Impact of NBP on acute ischemic stroke: Tracking therapy effect on neuroinflammation.

BACKGROUND: Ischemic stroke is the leading cause of death and long-term disability worldwide. After stroke, microglia exhibit not only pro-inflammatory phenotype to aggravate the neuroinflammation, but also anti-inflammatory phenotype to play a neuroprotective role. Studies on the spatial and temporal changes in microglia and the underlying mechanisms help to elucidate the inflammatory cascade after stroke. The regulation of microglia polarization provides new insights for the intervention of post-stroke inflammation. OBJECTIVE: We aimed to investigate the phenotypic change of microglia in the acute phase of ischemic stroke and the effects of Dl-3-n-butylphthalide (NBP) on microglia. TSPO-PET was used to image microglia and evaluate the efficacy of NBP. METHODS: We constructed an MCAO model in rats and administered NBP daily. The infarct volumes in the NBP-treated and control groups were measured. TSPO-PET/CT was used to demonstrate the activation of microglia and the effects of NBP. Additionally, we investigated the effects of NBP on TSPO expression. In vitro, microglia were exposed to glucose oxygen deprivation, and the effects of NBP on microglia and TSPO expression were verified. RESULTS: NBP improved neurological severity scores and reduced infarct volume in the acute phase of ischemic stroke. NBP facilitated microglia to adopt the anti-inflammatory phenotype and reduce the pro-inflammatory phenotype. NBP decreased the expressions of inflammatory cytokines. TSPO-PET/CT observed increase in uptake in the infarct lesion, and this uptake was reduced in response to NBP. NBP reduced TSPO expression in microglia after stroke. In vitro experiments further verified that NBP facilitated the transition of microglia towards the anti-inflammatory phenotype, and inhibited inflammatory cytokine secretion and TSPO expression. CONCLUSION: We illustrated that NBP fosters the shift of microglia towards the anti-inflammatory phenotype while diminishing their inclination towards the pro-inflammatory phenotype, thereby exerting neuroprotective effects. NBP reduces TSPO expression in microglia, which can be observed by TSPO-PET/CT imaging.

Efficacy and safety of Anlotinib based neoadjuvant chemotherapy for locally advanced triple negative breast cancer (TNBC).

BACKGROUND: Anlotinib, an oral multitarget tyrosine kinase inhibitor, has shown the ability to inhibit tumor angiogenesis. This study aimed to assess the effectiveness and safety of anlotinib plus docetaxel, epirubicin, and cyclophosphamide (TEC) as a neoadjuvant chemotherapy regimen for locally advanced TNBC. METHODS: Locally advanced TNBC patients who had received no prior systemic treatment were eligible for this study. The enrolled patients were scheduled to undergo six cycles of anlotinib (12 mg, d1-14, q3w) plus docetaxel (75 mg/m2, d1, q3w), epirubicin (75 mg/m2, d1, q3w) and cyclophosphamide (600 mg/m2, d1, q3w) prior to surgery, unless there was disease progression or severe toxicity. The primary objective of this study was the safety of this therapeutic regimen, and the secondary objective was the tumor response. The safety of this regimen was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and the efficacy of this treatment was measured using the Response Evaluation Criteria in Solid Tumors version 1.1. RESULTS: A total of 18 patients were included in this study. Participants completed an average of 5.56 neoadjuvant treatment cycles. The objective response rate (ORR) was 83.33%, and the disease control rate was 100%, respectively. The pCR was 55.6%. No patients discontinued therapy because of Adverse effects (AEs). Grade 3 or 4 AEs were observed in 5 cases (27.8%), with neutropenia and palmar-plantar erythrodysesthesia syndrome being the most common. CONCLUSIONS: Anlotinib combined with TEC as neoadjuvant therapy demonstrated manageable toxicity and promising antitumor activity for locally advanced TNBC. Further investigation of this combination regimen is warranted.

Coupling of two-dimensional MXenes and graphene for boosting the hydrogen storage performance of MgH2.

MgH2 used in solid-state hydrogen storage still suffers from high thermal stability and slow hydrogen absorption-desorption kinetics. Here, we report a hybrid of MgH2-Ti3C2/graphene prepared through a facile wet chemical method followed by a ball-milling method. It was confirmed that the coupling of Ti3C2 and graphene possesses a synergistic effect on the hydrogen desorption and absorption reactions of MgH2/Mg. The initial temperature of MgH2-Ti3C2/graphene to desorb hydrogen was reduced to 169 °C significantly and it could desorb 6.8 wt% H2 within 6 min at a constant temperature of 300 °C. Moreover, the desorbed sample could start to absorb hydrogen at room temperature and achieve a capacity of 6.0 wt% when the temperature was gradually increased to 350 °C. These results are far superior to pristine MgH2, disclosing that the addition of two-dimensional Ti3C2/graphene is an efficient strategy to boost the hydrogen storage performance of MgH2.

Micron-Scale Vertical MoS2/Porous g-C3N4 Piezocatalyst via a Precursor's Supramolecular Self-Template Architecture: Degradation and Hydrogen Evolution.

Piezocatalysis can effectively harvest various kinds of mechanical energy with high entropy from the environment and drive some redox reactions without light irradiation, where MoS2- and g-C3N4-based piezocatalysts are recent research hotspots. This study constructs an architecture of ordered melamine hydrochloride-cyanuric acid/MoO42- supramolecular precursor via self-assembly, serving as a self-template for in situ tight growth of vertically aligned micron-scale MoS2 on porous foam-like g-C3N4(CMx) under S vapor with a bioinspired rooting and sprouting-like process. Experiments, DFT calculations, and finite element simulations collectively confirm the high piezoresponse of the CMx with high exposure of active sites and enhanced mechanical energy collection. The vertical interfaces and built-in electric fields in the composite induce efficient charge carrier separation and transfer. The optimized CM0.77 efficiently degrades various organic dyes and antibiotic under dark ultrasound [rhodamine B (RhB): 0.47 s-1, methyl orange (MO): 0.05 s-1, methylene blue (MB): 0.21 s-1, and tetracycline hydrochloride (TC): 0.03 s-1] and achieves hydrogen evolution (2431 µmol·g-1·h-1). Under simulated water flow (10 L/min), the expanded CM0.77/Al2O3 porous foam ceramic (CM/alumina ceramic) purifier device degrades 95% of 400 mL of RhB within 25 min. The developed ordered vertical MoS2/g-C3N4 piezocatalyst demonstrates rapid pollutant degradation and efficient hydrogen evolution under water flow and ultrasound, providing new insights for constructing multidimensional piezoelectric composites for environmental remediation and clean energy production.

Trends in cancer imaging.

Molecular imaging of cancer is a collaborative endeavor, uniting scientists and physicians from diverse fields. Such collaboration is actively developing and translating cutting-edge molecular imaging approaches to enhance the diagnostic landscape of human malignancies. The advent of positron emission tomography (PET) and PET imaging tracers has realized non-invasive target annotation and tumor characterization at the molecular level. In surgical procedures, novel imaging techniques, such as fluorescence or Cherenkov luminescence, help identify tumors and enhance surgical precision. Simultaneously, progress in imaging equipment, innovative algorithms, and artificial intelligence has opened avenues for next-generation cancer screening and imaging, augmenting the efficiency and accuracy of cancer diagnosis. In this review, we provide a panorama of molecular cancer imaging and ongoing developments in the field.

ImmunoPET imaging of EpCAM in solid tumours with nanobody tracers: a preclinical study.

PURPOSE: Epithelial cell adhesion molecule (EpCAM) is a potential therapeutic target and anchoring molecule for circulating and disseminated tumour cells (CTC/DTC) in liquid biopsy. In this study, we aimed to construct EpCAM-specific immuno-positron emission tomography (immunoPET) imaging probes and assess the diagnostic abilities in preclinical cancer models. METHODS: By engineering six single-domain antibodies (e.g., EPCD1 - 6) targeting EpCAM of different binding properties and labelling with 68Ga (T1/2 = 1.1 h) and 18F (T1/2 = 110 min), we developed a series of EpCAM-targeted immunoPET imaging probes. The probes' pharmacokinetics and diagnostic accuracies were investigated in cell-derived human colorectal (LS174T) and esophageal cancer (OE19) tumour models. RESULTS: Based on in vitro binding affinities and in vivo pharmacokinetics of the first three tracers ([68Ga]Ga-NOTA-EPCD1, [68Ga]Ga-NOTA-EPCD2, and [68Ga]Ga-NOTA-EPCD3), we selected [68Ga]Ga-NOTA-EPCD3 for tumour imaging which showed an average tumour uptake of 2.06 ± 0.124%ID/g (n = 3) in LS174T cell-derived tumour model. Development and characterisation of [18F]AIF-RESCA-EPCD3 showed comparable tumour uptake of 1.73 ± 0.0471%ID/g (n = 3) in the same tumour model. Further validation of [68Ga]Ga-NOTA-EPCD3 in OE19 cell-derived tumour model showed an average tumour uptake of 4.27 ± 1.16%ID/g and liver uptake of 13.5 ± 1.30%ID/g (n = 3). Near-infrared fluorescence imaging with Cy7-EPCD3 confirmed the in vivo pharmacokinetics and relatively high liver accumulation. We further synthesized another three 18F-labeled nanobody tracers ([18F]AIF-RESCA-EPCD4, [18F]AIF-RESCA-EPCD5, and [18F]AIF-RESCA-EPCD6) and found that [18F]AIF-RESCA-EPCD6 had the best pharmacokinetics with low background. [18F]AIF-RESCA-EPCD6 showed explicit uptake in the subcutaneously inoculated OE19 tumour model with an average uptake of 4.70 ± 0.26%ID/g (n = 3). In comparison, the corresponding tumour uptake (0.17 ± 0.25%ID/g, n = 3) in the EPCD6 blocking group was substantially lower (P < 0.001), indicating the targeting specificity of the tracer. CONCLUSIONS: We developed a series of 68Ga/18F-labeled nanobody tracers targeting human EpCAM. ImmunoPET imaging with [18F]AIF-RESCA-EPCD6 may facilitate better use of EpCAM-targeted therapeutics by noninvasively displaying the target's expression dynamics.

Endogenous adenine is a potential driver of the cardiovascular-kidney-metabolic syndrome.

Mechanisms underlying the cardiovascular-kidney-metabolic (CKM) syndrome are unknown, although key small molecule metabolites may be involved. Bulk and spatial metabolomics identified adenine to be upregulated and specifically enriched in coronary blood vessels in hearts from patients with diabetes and left ventricular hypertrophy. Single nucleus gene expression studies revealed that endothelial methylthioadenosine phosphorylase (MTAP) was increased in human hearts with hypertrophic cardiomyopathy. The urine adenine/creatinine ratio in patients was predictive of incident heart failure with preserved ejection fraction. Heart adenine and MTAP gene expression was increased in a 2-hit mouse model of hypertrophic heart disease and in a model of diastolic dysfunction with diabetes. Inhibition of MTAP blocked adenine accumulation in the heart, restored heart dysfunction in mice with type 2 diabetes and prevented ischemic heart damage in a rat model of myocardial infarction. Mechanistically, adenine-induced impaired mitophagy was reversed by reduction of mTOR. These studies indicate that endogenous adenine is in a causal pathway for heart failure and ischemic heart disease in the context of CKM syndrome.

Electrochemical lithium storage of a biactive organic molecule containing cyano and imine groups.

With an electron-deficient rigid planar structure and excellent π-π stacking ability, hexaazatriphenylene (HAT) and its derivatives are widely used as basic building blocks for constructing covalent organic frameworks (COFs), components of organic light-emitting diodes and solar cells, and electrode materials for lithium-ion batteries (LIBs). Here, a HAT derivative, hexaazatriphenylenehexacarbonitrile, is explored as an anode material for LIBs. The HAT anode exhibited high initial reversible capacities of 672 mA h g-1 at 100 mA g-1 and 550 mA h g-1 at 400 mA g-1 and stable cycling with a capacity of 503 mA h g-1 after 1000 cycles at 400 mA g-1 corresponding to a capacity retention of 91.5%. Furthermore, the lithium storage mechanism and the cause of the first irreversible capacity loss of the HAT anode were investigated by X-ray photoelectron spectroscopy (XPS) analysis and density functional theory (DFT) calculations. We have carried out a series of analyses on the mechanism of initial capacity loss. This study provides new insight on initial capacity loss and provides valuable insights into the molecular design and the electrochemical properties of HAT-based anode materials.

Associations of urinary nicotine metabolites and essential metals with metabolic syndrome in older adults: The mediation effect of insulin resistance.

Exposure to tobacco smoke and essential metals is linked with metabolic syndrome (MS). However, the joint effect of them on MS in older adults and the underlying mechanisms are still unclear. This large-scale study measured the urinary concentrations of 8 nicotine metabolites and 8 essential metals in 4564 older adults from Shenzhen, China. The biomarker of insulin resistance, triglyceride-glucose index (TyG), was also calculated. Restricted cubic splines (RCS), Bayesian kernel machine regression and quantile-based g-computation were used to access the single and joint effects of urinary nicotine metabolites and essential metals on MS and insulin resistance. Mediation analysis was performed to investigate the role of TyG in these relationships. Single urinary nicotine metabolite and essential metal had non-linear relationships with MS in RCS. The overall effect of urinary nicotine metabolites and essential metals was positively associated with MS. Urinary zinc (52.2 %) and copper (20.1 %) were the major contributors to MS, whereas molybdenum had a negative association with MS. TyG mediated 64.7 % of the overall effect of urinary nicotine metabolites and essential metals on MS. Overall, the mixture of urinary nicotine metabolites and essential metals had a dose-response relationship with MS. Insulin resistance was as a crucial mediated pathway in this association.

Urolithin a Improves Motor Dysfunction Induced by Copper Exposure in SOD1G93A Transgenic Mice Via Activation of Mitophagy.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease pathologically characterized by selective degeneration of motor neurons resulting in a catastrophic loss of motor function. The present study aimed to investigate the effect of copper (Cu) exposure on progression of ALS and explore the therapeutic effect and mechanism of Urolithin A (UA) on ALS. 0.13 PPM copper chloride drinking water was administrated in SOD1G93A transgenic mice at 6 weeks, UA at a dosage of 50 mg/kg/day was given for 6 weeks after a 7-week Cu exposure. Motor ability was assessed before terminal anesthesia. Muscle atrophy and fibrosis, motor neurons, astrocytes and microglia in the spinal cord were evaluated by H&E, Masson, Sirius Red, Nissl and Immunohistochemistry Staining. Proteomics analysis, Western blotting and ELISA were conducted to detect protein expression. Mitochondrial adenosine triphosphate (ATP) and malondialdehyde (MDA) levels were measured using an assay kit. Cu-exposure worsened motor function, promoted muscle fibrosis, loss of motor neurons, and astrocyte and microglial activation. It also induced abnormal changes in mitochondria-related biological processes, leading to a significant reduction in ATP levels and an increase in MDA levels. Upregulation of P62 and downregulation of Parkin, PINK1, and LAMP1 were revealed in SOD1G93A mice with Cu exposure. Administration of UA activated mitophagy, modulated mitochondria dysfunction, reduced neuroinflammation, and improved gastrocnemius muscle atrophy and motor dysfunction in SOD1G93A mice with Cu exposure. Mitophagy plays critical role in ALS exacerbated by Cu exposure. UA administration may be a promising treatment strategy for ALS.

Increasing biomass concentration facilitates simultaneous nitrogen removal and sludge reduction under low C/N conditions.

To overcome the issues of limited carbon source and high sludge production in partial denitrification/anammox (PD/A) process, the effects of mixed liquor suspended solids (MLSS) and carbon/nitrogen ratio (C/N) on PD/A were investigated through parallel experiments. Nitrogen removal efficiencies decreased significantly when C/N was reduced (1.5 â†’ 0.75). When MLSS was doubled, the nitrogen removal efficiencies in the two parallel reactors increased from 75.3 %, 72.9 % to 86.9 %, 89.7 %, respectively, and sludge yields decreased obviously. Combining with in-situ test, it was speculated when MLSS increased, fermentation was enhanced, providing substrate for partial denitrification. Thauera, involved in partial denitrification, decreased obviously with reduced C/N, but increased from 9.93 % to 38.16 % when MLSS doubled, which could promote the PD/A process. Terrimonas and Ignavibacterium (fermentative bacteria) increased from 1.26 %, 5.22 % to 6.62 %, 6.30 %, respectively. These results proved that increasing MLSS under low C/N ratios promoted fermentation in PD/A system, facilitating efficient nitrogen removal and sludge reduction.

Cellular and molecular determinants of bacterial burden in leprosy granulomas revealed by single-cell multimodal omics.

BACKGROUND: Which cell populations that determine the fate of bacteria in infectious granulomas remain unclear. Leprosy, a granulomatous disease with a strong genetic predisposition, caused by Mycobacterium leprae infection, exhibits distinct sub-types with varying bacterial load and is considered an outstanding disease model for studying host-pathogen interactions. METHODS: We performed single-cell RNA and immune repertoire sequencing on 11 healthy controls and 20 patients with leprosy, and integrated single-cell data with genome-wide genetic data on leprosy. Multiplex immunohistochemistry, and in vitro and in vivo infection experiments were conducted to confirm the multimodal omics findings. FINDINGS: Lepromatous leprosy (L-LEP) granulomas with high bacterial burden were characterised by exhausted CD8+ T cells, and high RGS1 expression in CD8+ T cells was associated with L-LEP. By contrast, tuberculoid leprosy (T-LEP) granulomas with low bacterial burden displayed enrichment in resident memory IFNG+ CD8+ T cells (CD8+ Trm) with high GNLY expression. This enrichment was potentially attributable to the communication between IL1B macrophages and CD8+ Trm via CXCL10-CXCR3 signalling. Additionally, IL1B macrophages in L-LEP exhibited anti-inflammatory phenotype, with high APOE expression contributing to high bacterial burden. Conversely, IL1B macrophages in T-LEP were distinguished by interferon-γ induced GBP family genes. INTERPRETATION: The state of IL1B macrophages and functional CD8+ T cells, as well as the relationship between them, is crucial for controlling bacterial persistence within granulomas. These insights may indicate potential targets for host-directed immunotherapy in granulomatous diseases caused by mycobacteria and other intracellular bacteria. FUNDING: The Key research and development program of Shandong Province (2021LCZX07), Natural Science Foundation of Shandong Province (ZR2023MH046), Youth Science Foundation Cultivation Funding Plan of Shandong First Medical University (Shandong Academy of Medical Sciences) (202201-123), National Natural Science Foundation of China (82471800, 82230107, 82273545, 82304039), the China Postdoctoral Science Foundation (2023M742162), Shandong Province Taishan Scholar Project (tspd20230608), Joint Innovation Team for Clinical & Basic Research (202410), Central guidance for local scientific and technological development projects of Shandong Province (YDZX2023058).

Spatiotemporal analysis of tuberculosis in the Hunan Province, China, 2014-2022.

Background: Pulmonary tuberculosis (PTB) is a major infectious disease that threatens human health. China is a high tuberculosis-burden country and the Hunan Province has a high tuberculosis notification rate. However, no comprehensive analysis has been conducted on the spatiotemporal distribution of PTB in the Hunan Province. Therefore, this study investigated the spatiotemporal distribution of PTB in the Hunan Province to enable targeted control policies for tuberculosis. Methods: We obtained data about cases of PTB in the Hunan Province notified from January 2014 to December 2022 from the China Information System for Disease Control and Prevention. Time-series analysis was conducted to analyze the trends in PTB case notifications. Spatial autocorrelation analysis was conducted to detect the spatial distribution characteristics of PTB at a county level in Hunan Province. Space-time scan analysis was conducted to confirm specific times and locations of PTB clustering. Results: A total of 472,826 new cases of PTB were notified in the Hunan Province during the 9-year study period. The mean PTB notification rate showed a gradual, fluctuating downward trend over time. The number of PTB notifications per month showed significant seasonal variation, with an annual peak in notifications in January or March, followed by a fluctuating decline after March, reaching a trough in November or December. Moran's I index of spatial autocorrelation revealed that the notification rate of PTB by county ranged from 0.117 to 0.317 during the study period, indicating spatial clustering. The hotspot areas of PTB were mainly concentrated in the Xiangxi Autonomous Prefecture, Zhangjiajie City, and Hengyang City. The most likely clustering region was identified in the central-southern part of the province, and a secondary clustering region was identified in the northwest part of the province. Conclusion: This study identified the temporal trend and spatial distribution pattern of tuberculosis in the Hunan Province. PTB clustered mainly in the central-southern and northwestern regions of the province. Disease control programs should focus on strengthening tuberculosis control in these regions.

The causal effect of adult height on late-life handgrip strength: The Singapore Chinese Health Study.

BACKGROUND: Adult height has been associated with handgrip strength, which is a surrogate marker of physical frailty. However, it is uncertain if this association is causative or due to confounding bias. METHODS: We evaluated pairwise associations among handgrip strength, adult height and genetically determined height [using a polygenic score (PGS) for height in a mediation framework and a two-sample Mendelian randomisation approach] by means of multivariable regression model using a prospective cohort of Chinese living in Singapore. We additionally evaluated pathway enrichments of height-related genes in relation to increased handgrip strength to discover common biological mechanisms underlying associations of genetically determined height with handgrip strength. RESULTS: Height PGS exhibited a positive association with handgrip strength at late life after adjusting for midlife body weight and other baseline exposures (cigarette smoking, education and physical activity status, P=1.2×10-9). Approximately 66.4% of the total effect of height PGS on handgrip strength was mediated through adult height (ßindirect-effect=0.034, Pindirect-effect=1.4×10-40). Two-sample Mendelian randomisation evaluations showed a consistent causal relationship between increased height and increased handgrip strength in late life (P between 6.6×10-4 and 3.9×10-18), with insignificant horizontal pleiotropic effects (PMR-Egger  intercept=0.853). Pathway analyses of genes related to both increased adult height and handgrip strength revealed enrichment in ossification and adipogenesis pathways (Padj between 0.034 to 6.8×10-4). CONCLUSIONS: The study highlights on a potentially causal effect between increased adult height and increased handgrip strength at late life, which may be explained by related biological processes underlying preservation of muscle mass and strength in ageing.

The role of mitochondrial dysfunction in the association between trace metals and QTc prolongation in the aged population.

This study delves into the relationship between environmental metal exposure and QT interval corrected for heart rate (QTc) prolongation, a critical marker for cardiovascular risk in the elderly. Although the interplay between metal exposure and QTc prolongation is important for predicting sudden cardiac death, it remains underexplored. Our analysis of 6478 participants from the Shenzhen aging-related disorder cohort involved measuring urinary concentrations of 22 trace metals and using mitochondrial DNA copy number (mtDNA-CN) as an indicator of mitochondrial dysfunction. Utilizing Bayesian kernel machine regression, and structural equation modeling, we assessed the effects of mixed trace metals on QTc prolongation. Our findings indicated a direct association between certain metals (Sb, Cu, Zn) and a 7 % increase in QTc prolongation risk, while Li, V, and Rb were associated with a 5 % reduction in risk. Elevated levels of V, Ti, and Cr corresponded to higher mtDNA-CN. Notably, restricted cubic splines revealed a U-shaped, nonlinear relationship between mtDNA-CN and QTc prolongation. After adjusting for metal exposure, an inverse correlation was observed between mtDNA-CN and QTc prolongation, suggesting mitochondrial dysfunction as a partial mediator.

Protective signature of xanthohumol on cognitive function of APP/PS1 mice: a urine metabolomics approach by age.

Alzheimer's disease (AD) has an increasing prevalence, complicated pathogenesis and no effective cure. Emerging evidences show that flavonoid compounds such as xanthohumol (Xn) could play an important role as a dietary supplement or traditional Chinese herbal medicine in the management of diseases such as AD. This study aims to analyze the target molecules of Xn in the prevention and treatment of AD, and its potential mechanism from the perspective of metabolites. APP/PS1 mice 2- and 6-months old were treated with Xn for 3 months, respectively, the younger animals to test for AD-like brain disease prevention and the older animals to address therapeutic effects on the disease. Memantine (Mem) was selected as positive control. Behavioral tests were performed to assess the course of cognitive function. Urine samples were collected and analyzed by high-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS/MS) coupled with online Compound Discoverer software. Morris Water Maze (MWM) tests showed that Xn, like Mem, had a therapeutic but not a preventive effect on cognitive impairment. The expression levels of urinary metabolites appeared to show an opposite trend at different stages of Xn treatment, downregulated in the prevention phase while upregulated in the therapy phase. In addition, the metabolic mechanisms of Xn during preventive treatment were also different from that during therapeutic treatment. The signaling pathways metabolites nordiazepam and genistein were specifically regulated by Xn but not by Mem in the disease prevention stage. The signaling pathway metabolite ascorbic acid was specifically regulated by Xn in the therapeutic stage. In conclusion, dietary treatment with Xn altered the urinary metabolite profile at different stages of administration in APP/PS1 mice. The identified potential endogenous metabolic biomarkers and signal pathways open new avenues to investigate the pathogenesis and treatment of AD.

Anisotropic electronic coupling in three-dimensional assembly of CsPbBr3 quantum dots.

Cesium lead halide (CsPbX3, X = Cl, Br, or I) perovskite quantum dots (PeQDs) show promise for next-generation optoelectronics. In this study, we controlled the electronic coupling between PeQD multilayers using a layer-by-layer method and dithiol linkers of varying structures. The energy shift of the first excitonic peak from monolayer to bilayer decreases exponentially with increasing interlayer spacer distance, indicating the resonant tunnelling effect. X-ray diffraction measurements revealed anisotropic inter-PeQD distances in multiple layers. Photoluminescence (PL) analysis showed lower energy emission in the in-plane direction due to the electronic coupling in the out-of-plane direction, supporting the anisotropic electronic state in the PeQD multilayers. Temperature-dependent PL and PL lifetimes indicated changes in exciton behaviour due to the delocalized electronic state in PeQD multilayers. Particularly, the electron-phonon coupling strength increased, and the exciton recombination rate decreased. This is the first study demonstrating controlled electronic coupling in a three-dimensional ordered structure, emphasizing the importance of the anisotropic electronic state for high-performance PeQDs devices.

Co-exposure to parabens, bisphenol A, and triclosan and the associations with dyslipidemia in Chinese older adults: the mediation effect of oxidative stress.

Dyslipidemia is a prevalent metabolic disorder in older adults and has negative effects on cardiovascular health. However, the combined effect of paraben, bisphenol A (BPA), and triclosan (TCS) exposure on dyslipidemia and the underlying mechanisms remain unclear. This cross-sectional study recruited 486 individuals ≥60 years in Shenzhen, China. Morning spot urine samples were collected and analyzed for four parabens, BPA, TCS, and 8-hydroxy-2'-deoxyguanosine (8-OHdG), a typical biomarker for oxidative stress, using mass spectrometry. Blood samples were tested for lipid levels using an automated biochemical analyzer. Quantile-based g-computation (QGC) was used to assess the combined effects of exposures on dyslipidemia. Mediation analysis was applied to investigate the mediating role of 8-OHdG between exposure and dyslipidemia. QGC showed that co-exposure to parabens, BPA, and TCS was positively linked with hypercholesterolemia (OR: 1.17, 95%CI: 1.10-1.24, P<0.001) and hyper-LDL-cholesterolemia (OR: 1.35, 95%CI: 1.05-1.75, P=0.019). Methylparaben (MeP), n-propyl paraben (PrP), and butylparaben (BtP) were the major contributors. 8-OHdG mediated 6.5% and 13.0% of the overall effect of the examined chemicals on hypercholesterolemia and hyper-LDL-cholesterolemia, respectively (all P<0.05). Our study indicated that co-exposure to parabens, BPA, and TCS is associated with dyslipidemia and oxidative stress partially mediate the association. Future research is needed to explore additional mechanisms underlying these relationships.

Deciphering the Decomposition Mechanisms of Ether and Fluorinated Ether Electrolytes on Lithium Metal Surfaces: Insights from CMD and AIMD Simulations.

The performance of lithium metal batteries can be significantly enhanced by incorporating fluorinated ether-based electrolytes, yet the solid electrolyte interphase (SEI) formation mechanism on lithium metal surfaces remains elusive. This study employs classical and ab initio molecular dynamics simulations to investigate the decomposition mechanisms of lithium bis(fluoromethanesulfonyl)imide (LiFSI) in 1,2-diethoxyethane (DEE) and its fluorinated analogues, F5DEE and F2DEE, when in contact with lithium metal. Our findings indicate that F5DEE-based electrolytes favor the formation of a FSI-rich primary solvation shell around Li+, while F2DEE-based electrolytes yield a solvent-rich environment. The normalized number density at the Li/electrolyte/Li interface shows a depletion of FSI anions in the electrochemical double layer (EDL) structure near the Li anode upon charging, with the distance between the first main peak of the FSI anion and Li anode following the order F5DEE < DEE < F2DEE. Analysis of the electronic projected density of states and charge transfer dynamics unveils the reductive dissociation pathways of FSI anions and fluorinated DEE solvents on the lithium metal surface, taking into account the influence of the EDL structure. DEE is identified as the most reduction-stable solvent, leading to the selective dissociation of FSI anions and the formation of an entirely inorganic SEI. In contrast, F2DEE displays a pronounced reduction tendency, forming an organic-rich SEI due to the solvent-dominated lowest unoccupied molecular orbital at the interface. F5DEE, competing with FSI anions for reduction, results in the formation of an inorganic-rich hybrid SEI with the highest LiF content. The simulation results correlate well with experimental observations and underscore the pivotal role of various fluorinated functional groups in the formation of EDL and SEI near the lithium metal surface.

Kasai Portoenterostomy, Successful Liver Transplantation, and Immunosuppressive Therapy for Biliary Atresia in a Female Baby: A Case Report.

Background: Biliary atresia (BA) is a severe neonatal progressive cholangiopathy of unknown etiology. A timely Kasai portoenterostomy (KPE) improves survival of the native liver in patients with BA, although liver transplantation remains the ultimate treatment for most (60%-80%) patients. However, postoperative adverse effects of liver transplantation may be significant. In addition, patients require lifelong immunosuppressive therapy after liver transplantation. Case Summary: Here, we report a case of a newborn female baby (birthday: 10-03-2018) with congenital BA (confirmed at 76 days of life) who survived KPE (first surgery at 85 days of life) and underwent successful living-related liver transplantation (LRLT) (second surgery at 194 days of life). Additionally, we reviewed the existing literature on BA. After KPE (at 85 days of life), the liver function of the baby did not improve, and the indicators of liver and kidney function showed a trend of aggravation, indicating that the liver function had been seriously damaged before KPE (at 85 days of life), demonstrating the urgent need for liver transplantation surgery. The female baby survived after part of her father's liver was successfully transplanted into her body (at 194 days of life). The patient recovered successfully. No other diseases were found at the 4-year follow-up, and all indices of liver and kidney functions tended to be normal. Conclusion: This case highlights the following. Postoperative alkaline phosphatase was consistently above the normal range, although the reason for this was unclear; neither tacrolimus nor cyclosporine A has formulations designed specifically for infants, which does not meet the needs of clinical individualized medication, suggesting that these anti-rejection drugs are future development directions. Only one case of congenital BA has been found thus far in Hefei, and this case has extremely important reference significance for the prevention, treatment, and diagnosis of BA in Hefei, Anhui province.