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1.
Environ Sci Technol ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39141599

RESUMO

Ferrihydrite is omnipresent in nature, and its adsorption of As(III/V) decides the migration of arsenic. Although As(III) is commonly recognized as the more mobile species of inorganic arsenic, it sometimes exhibits less mobility in ferrihydrite systems, which calls for further insights. In this study, we elucidated the adsorption behavior and mechanisms of As(III/V) on ferrihydrite under different loading levels (molar ratio As/Fe = 0-0.38), solution pH (3-10), and coexisting ions [P(V) and Ca(II)] based on batch adsorption experiments, surface complexation modeling, density functional theory calculations, and X-ray photoelectron spectroscopy. Our results show that As(III) exhibits weaker adsorption affinity but a larger capacity compared with that of As(V). On ferrihydrite, As(III) and As(V) are adsorbed mainly as bidentate mononuclear complexes at type-a sites [≡Fe(OH-0.5)2] and bidentate binuclear complexes at type-b sites (2≡FeOH-0.5), respectively. As the dosage increases, As(III) further forms mononuclear monodentate complexes at both surface sites, resulting in a higher site utilization efficiency, while As(V) does not due to repulsive electrostatic interaction. The difference in surface species of As(III/V) also leads to complex responses when coexisting with high concentrations of P(V) and Ca(II). This study helps us to understand environmental behavior of As(III/V) and develop remediation strategy in As(III/V) contaminated systems.

2.
Water Res ; 263: 122158, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39088882

RESUMO

This study investigated the expediated transformation of halophenols in the presence of nitrite (NO2-) under slightly acidic conditions in ice, whereas such transformation was negligible in liquid water at 4 °C. We proposed that this phenomenon was attributed to the freeze-concentration effect, incurring a pH drop and the aggregation of NO2- and halophenols within the liquid-like grain boundary layer amid ice crystals. Within this micro-environment, NO2- underwent protonation to generate reactive nitrous acid (HNO2) and nitrosonium ions (NO+) that facilitate the nitration and oxidation of halophenols. When 10 µÐœ halophenol was treated by freezing in the presence of 5 µÐœ NO2-, the total yields of nitrated products reached 2.4 µÐœ and 1.4 µÐœ within 12 h for 2-chlorophenol (2CP) and 2-bromophenol (2BP), respectively. NO+ drove oxidative coupling reactions, generating hydroxyl polyhalogenated diphenyl ethers (OH-PBDEs) and hydroxyl polyhalogenated diphenyls via C-O or C-C coupling. These two pathways were intricately intertwined. The presence of natural organic matter (NOM) mitigated the formation of nitrated products and completely suppressed the coupling products. This study offers valuable insights into the fate of halophenols in ice and suggests potential pathways for the formation of nitrophenolic compounds and OH-PBDEs in natural cold environments. These findings also open up a new avenue in environmental chemistry research.

3.
Phys Rev Lett ; 133(4): 046502, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39121411

RESUMO

Understanding spin and lattice excitations in a metallic magnetic ordered system forms the basis to unveil the magnetic and lattice exchange couplings and their interactions with itinerant electrons. Kagome lattice antiferromagnet FeGe is interesting because it displays a rare charge density wave (CDW) deep inside the antiferromagnetic ordered phase that interacts with the magnetic order. We use neutron scattering to study the evolution of spin and lattice excitations across the CDW transition T_{CDW} in FeGe. While spin excitations below ∼100 meV can be well described by spin waves of a spin-1 Heisenberg Hamiltonian, spin excitations at higher energies are centered around the Brillouin zone boundary and extend up to ∼180 meV consistent with quasiparticle excitations across spin-polarized electron-hole Fermi surfaces. Furthermore, c-axis spin wave dispersion and Fe-Ge optical phonon modes show a clear hardening below T_{CDW} due to spin-charge-lattice coupling but with no evidence of a phonon Kohn anomaly. By comparing our experimental results with density functional theory calculations in absolute units, we conclude that FeGe is a Hund's metal in the intermediate correlated regime where magnetism has contributions from both itinerant and localized electrons arising from spin polarized electronic bands near the Fermi level.

4.
ACS Omega ; 9(32): 34370-34379, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39157100

RESUMO

Multiphase flash calculations are pivotal in compositional simulation, necessitating a robust and efficient computational algorithm. In this work, we have developed a line-search-based algorithm framework for stability analysis and multiphase flash calculations. This algorithm is rooted in the modified Newton step and line-search method. The modified Newton step, derived from modified Cholesky factorization, ensures a descent direction, while the line search determines the degree of decrease. This combination facilitates convergence even in challenging regions for phase stability analysis and multiphase flash calculations, exhibiting superlinear convergence speed. Unlike traditional approaches that rely on successive substitution iteration and may resort to Newton iteration only if the Hessian matrix is positive definite, our algorithm incorporates modification via modified Cholesky factorization upon encountering a nonpositive definite Hessian matrix. We tested our algorithm with several classical fluids, demonstrating its efficiency and robustness. Furthermore, we assessed the algorithm's performance by computing the pressure-composition diagram for the CO2-hydrocarbon system, where all calculations achieved rapid convergence without failure. This newly developed algorithm for phase stability analysis and multiphase flash calculations represents a significant advancement for compositional or chemical process simulations.

5.
Sci Rep ; 14(1): 18909, 2024 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143105

RESUMO

In recent years, sleep problems among college students have become increasingly prominent, especially in the context of the COVID-19 pandemic, and their sleep quality has deteriorated dramatically, severely affecting their physical and mental health. Numerous research studies have investigated the relationship between mindfulness and sleep quality; however, it is still unclear what psychological process underlies this relationship. In the current study, college students' bed procrastination and self-control as mediating factors in the association between mindfulness and sleep quality were investigated. Using the convenience sampling method, 763 Chinese college students (mean age = 19.48 years, SD = 2.06) were recruited to complete self-reported questionnaires that included the Mindful Attention Awareness Scale, Self-Control Scale, Bed Procrastination Scale, and Sleep Quality Scale. All statistical analyses were performed using SPSS 23.0 software. Results showed that (a) mindfulness was positively associated with sleep quality; (b) both self-control and bed procrastination mediated the relationship between mindfulness and sleep quality, and (c) self-control and bed procrastination sequentially mediated the relationship between mindfulness and sleep quality. These findings collectively suggest a potential mechanism for how mindfulness influences sleep quality, providing a therapeutic target for mindfulness-based interventions aimed at helping college students improve sleep quality.


Assuntos
COVID-19 , Atenção Plena , Procrastinação , Autocontrole , Qualidade do Sono , Estudantes , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , Masculino , Feminino , Estudantes/psicologia , Adulto Jovem , Autocontrole/psicologia , Universidades , Adolescente , Inquéritos e Questionários , Pandemias , SARS-CoV-2 , Adulto , Autorrelato , Sono/fisiologia , China/epidemiologia
6.
EMBO Mol Med ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39148004

RESUMO

Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood-brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.

7.
Brain Res ; 1841: 149114, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38977237

RESUMO

OBJECTIVES: Previous studies have shown that microstructural alterations in white matter (WM) could contribute to the symptom manifestation and support the dysconnectivity hypothesis in schizophrenia patients. These alterations were pervasive, non-specific, and reported inconsistently across the literature. This study aimed to specifically investigate the microstructure alterations of the posterior limb of the internal capsule (PLIC) in first-episode, drug-naive schizophrenia patients. Utilizing a multicompartmental biophysical model, we further explored the correlation between these alterations and syndrome scale scores. METHODS: Thirty-two individuals with first-episode, drug-naive schizophrenia (FES) and thirty demographically matched healthy controls were enrolled. High-resolution multi-shell diffusion MRI data were collected, followed by the application of a three-compartment Neurite Orientation Dispersion and Density Imaging (NODDI) model to scrutinize the alterations in white matter microstructure. Changes in sensory and motor fibers within the PLIC were specifically focused on. Additionally, the correlation between these pathological changes and scores on the Positive and Negative Syndrome Scale (PANSS) was investigated. RESULTS: The Neurite density index (NDI) in the left PLIC was significantly lower in FES patients compared to healthy individuals, and positively correlated with PANSS positive syndrome scores (r = 0.0379, p = 0.046). In the sensory component (left superior thalamic radiation within PLIC, STR_P), the NDI was significantly elevated (p < 0.0001). Conversely, the NDI in the motor component (left corticospinal tract within PLIC, CST_P) was reduced (p = 0.007) in FES patients compared to healthy individuals, and strongly correlated with PANSS positive syndrome scores (p < 0.020) and PANSS total scores (p < 0.045). Moreover, the NDI deviation of STR from total PLIC (fSTR_P) and NDI deviation in STR_P and CST_P compared to PLIC region (fPLIC) were significantly higher in FES patients than in healthy controls (p < 0.00001), with an area under the curve (AUC) of fPLIC reaching 0.872. CONCLUSION: The study's findings provided new insights into the discrepancy of white matter microstructure changes associated with the sensory and motor fibers in the PLIC region in FES patients. These results contribute to the growing body of evidence suggesting that WM microstructural alterations play a critical role in schizophrenia pathophysiology.


Assuntos
Cápsula Interna , Esquizofrenia , Substância Branca , Humanos , Esquizofrenia/patologia , Esquizofrenia/diagnóstico por imagem , Cápsula Interna/patologia , Cápsula Interna/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Feminino , Masculino , Adulto , Adulto Jovem , Imagem de Difusão por Ressonância Magnética/métodos , Imagem de Tensor de Difusão/métodos
8.
J Hazard Mater ; 476: 135167, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39029194

RESUMO

Microplastics (MPs) are emerging contaminants with significant ecological and human health implications. This study examines the abundance, characteristics, and distribution of MPs in the Yangtze River estuary, focusing on seasonal variations, tidal cycles, and anthropogenic influences. Surface samples were collected using the Manta trawl method to ensure consistency with previous marine MP research. The study found an average MP concentration of 1.01 (± 0.65) n m-3, predominantly comprising low-density polymers such as polystyrene (38 %), polypropylene (33 %), and polyethylene (29 %). MPs were mainly fragments (34.9 %) and foam (30.7 %), with a prevalence of white particles. Seasonal analysis indicated significantly higher MP concentrations during flood seasons (1.32 ± 1.09 n m-3), nearly 1.9 times higher than during non-flood seasons (0.70 ± 0.28 n m-3). Tidal cycles also impacted MP distribution, with ebb tides showing increased concentrations (2.44 ± 1.30 n m-3) compared to flood tides (1.48 ± 2.07 n m-3). Furthermore, MP abundance showed a decreasing trend with increasing distance from urban centers, with significant correlations (0.52 < R2 < 0.65, P < 0.001). These findings underscore the necessity for seasonally adjusted monitoring and robust management strategies to combat MP pollution. The study advocates for the integration of diverse sampling methods and the consideration of environmental factors in future MP assessments, laying the groundwork for understanding the MP transport mechanism in the Yangtze River estuary and similar estuarine systems worldwide.

10.
Chem Commun (Camb) ; 60(58): 7455-7458, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38946627

RESUMO

MnCo spinel oxide catalysts were successfully synthesized by the calcination of bimetallic Mn/Co-MOFs as sacrificial templates. The derived catalysts exhibited optimal catalytic activity, reusability and thermal stability for toluene oxidation, which was ascribed to their large specific surface area, higher number of octahedral metal ions and the weakest metal-oxygen bonds.

11.
Semin Liver Dis ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38955211

RESUMO

The liver has the great ability to regenerate after partial resection or injury, and the mechanisms underlying liver regeneration have been extensively investigated. Interestingly, acute liver injuries triggered by various etiologies are associated with the formation of necrotic lesions, and such necrotic lesions are also rapidly resolved. However, how necrotic liver lesions are repaired has not been carefully investigated until recently. In this review, we briefly summarize the spatiotemporal process of necrotic liver lesion resolution in several liver injury models including immune-mediated liver injury and drug-induced liver injury. The roles of liver nonparenchymal cells and infiltrating immune cells in controlling necrotic liver lesion resolution are discussed, which may help identify potential therapies for acute liver injury and failure.

12.
Cardiovasc Diabetol ; 23(1): 273, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39049086

RESUMO

BACKGROUND: Extracellular matrix (ECM) stiffness is closely related to the progress of diabetic cardiomyopathy (DCM) and the response of treatment of DCM to anti-diabetic drugs. Dapagliflozin (Dapa) has been proven to have cardio-protective efficacy for diabetes and listed as the first-line drug to treat heart failure. But the regulatory relationship between ECM stiffness and treatment efficacy of Dapa remains elusive. MATERIALS AND METHODS: This work investigated the effect of ECM stiffness on DCM progression and Dapa efficacy using both in vivo DCM rat model and in vitro myocardial cell model with high glucose injury. First, through DCM rat models with various levels of myocardial injury and administration with Dapa treatment for four weeks, the levels of myocardial injury, myocardial oxidative stress, expressions of AT1R (a mechanical signal protein) and the stiffness of myocardial tissues were obtained. Then for mimicking the stiffness of myocardial tissues at early and late stages of DCM, we constructed cell models through culturing H9c2 myocardial cells on the polyacrylamide gels with two stiffness and exposed to a high glucose level and without/with Dapa intervention. The cell viability, reactive oxygen species (ROS) levels and expressions of mechanical signal sensitive proteins were obtained. RESULTS: The DCM progression is accompanied by the increased myocardial tissue stiffness, which can synergistically exacerbate myocardial cell injury with high glucose. Dapa can improve the ECM stiffness-induced DCM progression and its efficacy on DCM is more pronounced on the soft ECM, which is related to the regulation pathway of AT1R-FAK-NOX2. Besides, Dapa can inhibit the expression of the ECM-induced integrin ß1, but without significant impact on piezo 1. CONCLUSIONS: Our study found the regulation and effect of biomechanics in the DCM progression and on the Dapa efficacy on DCM, providing the new insights for the DCM treatment. Additionally, our work showed the better clinical prognosis of DCM under early Dapa intervention.


Assuntos
Compostos Benzidrílicos , Cardiomiopatias Diabéticas , Matriz Extracelular , Glucosídeos , Miócitos Cardíacos , Estresse Oxidativo , Ratos Sprague-Dawley , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Cardiomiopatias Diabéticas/fisiopatologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/patologia , Glucosídeos/farmacologia , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/patologia , Compostos Benzidrílicos/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Miócitos Cardíacos/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Linhagem Celular , Modelos Animais de Doenças , Espécies Reativas de Oxigênio/metabolismo , Ratos , Quinase 1 de Adesão Focal/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicações
13.
Insects ; 15(7)2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-39057244

RESUMO

The intricate relationships between plants and insects are essential for understanding ecological dynamics. Among these interactions, HIPVs serve as a pivotal defense mechanism. Our findings reveal the highly conserved nature of the GOX gene within the Lepidoptera order, highly expressed in the salivary glands of S. frugiperda, and its role in mediating maize's defense responses. Notably, salivary GOX activity expression significantly decreases subsequent gene knockout. The presence of GOX in the saliva of S. frugiperda significantly modulates the emission of HIPVs during maize consumption. This research delineates that GOX selectively inhibits the emission of certain green leaf volatiles (GLVs) while concurrently enhancing the release of terpene volatiles. This study unveils a novel mechanism whereby S. frugiperda utilizes GOX proteins in OS to modulate volatile emissions from maize, offering fresh perspectives on the adaptive evolution of phytophagous insects and their interactions with their preferred host plants.

14.
Nat Metab ; 6(7): 1380-1396, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38902331

RESUMO

Alcohol use disorder (AUD) affects millions of people worldwide, causing extensive morbidity and mortality with limited pharmacological treatments. The liver is considered as the principal site for the detoxification of ethanol metabolite, acetaldehyde (AcH), by aldehyde dehydrogenase 2 (ALDH2) and as a target for AUD treatment, however, our recent data indicate that the liver only plays a partial role in clearing systemic AcH. Here we show that a liver-gut axis, rather than liver alone, synergistically drives systemic AcH clearance and voluntary alcohol drinking. Mechanistically, we find that after ethanol intake, a substantial proportion of AcH generated in the liver is excreted via the bile into the gastrointestinal tract where AcH is further metabolized by gut ALDH2. Modulating bile flow significantly affects serum AcH level and drinking behaviour. Thus, combined targeting of liver and gut ALDH2, and manipulation of bile flow and secretion are potential therapeutic strategies to treat AUD.


Assuntos
Consumo de Bebidas Alcoólicas , Aldeído-Desidrogenase Mitocondrial , Etanol , Fígado , Fígado/metabolismo , Animais , Etanol/metabolismo , Aldeído-Desidrogenase Mitocondrial/metabolismo , Camundongos , Consumo de Bebidas Alcoólicas/metabolismo , Acetaldeído/metabolismo , Inativação Metabólica , Trato Gastrointestinal/metabolismo , Alcoolismo/metabolismo , Humanos , Camundongos Endogâmicos C57BL , Masculino , Microbioma Gastrointestinal , Bile/metabolismo
15.
Bioengineering (Basel) ; 11(6)2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38927848

RESUMO

This study aimed to investigate the effect of the transverse sinus (TS) stenosis (TSS) position caused by arachnoid granulation on patients with venous pulsatile tinnitus (VPT) and to further identify the types of TSS that are of therapeutic significance for patients. Multiphysics interaction models of six patients with moderate TSS caused by arachnoid granulation and virtual stent placement in TSS were reconstructed, including three patients with TSS located in the middle segment of the TS (group 1) and three patients with TTS in the middle and proximal involvement segment of the TS (group 2). The transient multiphysics interaction simulation method was applied to elucidate the differences in biomechanical and acoustic parameters between the two groups. The results revealed that the blood flow pattern at the TS and sigmoid sinus junction was significantly changed depending on the stenosis position. Preoperative patients had increased blood flow in the TSS region and TSS downstream where the blood flow impacted the vessel wall. In group 1, the postoperative blood flow pattern, average wall pressure, vessel wall vibration, and sound pressure level of the three patients were comparable to the preoperative state. However, the postoperative blood flow velocity decreased in group 2. The postoperative average wall pressure, vessel wall vibration, and sound pressure level of the three patients were significantly improved compared with the preoperative state. Intravascular intervention therapy should be considered for patients with moderate TSS caused by arachnoid granulations in the middle and proximal involvement segment of the TS. TSS might not be considered the cause of VPT symptoms in patients with moderate TSS caused by arachnoid granulation in the middle segment of the TS.

16.
Comput Biol Chem ; 112: 108119, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38852361

RESUMO

Hepatocellular carcinoma (HCC) is a widespread primary liver cancer with a high fatality rate. Despite several genes with oncogenic effects in HCC have been identified, many remain undiscovered. In this study, we conducted a comprehensive computational analysis to explore the involvement of genes within the same families as known driver genes in HCC. Specifically, we expanded the concept beyond single-gene mutations to encompass gene families sharing homologous structures, integrating various omics data to comprehensively understand gene abnormalities in cancer. Our analysis identified 74 domains with an enriched mutation burden, 404 domain mutation hotspots, and 233 dysregulated driver genes. We observed that specific low-frequency somatic mutations may contribute to HCC occurrence, potentially overlooked by single-gene algorithms. Furthermore, we systematically analyzed how abnormalities in the ubiquitinated proteasome system (UPS) impact HCC, finding that abnormal genes in E3, E2, DUB families, and Degron genes often result in HCC by affecting the stability of oncogenic or tumor suppressor proteins. In conclusion, expanding the exploration of driver genes to include gene families with homologous structures emerges as a promising strategy for uncovering additional oncogenic alterations in HCC.

17.
Oncologist ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907674

RESUMO

BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

18.
J Comput Chem ; 45(25): 2136-2152, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38780502

RESUMO

A symbolic C++ library-Tinned-has been developed for symbolic differentiation and manipulation in response theory. By recognizing different key building blocks in the density matrix-based (Thorvaldsen et al., J. Chem. Phys. 2008, 129, 214108) and coupled-cluster response theories, we have implemented their corresponding C++ symbolic classes, including but not limited to one- and two-electron operators, exchange-correlation energy and potential, and coupled-cluster operator. Formulas of response theory can be well expressed in terms of the symbolic classes in the library Tinned. Their high-order perturbation-strength derivatives can be straightforwardly computed and extracted afterwards for numerical evaluation. The library Tinned will greatly facilitate the development work of response theory and may lead to a unified framework for response theory at different levels of electronic structure theory.

19.
PLoS Comput Biol ; 20(5): e1012113, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38728362

RESUMO

The heterogeneity of Hepatocellular Carcinoma (HCC) poses a barrier to effective treatment. Stratifying highly heterogeneous HCC into molecular subtypes with similar features is crucial for personalized anti-tumor therapies. Although driver genes play pivotal roles in cancer progression, their potential in HCC subtyping has been largely overlooked. This study aims to utilize driver genes to construct HCC subtype models and unravel their molecular mechanisms. Utilizing a novel computational framework, we expanded the initially identified 96 driver genes to 1192 based on mutational aspects and an additional 233 considering driver dysregulation. These genes were subsequently employed as stratification markers for further analyses. A novel multi-omics subtype classification algorithm was developed, leveraging mutation and expression data of the identified stratification genes. This algorithm successfully categorized HCC into two distinct subtypes, CLASS A and CLASS B, demonstrating significant differences in survival outcomes. Integrating multi-omics and single-cell data unveiled substantial distinctions between these subtypes regarding transcriptomics, mutations, copy number variations, and epigenomics. Moreover, our prognostic model exhibited excellent predictive performance in training and external validation cohorts. Finally, a 10-gene classification model for these subtypes identified TTK as a promising therapeutic target with robust classification capabilities. This comprehensive study provides a novel perspective on HCC stratification, offering crucial insights for a deeper understanding of its pathogenesis and the development of promising treatment strategies.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Aprendizado de Máquina , Medicina de Precisão , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/classificação , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/classificação , Medicina de Precisão/métodos , Mutação/genética , Biologia Computacional/métodos , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica/genética , Variações do Número de Cópias de DNA/genética , Perfilação da Expressão Gênica/métodos , Algoritmos , Genômica/métodos , Multiômica
20.
Gut ; 73(9): 1543-1553, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-38724220

RESUMO

OBJECTIVE: Previous studies indicate that eosinophils are recruited into the allograft following orthotopic liver transplantation and protect from ischaemia reperfusion (IR) injury. In the current studies, we aim to explore whether their protective function could outlast during liver repair. DESIGN: Eosinophil-deficient mice and adoptive transfer of bone marrow-derived eosinophils (bmEos) were employed to investigate the effects of eosinophils on tissue repair and regeneration after hepatic IR injury. Aside from exogenous cytokine or neutralising antibody treatments, mechanistic studies made use of a panel of mouse models of eosinophil-specific IL-4/IL-13-deletion, cell-specific IL-4rα-deletion in liver macrophages and hepatocytes and macrophage-specific deletion of heparin-binding epidermal growth factor-like growth factor (hb-egf). RESULT: We observed that eosinophils persisted over a week following hepatic IR injury. Their peak accumulation coincided with that of hepatocyte proliferation. Functional studies showed that eosinophil deficiency was associated with a dramatic delay in liver repair, which was normalised by the adoptive transfer of bmEos. Mechanistic studies demonstrated that eosinophil-derived IL-4, but not IL-13, was critically involved in the reparative function of these cells. The data further revealed a selective role of macrophage-dependent IL-4 signalling in liver regeneration. Eosinophil-derived IL-4 stimulated macrophages to produce HB-EGF. Moreover, macrophage-specific hb-egf deletion impaired hepatocyte regeneration after IR injury. CONCLUSION: Together, these studies uncovered an indispensable role of eosinophils in liver repair after acute injury and identified a novel crosstalk between eosinophils and macrophages through the IL-4/HB-EGF axis.


Assuntos
Eosinófilos , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Interleucina-4 , Regeneração Hepática , Macrófagos , Traumatismo por Reperfusão , Animais , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/metabolismo , Fator de Crescimento Semelhante a EGF de Ligação à Heparina/genética , Regeneração Hepática/fisiologia , Traumatismo por Reperfusão/metabolismo , Interleucina-4/metabolismo , Camundongos , Eosinófilos/metabolismo , Macrófagos/metabolismo , Fígado/patologia , Fígado/metabolismo , Fígado/irrigação sanguínea , Hepatócitos/metabolismo , Interleucina-13/metabolismo , Transferência Adotiva , Camundongos Endogâmicos C57BL
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