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This paper introduces CentIER, the first bioinformatic tool designed to detect complete centromeric regions without additional wet experiments. The accuracy of CentIER was validated on diverse plant genomes such as Arabidopsis, rice, maize and mulberry, and the results show that CentIER can perform significantly more complete and accurate detection than the existing tool.
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As the direct microenvironment of assisted reproductive technology, the evaluation of culture medium for human assisted reproduction technology is particularly important. This paper discussed the classification management, technical review points, clinical evaluation and review thinking, focusing on the basic requirements, raw material control, biological evaluation, sterilization process of culture medium for human assisted reproduction technology, combined with some material limit, new added material and quality system control to thoroughly assess management risk of the whole life cycle of culture medium for human assisted reproduction technology.
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Meios de Cultura , Técnicas de Reprodução Assistida , Humanos , Controle de Qualidade , EsterilizaçãoRESUMO
Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs). However, the role of platelets in epithelial-mesenchymal transition (EMT) of cancer cells at the primary tumor site, the crucial initial step of tumor metastasis, remains to be elucidated. Here, we found that platelet releasate enhanced EMT and motility of hepatocellular carcinoma (HCC) cells via AMPK/mTOR-induced autophagy. RNA-seq indicated that platelet releasate altered TGF-ß signaling pathway of cancer cells. Inhibiting TGFBR or deleting platelet TGF-ß1 suppressed AMPK/mTOR pathway activation and autophagy induced by platelet releasate. Compared with Pf4cre-; Tgfb1fl/fl mice, HCC orthotopic models established on Pf4cre+; Tgfb1fl/fl mice showed reduced TGF-ß1 in primary tumors, which corresponded with decreased cancer cell EMT, autophagy, migration ability and tumor metastasis. Inhibition of autophagy via Atg5 knockdown in cancer cells negated EMT and metastasis induced by platelet-released TGF-ß1. Clinically, higher platelet count correlated with increased TGF-ß1, LC3 and N-cad expression in primary tumors of HCC patients, suggesting a link between platelets and HCC progression. Our study indicates that platelets promote cancer cell EMT in the primary tumor and HCC metastasis through TGF-ß1-induced HCC cell autophagy via the AMPK/mTOR pathway. These findings offer novel insights into the role of platelets in HCC metastasis and the potential therapeutic targets for HCC metastasis.
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BACKGROUND: Elevated soluble stimulating factor 2 (sST2) level is observed in cardiovascular diseases, such as heart failure and acute coronary syndrome, which reflects myocardial fibrosis and hypertrophy, indicating adverse clinical outcomes. However, the association between sST2 and hypertensive heart disease are less understood. This study aimed to determine the relationship of sST2 with left ventricular hypertrophy (LVH) and geometric remodeling in essential hypertension (EH). METHODS: We enrolled 483 patients (aged 18-80 years; 51.35% female). sST2 measurements and echocardiographic analyses were performed. RESULTS: Stepwise multiple linear regression analysis showed significant associations between sST2, left ventricular (LV) mass, and LV mass index. The prevalence of LVH and concentric hypertrophy (CH) increased with higher sST2 grade levels (p for trend<0.05). Logistic regression analysis suggested that the highest tertile of sST2 was significantly associated with increased LVH risk, compared with the lowest tertile (multivariate-adjusted odds ratio [OR] of highest group: 6.61; p<0.001). Similar results were observed in the left ventricular geometric remodeling; the highest tertile of sST2 was significantly associated with increased CH risk (multivariate-adjusted OR of highest group: 5.80; p<0.001). The receiver operating characteristic analysis results revealed that sST2 had potential predictive value for LVH (area under the curve [AUC]: 0.752, 95% confidence interval [CI]: 0.704-0.800) and CH (AUC: 0.750, 95% CI: 0.699-0.802) in patients with EH. CONCLUSIONS: High sST2 level is strongly related to LVH and CH in patients with EH and can be used as a biomarker for the diagnosis and risk assessment of hypertensive heart disease.
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BACKGROUND: The volumes of the hippocampal subfields are related to poststroke cognitive dysfunctions. However, it remains unclear whether contralesional hippocampal subfield volume contributes to cognitive impairment. This study aimed to investigate the volumetric differences in the contralesional hippocampal subfields between patients with left and right hemisphere strokes (LHS/RHS). Additionally, correlations between contralesional hippocampal subfield volumes and clinical outcomes were explored. METHODS: Fourteen LHS (13 males, 52.57 ± 7.10 years), 13 RHS (11 males, 51.23 ± 15.23 years), and 18 healthy controls (11 males, 46.94 ± 12.74 years) were enrolled. Contralesional global and regional hippocampal volumes were obtained with T1-weighted images. Correlations between contralesional hippocampal subfield volumes and clinical outcomes, including the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), were analyzed. Bonferroni correction was applied for multiple comparisons. RESULTS: Significant reductions were found in contralesional hippocampal as a whole (adjusted p = .011) and its subfield volumes, including the hippocampal tail (adjusted p = .005), cornu ammonis 1 (CA1) (adjusted p = .002), molecular layer (ML) (adjusted p = .004), granule cell and ML of the dentate gyrus (GC-ML-DG) (adjusted p = .015), CA3 (adjusted p = .009), and CA4 (adjusted p = .014) in the RHS group compared to the LHS group. MoCA and MMSE had positive correlations with volumes of contralesional hippocampal tail (p = .015, r = .771; p = .017, r = .763) and fimbria (p = .020, r = .750; p = .019, r = .753) in the LHS group, and CA3 (p = .007, r = .857; p = .009, r = .838) in the RHS group, respectively. CONCLUSION: Unilateral stroke caused volumetric differences in different hippocampal subfields contralesionally, which correlated to cognitive impairment. RHS leads to greater volumetric reduction in the whole contralesional hippocampus and specific subfields (hippocampal tail, CA1, ML, GC-ML-DG, CA3, and CA4) compared to LHS. These changes are correlated with cognitive impairments, potentially due to disrupted neural pathways and interhemispheric communication.
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Disfunção Cognitiva , Hipocampo , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Hipocampo/patologia , Hipocampo/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Adulto , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/etiologia , Lateralidade Funcional/fisiologia , Cognição/fisiologia , Idoso , Testes de Estado Mental e DemênciaRESUMO
Background: The chronic pain arising from knee osteoarthritis (KOA) is a prevalent clinical manifestation. As a traditional Chinese approach, electroacupuncture (EA) has a positive influence in relieving chronic pain from KOA. The study aims to explore functional connectivity (FC) and effective connectivity (EC) alterations induced by EA in anterior cruciate ligament transection (ACLT) rat model of KOA using resting-state functional magnetic resonance imaging (fMRI). Methods: After the establishment of ACLT, rats were randomly divided into the EA group and the sham-EA group. The EA group received EA intervention while the sham-EA group received sham-intervention for 3 weeks. Mechanical pain threshold (MPT) assessment was performed before and after intervention, and fMRI was conducted after intervention. Results: EA intervention effectively relieved pain in post-ACLT rats. Results of rest-state functional connectivity (rs-FC) analysis revealed that compared with the sham-EA group, the EA group had higher FC between the right raphe and the left auditory cortex, the left caudate_ putamen and the left internal capsule (IC), as well as the right zona incerta (ZI) and the left piriform cortex, but lower FC between the right raphe and the left hippocampus ventral, as well as the right septum and the left septum. Furthermore, Granger causality analysis (GCA) found the altered EC between the right septum and the left septum, as well as the left IC and the right septum. Conclusion: The results confirmed the effect of EA on analgesia in post- ACLT rats. The alterations of FC and EC, mainly involving basal ganglia and limbic system neural connections, might be one of the neural mechanisms underlying the effect of EA, providing novel information about connectomics plasticity of EA following ACLT.
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Diabetic cardiomyopathy(DCM) is a chronic complication of diabetes mellitus that leads to cardiac damage in the later stages of the disease, and its pathogenesis is complex, involving metabolic disorders brought about by a variety of aberrant alterations such as endoplasmic reticulum stress, oxidative stress, inflammation, and apoptosis, defects in cardiomyocyte Ca~(2+) transporter, and myocardial fibrosis. Currently, there is a lack of specific diagnosis and treatment in the clinic. Autophagy is a highly conserved scavenging mechanism that removes proteins, damaged organelles or foreign contaminants and converts them into energy and amino acids to maintain the stability of the intracellular environment. Inhibition of autophagy can cause harmful metabolites to accumulate in the cell, while over-activation of autophagy can disrupt normal cellular structures and cause cell death. Prolonged high glucose levels disrupt cardiomyocyte autophagy levels and exacerbate the development of DCM. The protective or detrimental effects of autophagy on cells ring true with the traditional Chinese medicine theory of healthy Qi and pathogenic Qi. Autophagy in the physiological state of the removal of intracellular substances and the generation of substances beneficial to the survival of cells is the inhibition of pathogenic Qi to help the performance of healthy Qi, so the organism is healthy. In the early stages of the disease, when autophagy is impaired and incapable of removing waste substances, pathogenic Qi is prevalent; In the later stages of the disease, excessive activation of autophagy can destroy normal cells, leading to a weakening of healthy Qi. Traditional Chinese medicine has the advantage of targeting multiple sites and pathways. Studies in recent years have confirmed that traditional Chinese medicine monomers or formulas can target autophagy, promote the restoration of autophagy levels, maintain mitochondrial and endoplasmic reticulum homeostasis, and reduce oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis in order to prevent and control DCM. This study provides a review of the relationship between autophagy and DCM and the intervention of traditional Chinese medicine in autophagy for the treatment of DCM, with a view to providing new clinical ideas and methods for the treatment of DCM with traditional Chinese medicine.
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Autofagia , Cardiomiopatias Diabéticas , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Autofagia/efeitos dos fármacos , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/fisiopatologia , Humanos , Animais , Medicamentos de Ervas Chinesas/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacosRESUMO
To enhance the economic viability of photocatalytic materials for carbon capture and conversion, the challenge of employing expensive photosensitizer must be overcome. This study aims to improve the visible light utilization with zirconium-based metal-organic frameworks (Zr-MOFs) by employing a multi-component post-synthetic modification (PSM) strategy. An economical photosensitiser and copper ions are introduced into MOF 808 to enhance its photoreduction properties. Notably, the PSM of MOF 808 shows the highest CO yield up to 236.5 µmol g-1 h-1 with aHCOOH production of 993.6 µmol g-1 h-1 under non-noble metal, and its mechanistic insight for CO2 reaction is discussed in detail. The research results have important reference value for the potential application of photocatalytic metal-organic frameworks.
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Sepsis is a life-threatening condition arising from a dysregulated host immune response to infection, leading to a substantial global health burden. The accurate identification of bacterial pathogens in sepsis is essential for guiding effective antimicrobial therapy and optimising patient outcomes. Traditional culture-based bacterial typing methods present inherent limitations, necessitating the exploration of alternative diagnostic approaches. This study reports the successful application of Fourier-transform infrared (FT-IR) spectroscopy in combination with chemometrics as a potent tool for the classification and discrimination of microbial species and strains, primarily sourced from individuals with invasive infections. These samples were obtained from various children with suspected sepsis infections with bacteria and fungi originating at different sites. We conducted a comprehensive analysis utilising 212 isolates from 14 distinct genera, comprising 202 bacterial and 10 fungal isolates. With the spectral analysis taking several weeks, we present the incorporation of quality control samples to mitigate potential variations that may arise between different sample plates, especially when dealing with a large sample size. The results demonstrated a remarkable consistency in clustering patterns among 14 genera when subjected to principal component analysis (PCA). Particularly, Candida, a fungal genus, was distinctly recovered away from bacterial samples. Principal component discriminant function analysis (PC-DFA) allowed for distinct discrimination between different bacterial groups, particularly Gram-negative and Gram-positive bacteria. Clear differentiation was also observed between coagulase-negative staphylococci (CNS) and Staphylococcus aureus isolates, while methicillin-resistant S. aureus (MRSA) was also separated from methicillin-susceptible S. aureus (MSSA) isolates. Furthermore, highly accurate discrimination was achieved between Enterococcus and vancomycin-resistant enterococci isolates with 98.4% accuracy using partial least squares-discriminant analysis. The study also demonstrates the specificity of FT-IR, as it effectively discriminates between individual isolates of Streptococcus and Candida at their respective species levels. The findings of this study establish a strong groundwork for the broader implementation of FT-IR and chemometrics in clinical and microbiological applications. The potential of these techniques for enhanced microbial classification holds significant promise in the diagnosis and management of invasive bacterial infections, thereby contributing to improved patient outcomes.
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This study sought to explore potential roles of endothelial ferroptosis in radiation-associated atherosclerosis (RAA) and molecular mechanisms behind this phenomenon. Here, an in vivo RAA mouse model was used and treated with ferroptosis inhibitors. We found that the RAA group had a higher plaque burden and a reduction in endothelial cells with increased lipid peroxidation compared to the control group, while ameliorated by liproxstatin-1. In vitro experiments further confirmed that radiation induced the occurrence of ferroptosis in human artery endothelial cells (HAECs). Then, proteomics analysis of HAECs identified domain-containing protein 2 (DDHD2) as a co-differentially expressed protein, which was enriched in the lipid metabolism pathway. In addition, the level of lipid peroxidation was elevated in DDHD2-knockdown HAECs. Mechanistically, a significant decrease in the protein and mRNA expression of glutathione peroxidase 4 (GPX4) was observed in HAECs following DDHD2 knockdown. Co-immunoprecipitation assays indicated a potential interaction between DDHD2 and nuclear factor erythroid 2-related factor 2 (Nrf2). The downregulation of Nrf2 protein was also detected in DDHD2-knockdown HAECs. In conclusion, our findings suggest that radiation-induced endothelial ferroptosis accelerates atherosclerosis, and DDHD2 is a potential regulatory protein in radiation-induced endothelial ferroptosis through the Nrf2/GPX4 pathway.
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Aterosclerose , Células Endoteliais , Ferroptose , Fator 2 Relacionado a NF-E2 , Fosfolipases , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Animais , Humanos , Masculino , Camundongos , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/etiologia , Aterosclerose/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Peroxidação de Lipídeos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Transdução de Sinais , Fosfolipases/genética , Fosfolipases/metabolismoRESUMO
BACKGROUND: Microglia-mediated inflammation is a critical factor in the progression of ischemic stroke. Consequently, mitigating excessive microglial activation represents a potential therapeutic strategy for ischemic injury. Thymol, a monophenol derived from plant essential oils, exhibits diverse beneficial biological activities, including anti-inflammatory and antioxidant properties, with demonstrated protective effects in various disease models. However, its specific effects on ischemic stroke and microglial inflammation remain unexplored. METHODS: Rodent transient middle cerebral artery occlusion (tMCAO) model was established to simulate ischemic stroke. TTC staining, modified neurological function score (mNSS), and behavioral tests were used to assess the severity of neurological damage. Then immunofluorescence staining and cytoskeleton analysis were used to determine activation of microglia. Lipopolysaccharide (LPS) was utilized to induce the inflammatory response of primary microglia in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to exam the expression of inflammatory cytokines. And western blot was used to investigate the mechanism of the anti-inflammatory effect of thymol. RESULTS: In this study, we found that thymol treatment could ameliorate post-stroke neurological impairment and reduce infarct volume by mitigating microglial activation and pro-inflammatory response (IL-1ß, IL-6, and TNF-α). Mechanically, thymol could inhibit the phosphorylation of phosphatidylinositol-3-kinase (PI3K), sink serine/threonine kinase (Akt), and mammalian target of rapamycin (mTOR), thereby suppressing the activation of nuclear factor-κB (NF-κB). CONCLUSIONS: Our study demonstrated that thymol could reduce the microglial inflammation by targeting PI3K/Akt/mTOR/NF-κB signaling pathway, ultimately alleviating ischemic brain injury. These findings suggest that thymol is a promising candidate as a neuroprotective agent against ischemic stroke.
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Isquemia Encefálica , Microglia , Doenças Neuroinflamatórias , Fármacos Neuroprotetores , Timol , Animais , Timol/farmacologia , Timol/uso terapêutico , Microglia/efeitos dos fármacos , Microglia/metabolismo , Masculino , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Fármacos Neuroprotetores/farmacologia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Ratos , Ratos Sprague-Dawley , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos , Camundongos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Citocinas/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Axillary malodour is caused by the microbial conversion of human-derived precursors to volatile organic compounds. Thiols strongly contribute to this odour but are hard to detect as they are present at low concentrations. Additionally, thiols are highly volatile and small making sampling and quantification difficult, including by gas chromatography-mass spectrometry. In this study, surface-enhanced Raman scattering (SERS), combined with chemometrics, was utilised to simultaneously quantify four malodourous thiols associated with axillary odour, both in individual and multiplex solutions. Univariate and multivariate methods of partial least squares regression (PLS-R) were used to calculate the limit of detection (LoD) and results compared. Both methods yielded comparable LoD values, with LoDs using PLS-R ranging from 0.0227 ppm to 0.0153 ppm for the thiols studied. These thiols were then examined and quantified simultaneously in 120 mixtures using PLS-R. The resultant models showed high linearity (Q2 values between 0.9712 and 0.9827 for both PLS-1 and PLS-2) and low values of root mean squared error of predictions (0.0359 ppm and 0.0459 ppm for PLS-1 and PLS-2, respectively). To test this approach further, these models were challenged with 15 new blind test samples, collected independently from the initial samples. This test demonstrated that SERS combined with PLS-R could be used to predict the unknown concentrations of these thiols in a mixture. These results display the ability of SERS for the simultaneous multiplex detection and quantification of analytes and its potential for future development for detecting gaseous thiols produced from skin and other body sites.
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Odorantes , Análise Espectral Raman , Compostos de Sulfidrila , Análise Espectral Raman/métodos , Compostos de Sulfidrila/análise , Compostos de Sulfidrila/química , Humanos , Odorantes/análise , Limite de Detecção , Análise dos Mínimos Quadrados , AxilaRESUMO
Here, we report a novel ourmia-like mycovirus, named "Phomopsis asparagi magoulivirus 1" (PaMV1), derived from the phytopathogenic fungus Phomopsis asparagi. The genome of PaMV1 consists of a positive-sense single-stranded RNA (+ ssRNA) that is 2,639 nucleotides in length, with a GC content of 57.13%. It contains a single open reading frame (ORF) encoding a putative RNA-dependent RNA polymerase (RdRp) consisting of 686 amino acids with a molecular mass of 78.57 kDa. Phylogenetic analysis based on RdRp sequences revealed that PaMV1 grouped together with Diaporthe gulyae magoulivirus 1 (DgMV1) in a distinct clade. Sequence comparisons and phylogenetic analysis suggest that PaMV1 is a novel member of the genus Magoulivirus, family Botourmiaviridae.
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Micovírus , Genoma Viral , Fases de Leitura Aberta , Phomopsis , Filogenia , RNA Viral , Micovírus/genética , Micovírus/classificação , Micovírus/isolamento & purificação , Phomopsis/virologia , RNA Viral/genética , Sequenciamento Completo do Genoma , RNA Polimerase Dependente de RNA/genética , Composição de Bases , Doenças das Plantas/microbiologia , Doenças das Plantas/virologia , Proteínas Virais/genética , Sequência de Bases , Vírus de RNA/genética , Vírus de RNA/isolamento & purificação , Vírus de RNA/classificaçãoRESUMO
The elucidation of the interaction mechanism between phospholipids and milk proteins within emulsions is pivotal for comprehending the properties of infant formula fat globules. In this study, multispectral methods and molecular docking were employed to explore the relationship between phosphatidylcholine (PC) and whey protein isolate (WPI). Observations indicate that the binding constant, alongside thermodynamic parameters, diminishes as temperature ascends, hinting at a predominantly static quenching mechanism. Predominantly, van der Waals forces and hydrogen bonds constitute the core interactions between WPI and PC. This assertion is further substantiated by Fourier transform infrared spectroscopy, which verifies PC's influence on WPI's secondary structure. A detailed assessment of thermodynamic parameters coupled with molecular docking reveals that PC predominantly adheres to specific sites within α-lactalbumin, ß-lactoglobulin, and bovine serum albumin, propelled by a synergy of hydrophobic interactions, hydrogen bonding, and van der Waals forces, with binding energies noted at -5.59, -6.71, and -7.85 kcal/mol, respectively. An increment in PC concentration is observed to amplify the emulsification properties of WPI whilst concurrently diminishing the zeta potential. This study establishes a theoretical foundation for applying the PC-WPI interaction mechanism in food.
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Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Fosfatidilcolinas , Termodinâmica , Proteínas do Soro do Leite , Proteínas do Soro do Leite/química , Fosfatidilcolinas/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Lactoglobulinas/química , Lactoglobulinas/metabolismo , Emulsões/química , Lactalbumina/química , Lactalbumina/metabolismo , Soroalbumina Bovina/química , Fórmulas Infantis/químicaRESUMO
BACKGROUND: Although white matter hyperintensity (WMH) is closely associated with cognitive decline, the precise neurobiological mechanisms underlying this relationship are not fully elucidated. Connectome studies have identified a primary-to-transmodal gradient in functional brain networks that support the spectrum from sensation to cognition. However, whether connectome gradient structure is altered as WMH progresses and how this alteration is associated with WMH-related cognitive decline remain unknown. METHODS: A total of 758 WMH individuals completed cognitive assessment and resting-state functional MRI (rs-fMRI). The functional connectome gradient was reconstructed based on rs-fMRI by using a gradient decomposition framework. Interrelations among the spatial distribution of WMH, functional gradient measures, and specific cognitive domains were explored. RESULTS: As the WMH volume increased, the executive function (r = -0.135, p = 0.001) and information-processing speed (r = -0.224, p = 0.001) became poorer, the gradient range (r = -0.099, p = 0.006), and variance (r = -0.121, p < 0.001) of the primary-to-transmodal gradient reduced. A narrower gradient range (r = 0.131, p = 0.001) and a smaller gradient variance (r = 0.136, p = 0.001) corresponded to a poorer executive function. In particular, the relationship between the frontal/occipital WMH and executive function was partly mediated by gradient range/variance of the primary-to-transmodal gradient. CONCLUSIONS: These findings indicated that WMH volume, the primary-to-transmodal gradient, and cognition were interrelated. The detrimental effect of the frontal/occipital WMH on executive function was partly mediated by the decreased differentiation of the connectivity pattern between the primary and transmodal areas.
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Disfunção Cognitiva , Conectoma , Imageamento por Ressonância Magnética , Substância Branca , Humanos , Masculino , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/patologia , Feminino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Idoso , Função Executiva/fisiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologiaRESUMO
Microplastics (MPs) have the potential to adsorb heavy metals (HMs), resulting in a combined pollution threat in aquatic and terrestrial environments. However, due to the complexity of MP/HM properties and experimental conditions, research on the adsorption of HMs onto MPs often yields inconsistent findings. To address this issue, we conducted a comprehensive meta-analysis assisted with machine learning by analyzing a dataset comprising 3340 records from 134 references. The results indicated that polyamide (PA) (ES = -1.26) exhibited the highest adsorption capacity for commonly studied HMs (such as Pb, Cd, Cu, and Cr), which can be primarily attributed to the presence of C=O and N-H groups. In contrast, polyvinyl chloride (PVC) demonstrated a lower adsorption capacity, but the strongest adsorption strength resulting from the halogen atom on its surface. In terms of HMs, metal cations were more readily adsorbed by MPs compared with metalloids and metal oxyanions, with Pb (ES = -0.78) exhibiting the most significant adsorption. As the pH and temperature increased, the adsorption of HMs initially increased and subsequently decreased. Using a random forest model, we accurately predicted the adsorption capacity of MPs based on MP/HM properties and experimental conditions. The main factors affecting HM adsorption onto MPs were HM and MP concentrations, specific surface area of MP, and pH. Additionally, surface complexation and electrostatic interaction were the predominant mechanisms in the adsorption of Pb and Cd, with surface functional groups being the primary factors affecting the mechanism of MPs. These findings provide a quantitative summary of the interactions between MPs and HMs, contributing to our understanding of the environmental behavior and ecological risks associated with their correlation.
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OBJECTIVE: Bladder cancer (BCa) is a highly lethal urological malignancy characterized by its notable histological heterogeneity. Autophagy has swiftly emerged as a diagnostic and prognostic biomarker in diverse cancer types. Nonetheless, the currently accessible autophagy-related signature specific to BCa remains limited. METHODS: A refined autophagy-related signature was developed through a 10-fold cross-validation framework, incorporating 101 combinations of machine learning algorithms. The performance of this signature in predicting prognosis and response to immunotherapy was thoroughly evaluated, along with an exploration of potential drug targets and compounds. In vitro and in vivo experiments were conducted to verify the regulatory mechanism of hub gene. RESULTS: The autophagy-related prognostic signature (ARPS) has exhibited superior performance in predicting the prognosis of BCa compared to the majority of clinical features and other developed markers. Higher ARPS is associated with poorer prognosis and reduced sensitivity to immunotherapy. Four potential targets and five therapeutic agents were screened for patients in the high-ARPS group. In vitro and vivo experiments have confirmed that FKBP9 promotes the proliferation, invasion, and metastasis of BCa. CONCLUSIONS: Overall, our study developed a valuable tool to optimize risk stratification and decision-making for BCa patients.
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Autofagia , Aprendizado de Máquina , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Neoplasias da Bexiga Urinária/patologia , Humanos , Prognóstico , Animais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Medicina de Precisão , Imunoterapia/métodos , Regulação Neoplásica da Expressão Gênica , Camundongos , Medição de RiscoRESUMO
The novel HLA-A*02:1144 allele differs from HLA-A*02:03:01:01 by 3 nucleotides in exon 7.
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Éxons , Antígeno HLA-A2 , Humanos , Alelos , Doadores de Sangue , População do Leste Asiático/genética , Antígeno HLA-A2/genética , Análise de Sequência de DNARESUMO
Integrating genomics and histology for cancer prognosis demonstrates promise. Here, we develop a multi-classifier system integrating a lncRNA-based classifier, a deep learning whole-slide-image-based classifier, and a clinicopathological classifier to accurately predict post-surgery localized (stage I-III) papillary renal cell carcinoma (pRCC) recurrence. The multi-classifier system demonstrates significantly higher predictive accuracy for recurrence-free survival (RFS) compared to the three single classifiers alone in the training set and in both validation sets (C-index 0.831-0.858 vs. 0.642-0.777, p < 0.05). The RFS in our multi-classifier-defined high-risk stage I/II and grade 1/2 groups is significantly worse than in the low-risk stage III and grade 3/4 groups (p < 0.05). Our multi-classifier system is a practical and reliable predictor for recurrence of localized pRCC after surgery that can be used with the current staging system to more accurately predict disease course and inform strategies for individualized adjuvant therapy.