Peracetic acid (PAA), an emerging oxidant in advanced oxidation processes, has attracted widespread attention in water treatment. However, there is still a lack of an efficient and environmentally friendly method for activating PAA to remove alkyl imidazolium based ionic liquids ([Bmim]+) in water. This study introduces MnFe2O4/PAA system as an effective approach for the degradation of [Bmim]+, which have garnered significant attention due to their wide-ranging industry applications and potential biotoxicity. The degradation kinetics, mechanisms, pathways, and ecotoxicity (acute toxicity test and ecological structure-activity relationship program) of [Bmim]+ were comprehensively investigated. The results showed that the highest removal efficiency of 1-Butyl-3-methylimidazolium chloride ([Bmim]Cl) reached 93.9 %. Electron paramagnetic resonance and quenching experiments confirmed that the reactive oxygen species (such as center dot OH and R-O center dot) participated in the degradation of [Bmim]Cl. Density functional theory calculations identified the imidazole ring of [Bmim]+ as the primary active site for free radical attack. Thirteen oxidation products and two major reaction pathways were identified through ultra performance liquid chromatography/tandem mass spectrometry analysis, showing hydroxylation and carbonylation as the key reactions. Furthermore, ecotoxicity evaluations demonstrated that the degradation intermediates were harmless. This study demonstrates that the MnFe2O4/PAA system is an efficient and environmentally friendly technology for removing [Bmim]Cl, addressing a critical gap in advanced oxidation processes. Mechanism studies and theoretical calculation of MnFe2O4-activated PAA provide theoretical references for the PAA-based studies, which may further the commercial application of PAA in removing recalcitrant organic pollutants.

INTRODUCTION:Novel fluid biomarkers for tracking neurodegeneration specific to Alzheimer's disease (AD) are greatly needed. METHODS:Using two independent well-characterized cohorts (n = 881 in total), we investigated the group differences in plasma N-terminal tau (NT1-tau) fragments across different AD stages and their association with cross-sectional and longitudinal amyloid beta (Aβ) plaques, tau tangles, brain atrophy, and cognitive decline. RESULTS:Plasma NT1-tau significantly increased in symptomatic AD and displayed positive associations with Aβ PET (positron emission tomography) and tau PET. Higher baseline NT1-tau levels predicted greater tau PET, with 2- to 10-year intervals and faster longitudinal Aβ PET increases, AD-typical neurodegeneration, and cognitive decline. Plasma NT1-tau showed negative correlations with baseline regional brain volume and thickness, superior to plasma brain-derived tau (BD-tau) and neurofilament light (NfL) in Aβ-positive participants. DISCUSSION:This study suggests that plasma NT1-tau is an Aβ-dependent biomarker and outperforms BD-tau and NfL in detecting cross-sectional neurodegeneration in the AD continuum. HIGHLIGHTS:Plasma N-terminal tau (NT1-tau) was specifically increased in the A+/T+ stage. Plasma NT1-tau was positively associated with greater amyloid beta (Aβ) and tau PET (positron emission tomography) accumulations. Higher plasma NT1-tau predicted greater tau burden and faster Aβ increases. Plasma NT1-tau was more related to neurodegeneration than plasma brain-derived tau (BD-tau) and neurofilament light (NfL).

Periodontitis is a chronic inflammatory disease caused by dental plaque, which leads to tooth loosening and shifting or even tooth loss. Current treatments, including mechanical debridement and antibiotics, often fail to eradicate recalcitrant biofilms and mitigate excessive inflammation. Moreover, these interventions can disrupt the oral microbiome, potentially compromising long-term treatment outcomes. To address these limitations, an injectable nanoenzyme hydrogel composed of a dopamine (DA)-modified hyaluronic acid (HA) scaffold and a graphdiyne-iron (GDY-Fe) complex, named GDY-Fe@HA-DA, exhibits excellent tissue adhesion, self-healing, antibacterial properties, and biocompatibility. Under near-infrared laser irradiation, GDY-Fe@HA-DA effectively eradicates a variety of pathogens, including Escherichia coli, Staphylococcus aureus, and Porphyromonas gingivalis, through a synergistic combination of chemodynamical and photothermal therapies. The hydrogel's efficacy is further validated in both bacterial-infected skin wounds and rat periodontitis models. It effectively alleviates the inflammatory environment and promotes wound healing and periodontal tissue recovery. This findings highlight the potential of GDY-Fe@HA-DA as a promising therapeutic material for periodontitis and other tissue injuries.

The cynomolgus monkey has emerged as a predominant nonhuman primate model in neuroscience research. A comprehensive grasp of the growth and development patterns in the cynomolgus monkey brain is crucial for the judicious utilization of this species in neuroscience investigations. This project involved the collection of brain [18F]FDG PET-MRI data from 228 healthy cynomolgus monkeys spanning the age range of 0.5-29.5 years to construct an age-specific multimodal image brain template toolset tailored to cynomolgus monkeys. Their brain volume and glucose metabolism were quantitatively analyzed by utilizing an individualized spatial segmentation algorithm. Our findings encapsulated the growth and development trends, sex differences, and asymmetrical variations in brain volume and glucose metabolism in cynomolgus monkeys, and analyzed the correlation between the brain volume and glucose metabolism. This endeavor enhances our capacity to leverage the cynomolgus monkey model in neuroscience research by providing a valuable resource for researchers. The age- specific brain template toolset and associated data offer a robust foundation for future investigations, facilitating a nuanced understanding of brain development in this primate species and, consequently, informing and advancing neuroscience research employing cynomolgus monkeys.

AbstractThis study aimed to evaluate [18F]GSK1482160 Positron emission tomography imaging for targeting P2X7R, a biomarker for neuroinflammation. Studies of acute neuroinflammation in rodents and transgenic mice with Alzheimer's disease (AD), as well as wild‐type (WT) controls, were conducted via PET‐CT‐MRI scans after tail vein injection of [18F]GSK1482160. Imaging was quantified based on the time‐activity curve, the standardized uptake value ratio, and the binding kinetics distribution volume ratio (DVR) to assess the expression of P2X7R. Tissues were collected post‐PET for immunofluorescence staining. Correlation analysis was performed between DVR and Morris water maze test results. Finally, dynamic Positron Emission Tomography‐Magnetic Resonance Imaging (PET‐MRI) scans were performed in healthy non‐human primates (NHPs). Our study demonstrated that AD mice had a significantly higher DVR than WT mice in the hippocampus (0.92 ± 0.06 vs. 0.79 ± 0.02, p < 0.05), cortex (1.09 ± 0.03 vs. 0.88 ± 0.04, p < 0.05), and striatum (1.02 ± 0.10 vs. 0.83 ± 0.1, p < 0.05). Immunofluorescence staining showed increased expression of P2X7R in the AD, along with its colocalization with activated microglia and astrocytes. Correlation analysis indicated that brain regions with higher binding of [18F]GSK1482160 (i.e., the cortex, striatum, and hippocampus) were more vulnerable to cognitive impairment. PET‐MRI scans of healthy NHPs demonstrated the feasibility of brain penetration and P2X7R target engagement for the translation of [18F]GSK1482160 in human studies.

Receptor-interacting serine/threonine protein kinase 1 (RIPK1) has emerged as an important regulator of pathologic cell death and inflammation and is implicated in the pathologies of various central nervous system diseases. In this study, we reported the development of three potent dihydropyrazole-cored RIPK1 positron emission tomography (PET) ligands [F-18]WL1-3. Among these, [F-18]WL1 showed specific binding to RIPK1 in mouse brain sections in vitro through autoradiography and exhibited favorable brain kinetics in mice, characterized by a high initial uptake (brain(2 min) = 4.89% ID/g) and rapid washout (brain(60 min) = 0.21% ID/g). PET studies in rat brains revealed that [F-18]WL1 could readily penetrate the brain with specific binding confirmed by inhibition effects of unlabeled WL1 and GSK ' 547. Notably, [F-18]WL1 showed significant potential in imaging the alterations of RIPK1 in a rat brain of tumor necrosis factor alpha-induced systemic inflammatory response syndrome model. These findings may pave the way for the future design of potent RIPK1 PET ligands.

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts in more than 90% of epithelial tumors. Several radiotracers targeting FAPs have been used in clinical settings in recent years. However, the number of 18F-labeled FAP tracers is still limited. Herein, we aimed to develop 18F-labeled FAP tracers with optimized pharmacokinetics. Labeling precursors (NOTA-DD-FAPI and NOTA-PD-FAPI) were synthesized and labeled with fluorine-18. The precursors NOTA-DD-FAPI (IC50 = 0.21 +/- 0.06 nM) and NOTA-PD-FAPI (IC50 = 0.13 +/- 0.07 nM) showed a higher affinity for FAP compared to NOTA-FAPI-42 (IC50 = 0.66 +/- 0.19 nM). Novel 18F-labeled FAP tracers showed a specific uptake, high internalized fraction, and low cellular efflux in vitro. Compared to the clinically used tracer [18F]AlF-FAPI-42, both the novel 18F-labeled FAP tracers, and especially the [18F]AlF-PD-FAPI tracer with a higher tumor-to-background ratio demonstrated rapid renal excretion and higher tumor uptake during preclinical evaluation, resulting in images with higher contrast. Thus, [18F]AlF-PD-FAPI shows promise for use as a FAP-targeting tracer for clinical translation.

The arginine-vasopressin (AVP) hormone plays a pivotal role in regulating various physiological processes, such as hormone secretion, cardiovascular modulation, and social behavior. Recent studies have highlighted the V1a receptor as a promising therapeutic target. In-depth insights into V1a receptor-related pathologies, attained through in vivo imaging and quantification in both peripheral organs and the central nervous system (CNS), could significantly advance the development of effective V1a inhibitors. To address this need, we develop a novel V1a-targeted positron emission tomography (PET) ligand, [18F]V1A-2303 ([18F]8), which demonstrates favorable in vitro binding affinity and selectivity for the V1a receptor. Specific tracer binding in peripheral tissues was also confirmed through rigorous cell uptake studies, autoradiography, biodistribution assessments. Furthermore, [18F]8 was employed in PET imaging and arterial blood sampling studies in healthy rhesus monkeys to assess its brain permeability and specificity, whole-body distribution, and kinetic properties. Our research indicated [18F]8 as a valuable tool for noninvasively studying V1a receptors in peripheral organs, and as a foundational element for the development of next-generation, brain-penetrant ligands specifically designed for the CNS.

Objectives: Translocator protein 18 kDa (TSPO) positron emission tomography (PET) can be harnessed for the non-invasive detection of macrophage-driven inflammation. [F-18]LW223, a newly reported TSPO PET tracer which was insensitive to rs6971 polymorphism, showed favorable performance characteristics in a recent im-aging study involving a rat myocardial infarction model. To enable quantitative neuroimaging with [F-18]LW223, we conducted kinetic analysis in the non-human primate (NHP) brain. Further, we sought to assess the utility of [F-18]LW223-based TSPO imaging in a first-in-human study. Methods: Radiosynthesis of [F-18]LW223 was accomplished on an automated module, whereas molar activities, stability in formulation, lipophilicity and unbound free fraction (fu) of the probe were measured. Brain pene-tration and target specificity of [F-18]LW223 in NHPs were corroborated by PET-MR imaging under baseline and pre-blocking conditions using the validated TSPO inhibitor, (R)-PK11195, at doses ranging from 5 to 10 mg/kg. Kinetic modeling was performed using one-tissue compartment model (1TCM), two-tissue compartment model (2TCM) and Logan graphical analyses, using dynamic PET data acquisition, arterial blood collection and metabolic stability testing. Clinical PET scans were performed in two healthy volunteers (HVs). Regional brain standard uptake value ratio (SUVr) was assessed for different time intervals. Results: [F-18]LW223 was synthesized in non-decay corrected radiochemical yields (n.d.c. RCYs) of 33.3 +/- 6.5% with molar activities ranging from 1.8 +/- 0.7 Ci/mu mol (n = 11). [F-18]LW223 was stable in formulation for up to 4 h and LogD7.4 of 2.31 +/- 0.13 (n = 6) and fu of 5.80 +/- 1.42% (n = 6) were determined. [F-18]LW223 exhibited good brain penetration in NHPs, with a peak SUV value of ca. 1.79 in the whole brain. Pre-treatment with (R)-PK11195 substantially accelerated the washout and attenuated the area under the time-activity curve, indicating in vivo specificity of [F-18]LW223 towards TSPO. Kinetic modeling demonstrated that 2TCM was the most suitable model for [F-18]LW223-based neuroimaging. Global transfer rate constants (K1) and total volumes of distribution (VT) were found to be 0.10 +/- 0.01 mL/cm(3)/min and 2.30 +/- 0.17 mL/cm3, respectively. Dynamic PET data analyses across distinct time windows revealed that the VT values were relatively stable after 60 min post-injection. In a preliminary clinical study with two healthy volunteers, [F-18]LW223 exhibited good brain uptake and considerable tracer retention across all analyzed brain regions. Of note, an excellent correlation between SUVr with VT was obtained when assessing the time interval from 20 to 40 min post tracer injection (SUVr(20-40 min), R-2 = 0.94, p < 0.0001), suggesting this time window may be suitable to estimate specific binding to TSPO in human brain. Conclusion: Our findings indicate that [F-18]LW223 is suitable for quantitative TSPO-targeted PET imaging in higher species. Employing state-of-the-art kinetic modeling, we found that [F-18]LW223 was effective in mapping TSPO throughout the NHP brain, with best model fits obtained from 2TCM and Logan graphical analyses. Overall, our results indicate that [F-18]LW223 exhibits favorable tracer performance characteristics in higher species, and this novel imaging tool may hold promise to provide effective neuroinflammation imaging in pa-tients with neurological disease.

As a subclass of ionotropic glutamate receptors (iGluRs), α-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptors have been implicated in various neurological disorders and neurodegenerative diseases. To further our understanding of AMPA receptor-related disorders in the central nervous system (CNS), it is important to be able to image and quantify AMPA receptors in vivo. In this study, we identified a novel F-containing AMPA positive allosteric modulator (PAM) 6 as a potential lead compound. Molecular docking studies and CNS PET multi-parameter optimization (MPO) analysis were used to predict the absorption, distribution, metabolism, and excretion (ADME) characteristics of 6 as a PET probe. The resulting PET probe, [18F]6 (codename [18F]AMPA-2109), was successfully radiolabeled and demonstrated excellent blood-brain barrier (BBB) permeability and high brain uptake in rodents and non-human primates. However, [18F]6 did not show substantial specific binding in the rodent or non-human primate brain. Further medicinal chemistry efforts are necessary to improve specific binding, and our work may serve as a starting point for the design of novel 18F-labeled AMPA receptor-targeted PET radioligands aimed for clinical translation.

Our previous work showed that [ 18 F]P10A-1910 was a potential radioligand for use in imaging phosphodiesterase 10A (PDE10A). Specifically, it had high brain penetration and specific binding that was demonstrated in both rodents and non-human primates. Here, we present the first automatic cGMP-level production of [ 18 F]P10A-1910 and translational PET/MRI study in living human brains. Successful one-step radiolabeling of [ 18 F]P10A-1910 on a GE TRACERlab FX2N synthesis module was realized via two different methods. First, formulated [ 18 F]P10A-1910 was derived from heating spirocyclic iodonium ylide in a tetra- n -butyl ammonium methanesulfonate solution. At the end of synthesis, it was obtained in non-decay corrected radiochemical yields (n.d.c. RCYs) of 12.4 ± 1.3%, with molar activities (MAs) of 90.3 ± 12.6 μmol ( n = 7) ( Method I ). The boronic pinacol ester combined with copper and oxygen also delivered the radioligand with 16.8 ± 1.0% n. d.c. RCYs and 77.3 ± 20.7 GBq/μmol ( n = 7) MAs after formulation ( Method II ). The radiochemical purity, radionuclidic purity, solvent residue, sterility, endotoxin content and other parameters were all validated for human use. Consistent with the distribution of PDE10A in the brain, escalating uptake of [ 18 F]P10A-1910 was observed in the order of cerebellum (reference region), substantial nigra, caudate and putamen. The non-displaceable binding potential ( BP ND ) was estimated by simplified reference-tissue model (SRTM); linear regressions demonstrated that BP ND was well correlated with the most widely used semiquantitative parameter SUV. The strongest correlation was observed with SUV (50–60 min) ( R 2 = 0.966, p < 0.01). Collectively, these results indicated that a static scan protocol could be easily performed for PET imaging of PDE10A. Most importantly, that [ 18 F]P10A-1910 is a promising radioligand to clinically quantify PDE10A.

Autism spectrum disorder (ASD) is a basket term for neurodevelopmental disorders characterized by marked impairments in social interactions, repetitive and stereotypical behaviors, and restricted interests and activities. Subtypes include (A) disorders with known genetic abnormalities including fragile X syndrome, Rett syndrome, and tuberous sclerosis and (B) idiopathic ASD, conditions with unknown etiologies. Positron emission tomography (PET) is a molecular imaging technology that can be utilized in vivo for dynamic and quantitative research, and is a valuable tool for exploring pathophysiological mechanisms, evaluating therapeutic efficacy, and accelerating drug development in ASD. Recently, several imaging studies on ASD have been published and physiological changes during ASD progression was disclosed by PET. This paper reviews the specific radioligands for PET imaging of critical biomarkers in ASD, and summarizes and discusses the similar and different discoveries in outcomes of previous studies. It is of great importance to identify general physiological changes in cerebral glucose metabolism, cerebral blood flow perfusion, abnormalities in neurotransmitter systems, and inflammation in the central nervous system in ASD, which may provide excellent points for further ASD research.

以涵化理论为框架进行实证研究,回收188份有效调查问卷,通过分层回归,分析新媒体背景下"内卷文化"传播对青年群体的涵化效果,并验证了这一过程中共鸣效应的存在.研究发现,青年群体的新媒体媒介使用于受众身份背景-涵化效果之间存在正向调节效应,且这一涵化过程中的共鸣效应主要与年龄有关.

Multiple myeloma (MM) is a neoplastic plasma cell proliferative disorder characterized by various osteolytic bone destruction as a radiological morphological marker. Functional imaging, particularly nuclear medicine imaging, is a promising method to visualize disease processes before the appearance of structural changes by targeting specific biomarkers related to metabolism ability, tumor microenvironment as well as neoplastic receptors. In addition, by targeting particular antigens with therapeutic antibodies, immuno-PET imaging can support the development of personalized theranostics. At present, various imaging agents have been prepared and evaluated in MM at preclinical and clinical levels. A summary overview of molecular functional imaging in MM is provided, and commonly used radiotracers are characterized.

The P2X7 receptor (P2X7R) is a key neuroinflammation target in a variety of neurodegenerative diseases. Improved radiosynthesis was developed according to the previously reported P2X7R antagonist GSK1482160. Biodistribution, radiometabolite, and dynamic positron emission tomography/computed tomography-magnetic resonance imaging (PET/CT-MRI) of the lipopolysaccharide (LPS) rat model and the transgenic mouse model of Alzheimer's disease (AD) revealed a stable, low uptake of [18F]4A in the brain of healthy rats but a higher standardized uptake value ratio (SUVR) in LPS-treated rats (1.316 ± 0.062, n = 3) than in sham (1.093 ± 0.029, n = 3). There were higher area under curves (AUCs) in the neocortex (25.12 ± 1.11 vs 18.94 ± 1.47), hippocampus (22.50 ± 3.41 vs 15.90 ± 1.59), and basal ganglia (22.26 ± 0.81 vs 15.32 ± 1.76) of AD mice (n = 3) than the controls (n = 3) (p < 0.05). Furthermore, 50 min dynamic PET in healthy nonhuman primates (NHPs) indicated [18F]4A could penetrate the blood-brain barrier (BBB). In conclusion, [18F]4A from this study is a potent P2X7R PET tracer that warrants further neuroinflammation quantification in human studies.

Alterations in brain cholesterol homeostasis have been broadly implicated in neurological disorders. Notwithstanding the complexity by which cholesterol biology is governed in the mammalian brain, excess neuronal cholesterol is primarily eliminated by metabolic clearance via cytochrome P450 46A1 (CYP46A1). No methods are currently available for visualizing cholesterol metabolism in the living human brain; therefore, a noninvasive technology that quantitatively measures the extent of brain cholesterol metabolism via CYP46A1 could broadly affect disease diagnosis and treatment options using targeted therapies. Here, we describe the development and testing of a CYP46A1-targeted positron emission tomography (PET) tracer, 18 F-CHL-2205 ( 18 F-Cholestify). Our data show that PET imaging readouts correlate with CYP46A1 protein expression and with the extent to which cholesterol is metabolized in the brain, as assessed by cross-species postmortem analyses of specimens from rodents, nonhuman primates, and humans. Proof of concept of in vivo efficacy is provided in the well-established 3xTg-AD murine model of Alzheimer’s disease (AD), where we show that the probe is sensitive to differences in brain cholesterol metabolism between 3xTg-AD mice and control animals. Furthermore, our clinical observations point toward a considerably higher baseline brain cholesterol clearance via CYP46A1 in women, as compared to age-matched men. These findings illustrate the vast potential of assessing brain cholesterol metabolism using PET and establish PET as a sensitive tool for noninvasive assessment of brain cholesterol homeostasis in the clinic.

Additional file 12: Table S2. The expression of circ-GALNT16 in 100 pairs of CRC tissues and relative expression in different pathological groups.

实施环境工程项目驱动教学法,创设真实的环境工程教学情境,巧妙设计教学过程,激发学生的学习兴趣.根据课程教学目标与教学内容,将知识点隐含于所设置的"任务"之中,"驱动"学生对任务主动摸索、探究、实践,培养其提出、分析、解决问题等综合能力.文章通过教学实践证明,基于环境工程项目驱动教学法的《环境工程施工与概预算》课程教学效果显著,在教学实践过程中也发现了一些问题,并提出了后续完善和改进措施.

《视听表演北京条约》生效,建立起视听表演者权利国际保护法律框架,在表演者权利归属及利益分配上为缔约国提供了几种可供选择的方案,给各国立法带来影响.结合我国《著作权法(修改草案)》(送审稿)分析,综合考量我国影视产业实践,适合我国现阶段国情的视听表演者权利归属模式应调整为“推定授权”,并且对表演者精神权利以及“二次获酬权”的规定调整完善.

在"互联网+"背景下,迎来了全民直播的时代,网红主播也成为了名利双高的全新职业.网络直播行业光鲜亮丽的背后是网络主播寻求劳动法保护基本劳动权益的征途.现行劳动法现行劳动法单一调整模式对劳动关系的抽象性规定影响相关案件获得司法的终局救济,导致"网红"行业用工这类新生事物无法使用劳动法而无法获得有效保护,本文结合几个典型案例来展开分析,透过分析案例体现的法律适用困境来思考对策探寻.