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There have been reports of potential health risks for people from hydrophobic organic pollutants, such as polycyclic aromatic hydrocarbons (PAHs), polychlorinated hydrocarbons (PCHs), and organophosphate flame retardants (OPFRs). When a contaminated site is used for residential housing or public utility and recreation areas, the soil-bound organic pollutants might pose a threat to human health. In this study, we investigated the contamination profiles and potential risks to human health of 15 PAHs, 6 PCHs, and 12 OPFRs in soils from four contaminated sites in China. We used an in vitro method to determine the oral bioaccessibility of soil pollutants. Total PAHs were found at concentrations ranging from 26.4 ng/g to 987 ng/g. PCHs (0.27â14.3 ng/g) and OPFRs (6.30â310 ng/g) were detected, but at low levels compared to earlier reports. The levels of PAHs, PCHs, and OPFRs released from contaminated soils into simulated gastrointestinal fluids ranged from 1.74% to 91.0%, 2.51% to 39.6%, and 1.37% to 96.9%, respectively. Based on both spiked and unspiked samples, we found that the oral bioaccessibility of pollutants was correlated with their logKow and molecular weight, and the total organic carbon content and pH of soils. PAHs in 13 out of 38 contaminated soil samples posed potential high risks to children. When considering oral bioaccessibility, nine soils still posed potential risks, while the risks in the remaining soils became negligible. The contribution of this paper is that it corrects the health risk of soil-bound organic pollutants by detecting bioaccessibility in actual soils from different contaminated sites.
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Monitoreo del Ambiente , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Suelo , Contaminantes del Suelo/análisis , China , Medición de Riesgo , Hidrocarburos Policíclicos Aromáticos/análisis , Humanos , Suelo/química , Interacciones Hidrofóbicas e Hidrofílicas , Retardadores de Llama/análisis , Hidrocarburos Clorados/análisisRESUMEN
Emphysema, the progressive destruction of gas exchange surfaces in the lungs, is a hallmark of chronic obstructive pulmonary disease (COPD) that is presently incurable. This therapeutic gap is largely due to a poor understanding of potential drivers of impaired tissue regeneration, such as abnormal lung epithelial progenitor cells, including alveolar type II (ATII) and airway club cells. We discovered an emphysema-specific sub-population of ATII cells located in enlarged distal alveolar sacs, termed asATII cells. Single cell RNA-seq and in situ localisation revealed that asATII cells co-express the alveolar marker surfactant protein C (SPC) and the club cell marker secretaglobin-3A2 (SCGB3A2). A similar ATII sub-population derived from club cells was also identified in mouse COPD models using lineage labeling. Human and mouse ATII sub-populations formed 80-90% fewer alveolar organoids than healthy controls, indicating reduced progenitor function. Targeting asATII cells or their progenitor club cells could reveal novel COPD treatment strategies.
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Probiotics regulate intestinal flora balance and enhance the intestinal barrier, which is useful in preventing and treating colitis. However, they have strict storage requirements. In addition, they degrade in a strongly acidic environment, resulting in a significant decrease in their activity when used as microbial agents. Lactobacillus rhamnosus GG (LGG) was loaded into acid-resistant and colon-targeting double-layer microgels. The inner layer consists of guar gum (GG) and low methoxyl pectin (LMP), which can achieve retention and degradation in the colon. To achieve colon localization, the outer layer was composed of chitosan (CS) and sodium alginate (SA). The formulation demonstrated favorable bio-responses across various pH conditions in vitro and sustained release of LGG in the colon lesions. Bare LGG survival decreased by 52.2â¯% in simulated gastric juice (pHâ¯1.2) for 2â¯h, whereas that of encapsulated LGG decreased by 18.5â¯%. In the DSS-induced inflammatory model, LGG-loaded microgel significantly alleviated UC symptoms in mice and reduced inflammatory factor levels in the colon. Encapsulation of LGG improved its stability in acidic conditions, thus increasing its content at the colon lesions and reducing pathogenic bacteria. These findings provide an experimental basis and a technical reference for developing and applying probiotic microgel preparations.
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INTRODUCTION: Heterosis has revolutionized crop breeding, enhancing global agricultural production. However, the mechanisms underlying heterosis remain obscure. Xiangzamian 2# (XZM2), a super hybrid upland cotton (Gossypium hirsutum L.) characterized by high-yield heterosis, has been developed and extensively planted in China. OBJECTIVES: We conducted a systematic analysis of CRI12 and J8891, two parents of XZM2. We aimed to reveal the precise genetic information and the role of non-syntenic divergence in shaping heterosis, laying a foundation for advancing understanding of heterosis. METHODS: We de novo assembled high-quality genomes of CRI12 and J8891, and further uncovered abundant genetic variations and non-syntenic regions between the parents. Whole-genome comparison, association analysis, transcriptomic analysis and relative identity-by-descent (rIBD) estimation were conducted to identify structural variations (SVs) and introgressions within non-syntenic blocks and to analyze their impacts on promoting heterosis. RESULTS: Parental genetic divergence increased in non-syntenic regions. Furthermore, these regions, accounting for only 16.71% of the total genome, contained more loci with significantly higher heterotic effects, far exceeding the syntenic background. SVs covered 97.26% of non-syntenic sequences and caused widespread gene expression differences in these regions, driving dynamic complementation of gene expression in the hybrid. A set of SVs were responsible for trait improvement and had positive effects on heterosis, contributing larger heritability than short variations. We characterized numerous parental-specific introgressions from G. barbadense. Specifically, a functional introgression segment within non-syntenic blocks introduced an elite haplotype, which significantly increased lint yield and enhanced heterosis. CONCLUSION: Our study clarified non-syntenic regions to harbor more loci with higher heterotic effects, revealed their importance in promoting heterosis and supported the crucial role of genetic complementation in heterosis. SVs and introgressions were identified as key factors responsible for non-syntenic divergence between the parents. They had important effects on gene expression and trait improvement, positively contributing to heterosis.
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Objectives: To investigate the prevalence of Mycobacterium abscessus complex (MABC), drug resistance characteristics, and the relationship between clarithromycin (CLA) susceptibility and MABC genotype in Chongqing, China. Methods: A total of 434 NTM patient isolates were collected between October 2018 and October 2019. Isolates confirmed to be non-tuberculous mycobacteria (NTM) were tested for minimal inhibitory concentrations of antimicrobial agents. In addition, rrl and erm(41) gene sequences were used to analyze the acquired macrolide resistance and inducible macrolide resistance. Results: Overall, 17 different NTM species were detected, of which M. abscessus (22.6 %, 91/403) was most prevalent. Amikacin, CLA, azithromycin and cefoxitin exhibited potent activities against MABC organisms, but no significant differences were observed in drug resistance rates between M. abscessus and M. massiliense (P > 0.05). On day 3 of culture, the acquired resistance rate against CLA was 7.4 % (9/121). Of 41 MABC isolates with inducible CLA resistant, 95.1 % (39/41) isolates belonged to the erm(41) T28 sequevar, while the remaining 4.9 % (2/41) possessed the M. massiliense genotype. All erm(41) C28 sequevar isolates were sensitive to CLA on day3 and day 14 of culture. Meanwhile, of the 5 erm(41) T28 isolates with acquired resistance, all possessed rrl 2058/2059 mutations, including 3 isolates with A2058C mutation and 2 isolates with A2059G mutation. While 2 of the 4 M. massiliense isolates with acquired resistance possessed the A2059G mutation, and one isolate possessed the A2058G mutation. Conclusion: Erm(41) and rrl gene could serve as useful markers for predicting macrolide susceptibility of MABC complex isolates.
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This study investigated the effects of canagliflozin on myocardial dysfunction after cardiac arrest and cardiopulmonary resuscitation in diabetic rats and the underlying mechanisms. Male rats with type 2 diabetes mellitus (T2DM) were subjected to a modified epicardial fibrillation model. Pretreatment with canagliflozin (10 mg/kg/day) for four weeks improved ATP levels, post-resuscitation ejection fraction, acidosis, and hemodynamics. Canagliflozin also reduced myocardial edema, mitochondrial damage and, post-resuscitation autophagy levels. In vitro analyses showed that canagliflozin significantly reduced reactive oxygen species and preserved mitochondrial membrane potential. Using the PI3K/Akt pathway inhibitor Ly294002, canagliflozin was shown to attenuate hyperautophagy and cardiac injury induced by high glucose and hypoxia-reoxygenation through activation of the PI3K/Akt/mTOR pathway. This study highlights the therapeutic potential of canagliflozin in post-resuscitation myocardial dysfunction in diabetes, providing new insights for clinical treatment and experimental research.
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The methylation of N6-methyladenosine (m6A) involves writers, erasers, and readers, acting synergistically in posttranscriptional regulation. These processes influence various biological processes, including plant floral transition. However, the specific role of m6A modifications in photoperiod sensitivity in cotton (Gossypium hirsutum) remains obscure. To elucidate this, in this study, we conducted transcriptome-wide m6A sequencing during critical flowering transition stages in the photoperiod-sensitive wild G. hirsutum var. yucatanense (yucatanense) and the photoperiod-insensitive cultivated cotton G. hirsutum acc. TM-1 (TM-1). Our results revealed significant variations in m6A methylation of 2 cotton varieties, with yucatanense exhibiting elevated m6A modification levels compared with TM-1 under long-day conditions. Notably, distinct m6A peaks between TM-1 and yucatanense correlated significantly with photoperiod sensitivity. Moreover, our study highlighted the role of the demethylase G. hirsutum ALKB homolog 5 (GhALKBH5) in modulating m6A modification levels. Silencing GhALKBH5 led to a decreased mRNA level of key photoperiodic flowering genes (GhADO3, GhAGL24, and GhFT1), resulting in delayed bud emergence and flowering. Reverse transcription quantitative PCR analyses confirmed that silencing GhADO3 and GhAGL24 significantly downregulated the expression of the floral integrator GhFT1. Collectively, our findings unveiled a transcriptional regulatory mechanism in which GhALKBH5-mediated m6A demethylation of crucial photoperiodic flowering transcripts modulated photoperiod sensitivity in cotton.
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Recently, it has been discovered surprisingly that tRNA can be cleaved into specific small fragments under certain conditions. Most importantly, these tRNA-derived fragments (tRFs) participate in the regulation of gene expression, playing pivotal roles in various physiological and pathological processes and thus attracting widespread attention. Detecting tRF expression in tissues and cells often involves using tRF-specific stem-loop primers for reverse transcription. However, the high specificity offered by this method limits it to transcribing only one specific tRF sequence per reaction, necessitating separate reverse transcription and qPCR steps for multiple tRFs, leading to substantially increased time and resource consumption. This becomes especially challenging in precious samples with limited RNA availability. To address these issues, there is an urgent need for a universal and cost-effective tRF identification method. This study introduces a versatile tRF detection approach based on the uniform polyadenylation of all tRFs, allowing reverse transcription with a universal oligo(dT) primer. This method enables simultaneous reverse transcription of all target tRFs in one reaction, greatly facilitating subsequent qPCR analysis. Furthermore, it demonstrates exceptional sensitivity and specificity, offering significant value in tRF-related research.
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Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) is a crop of significant interest due to its nutritional value and resilience to drought conditions. However, drought, particularly following flowering, is a major factor contributing to yield reduction. This research employed two distinct Tartary buckwheat genotypes to investigate the effects of post-anthesis drought on growth and physicochemical characteristics. The study aimed to elucidate the response of Tartary buckwheat to drought stress. The findings indicated that post-anthesis drought adversely impacted the growth, morphology, and biomass accumulation of Tartary buckwheat. Drought stress enhanced the maximum photosynthetic capacity (Fv/Fm) and light protection ability (NPQ) of the 'Xiqiao-2' genotype. In response to drought stress, 'Dingku-1' and 'Xiqiao-2' maintained osmotic balance by accumulating soluble sugars and proline, respectively. Notably, 'Xiqiao-2' exhibited elevated levels of flavonoids and polyphenols in its leaves, which helped mitigate oxidative damage caused by drought. Furthermore, rewatering after a brief drought period significantly improved plant height, stem diameter, and biomass accumulation in 'Dingku-1'. Overall, 'Xiqiao-2' demonstrated greater long-term tolerance to post-anthesis drought, while 'Dingku-1' was less adversely affected by short-term post-anthesis drought.
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Beer fish is characterized by its distinctive spicy flavor and strong beer aroma. Currently, there is a lack of comprehensive research analyzing the changes in taste and volatile compounds that occur during the processing of beer fish. Thus, this study used HS-GC-IMS, electronic tongue, and electronic nose to investigate the changes in flavor components during various processing stages of beer fish. The obtained results were subsequently analyzed using multivariate statistical analysis. The results showed that the final beer fish product (SF) had the greatest amount of free amino acids (888.28 mg/100 g), with alanine, glutamic acid, and glycine contributing to the taste of SF. The inosine monophosphate (IMP) content of beer fish meat varied noticeably depending on processing stages, with deep-fried fish (FF) having the greatest IMP content (61.93 mg/100 g), followed by the final product (SF) and ultrasonic-cured fish (UF). A total of 67 volatiles were detected by GC-IMS, mainly consisting of aldehydes, ketones, and alcohols, of which aldehydes accounted for >37%, which had a great influence on the volatile flavor of beer fish. The flavor components' composition varied noticeably depending on the stage of processing. PLS-DA model screened 35 volatile flavor components (VIP > 1) as markers; the most significant differences were 1-propanethiol, isoamyl alcohol, ethanol, and eucalyptol. Ultrasonic processing, frying, and soaking sauce can significantly improve the formation of flavor compounds, resulting in a notable enhancement of the final beer fish's umami taste and overall flavor quality.
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Although cancer is an age-related disease, how the processes of aging contribute to cancer progression is not well understood. In this study, we uncovered how mouse B cell lymphoma develops as a consequence of a naturally aged system. We show here that this malignancy is associated with an age-associated clonal B cell (ACBC) population that likely originates from age-associated B cells. Driven by c-Myc activation, promoter hypermethylation and somatic mutations, IgM+ ACBCs clonally expand independently of germinal centers and show increased biological age. ACBCs become self-sufficient and support malignancy when transferred into young recipients. Inhibition of mTOR or c-Myc in old mice attenuates pre-malignant changes in B cells during aging. Although the etiology of mouse and human B cell lymphomas is considered distinct, epigenetic changes in transformed mouse B cells are enriched for changes observed in human B cell lymphomas. Together, our findings characterize the spontaneous progression of cancer during aging through both cell-intrinsic and microenvironmental changes and suggest interventions for its prevention.
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Central lymph node (CLN) status is considered to be an important risk factor in patients with papillary thyroid carcinoma (PTC). The aim of the present study was to identify risk factors associated with CLN metastasis (CLNM) for patients with PTC based on preoperative clinical, ultrasound (US) and contrast-enhanced computed tomography (CT) characteristics, and establish a prediction model for treatment plans. A total of 786 patients with a confirmed pathological diagnosis of PTC between January 2021 to December 2022 were included in the present retrospective study, with 550 patients included in the training group and 236 patients enrolled in the validation group (ratio of 7:3). Based on the preoperative clinical, US and contrast-enhanced CT features, univariate and multivariate logistic regression analyses were used to determine the independent predictive factors of CLNM, and a personalized nomogram was constructed. Calibration curve, receiver operating characteristic (ROC) curve and decision curve analyses were used to assess discrimination, calibration and clinical application of the prediction model. As a result, 38.9% (306/786) of patients with PTC and CLNM(-) status before surgery had confirmed CLNM using postoperative pathology. In multivariate analysis, a young age (≤45 years), the male sex, no presence of Hashimoto thyroiditis, isthmic location, microcalcification, inhomogeneous enhancement and capsule invasion were independent predictors of CLNM in patients with PTC. The nomogram integrating these 7 factors exhibited strong discrimination in both the training group [Area under the curve (AUC)=0.826] and the validation group (AUC=0.818). Furthermore, the area under the ROC curve for predicting CLNM based on clinical, US and contrast-enhanced CT features was higher than that without contrast-enhanced CT features (AUC=0.818 and AUC=0.712, respectively). In addition, the calibration curve was appropriately fitted and decision curve analysis confirmed the clinical utility of the nomogram. In conclusion, the present study developed a novel nomogram for preoperative prediction of CLNM, which could provide a basis for prophylactic central lymph node dissection in patients with PTC.
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AIMS: To investigate the effects and mechanisms of LCZ696, an angiotensin receptor-neprilysin inhibitor (ARNI), on epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells and on macrophage M2 polarization. METHODS: We examined the effects of LCZ696 in a 4.25% high glucose peritoneal dialysis fluid (PDF)-induced peritoneal fibrosis (PF) mouse model, and explored the mechanisms of LCZ696 on human peritoneal mesothelial cells (HPMCs) stimulated by TGF-ß1 (5 ng/mL) and on Raw264.7 cells stimulated by IL-4 (10 ng/mL). To further elucidate the mechanism, we treated HPMCs with the conditioned medium of Raw264.7 cells. RESULTS: LCZ696 effectively improved PF and inhibited the process of EMT in PDF mice. In vitro, LCZ696 also significantly alleviated the EMT of TGF-ß1 induced HPMCs, although there was no statistically significant difference when compared to the Valsartan treatment group. Moreover, LCZ696 ameliorates the increased expression of Snail and Slug, two nuclear transcription factors that drive the EMT. Mechanistically, TGF-ß1 increased the expression of TGFßRI, p-Smad3, p-PDGFRß and p-EGFR, while treatment with LCZ696 abrogated the activation of TGF-ß/Smad3, PDGFRß and EGFR signaling pathways. Additionally, exposure of Raw264.7 to IL-4 results in increasing expression of Arginase-1, CD163 and p-STAT6. Treatment with LCZ696 inhibited IL-4-elicited M2 macrophage polarization by inactivating the STAT6 signaling pathway. Furthermore, we observed that LCZ696 inhibits EMT by blocking TGF-ß1 secretion from M2 macrophages. CONCLUSION: Our study demonstrated that LCZ696 improves PF and ameliorates TGF-ß1-induced EMT of HPMCs by blocking TGF-ß/Smad3, PDGFRß and EGFR pathways. Meanwhile, LCZ696 also inhibits M2 macrophage polarization by regulating STAT6 pathway.
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Antagonistas de Receptores de Angiotensina , Compuestos de Bifenilo , Transición Epitelial-Mesenquimal , Macrófagos , Fibrosis Peritoneal , Tetrazoles , Valsartán , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ratones , Animales , Valsartán/farmacología , Compuestos de Bifenilo/farmacología , Antagonistas de Receptores de Angiotensina/farmacología , Fibrosis Peritoneal/metabolismo , Fibrosis Peritoneal/patología , Fibrosis Peritoneal/prevención & control , Humanos , Tetrazoles/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Aminobutiratos/farmacología , Células RAW 264.7 , Modelos Animales de Enfermedad , Combinación de Medicamentos , Neprilisina/antagonistas & inhibidores , Neprilisina/metabolismo , Masculino , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Transcripción STAT6/metabolismo , Peritoneo/patología , Peritoneo/citología , Peritoneo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos C57BLRESUMEN
Radiotherapy (RT) serves as the primary treatment for solid tumors. Its potential to incite an immune response against tumors both locally and distally profoundly impacts clinical outcomes. However, RT may also promote the accumulation of immunosuppressive cytokines and immunosuppressive cells, greatly impeding the activation of antitumor immune responses and substantially limiting the effectiveness of RT. Therefore, regulating post-RT immunosuppression to steer the immune milieu toward heightened activation potentially enhances RT's therapeutic potential. Cytokines, potent orchestrators of diverse cellular responses, play a pivotal role in regulating this immunosuppressive response. Identifying and promptly neutralizing early released immunosuppressive cytokines are a crucial development in augmenting RT's immunomodulatory effects. To this end, we conducted a screen of immunosuppressive cytokines following RT and identified macrophage colony-stimulating factor (MCSF) as an early up-regulated and persistent immune suppressor. Single-cell sequencing revealed that the main source of up-regulated MCSF derived from tumor cells. Mechanistic exploration revealed that irradiation-dependent phosphorylation of the p65 protein facilitated its binding to the MCSF gene promoter, enhancing transcription. Knockdown and chemical inhibitor experiments conclusively demonstrated that suppressing tumor cell-derived MCSF amplifies RT's immune-activating effects, with optimal results achieved by early MCSF blockade after irradiation. Additionally, we validated that MCSF acted on macrophages, inducing the secretion of a large number of inhibitory cytokines. In summary, we propose a novel approach to enhance the immune activation effects of RT by blocking the MCSF-CSF1R signaling pathway early after irradiation.
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Purpose: Although the application of heterosis has significantly increased crop yield over the past century, the mechanisms underlying this phenomenon still remain obscure. Here, we applied transcriptome sequencing to unravel the impacts of parental expression differences and transcriptomic reprogramming in cotton heterosis. Methods: A high-quality transcriptomic atlas covering 15 developmental stages and tissues was constructed for XZM2, an elite hybrid of upland cotton (Gossypium hirsutum L.), and its parental lines, CRI12 and J8891. This atlas allowed us to identify gene expression differences between the parents and to characterize the transcriptomic reprogramming that occurs in the hybrid. Results: Our analysis revealed abundant gene expression differences between the parents, with pronounced tissue specificity; a total of 1,112 genes exhibited single-parent expression in at least one tissue. It also illuminated transcriptomic reprogramming in the hybrid XZM2, which included both additive and non-additive expression patterns. Coexpression networks between parents and hybrid constructed via weighted gene coexpression network analysis identified modules closely associated with fiber development. In particular, key regulatory hub genes involved in fiber development showed high-parent dominant or over dominant patterns in the hybrid, potentially driving the emergence of heterosis. Finally, high-depth resequencing data was generated and allele-specific expression patterns examined in the hybrid, enabling the dissection of cis- and trans-regulation contributions to the observed expression differences. Conclusion: Parental transcriptional differences and transcriptomic reprogramming in the hybrid, especially the non-additive upregulation of key genes, play an important role in shaping heterosis. Collectively, these findings provide new insights into the molecular basis of heterosis in cotton.
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Identifying the aging time of Liupao Tea (LPT) presents a persistent challenge. We utilized an AI-Multimodal fusion method combining FTIR, E-nose, and E-tongue to discern LPT's aging years. Compared to single-source and two-source fusion methods, the three-source fusion significantly enhanced identifying accuracy across all four machine learning algorithms (Decision tree, Random forest, K-nearest neighbor, and Partial least squares Discriminant Analysis), achieving optimal accuracy of 98-100 %. Physicochemical analysis revealed monotonic variations in tea polysaccharide (TPS) conjugates with aging, observed through SEM imaging as a transition from lamellar to granular TPS conjugate structures. These quality changes were reflected in FTIR spectral characteristics. Two-dimensional correlation spectroscopy (2D-COS) identified sensitive wavelength regions of FTIR from LPT and TPS conjugates, indicating a high similarity in spectral changes between TPS conjugates and LPT with aging years, highlighting the significant role of TPS conjugates variation in LPT quality. Additionally, we established an index for evaluating quality of aging, which is sum of three fingerprint peaks (1029 cm-1, 1635 cm-1, 2920 cm-1) intensities. The index could effectively signify the changes in aging years on macro-scale (R2 = 0.94) and micro-scale (R2 = 0.88). These findings demonstrate FTIR's effectiveness in identifying aging time, providing robust evidence for quality assessment.
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Rapid capacity fading, interfacial instability, and thermal runaway due to oxygen loss are critical obstacles hindering the practical application and commercialization of Ni-rich cathodes (LiNi0.8Co0.1Mn0.1O2, NCM811). Herein, a Sn4+/F- codoping and LiF-coated Ni-rich cathode, denoted as NCM811-SF, is structurally fabricated that demonstrates very high cyclic and thermal stabilities. The introduction of Sn4+ regulates the local electronic structure and facilitates the conversion of the layered structure into a spinel phase; F- captures lithium impurities to form LiF coatings and forms TM-F bonds to reduce Ni/Li disordering. The compositionally complex codoping strategy reduces the internal structure strain, inhibits the Li+/Ni2+ intermixing during cycling and degradation of the nanoscale structure, and further improves the thermal stability and the crystal structure. The cathodic electrode showed a little volume shift at 2.8-4.5 V, which significantly decreased lattice flaws and fractures generated by local strain, based on detailed analyses performed using COMSOL simulations, X-ray diffraction, and scanning transmission electron microscopy. Benefiting from this, after 300 cycles, our as-prepared NCM811-SF cathode maintains 85.4% of its initial capacity at 4.5 V and has an excellent reversible capacity equal to 169 mAh·g-1 at 1 C. In addition, the NCM811-SF/graphite cell in a pouch-type complete cell retained 94.8% of its starting capacity following 500 cycles. These findings underscore the effectiveness of introducing the Sn-O and TM-F bonds in improving the durability and electrochemical efficiency of the cathode material, which makes it a good choice for high-efficiency Li-ion batteries.
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BACKGROUND: Benign childhood epilepsy with centrotemporal spikes (BECTS), a common pediatric epilepsy, may lead to cognitive decline when compounded by Electrical Status Epilepticus during Sleep (ESES). Emerging evidence suggests that disruptions in the Salience Network (SN) contribute significantly to the cognitive deficits observed in BECTS-ESES. Our study rigorously investigates the dynamic functional connectivity (dFC) within the SN and its correlation with cognitive impairments in BECTS-ESES, employing advanced neuroimaging and neuropsychological assessments. METHODS: In this research, 45 patients diagnosed with BECTS-ESES and 55 age-matched healthy controls (HCs) participated. We utilized resting-state functional magnetic resonance imaging (fMRI) and Independent Component Analysis (ICA) to identify three fundamental SN nodes: the right Anterior Insula (rAI), left Anterior Insula (lAI), and the Anterior Cingulate Cortex (ACC). A two-sample t-test facilitated the comparison of dFC between these pivotal regions and other brain areas. RESULTS: Significantly, the BECTS-ESES group demonstrated increased dFC, particularly between the ACC and the right Middle Occipital Gyrus, and from the rAI to the right Superior Parietal Gyrus and Cerebellum, and from the lAI to the left Postcentral Gyrus. Such dFC augmentations provide neural insights potentially explaining the neuropsychological deficits in BECTS-ESES children. Employing comprehensive neuropsychological evaluations, we mapped these dFC disruptions to specific cognitive impairments encompassing memory, executive functioning, language, and attention. Through multiple regression analysis and path analysis, a preliminary but compelling association was discovered linking dFC disturbances directly to cognitive impairments. These findings underscore the critical role of SN disruptions in BECTS-ESES cognitive dysfunctions. LIMITATION: Our cross-sectional design and analytic methods preclude definitive mediation models and causal inferences, leaving the precise nature of dFC's mediating role and its direct impact by BECTS-ESES partially unresolved. Future longitudinal and confirmatory studies are needed to comprehensively delineate these associations. CONCLUSION: Our study heralds dFC within the SN as a vital biomarker for cognitive impairment in pediatric epilepsy, advocating for targeted cognitive-specific interventions in managing BECTS-ESES. The preliminary nature of our findings invites further studies to substantiate these associations, offering profound implications for the prognosis and therapeutic strategies in BECTS-ESES, thereby underlining the importance of this research in the field of pediatric neurology and epilepsy management.
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Previous studies have highlighted the toxicity of pharmaceuticals and personal care products (PPCPs) in plants, yet understanding their spatial distribution within plant tissues and specific toxic effects remains limited. This study investigates the spatial-specific toxic effects of carbamazepine (CBZ), a prevalent PPCP, in plants. Utilizing desorption electrospray ionization mass spectrometry imaging (DESI-MSI), CBZ and its transformation products were observed predominantly at the leaf edges, with 2.3-fold higher concentrations than inner regions, which was confirmed by LC-MS. Transcriptomic and metabolic analyses revealed significant differences in gene expression and metabolite levels between the inner and outer leaf regions, emphasizing the spatial location's role in CBZ response. Notably, photosynthesis-related genes were markedly downregulated, and photosynthetic efficiency was reduced at leaf edges. Additionally, elevated oxidative stress at leaf edges was indicated by higher antioxidant enzyme activity, cell membrane impairment, and increased free fatty acids. Given the increased oxidative stress at the leaf margins, the study suggests using in situ Raman spectroscopy for early detection of CBZ-induced damage by monitoring reactive oxygen species levels. These findings provide crucial insights into the spatial toxicological mechanisms of CBZ in plants, forming a basis for future spatial toxicology research of PPCPs.
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Carbamazepina , Carbamazepina/toxicidad , Hojas de la Planta/efectos de los fármacos , Estrés Oxidativo , MultiómicaRESUMEN
The development of new antibiotics continues to pose challenges, particularly considering the growing threat of multidrug-resistant Staphylococcus aureus. Structurally diverse natural products provide a promising source of antibiotics. Herein, we outline a concise approach for the collective asymmetric total synthesis of polycyclic xanthene myrtucommulone D and five related congeners. The strategy involves rapid assembly of the challenging benzopyrano[2,3-a]xanthene core, highly diastereoselective establishment of three contiguous stereocenters through a retro-hemiketalization/double Michael cascade reaction, and a Mitsunobu-mediated chiral resolution approach with high optical purity and broad substrate scope. Quantum mechanical calculations provide insight into stereoselective construction mechanism of the three contiguous stereocenters. Additionally, this work leads to the discovery of an antibacterial agent against both drug-sensitive and drug-resistant S. aureus. This compound operates through a unique mechanism that promotes bacterial autolysis by activating the two-component sensory histidine kinase WalK. Our research holds potential for future antibacterial drug development.