Exposure to hexafluoropropylene oxide trimer acid (HFPO-TA) impairs 5-HT metabolism by impacting the brain-gut axis in mice.

Hexafluoropropylene oxide trimer acid (HFPO-TA) has been found to cause hepatotoxicity, lipotoxicity, and cytotoxicity. However, the effects of HFPO-TA exposure on nervous system toxicity are still unclear. Here, six-week-old male C57BL/6J mice were treated with 2, 20, and 200 µg/L HFPO-TA for six weeks. The untargeted transcriptome analysis was employed to identify differentially expressed mRNAs in the tissue of mouse hippocampi. Then, the levels of neurotransmitters were detected by ELISA analysis in hippocampal and colonic tissues. Real-time quantitative PCR and western blotting analysis were performed to detect the expression of genes associated with modulation of serotonin (5-HT) metabolism and blood-brain barrier. HFPO-TA exposure reduced the mRNA and protein expression of several tight junction protein-coded genes, including Occludin, Claudin-1, and ZO-1, in mice hippocampi, indicating that the blood-brain barrier was disrupted. Moreover, HFPO-TA exposure elevated the expression of neuroinflammatory factors, including TNF-α, IL-6, IL-1ß, TGF-α, and TGF-ß. Analysis of hippocampal transcriptomics suggested that HFPO-TA exposure would impair 5-HT generation and metabolic pathways. In keeping with this prediction, our findings confirmed that the levels of several neurotransmitters, including tryptophan (TRP), 5-HT, 5-HTP, and 5-HIAA, were all impaired by HFPO-TA exposure in the serum, colon, and hippocampus, as was the colonic and hippocampal expression of TRP and 5-HT metabolism-related genes such as SERT, MAO-A, and IDO. These results suggest that HFPO-TA nervous system toxicity in mice may be partly modulated by the brain-gut axis and that HFPO-TA exposure may negatively impact human mental health.

Temporal transcriptomic dynamics in developing macaque neocortex.

Despite intense research on mice, the transcriptional regulation of neocortical neurogenesis remains limited in humans and non-human primates. Cortical development in rhesus macaque is known to recapitulate multiple facets of cortical development in humans, including the complex composition of neural stem cells and the thicker supragranular layer. To characterize temporal shifts in transcriptomic programming responsible for differentiation from stem cells to neurons, we sampled parietal lobes of rhesus macaque at E40, E50, E70, E80, and E90, spanning the full period of prenatal neurogenesis. Single-cell RNA sequencing produced a transcriptomic atlas of developing parietal lobe in rhesus macaque neocortex. Identification of distinct cell types and neural stem cells emerging in different developmental stages revealed a terminally bifurcating trajectory from stem cells to neurons. Notably, deep-layer neurons appear in the early stages of neurogenesis, while upper-layer neurons appear later. While these different lineages show overlap in their differentiation program, cell fates are determined post-mitotically. Trajectories analysis from ventricular radial glia (vRGs) to outer radial glia (oRGs) revealed dynamic gene expression profiles and identified differential activation of BMP, FGF, and WNT signaling pathways between vRGs and oRGs. These results provide a comprehensive overview of the temporal patterns of gene expression leading to different fates of radial glial progenitors during neocortex layer formation.

Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy.

The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits, and this process requires the proper recruitment of adaptor molecules to selectively activate downstream pathways. Here, we identified that DOK6, a member of the Dok (downstream of tyrosine kinases) family, is required for the maintenance of peripheral axons, and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice, manifested as impaired sensory, abnormal posture, paw deformities, blocked nerve conduction, and dysmyelination. Furthermore, Dok6 is highly expressed in peripheral neurons but not in Schwann cells, and genetic deletion of Dok6 in peripheral neurons led to typical peripheral myelin outfolding, axon destruction, and hindered retrograde axonal transport. Specifically, DOK6 acts as an adaptor protein for selectivity-mediated neurotrophic signal transduction and retrograde transport for TrkC and Ret but not for TrkA and TrkB. DOK6 interacts with certain proteins in the trafficking machinery and controls their phosphorylation, including MAP1B, Tau and Dynein for axonal transport, and specifically activates the downstream ERK1/2 kinase pathway to maintain axonal survival and homeostasis. This finding provides new clues to potential insights into the pathogenesis and treatment of hereditary peripheral neuropathies and other degenerative diseases.

Regulation of aggregation-induced emission properties of Ag(0)@Ag(I) rich-thiolate core-shell nanoclusters: Ligand assembly dominated.

Aggregation-induced emission (AIE) is an effective strategy for improving the photoluminescence (PL) performance of metal nanoclusters (MNCs). However, the origin of AIE in MNCs is still not fully understood, which is pivotal for the design of AIE luminogens (AIEgens). Here, water soluble silver nanoclusters (Ag NCs) with AIE properties were synthesized. These as-synthesized non-luminescent Ag NCs will become photoluminescent when transferred from water to ethanol, and the emission peak was redshifted from ∼560 to ∼600 nm and largely intensified with the addition of Cu2+. The addition of Cu2+ makes a big difference in the PL properties of Ag NCs. That is, the PL will be enhanced if Cu2+ is added with the sequence "Ag NCs + Cu2++EtOH." In contrast, the PL will be quenched if Cu2+ is added with the sequence "Ag NCs + EtOH + Cu2+." The PL was from the supramolecular clusters formed by the assembly of capping ligands on the confined surface of individual silver clusters through weak interactions. The addition of Cu2+ could regulate the assembly structure and further affect the energy lever (p-band) through space electron interactions. These results provide new insights into the AIE process in metal nanoclusters.

Ideal serum non-ceruloplasmin bound copper prediction for long-term treated patients with Wilson disease: a nomogram model.

Purpose: This study aimed to explore the factors associated with the optimal serum non-ceruloplasmin bound copper (NCBC) level and develop a flexible predictive model to guide lifelong therapy in Wilson disease (WD) and delay disease progression. Methods: We retrospectively collected clinical data from 144 patients hospitalized in the Encephalopathy Center of the first affiliated hospital of Anhui University of Chinese Medicine between May 2012 and April 2023. Independent variables were selected using variate COX and LASSO regressions, followed by multivariate COX regression analysis. A predictive nomogram was constructed and validated using the concordance index (C-index), calibration curves, and clinical decision curve analysis, of which nomogram pictures were utilized for model visualization. Results: A total of 61 (42.36%) patients were included, with an average treatment duration of 55.0 (range, 28.0, 97.0) months. Multivariate regression analysis identified several independent risk factors for serum NCBC level, including age of diagnosis, clinical classification, laminin liver stiffness measurement, and copper to zinc ratio in 24-h urinary excretion. The C-index indicated moderate discriminative ability (48 months: 0.829, 60 months: 0.811, and 72 months: 0.819). The calibration curves showed good consistency and calibration; clinical decision curve analysis demonstrated clinically beneficial threshold probabilities at different time intervals. Conclusion: The predictive nomogram model can predict serum NCBC level; consequently, we recommend its use in clinical practice to delay disease progression and improve the clinical prognosis of WD.

N4BP1 mediates RAM domain-dependent notch signaling turnover during neocortical development.

Notch signaling pathway activity, particularly fluctuations in the biologically active effector fragment NICD, is required for rapid and efficient dynamic regulation of proper fate decisions in stem cells. In this study, we identified NEDD4-binding protein 1 (N4BP1), which is highly expressed in the developing mouse cerebral cortex, as a negative modulator of Notch signaling dynamics in neural progenitor cells. Intriguingly, N4BP1 regulated NICD stability specifically after Notch1 S3 cleavage through ubiquitin-mediated degradation that depended on its RAM domain, not its PEST domain, as had been extensively and previously described. The CoCUN domain in N4BP1, particularly the "Phe-Pro" motif (862/863 amino acid), was indispensable for mediating NICD degradation. The Ring family E3 ligase Trim21 was, in contrast to other NEDD4 family members, required for N4BP1-regulated NICD degradation. Overexpression of N4BP1 in cortical neural progenitors promoted neural stem cell differentiation, whereas neural progenitor cells lacking N4BP1 were sensitized to Notch signaling, resulting in the maintenance of stem-like properties in neural progenitor cells and lower production of cortical neurons.

Predicting the formation of mixed pattern hemorrhages in ruptured middle cerebral artery aneurysms based on a decision tree model: A multicenter study.

OBJECTIVE: Mixed-pattern hemorrhages (MPH) commonly occur in ruptured middle cerebral artery (MCA) aneurysms and are associated with poor clinical outcomes. This study aimed to predict the formation of MPH in a multicenter database of MCA aneurysms using a decision tree model. METHODS: We retrospectively reviewed patients with ruptured MCA aneurysms between January 2009 and June 2020. The MPH was defined as subarachnoid hemorrhages with intracranial hematomas and/or intraventricular hemorrhages and/or subdural hematomas. Univariate and multivariate logistic regression analyses were used to explore the prediction factors of the formation of MPH. Based on these prediction factors, a decision tree model was developed to predict the formation of MPH. Additional independent datasets were used for external validation. RESULTS: We enrolled 436 patients with ruptured MCA aneurysms detected by computed tomography angiography; 285 patients had MPH (65.4%). A multivariate logistic regression analysis showed that age, aneurysm size, multiple aneurysms, and the presence of a daughter dome were the independent prediction factors of the formation of MPH. The areas under receiver operating characteristic curves of the decision tree model in the training, internal, and external validation cohorts were 0.951, 0.927, and 0.901, respectively. CONCLUSION: Age, aneurysm size, the presence of a daughter dome, and multiple aneurysms were the independent prediction factors of the formation of MPH. The decision tree model is a useful visual triage tool to predict the formation of MPH that could facilitate the management of unruptured aneurysms in routine clinical work.

Machine learning prediction model for the rupture status of middle cerebral artery aneurysm in patients with hypertension: a Chinese multicenter study.

Background: Hypertension is a common comorbidity in patients with unruptured intracranial aneurysms and is closely associated with the rupture of aneurysms. However, only a few studies have focused on the rupture risk of aneurysms comorbid with hypertension. This retrospective study aimed to construct prediction models for the rupture of middle cerebral artery (MCA) aneurysm associated with hypertension using machine learning (ML) algorithms, and the constructed models were externally validated with multicenter datasets. Methods: We included 322 MCA aneurysm patients comorbid with hypertension who were being treated in four hospitals. All participants underwent computed tomography angiography (CTA), and aneurysm morphological features were measured. Clinical characteristics included sex, age, smoking, and hypertension history. Based on the clinical and morphological characteristics, the training datasets (n=277) were used to fit the ML algorithms to construct prediction models, which were externally validated with the testing datasets (n=45). The prediction performances of the models were assessed by receiver operating characteristic (ROC) curves. Results: The areas under the ROC curve (AUCs) of the k-nearest-neighbor (KNN), neural network (NNet), support vector machine (SVM) and logistic regression (LR) models in the training datasets were 0.83 [95% confidence interval (CI): 0.78-0.88], 0.87 (95% CI: 0.82-0.92), 0.91 (95% CI: 0.88-0.95), and 0.83 (95% CI: 0.77-0.88), respectively, and in the testing datasets were 0.74 (95% CI: 0.59-0.89), 0.82 (95% CI: 0.69-0.94), 0.73 (95% CI: 0.58-0.88), and 0.76 (95% CI: 0.61-0.90), respectively. The aspect ratio (AR) was ranked as the most important variable in the ML models except for NNet. Further analysis showed that the AR had good diagnostic performance, with AUC values of 0.75 in the training datasets and 0.77 in the testing datasets. Conclusions: The ML models performed reasonably accurately in predicting MCA aneurysm rupture comorbid with hypertension. AR was demonstrated as the leading predictor for the rupture of MCA aneurysm with hypertension.

A deep-learning method for the end-to-end prediction of intracranial aneurysm rupture risk.

It is critical to accurately predict the rupture risk of an intracranial aneurysm (IA) for timely and appropriate treatment because the fatality rate after rupture is 50 % . Existing methods relying on morphological features (e.g., height-width ratio) measured manually by neuroradiologists are labor intensive and have limited use for risk assessment. Therefore, we propose an end-to-end deep-learning method, called TransIAR net, to automatically learn the morphological features from 3D computed tomography angiography (CTA) data and accurately predict the status of IA rupture. We devise a multiscale 3D convolutional neural network (CNN) to extract the structural patterns of the IA and its neighborhood with a dual branch of shared network structures. Moreover, we learn the spatial dependence within the IA neighborhood with a transformer encoder. Our experiments demonstrated that the features learned by TransIAR are more effective and robust than handcrafted features, resulting in a 10 % - 15 % improvement in the accuracy of rupture status prediction.

Structural water molecules dominated p band intermediate states as a unified model for the origin on the photoluminescence emission of noble metal nanoclusters: from monolayer protected clusters to cage confined nanoclusters.

In the past several decades, noble metal nanoclusters (NMNCs) have been developed as an emerging class of luminescent materials due to their superior photo-stability and biocompatibility, but their luminous quantum yield is relatively low and the physical origin of the bright photoluminescence (PL) of NMNCs remain elusive, which limited their practical application. As the well-defined structure and composition of NMNCs have been determined, in this mini-review, the effect of each component (metal core, ligand shell and interfacial water) on their PL properties and corresponded working mechanism were comprehensively introduced, and a model that structural water molecules dominated p band intermediate state was proposed to give a unified understanding on the PL mechanism of NMNCs and a further perspective to the future developments of NMNCs by revisiting the development of our studies on the PL mechanism of NMNCs in the past decade.

Tetraalkoxysilane-Assisted Self-Emulsification Templating for Controlled Mesostructured Silica Nanoparticles.

Although mesoporous silica nanoparticles (MSNs) have been intensively investigated, their mesostructure and formation mechanism are still a topic of debate. Here, we show that MSNS are generated at the interface of the biphasic water-surfactant-triethanolamine-tetraalkoxysilane (TAOS) quaternary system. The spontaneous microemulsification of the hydrophobic TAOS generates microdroplets and direct micelles that both determine the particle size and the pore size. We confirmed also that the dendritic morphology with conical pores is an intermediate species, which readily transforms into regular MSNs concomitantly with the collapse of the microemulsion due to the continuous consumption of TAOS. The prominent effect of the microemulsion on the mechanism growth as a primary template is thoroughly investigated and named here tetraalkoxysilane-assisted self-emulsification templating.

Predicting the rupture status of small middle cerebral artery aneurysms using random forest modeling.

Objective: Small intracranial aneurysms are increasingly being detected; however, a prediction model for their rupture is rare. Random forest modeling was used to predict the rupture status of small middle cerebral artery (MCA) aneurysms with morphological features. Methods: From January 2009 to June 2020, we retrospectively reviewed patients with small MCA aneurysms (<7 mm). The aneurysms were randomly split into training (70%) and internal validation (30%) cohorts. Additional independent datasets were used for the external validation of 78 small MCA aneurysms from another four hospitals. Aneurysm morphology was determined using computed tomography angiography (CTA). Prediction models were developed using the random forest and multivariate logistic regression. Results: A total of 426 consecutive patients with 454 small MCA aneurysms (<7 mm) were included. A multivariate logistic regression analysis showed that size ratio (SR), aspect ratio (AR), and daughter dome were associated with aneurysm rupture, whereas aneurysm angle and multiplicity were inversely associated with aneurysm rupture. The areas under the receiver operating characteristic (ROC) curves (AUCs) of random forest models using the five independent risk factors in the training, internal validation, and external validation cohorts were 0.922, 0.889, and 0.92, respectively. The random forest model outperformed the logistic regression model (p = 0.048). A nomogram was developed to assess the rupture of small MCA aneurysms. Conclusion: Random forest modeling is a good tool for evaluating the rupture status of small MCA aneurysms and may be considered for the management of small aneurysms.

Activation of H2O Tailored by Interfacial Electronic States at a Nanoscale Interface for Enhanced Electrocatalytic Hydrogen Evolution.

Despite the fundamental and practical significance of the hydrogen evolution reaction (HER), the reaction kinetics at the molecular level are not well-understood, especially in basic media. Here, with ZIF-67-derived Co-based carbon frameworks (Co/NCs) as model catalysts, we systematically investigated the effects of different reaction parameters on the HER kinetics and discovered that the HER activity was directly dependent not on the type of nitrogen in the carbon framework but on the relative content of surface hydroxyl and water (OH-/H2O) adsorbed on Co active sites embedded in carbon frameworks. When the ratio of the OH-/H2O was close to 1:1, the Co/NC nanocatalyst showed the best reaction performance under the condition of high-pH electrolytes, e.g., an overpotential of only 232 mV at a current density of 10 mA cm-2 in the 1 M KOH electrolyte. We unambiguously identified that the structural water molecules (SWs) in the form of hydrous hydroxyl complexes absorbed on metal centers {OHad·H2O@M+} were catalytic active sites for the enhanced HER, where M+ could be transition or alkaline metal cations. Different from the traditional hydrogen bonding of water, the hydroxyl (hydroxide) groups and water molecules in the SWs were mainly bonded together via the spatial interaction between the p orbitals of O atoms, exhibiting features of a delocalized π-bond with a metastable state. These newly formed surface bonds or transitory states could be new weak interactions that synergistically promote both interfacial electron transfer and the activation of water (dissociation of O-H bonds) at the electrode surface, i.e., the formation of activated H adducts (H*). The capture of new surface states not only explains pH-, cation-, and transition-metal-dependent hydrogen evolution kinetics but also provides completely new insights into the understanding of other electrocatalytic reductions involving other small molecules, including CO2, CO, and N2.

Rupture Risk Assessment for Anterior Communicating Artery Aneurysms Using Decision Tree Modeling.

Background: Although anterior communicating artery (ACoA) aneurysms have a higher risk of rupture than aneurysms in other locations, whether to treat unruptured ACoA aneurysms incidentally found is a dilemma because of treatment-related complications. Machine learning models have been widely used in the prediction of clinical medicine. In this study, we aimed to develop an easy-to-use decision tree model to assess the rupture risk of ACoA aneurysms. Methods: This is a retrospective analysis of rupture risk for patients with ACoA aneurysms from two medical centers. Morphologic parameters of these aneurysms were measured and evaluated. Univariate analysis and multivariate logistic regression analysis were performed to investigate the risk factors of aneurysm rupture. A decision tree model was developed to assess the rupture risk of ACoA aneurysms based on significant risk factors. Results: In this study, 285 patients were included, among which 67 had unruptured aneurysms and 218 had ruptured aneurysms. Aneurysm irregularity and vessel angle were independent predictors of rupture of ACoA aneurysms. There were five features, including size ratio, aneurysm irregularity, flow angle, vessel angle, and aneurysm size, selected for decision tree modeling. The model provided a visual representation of a decision tree and achieved a good prediction performance with an area under the receiver operating characteristic curve of 0.864 in the training dataset and 0.787 in the test dataset. Conclusion: The decision tree model is a simple tool to assess the rupture risk of ACoA aneurysms and may be considered for treatment decision-making of unruptured intracranial aneurysms.

The Ash2l SDI Domain Is Required to Maintain the Stability and Binding of DPY30.

ASH2L and DPY30 are important for the assembly and catalytic activity of the complex associated with SET1 (COMPASS), which catalyzes histone methylation and regulates gene expression. However, the regulations among COMPASS components are not fully understood. Here, we leveraged a mouse model and cell lines to observe the outcome of Ash2l depletion and found a significant decrease in DPY30. Analyzing ASH2L ChIP-seq and RNA-seq data excluded transcriptional and translational regulation of ASH2L to DPY30. The decrease in DPY30 was further attributed to the degradation via the ubiquitin-mediated proteasomal pathway. We also verified that three amino acids in the ASH2L Sdc1 DPY30 interaction (SDI) domain are essential for the recognition and binding of DPY30. Lastly, we unexpectedly observed that overexpression of DPY30 in Ash2l-depleted cells rescued the decrease in Ccnd1 and the abnormal cell cycle, which indicates that DPY30 can participate in other complexes to regulate gene expression. Overall, our results, for the first time, reveal that the existence of DPY30 relies on the binding with ASH2L, with degradation of DPY30 via the ubiquitin-proteasome system, and they further indicate that the function of DPY30 can be independent of ASH2L.

Impact of a hexafluoropropylene oxide trimer acid (HFPO-TA) exposure on impairing the gut microbiota in mice.

Hexafluoropropylene oxide trimer acid (HFPO-TA) has been used as an alternative of perfluorooctanoic acid (PFOA) in the fluoropolymer industry for several years. HFPO-TA is reported to have high capability of bioaccumulation, widespread environmental distribution, and multiple toxicities. However, its potential toxicity on the intestines and gut microbiota remains unknown. In the present study, male mice were orally exposed to 200 µg/L HFPO-TA for 6 weeks, and after total genomic DNA extraction, 16S rRNA amplicon pyrosequencing was performed. Our results demonstrated that HFPO-TA exposure resulted in the imbalance of cecal microbiota and alterations of cecal microbiota diversity. At the phylum level, the relative abundances of Proteobacteria, Deferribacteres, and Tenericutes increased in mice after exposure to HFPO-TA, while the relative abundances of Verrucomicrobia, Cyanobacteria, and TM7 decreased. At the genus level, the relative abundances of Ver Akkermansia, Pre Prevotella, Lac Coprococcus, Por_Parabacteroides, and Lac Dorea decreased in HFPO-TA exposed mice. Meanwhile, the increased relative abundances of Def_Mucispirillum, Des_Desulfovibrio and Odo Odoribacter were observed in HFPO-TA exposed mice. Additionally, KEGG metabolic pathway analysis revealed that HFPO-TA exposure changed the unsaturated fatty acid synthesis, fatty acid metabolism, glyoxylic acid and dicarboxylic acid metabolism, galactose metabolism pathway and other metabolic pathways. Collectively, all these findings indicate the potential gut toxicity of HFPO-TA and is perceived as a risk of health on gut microbiota. Future investigations should be warranted.

Dynamic Pt-OH-·H2O-Ag species mediate coupled electron and proton transfer for catalytic hydride reduction of 4-nitrophenol at the confined nanoscale interface.

Generally, the catalytic transformation of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) at heterogeneous metal surfaces follows a Langmuir-Hinshelwood (L-H) mechanism when sodium borohydride (NaBH4) is used as the sacrificial reductant. Herein, with Pt-Ag bimetallic nanoparticles confined in dendritic mesoporous silica nanospheres (DMSNs) as a model catalyst, we demonstrated that the conversion of 4-NP did not pass through the direct hydrogen transfer route with the hydride equivalents being supplied by borohydride via the bimolecular L-H mechanism, since Fourier transform infrared (FTIR) spectroscopy with the use of isotopically labeled reactants (NaBD4 and D2O) showed that the final product of 4-AP was composed of protons (or deuterons) that originated from the solvent water (or heavy water). Combined characterization by X-ray photoelectron spectroscopy (XPS), 1H nuclear magnetic resonance (NMR) and the optical excitation and photoluminescence spectrum evidenced that the surface hydrous hydroxide complex bound to the metal surface (also called structural water molecules, SWs), due to the space overlap of p orbitals of two O atoms in SWs, could form an ensemble of dynamic interface transient states, which provided the alternative electron and proton transfer channels for selective transformation of 4-NP. The cationic Pt species in the Ag-Pt bimetallic catalyst mainly acts as a dynamic adsorption center to temporally anchor SWs and related reactants, and not as the active site for hydrogen activation.

Irregular Pulsation of Intracranial Aneurysm Detected by Four-Dimensional CT Angiography and Associated With Small Aneurysm Rupture: A Single-Center Prospective Analysis.

Objectives: Predicting the risk of rupture of small intracranial aneurysms remains challenging. The irregular pulsation of aneurysms detected by four-dimensional CT angiography (4D-CTA) could be an imaging marker of aneurysm vulnerability. We aimed to investigate the association of irregular pulsation with small aneurysm rupture. Materials and Methods: This was a prospective study on intracranial aneurysms detected by 4D-CTA from October 2017 to January 2020. A total of 242 consecutive patients with 316 aneurysms were enrolled. Irregular pulsation was defined as a temporary focal protuberance on more than 3 consecutive frames of the 20 phases in the RR interval. Small aneurysms were defined as those <7 mm. Univariate and multivariate analyses were performed to determine the independent predictors of small aneurysm rupture. Results: A total of 169 patients with 217 small intracranial aneurysms were included. Fourteen (6.5%) of the aneurysms had ruptured, and 77 (35.5%) had irregular pulsation. There were no significant differences in age, sex, hypertension, smoking, diabetes, drinking, or hyperlipidemia between the ruptured and unruptured aneurysm groups. The univariate analysis showed that smaller vessel size (p = 0.008), larger size ratio (p = 0.003), larger aspect ratio (p = 0.006), larger flow angle (p = 0.001), large vessel angle (p = 0.004), middle cerebral artery aneurysms (p = 0.046), anterior cerebral artery/posterior communicating artery/posterior circulation aneurysm (p = 0.006), irregular aneurysm (p = 0.001), and t presence of irregular pulsation (p = 0.001) were associated with small aneurysm rupture. The multivariate analysis showed that the presence of irregular pulsation (p = 0.003), anterior cerebral artery/posterior communicating artery/posterior circulation aneurysms (p = 0.014), and larger flow angle (p = 0.006) was independently associated with aneurysm rupture. Multivariate analysis of predictors of the irregular pulsation of small aneurysms showed that the aneurysm rupture (p = 0.022), irregular aneurysm (p < 0.001), and large size ratio (p = 0.005) were independently associated with the presence of irregular pulsation. Conclusions: The ruptured small aneurysms more often had irregular pulsation. The irregular pulsation was independently associated with aneurysm rupture and may help evaluate the risk of rupture of small intracranial aneurysms.

Oral exposure to a hexafluoropropylene oxide trimer acid (HFPO-TA) disrupts mitochondrial function and biogenesis in mice.

Hexafluoropropylene oxide trimer acid (HFPO-TA) is reported to have hepatotoxicity, lipotoxicity, and cytotoxicity. In this study, the toxicological effects of HFPO-TA on mitochondrial function and biogenesis were studied. Mice were exposed to drinking water which contained either 2, 20, or 200 µg/L HFPO-TA. Results showed exposure to HFPO-TA induced disadvantageous physiological changes in mice, including increases in liver weight, altered cell morphology, and inflammatory responses. Specifically, exposure to 200 µg/L HFPO-TA increased mitochondria number, relative mitochondrial DNA (mtDNA) content, and mRNA levels of mitochondrial genes encoded by mtDNA. Significant increases in TFAM mRNA and protein levels were also observed. Liver metabolome analysis also showed exposure to 200 µg/L HFPO-TA further enhanced increases in metabolites and altered metabolic pathways that correlated with mitochondrial function, especially the production of ATP. HFPO-TA exposure increased protein expression of mitochondrial complex I-V, and the activities of key enzymes involved in TCA cycle (α-ketoglutarate dehydrogenase, citrate synthase, and succinate dehydrogenase). Furthermore, exposure to 200 µg/L HFPO-TA significantly up-regulating mRNA and protein levels of Opa1, Mfn1, Mfn2, Fis1, and Mff, but did not change Drp1. These findings suggest HFPO-TA could have detrimental effects on health of animals, particularly it was associated with disrupted mitochondrial energy metabolism.

Hydrated Hydroxide Complex Dominates the AIE Properties of Nonconjugated Polymeric Luminophores.

Nontraditional intrinsic luminescence (NTIL) which always accompanied with aggregation-induced emission (AIE) features has received considerable attention due to their importance in the understanding of basic luminescence principle and potential practical applications. However, the rational modulation of the NTIL of nonconventional luminophores remains difficult, on account of the limited understanding of emission mechanisms. Herein, the emission color of nonconjugated poly(methyl vinyl ether-alt-maleic anhydride) (PMVEMA) can be readily regulated from blue to red by controlling the alkalinity during the hydrolysis process. The nontraditional photoluminescence with AIE property is from the new formed p-band state, resulting from the strong overlapping of p orbitals of the clustered O atoms through space interactions. Hydrated hydroxide complexes embedded in the entangled polymer chain make big difference on the clustering of O atoms which dominates the AIE property of nonconjugated PMVEMA. These new insights into the photoluminescence mechanism of NTIL should stimulate additional experimental and theoretical studies and can benefit the molecular-level design of nontraditional chromophores for optoelectronics and other applications.