Acute exposure to tris(2,4-di-tert-butylphenyl)phosphate elicits cardiotoxicity in zebrafish (Danio rerio) larvae via inducing ferroptosis.

Tris(2,4-di-tert-butylphenyl)phosphate (AO168 =O), a novel organophosphate ester, is prevalent and abundant in the environment, posing great exposure risks to ecological and public health. Nevertheless, the toxicological effects of AO168 =O remain entirely unknown to date. The results in this study indicated that acute exposure to AO168 =O at 10 and 100 µg/L for 5 days obviously impaired cardiac morphology and function of zebrafish larvae, as proofed by decreased heartbeat, stroke volume, and cardiac output and the occurrence of pericardial edema and ventricular hypertrophy. Transcriptomics, polymerase chain reaction, and molecular docking revealed that the strong interaction of AO168 =O and transferrin receptor 1 activated the transportation of ferric iron into intracellular environment. The release of free ferrous ion to cytoplasmic iron pool also contributed to the iron overload in heart region, thus inducing ferroptosis in larvae via generation of excessive reactive oxygen species, glutathione peroxidase 4 inhibition, glutathione depletion and lipid peroxidation. Ferroptosis inhibitor (Fer-1) co-exposure effectively relieved the cardiac dysfunctions of zebrafish, verifying the dominant role of ferroptosis in the cardiotoxicity caused by AO168 =O. This research firstly reported the adverse impact and associated mechanisms of AO168 =O in cardiomyogenesis of vertebrates, underlining the urgency of concerning the health risks of AO168 =O.

Automatic IMRT treatment planning through fluence prediction and plan fine-tuning for nasopharyngeal carcinoma.

BACKGROUND: At present, the implementation of intensity-modulated radiation therapy (IMRT) treatment planning for geometrically complex nasopharyngeal carcinoma (NPC) through manual trial-and-error fashion presents challenges to the improvement of planning efficiency and the obtaining of high-consistency plan quality. This paper aims to propose an automatic IMRT plan generation method through fluence prediction and further plan fine-tuning for patients with NPC and evaluates the planning efficiency and plan quality. METHODS: A total of 38 patients with NPC treated with nine-beam IMRT were enrolled in this study and automatically re-planned with the proposed method. A trained deep learning model was employed to generate static field fluence maps for each patient with 3D computed tomography images and structure contours as input. Automatic IMRT treatment planning was achieved by using its generated dose with slight tightening for further plan fine-tuning. Lastly, the plan quality was compared between automatic plans and clinical plans. RESULTS: The average time for automatic plan generation was less than 4 min, including fluence maps prediction with a python script and automated plan tuning with a C# script. Compared with clinical plans, automatic plans showed better conformity and homogeneity for planning target volumes (PTVs) except for the conformity of PTV-1. Meanwhile, the dosimetric metrics for most organs at risk (OARs) were ameliorated in the automatic plan, especially Dmax of the brainstem and spinal cord, and Dmean of the left and right parotid glands significantly decreased (P < 0.05). CONCLUSION: We have successfully implemented an automatic IMRT plan generation method for patients with NPC. This method shows high planning efficiency and comparable or superior plan quality than clinical plans. The qualitative results before and after the plan fine-tuning indicates that further optimization using dose objectives generated by predicted fluence maps is crucial to obtain high-quality automatic plans.

New Insights into Identification, Distribution, and Health Benefits of Polyamines and Their Derivatives.

Polyamines and their derivatives are ubiquitously present in free or conjugated forms in various foods from animal, plant, and microbial origins. The current knowledge of free polyamines in foods and their contents is readily available; furthermore, conjugated polyamines generate considerable recent research interest due to their potential health benefits. The structural diversity of conjugated polyamines results in challenging their qualitative and quantitative analysis in food. Herein, we review and summarize the knowledge published on polyamines and their derivatives in foods, including their identification, sources, quantities, and health benefits. Particularly, facing the inherent challenges of isomer identification in conjugated polyamines, this paper provides a comprehensive overview of conjugated polyamines' structural characteristics, including the cleavage patterns and characteristic ion fragments of MS/MS for isomer identification. Free polyamines are present in all types of food, while conjugated polyamines are limited to plant-derived foods. Spermidine is renowned for antiaging properties, acclaimed as antiaging vitamins. Conjugated polyamines highlight their anti-inflammatory properties and have emerged as the mainstream drugs for antiprostatitis. This paper will likely help us gain better insight into polyamines and their derivatives to further develop functional foods and personalized nutraceuticals.

CD44-targeted melanin-based nanoplatform for alleviation of ischemia/reperfusion-induced acute kidney injury.

Ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) is a serious kidney disease with high morbidity and mortality. However, there is no effective clinical treatment strategy. Herein, we developed a CD44 targeting nanoplatform based on HA-assembled melanin NPs covalently coupled with dexamethasone for I/R-induced AKI therapy by alleviating oxidative/inflammatory- induced damage. The constructed HA-MNP-DXM NPs had good dispersion, stability, and broad-spectrum scavenging capabilities against multiple reactive free radicals. Moreover, the NPs could be efficiently internalized and exhibited antioxidative, anti-inflammatory, and antiapoptotic effects in CoCl2-stimulated renal tubular epithelial NRK-52E cells. Furthermore, the I/R-induced AKI murine model was established to evaluate the in vivo performance of NPs. The results suggested the NPs could specifically target impaired kidneys upon intravenous administration according to NIR-II fluorescence imaging and showed high biosafety. Importantly, the NPs could improve renal function, alleviate oxidative stress and inflammatory reactions, inhibit apoptosis of tubular cells, and restore mitochondrial structure and function, exhibiting excellent therapeutic effects. Further therapeutic mechanism indicated the NPs maintained the cellular/mitochondrial redox balance by modulating the Nrf2 and HO-1 expression. Therefore, the NPs can be a promising therapeutic candidate for the treatment of I/R-induced AKI.

Assessment of Human Exposure to Traditional and Novel Organophosphate Esters via Multiple Personal Matrices.

Herein, 16 traditional and 13 novel organophosphate esters (OPEs) in skin wipes, personal PM2.5, sputum, and nails (fingernails and toenails) and 7 OPE metabolites in urine synchronously obtained from 64 college students were analyzed. Similar compositional profiles of the OPEs were found in skin wipes and nails and in personal PM2.5 and induced sputum. Significant correlations were observed between the concentrations of high-lipophilicity low-volatility OPEs in skin wipes and nails and between the concentrations of high-volatility low-lipophilicity OPEs in personal PM2.5 and sputum. These results imply that OPEs in fingernails and toenails may mainly come from external sources rather than internal exposure, and human nails and sputum can be used as indicators of human exposure to OPEs. A comparison between the daily exposure doses of the OPEs in personal PM2.5 and sputum shows that more volatile compounds may have higher inhalation bioavailability, which should be considered to improve the accuracy of inhalation exposure assessments. According to comprehensive external and internal exposure assessment, dermal absorption may be a more dominant pathway than inhalation, and skin wipes may be the best representative environmental matrix of human exposure to OPEs.

Strong p-d Orbital Hybridization on Bismuth Nanosheets for High Performing CO2 Electroreduction.

Single-atom alloys (SAAs) show great potential for a variety of electrocatalytic reactions. However, the atomic orbital hybridization effect of SAAs on the electrochemical reactions is unclear yet. Herein, the in situ confinement of vanadium/molybdenum/tungsten atoms on bismuth nanosheet is shown to create SAAs with rich grain boundaries, respectively. With the detailed analysis of microstructure and composition, the strong p-d orbital hybridization between bismuth and vanadium enables the exceptional electrocatalytic performance for carbon dioxide (CO2 ) reduction with the Faradaic efficiency nearly 100% for C1 products in a wide potential range from -0.6 to -1.4 V, and a long-term electrolysis stability for 90 h. In-depth in situ investigations with theoretical computations reveal that the electron delocalization toward vanadium atoms via the p-d orbital hybridization evokes the bismuth active centers for efficient CO2 activation via the σ-donation of O-to-Bi, thus reduces protonation energy barriers for formate production. With such fundamental understanding, SAA electrocatalyst is employed to fabricated the solar-driven electrolytic cell of CO2 reduction and 5-hydroxymethylfurfural oxidation, achieving an outstanding 2,5-furandicarboxylic acid yield of 90.5%. This study demonstrates a feasible strategy to rationally design advanced SAA electrocatalysts via the basic principles of p-d orbital hybridization.

Retinal Ganglion Cell Fate Induction by Ngn-Family Transcription Factors.

Purpose: Retinal ganglion cells (RGCs) are the projection neurons of the retina. Loss of RGCs is the cellular basis for vision loss in patients with glaucoma. Finding ways to regenerate RGCs will aid in the development of regenerative therapies for patients with glaucoma. The aim of this study was to examine the ability of Ngn-family transcription factors (TFs) to induce RGC regeneration through reprogramming in vitro and in vivo. Methods: In vitro, lentiviruses were used to deliver Ngn-TFs into mouse embryonic fibroblasts (MEFs). In vivo, mouse pup retina electroporation was used to deliver Ngn-TFs into late-stage retinal progenitor cells (RPCs). Immunofluorescence staining and RNA sequencing were used to examine cell fate reprogramming; patch-clamp recording was used to examine neuronal electrophysiologic functions. Results: In vitro, all three Ngn-TFs, Ngn1, Ngn2, and Ngn3, were able to work alone to reprogram MEFs into RGC-like neurons that resembled RGCs at the transcriptome level, exhibited typical neuronal membrane electrophysiologic properties, and formed functional synaptic communications with retinal neurons. In vivo, Ngn-TFs reprogrammed the differentiation-competent state of late-stage RPCs to generate RGCs. Conclusions: Ngn-TFs are effective in inducing an RGC-like fate both in vitro and in vivo and might be explored further in the future for glaucoma translational applications.

Br-Doped BiOCl Nanosheet Exposed (001) Facet: Surface Oxygen Vacancy and Directed Electron Flow Boosting the Photocatalytic Performance.

The defective BiOCl nanosheet exposed (001) facet with favorable photocatalytic performance was designed. The surface microstructure analysis and theoretical calculation certified the dominant exposed (001) facet and rich surface oxygen defects of Br--doped BiOCl (B-6) nanosheets. The energy level structure analysis indicates that the band gap can be narrowed and the light absorption range can be widened by introducing Br- to BiOCl, and the presence of defective energy levels increases the photogenerated carrier transfer efficiency. Moreover, the doping of Br- in BiOCl promotes the directional flow of electrons to the surface of B-6, which improves the photocatalytic performance of the sample. Thus, the Br--doped BiOCl can degrade 96.5% RhB within 6 min under visible-light irradiation with high apparent reaction rate constants of 0.51 min-1, exhibiting the strongest photocatalytic degradation performance. This work provides guidance for the preparation of Bi-based photocatalysts with excellent performance.

Generating Retinas through Guided Pluripotent Stem Cell Differentiation and Direct Somatic Cell Reprogramming.

Retinal degeneration diseases affect millions of people worldwide but are among the most difficult eye diseases to cure. Studying the mechanisms and developing new therapies for these blinding diseases requires researchers to have access to many retinal cells. In recent years there has been substantial advances in the field of biotechnology in generating retinal cells and even tissues in vitro, either through programmed sequential stem cell differentiation or direct somatic cell lineage reprogramming. The resemblance of these in vitro-generated retinal cells to native cells has been increasingly utilized by researchers. With the help of these in vitro retinal models, we now have a better understanding of human retinas and retinal diseases. Furthermore, these in vitro-generated retinal cells can be used as donor cells which solves a major hurdle in the development of cell replacement therapy for retinal degeneration diseases, while providing a promising option for patients suffering from these diseases. In this review, we summarize the development of pluripotent stem cell-to-retinal cell differentiation methods, the recent advances in generating retinal cells through direct somatic cell reprogramming, and the translational applications of retinal cells generated in vitro. Finally, we discuss the limitations of the current protocols and possible future directions for improvement.

Effect of heavy metal co-contaminants on the sorption of thirteen anionic per- and poly-fluoroalkyl substances (PFAS) in soils.

Understanding the sorption behavior of per- and poly-fluoroalkyl substances (PFAS) in soils are essential for assessing their mobility and risk in the environment. Heavy metals often coexist with PFAS depending on the source and history of contamination. In this study, we investigated the effect of heavy metal co-contaminants (Pb2+, Cu2+ and Zn2+) on the sorption of 13 anionic PFAS with different perfluorocarbon chain length (C3-C9) in two soils with different properties. Results revealed that Pb2+, Cu2+ and Zn2+ had little effect on the sorption of most short-chain compounds, while the presence of these heavy metals enhanced the sorption of long-chain PFAS in two soils. The distribution coefficients (Kd) of several long-chain PFAS linearly increased with increasing concentrations of heavy metal, especially in the presence of Pb2+ (ΔKd/Δ [Pb2+] > 3 for PFOS and PFNA vs <1 for PFPeS and PFHxS). While several mechanisms may have contributed to the enhancement of sorption of PFAS, the heavy metals most likely contributed through enhanced hydrophobic interactions of PFAS by neutralizing the negative charge of adsorption surfaces in soils and thus making it more favorable for their partitioning onto the solid phase. Moreover, the increase in the concentrations of heavy metals led to a decrease in the pH of the system and promoted sorption of long-chain compounds, especially in soil with lower organic carbon content. Overall, this study provides evidence that the presence of co-existing heavy metal cations in soils can significantly enhance the sorption of long-chain PFAS onto soil, thereby potentially limiting their mobility in the environment.

Simultaneous dose distribution and fluence prediction for nasopharyngeal carcinoma IMRT.

BACKGROUND: Current intensity-modulated radiation therapy (IMRT) treatment planning is still a manual and time/resource consuming task, knowledge-based planning methods with appropriate predictions have been shown to enhance the plan quality consistency and improve planning efficiency. This study aims to develop a novel prediction framework to simultaneously predict dose distribution and fluence for nasopharyngeal carcinoma treated with IMRT, the predicted dose information and fluence can be used as the dose objectives and initial solution for an automatic IMRT plan optimization scheme, respectively. METHODS: We proposed a shared encoder network to simultaneously generate dose distribution and fluence maps. The same inputs (three-dimensional contours and CT images) were used for both dose distribution and fluence prediction. The model was trained with datasets of 340 nasopharyngeal carcinoma patients (260 cases for training, 40 cases for validation, 40 cases for testing) treated with nine-beam IMRT. The predicted fluence was then imported back to treatment planning system to generate the final deliverable plan. Predicted fluence accuracy was quantitatively evaluated within projected planning target volumes in beams-eye-view with 5 mm margin. The comparison between predicted doses, predicted fluence generated doses and ground truth doses were also conducted inside patient body. RESULTS: The proposed network successfully predicted similar dose distribution and fluence maps compared with ground truth. The quantitative evaluation showed that the pixel-based mean absolute error between predicted fluence and ground truth fluence was 0.53% ± 0.13%. The structural similarity index also showed high fluence similarity with values of 0.96 ± 0.02. Meanwhile, the difference in the clinical dose indices for most structures between predicted dose, predicted fluence generated dose and ground truth dose were less than 1 Gy. As a comparison, the predicted dose achieved better target dose coverage and dose hot spot than predicted fluence generated dose compared with ground truth dose. CONCLUSION: We proposed an approach to predict 3D dose distribution and fluence maps simultaneously for nasopharyngeal carcinoma patients. Hence, the proposed method can be potentially integrated in a fast automatic plan generation scheme by using predicted dose as dose objectives and predicted fluence as a warm start.

Multimodality MRI synchronous construction based deep learning framework for MRI-guided radiotherapy synthetic CT generation.

Synthesizing computed tomography (CT) images from magnetic resonance imaging (MRI) data can provide the necessary electron density information for accurate dose calculation in the treatment planning of MRI-guided radiation therapy (MRIgRT). Inputting multimodality MRI data can provide sufficient information for accurate CT synthesis: however, obtaining the necessary number of MRI modalities is clinically expensive and time-consuming. In this study, we propose a multimodality MRI synchronous construction based deep learning framework from a single T1-weight (T1) image for MRIgRT synthetic CT (sCT) image generation. The network is mainly based on a generative adversarial network with sequential subtasks of intermediately generating synthetic MRIs and jointly generating the sCT image from the single T1 MRI. It contains a multitask generator and a multibranch discriminator, where the generator consists of a shared encoder and a splitted multibranch decoder. Specific attention modules are designed within the generator for feasible high-dimensional feature representation and fusion. Fifty patients with nasopharyngeal carcinoma who had undergone radiotherapy and had CT and sufficient MRI modalities scanned (5550 image slices for each modality) were used in the experiment. Results showed that our proposed network outperforms state-of-the-art sCT generation methods well with the least MAE, NRMSE, and comparable PSNR and SSIM index measure. Our proposed network exhibits comparable or even superior performance than the multimodality MRI-based generation method although it only takes a single T1 MRI image as input, thereby providing a more effective and economic solution for the laborious and high-cost generation of sCT images in clinical applications.

Viscosity-responsive NIR-II fluorescent probe with aggregation-induced emission features for early diagnosis of liver injury.

As the primary organ for drug metabolism and detoxification, the liver is susceptible to damage and seriously impaired function. In situ diagnosing and real-time monitoring of liver damage are thus of great significance but remain limited owing to the lack of reliable in vivo visualization protocols with minimal invasion. Herein, we reported for the first time an aggregation-induced emission (AIE) probe, namely DPXBI, emitting light in the second near-infrared window (NIR-II) for early diagnosis liver injury. DPXBI featured by strong intramolecular rotations, excellent aqueous solubility and robust chemical stability, is powerfully sensitive to viscosity alteration affording rapid response and high selectivity, through NIR-Ⅱ fluorescence intensity changes. The prominent viscosity-responsive performance enables DPXBI to accurately monitor both drug-induced liver injury (DILI) and hepatic ischemia-reperfusion injury (HIRI) with excellent image contrast to the background. By using the presented strategy, the detection of liver injury in mouse model can be achieved at least several hours earlier than typical clinical assays. Moreover, DPXBI is able to dynamically track the liver improvement process in vivo in the case of DILI when the hepatotoxicity is alleviated by using hepatoprotective medication. All these results demonstrate that DPXBI is a promising probe for investigating viscosity-associated pathological and physiological processes.

Bifunctional Hot Water Vapor Template-Mediated Synthesis of Nanostructured Polymeric Carbon Nitride for Efficient Hydrogen Evolution.

Regulating bulk polymeric carbon nitride (PCN) into nanostructured PCN has long been proven effective in enhancing its photocatalytic activity. However, simplifying the synthesis of nanostructured PCN remains a considerable challenge and has drawn widespread attention. This work reported the one-step green and sustainable synthesis of nanostructured PCN in the direct thermal polymerization of the guanidine thiocyanate precursor via the judicious introduction of hot water vapor's dual function as gas-bubble templates along with a green etching reagent. By optimizing the temperature of the water vapor and polymerization reaction time, the as-prepared nanostructured PCN exhibited a highly boosted visible-light-driven photocatalytic hydrogen evolution activity. The highest H2 evolution rate achieved was 4.81mmol∙g-1∙h-1, which is over four times larger than that of the bulk PCN (1.19 mmol∙g-1∙h-1) prepared only by thermal polymerization of the guanidine thiocyanate precursor without the assistance of bifunctional hot water vapor. The enhanced photocatalytic activity might be attributed to the enlarged BET specific surface area, increased active site quantity, and highly accelerated photo-excited charge-carrier transfer and separation. Moreover, the sustainability of this environmentally friendly hot water vapor dual-function mediated method was also shown to be versatile in preparing other nanostructured PCN photocatalysts derived from other precursors such as dicyandiamide and melamine. This work is expected to provide a novel pathway for exploring the rational design of nanostructured PCN for highly efficient solar energy conversion.

Protein-rich yeast extract (®fermgard) has potential antioxidant and anti-aging activities.

There existed a deficiency in the research on the nutritional activities of microbial (yeast) active substances in antioxidant and anti-aging activities, although the research objects were concentrated in animals and plants in recent years. In this study, the anti-oxidant and anti-aging activities of protein-rich yeast extract (®fermgard) (YE) were investigated through Caenorhabditis elegans (C. elegans). The results indicated that YE could improve the lifespan and anti-stress ability by up-regulating the activities of antioxidant enzymes in C. elegans. Meanwhile, the mRNA transcriptional level of daf-16, skn-1 and sod-3 was significantly up-regulated. In addition, the composition and level of the gut microbiota and metabolite were modulated. YE exerts antioxidant and anti-aging activities by regulating the expression of anti-oxidation-related mRNA, gut microbiota and metabolites in C. elegans, providing a basis for exploring the deep mechanism of YE improving health. At the same time, it provides new ideas for the development of functional foods.

A Multivariable Model Based on Ultrasound Imaging Features of Gastrocnemius Muscle to Identify Patients With Sarcopenia.

OBJECTIVES: Low skeletal muscle mass, strength, or somatic function are used to diagnose sarcopenia; however, effective assessment methods are still lacking. Therefore, we evaluated the effectiveness of ultrasound in identifying patients with sarcopenia. METHODS: This study included 167 patients, 78 with sarcopenia and 89 healthy participants, from two hospitals. We evaluated clinical factors and five ultrasound imaging features, of which three ultrasound imaging features were used to create the model. In both the training and validation datasets, the sarcopenia detection performances of chosen ultrasonic characteristics and the constructed model were evaluated using receiver operating characteristic (ROC) curves. The predictive performance was evaluated by area under the ROC (AUROC), calibration, and decision curves. RESULTS: There were statistically significant differences in muscle thickness (MT) of gastrocnemius medialis muscle (GM), flaky myosteatosis echo (FE), pennation angle (PA), average shear wave velocity (SWV) in the relaxed state (RASWV), and average SWV in the passive stretched state (PASWV) between sarcopenic and normal subjects. PA, RASWV, and PASWV were effective predictors of sarcopenia. The AUROC (95% confidence interval) for these three parameters were 0.930 (0.882-0.978), 0.865 (0.791-0.940), and 0.849 (0.770-0.928), respectively, in the training set, and 0.873 (0.777-0.969), 0.936 (0.878-0.993), and 0.826 (0.716-0.935), respectively, in the validation set. The combined model had better detection power. Finally, the calibration curve showed that the combined model had good prediction accuracy. CONCLUSION: Our model can be used to identify sarcopenia in primary medical institutions, which is valuable for the early recognition and management of sarcopenia patients.

Physiological Roles of ß-amyloid in Regulating Synaptic Function: Implications for AD Pathophysiology.

The physiological functions of endogenous amyloid-ß (Aß), which plays important role in the pathology of Alzheimer's disease (AD), have not been paid enough attention. Here, we review the multiple physiological effects of Aß, particularly in regulating synaptic transmission, and the possible mechanisms, in order to decipher the real characters of Aß under both physiological and pathological conditions. Some worthy studies have shown that the deprivation of endogenous Aß gives rise to synaptic dysfunction and cognitive deficiency, while the moderate elevation of this peptide enhances long term potentiation and leads to neuronal hyperexcitability. In this review, we provide a new view for understanding the role of Aß in AD pathophysiology from the perspective of physiological meaning.

Identification of neurotoxic compounds in cyanobacteria exudate mixtures.

Release of toxic cyanobacterial secondary metabolites threatens biosecurity, foodwebs and public health. Microcystis aeruginosa (Ma), the dominant species in global freshwater cyanobacterial blooms, produces exudates (MaE) that cause adverse outcomes including nerve damage. Previously, we identified > 300 chemicals in MaE. It is critical to investigate neurotoxicity mechanisms of active substances among this suite of Ma compounds. Here, we screened 103 neurotoxicity assays from the ToxCast database to reveal targets of action of MaE using machine learning. We then built a potential Adverse Outcome Pathway (AOP) to identify neurotoxicity mechanisms of MaE as well as key targets. Finally, we selected potential neurotoxins matched with those targets using molecular docking. We found 38 targets that were inhibited and eight targets that were activated, collectively mainly related to neurotransmission (i.e. cholinergic, dopaminergic and serotonergic neurotransmitter systems). The potential AOP of MaE neurotoxicity could be caused by blocking calcium voltage-gated channel (CACNA1A), because of antagonizing neurotransmitter receptors, or because of inhibiting solute carrier transporters. We identified nine neurotoxic MaE compounds with high affinity to those targets, including LysoPC(16:0), 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine, egonol glucoside, polyoxyethylene (600) monoricinoleate, and phytosphingosine. Our study enhances understanding of neurotoxicity mechanisms and identifies neurotoxins in cyanobacterial bloom exudates, which may help identify priority compounds for cyanobacteria management.

The Dynamic SUMOylation Changes and Their Potential Role in the Senescence of APOE4 Mice.

The ε4 allele of apolipoprotein E (APOE4) and aging are the major risk factors for Alzheimer's disease (AD). SUMOylation is intimately linked to the development of AD and the aging process. However, the SUMOylation status in APOE4 mice has not been uncovered. In this study, we investigated SENP1 and SUMOylation changes in the brains of aged APOE3 and APOE4 mice, aiming to understand their potential impact on mitochondrial metabolism and their contribution to cellular senescence in APOE4 mice. Concurrently, SUMO1-conjugated protein levels decreased, while SUMO2/3-conjugated protein levels increased relatively with the aging of APOE4 mice. This suggests that the equilibrium between the SUMOylation and deSUMOylation processes may be associated with senescence and longevity. Our findings highlight the significant roles of SENP1 and SUMOylation changes in APOE4-driven pathology and the aging process.

Distribution of flame retardants among indoor dust, airborne particles and vapour phase from Beijing: spatial-temporal variation and human exposure characteristics.

The occurrence and distribution of 10 brominated flame retardants (BFRs) and 10 organophosphate flame retardants (OPFRs) were investigated in indoor dust, total suspended particles (TSP), and vapour phase from offices (n = 10), homes (n = 9), and day-care centres (n = 10) in Beijing, China. Three types of samples were collected biweekly from one office and one home over a year to examine temporal trends. BFRs in dust significantly correlated with those in TSP, while OPFRs significantly correlated among all three matrices. In addition, BFRs in dust (ng/g) and TSP (pg/m3) exhibited similar temporal trends with higher levels in the cold season, whereas OPFRs in TSP and vapour phase (pg/m3) showed similar temporal trends with higher levels in the warm season. The geometric mean concentrations of BFRs and OPFRs in the three matrices from the above mentioned three types of indoor microenvironments were used for exposure and health risk estimation, and ∑7OPFRs showed much higher hazard index (HI) values than ∑10BFRs for all subpopulations, and inhalation of OPFRs was a major risk source. With the volatility of flame retardants (FRs) decreasing, the contribution of dust ingestion and dermal absorption showed an increasing trend, and the contribution of inhalation exhibited a gradual decreasing trend, which implied the dominant exposure pathway to FRs is strongly related to the vapour pressure (25 °C, Pa) of these substances. Using a single type of microenvironment or the collection of samples at a single point in time can lead to overestimation or underestimation of overall exposure and risk for people to some extent. The correlations of FRs in dust, TSP, and vapour phase from indoor microenvironments, as well as their temporal trends were first reported in this study, which will provide a basis for more accurate FR exposure assessments in the future.