. The pNfL levels between groups were compared using Kruskal-Wallis test. Linear mixed models were performed to explore the disease progression-associated factors in longitudinal MSA cohort. Random forest model as a complement to linear models was employed to quantify the importance of predictors. RESULTS: Before and after matching the age by PSM, the pNfL levels could reliably differentiate MSA from HC and PD groups, but only had mild potential to distinguish PD from HC. By combining linear and nonlinear models, we demonstrated that pNfL levels at baseline, rather than the change rate of pNfL, displayed potential prognostic value for progression of MSA. The combination of baseline pNfL levels and other modifiers, such as subtypes, Hoehn-Yahr stage at baseline, was first shown to improve the diagnosis accuracy. CONCLUSIONS: Our study contributed to a better understanding of longitudinal dynamics of pNfL in MSA, and validated the values of pNfL as a non-invasive sensitive biomarker for the diagnosis and progression. The combination of pNfL and other factors is recommended for better monitoring and prediction of MSA progression.

[Application and problems analysis of traditional Chinese medicine volatile oil preparation technology based on ionic liquids].

Ionic liquids(ILs) are salts composed entirely of anions and cations in a liquid state at or near room temperature, which have a variety of good physicochemical properties such as low volatility and high stability. This paper mainly reviewed the research overview of ILs in the application of traditional Chinese medicine(TCM) volatile oil preparation technology. Firstly, it briefly introduced the application of TCM volatile oil preparation technology and composition classification and physicochemical properties of ILs, and then summarized the application of ILs in the extraction, separation, analysis, and preparation of TCM volatile oil. Finally, the problems and challenges of ILs in the application of TCM volatile oil were explained, and the application of ILs in TCM volatile oil in the future was prospected.

Synaptic Loss in Spinocerebellar Ataxia Type 3 Revealed by SV2A Positron Emission Tomography.

BACKGROUND: Severe reduced synaptic density was observed in spinocerebellar ataxia (SCA) in postmortem neuropathology, but in vivo assessment of synaptic loss remains challenging. OBJECTIVE SPINOCEREBELLAR ATAXIA TYPE 3: The objective of this study was to assess in vivo synaptic loss and its clinical correlates in spinocerebellar ataxia type 3 (SCA3) patients by synaptic vesicle glycoprotein 2A (SV2A)-positron emission tomography (PET) imaging. METHODS: We recruited 74 SCA3 individuals including preataxic and ataxic stages and divided into two cohorts. All participants received SV2A-PET imaging using 18 F-SynVesT-1 for synaptic density assessment. Specifically, cohort 1 received standard PET procedure and quantified neurofilament light chain (NfL), and cohort 2 received simplified PET procedure for exploratory purpose. Bivariate correlation was performed between synaptic loss and clinical as well as genetic assessments. RESULTS: In cohort 1, significant reductions of synaptic density were observed in cerebellum and brainstem in SCA3 ataxia stage compared to preataxic stage and controls. Vermis was found significantly involved in preataxic stage compared to controls. Receiver operating characteristic (ROC) curves highlighted SV2A of vermis, pons, and medulla differentiating preataxic stage from ataxic stage, and SV2A combined with NfL improved the performance. Synaptic density was significantly negatively correlated with disease severity in cerebellum and brainstem (International Co-operative Ataxia Rating Scale: ρ ranging from -0.467 to -0.667, P ≤ 0.002; Scale of Assessment and Rating of Ataxia: ρ ranging from -0.465 to -0.586, P ≤ 0.002). SV2A reduction tendency of cerebellum and brainstem identified in cohort 1 was observed in cohort 2 with simplified PET procedure. CONCLUSIONS: We first identified in vivo synaptic loss was related to disease severity of SCA3, suggesting SV2A PET could be a promising clinical biomarker for disease progression of SCA3. © 2023 International Parkinson and Movement Disorder Society.

Molecular characteristics and biological effects of dissolved organic matter leached from microplastics during sludge hydrothermal treatment.

Previous knowledge of dissolved organic matter leached from microplastics (MP-DOM) was mainly based on the aquatic environment. The molecular characteristics and biological effects of MP-DOM in other environments have rarely been examined. In this work, FT-ICR-MS was applied to identify MP-DOM leached from sludge hydrothermal treatment (HTT) at different temperatures, and the plant effects and acute toxicity were investigated. The results showed that the molecular richness and diversity of MP-DOM increased with rising temperature, accompanied by molecular transformation in the meantime. The oxidation was crucial whereas the amide reactions mainly occurred at 180-220 oC. MP-DOM promoted root development of Brassica rapa (field mustard) by affecting the expression of genes and the effect was enhanced with rising temperature. Specifically, the lignin-like compounds in MP-DOM down-regulated Phenylpropanoids biosynthesis, while CHNO compounds up-regulated the nitrogen metabolism. Correlation analysis presented that alcohols/esters leached at 120-160 oC were responsible for the promotion of root, while glucopyranoside leached at 180-220 oC was vital for root development. However, MP-DOM produced at 220 oC showed the acute toxicity to luminous bacteria. Considering the further-treatment of sludge, the optimum HTT temperature could be controlled at 180 oC. This work provides novel insight into the environmental fate and eco-environmental effects of MP-DOM in sewage sludge.