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Electrochemical carbon-capture technologies, with renewable electricity as the energy input, are promising for carbon management but still suffer from low capture rates, oxygen sensitivity or system complexity1-6. Here we demonstrate a continuous electrochemical carbon-capture design by coupling oxygen/water (O2/H2O) redox couple with a modular solid-electrolyte reactor7. By performing oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) redox electrolysis, our device can efficiently absorb dilute carbon dioxide (CO2) molecules at the high-alkaline cathode-membrane interface to form carbonate ions, followed by a neutralization process through the proton flux from the anode to continuously output a high-purity (>99%) CO2 stream from the middle solid-electrolyte layer. No chemical inputs were needed nor side products generated during the whole carbon absorption/release process. High carbon-capture rates (440 mA cm-2, 0.137 mmolCO2 min-1 cm-2 or 86.7 kgCO2 day-1 m-2), high Faradaic efficiencies (>90% based on carbonate), high carbon-removal efficiency (>98%) in simulated flue gas and low energy consumption (starting from about 150 kJ per molCO2) were demonstrated in our carbon-capture solid-electrolyte reactor, suggesting promising practical applications.
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Unveiling the principles governing embryonic stem cell (ESC) differentiation into specific lineages is critical for understanding embryonic development and for stem cell applications in regenerative medicine. Here, we establish an intersection between LIF-Stat3 signaling that is essential for maintaining murine (m) ESCs pluripotency, and the glycolytic enzyme, the platelet isoform of phosphofructokinase (Pfkp). In the pluripotent state, Stat3 transcriptionally suppresses Pfkp in mESCs while manipulating the cells to lift this repression results in differentiation towards the ectodermal lineage. Pfkp exhibits substrate specificity changes to act as a protein kinase, catalyzing serine phosphorylation of the developmental regulator Lin41. Such phosphorylation stabilizes Lin41 by impeding its autoubiquitination and proteasomal degradation, permitting Lin41-mediated binding and destabilization of mRNAs encoding ectodermal specification markers to favor the expression of endodermal specification genes. This provides new insights into the wiring of pluripotency-differentiation circuitry where Pfkp plays a role in germ layer specification during mESC differentiation.
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Fosfofrutoquinases , Proteínas Quinases , Gravidez , Feminino , Camundongos , Animais , Proteínas Quinases/metabolismo , Fosfofrutoquinases/metabolismo , Células-Tronco Embrionárias/metabolismo , Diferenciação Celular/genética , Transdução de Sinais , Células-Tronco Embrionárias Murinas/metabolismoRESUMO
The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.
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Ritmo Gama , Camundongos Endogâmicos C57BL , Estimulação Luminosa , Córtex Visual Primário , Animais , Ritmo Gama/fisiologia , Camundongos , Estimulação Luminosa/métodos , Córtex Visual Primário/fisiologia , Masculino , Microeletrodos , Córtex Visual/fisiologia , EletrodosRESUMO
Hippo-Yes-associated protein 1 (YAP1) plays an important role in gastric cancer (GC) progression; however, its regulatory network remains unclear. In this study, we identified Copine III (CPNE3) was identified as a novel direct target gene regulated by the YAP1/TEADs transcription factor complex. The downregulation of CPNE3 inhibited proliferation and invasion, and increased the chemosensitivity of GC cells, whereas the overexpression of CPNE3 had the opposite biological effects. Mechanistically, CPNE3 binds to the YAP1 protein in the cytoplasm, inhibiting YAP1 ubiquitination and degradation mediated by the E3 ubiquitination ligase ß-transducin repeat-containing protein (ß-TRCP). Thereby activating the transcription of YAP1 downstream target genes, which creates a positive feedback cycle to facilitate GC progression. Immunohistochemical analysis demonstrated significant upregulation of CPNE3 in GC tissues. Survival and Cox regression analyses indicated that high CPNE3 expression was an independent prognostic marker for GC. This study elucidated the pivotal involvement of an aberrantly activated CPNE3/YAP1 positive feedback loop in the malignant progression of GC, thereby uncovering novel prognostic factors and therapeutic targets in GC.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Transdução de Sinais , Retroalimentação , Linhagem Celular Tumoral , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proliferação de Células , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and metabolic-associated fatty liver disease (MAFLD) shares common pathophysiological mechanisms with type 2 diabetes, making them significant risk factors for type 2 diabetes. The present study aimed to assess the epidemiological feature of type 2 diabetes in patients with NAFLD or MAFLD at global levels. METHODS: Published studies were searched for terms that included type 2 diabetes, and NAFLD or MAFLD using PubMed, EMBASE, MEDLINE, and Web of Science databases from their inception to December 2022. The pooled global and regional prevalence and incidence density of type 2 diabetes in patients with NAFLD or MAFLD were evaluated using random-effects meta-analysis. Potential sources of heterogeneity were investigated using stratified meta-analysis and meta-regression. RESULTS: A total of 395 studies (6,878,568 participants with NAFLD; 1,172,637 participants with MAFLD) from 40 countries or areas were included in the meta-analysis. The pooled prevalence of type 2 diabetes among NAFLD or MAFLD patients was 28.3% (95% confidence interval 25.2-31.6%) and 26.2% (23.9-28.6%) globally. The incidence density of type 2 diabetes in NAFLD or MAFLD patients was 24.6 per 1000-person year (20.7 to 29.2) and 26.9 per 1000-person year (7.3 to 44.4), respectively. CONCLUSIONS: The present study describes the global prevalence and incidence of type 2 diabetes in patients with NAFLD or MAFLD. The study findings serve as a valuable resource to assess the global clinical and economic impact of type 2 diabetes in patients with NAFLD or MAFLD.
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Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Fatores de Risco , Bases de Dados Factuais , PacientesRESUMO
The design and fabrication of novel carbon hosts with high conductivity, accelerated electrochemical catalytic activities, and superior physical/chemical confinement on sulfur and its reaction intermediates polysulfides are essential for the construction of high-performance C/S cathodes for lithium-sulfur batteries (LSBs). In this work, a novel biofermentation coupled gel composite assembly technology is developed to prepare cross-linked carbon composite hosts consisting of conductive Rhizopus hyphae carbon fiber (RHCF) skeleton and lamellar sodium alginate carbon (SAC) uniformly implanted with polarized nanoparticles (V2O3, Ag, Co, etc.) with diameters of several nanometers. Impressively, the RHCF/SAC/V2O3 composites exhibit enhanced physical/chemical adsorption of polysulfides due to the synergistic effect between hierarchical pore structures, heteroatoms (N, P) doping, and polar V2O3 generation. Additionally, the catalytic conversion kinetics of cathodes are effectively improved by regulating the 3D carbon structure and optimizing the V2O3 catalyst. Consequently, the LSBs assembled with RHCF/SAC/V2O3-S cathode show exceptional cycle stability (capacity retention rate of 94.0% after 200 cycles at 0.1 C) and excellent rate performance (specific capacity of 578 mA h g-1 at 5 C). This work opens a new door for the fabrication of hyphae carbon composites via fermentation for electrochemical energy storage.
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All-solid-state lithium metal batteries (LMBs) are regarded as one of the most viable energy storage devices and their comprehensive properties are mainly controlled by solid electrolytes and interface compatibility. This work proposes an advanced poly(vinylidene fluoride-hexafluoropropylene) based gel polymer electrolyte (AP-GPEs) via functional superposition strategy, which involves incorporating butyl acrylate and polyethylene glycol diacrylate as elastic optimization framework, triethyl phosphate and fluoroethylene carbonate as flameproof liquid plasticizers, and Li7La3Zr2O12 nanowires (LLZO-w) as ion-conductive fillers, endowing the designed AP-GPEs/LLZO-w membrane with high mechanical strength, excellent flexibility, low flammability, low activation energy (0.137 eV), and improved ionic conductivity (0.42 × 10-3 S cm-1 at 20 °C) due to continuous ionic transport pathways. Additionally, the AP-GPEs/LLZO-w membrane shows good safety and chemical/electrochemical compatibility with the lithium anode, owing to the synergistic effect of LLZO-w filler, flexible frameworks, and flame retardants. Consequently, the LiFePO4/Li batteries assembled with AP-GPEs/LLZO-w electrolyte exhibit enhanced cycling performance (87.3% capacity retention after 600 cycles at 1 C) and notable high-rate capacity (93.3 mAh g-1 at 5 C). This work proposes a novel functional superposition strategy for the synthesis of high-performance comprehensive GPEs for LMBs.
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The design and fabrication of a lithiophilic skeleton are highly important for constructing advanced Li metal anodes. In this work, a new lithiophilic skeleton is reported by planting metal sulfides (e.g., Ni3S2) on vertical graphene (VG) via a facile ultrafast Joule heating (UJH) method, which facilitates the homogeneous distribution of lithiophilic sites on carbon cloth (CC) supported VG substrate with firm bonding. Ni3S2 nanoparticles are homogeneously anchored on the optimized skeleton as CC/VG@Ni3S2, which ensures high conductivity and uniform deposition of Li metal with non-dendrites. By means of systematic electrochemical characterizations, the symmetric cells coupled with CC/VG@Ni3S2 deliver a steady long-term cycle within 14 mV overpotential for 1800 h (900 cycles) at 1 mA cm-2 and 1 mAh cm-2. Meanwhile, the designed CC/VG@Ni3S2-Li||LFP full cell shows notable electrochemical performance with a capacity retention of 92.44% at 0.5 C after 500 cycles and exceptional rate performance. This novel synthesis strategy for metal sulfides on hierarchical carbon-based materials sheds new light on the development of high-performance lithium metal batteries (LMBs).
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Lithium-sulfur (Li-S) batteries are expected to be the next-generation energy storage system due to the ultrahigh theoretical energy density and low cost. However, the notorious shuttle effect of higher-order polysulfides and the uncontrollable lithium dendrite growth are the two biggest challenges for commercially viable Li-S batteries. Herein, these two main challenges are solved by in situ polymerization of bi-functional gel polymer electrolyte (GPE). The initiator (SiCl4) not only drives the polymerization of 1,3-dioxolane (DOL) but also induces the construction of a hybrid solid electrolyte interphase (SEI) with inorganic-rich compositions on the Li anode. In addition, diatomaceous earth (DE) is added and anchored in the GPE to obtain PDOL-SiCl4-DE electrolyte through in situ polymerization. Combined with density functional theory (DFT) calculations, the hybrid SEI provides abundant adsorption sites for the deposition of Li+, inhibiting the growth of lithium dendrites. Meanwhile, the shuttle effect is greatly alleviated due to the strong adsorption capacity of DE toward lithium polysulfides. Therefore, the Li/Li symmetric cell and Li-S full cell assembled with PDOL-SiCl4-DE exhibit excellent cycling stability. This study offers a valuable reference for the development of high performance and safe Li-S batteries.
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RATIONALE & OBJECTIVE: Kidney stone disease (KSD), a significant health care problem within both developed and developing countries, has been associated with genetic risk factors. An association between physical activity and KSD risk also has been hypothesized, but studies have yielded inconsistent findings. This study investigated the association between the intensity of physical activity and the incidence of KSD accounting for genetic risk. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 80,473 participants from the UK Biobank Study. EXPOSURE: Physical activity levels, including total physical activity (TPA), moderate-to-vigorous intensity physical activity (MVPA), and light-intensity physical activity (LPA), were measured using accelerometers and quantified using a machine learning model. A polygenic risk score (PRS) for KSD was also constructed. OUTCOME: Individuals with KSD were identified using the International Classification of Diseases, Tenth Revision (ICD-10), and procedure codes for KSD surgery. ANALYTICAL APPROACH: A Fine and Gray survival model was used to estimate the associations of incident KSD with TPA, MVPA, LPA, and PRS (as categorical variables). Restricted cubic splines were used to examine potential nonlinear associations within the fully adjusted models. RESULTS: During an average follow-up of 6.19 years, 421 participants developed KSD. Participants in the highest quartiles of TPA, MVPA, and LPA had lower adjusted rates of KSD compared with those in the lowest quartiles: HR, 0.50 (95% CI, 0.44-0.56), 0.57 (95% CI, 0.51-0.64), and 0.66 (95% CI, 0.59-0.74), respectively. TPA, MVPA, and LPA were associated with a lower risk of KSD in participants with low and high genetic predisposition for KSD. LIMITATIONS: Selection bias as participants who provided accelerometry data may have been more adherent to health care. CONCLUSIONS: Physical activity was negatively associated with the risk of KSD, regardless of the genetic risk. Future large studies are warranted to confirm and explain the mechanisms underlying these associations. PLAIN-LANGUAGE SUMMARY: The association between the intensity of physical activity (PA) and the incidence of kidney stone disease (KSD) after accounting for genetic risk is unclear. We conducted a comprehensive prospective cohort study utilizing participants from the UK Biobank to assess the intensity of PA using accelerometers. Our study findings indicated that greater total PA, moderate-to-vigorous-intensity PA, and light-intensity PA were each associated with a lower risk of KSD irrespective of an individual's genetic risk. Our study informs the understanding of risk factors for KSD.
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OBJECTIVE: This study aimed to examine the interactions between ultraprocessed food (UPF) consumption and genetic predisposition with the risk of gout. METHODS: This prospective cohort study analysed 181 559 individuals from the UK Biobank study who were free of gout at baseline. UPF was defined according to the NOVA classification. Assessment of genetic predisposition for gout was developed from a genetic risk score of 33 single nucleotide polymorphisms. Cox proportional hazards were used to estimate the associations between UPF consumption, genetic predisposition and the risk of gout. RESULTS: Among the 181 559 individuals in the study, 1558 patients developed gout over 1â648â167 person-years of follow-up. In the multivariable adjustment model, compared with the lowest quartile of UPF consumption, the hazard ratio (HR) and 95% CI of the highest UPF consumption was 1.16 (1.01, 1.33) for gout risk, and there was a non-linear correlation between UPF consumption and the development of gout. In substitution analyses, replacing 20% of the weight of UPF in the daily intake with an equal amount of unprocessed or minimally processed food resulted in a 13% lower risk of gout (HR: 0.87; 95% CI: 0.79, 0.95). In the joint-effect analysis, the HR (95% CI) for gout was 1.90 (1.39, 2.60) in participants with high genetic predisposition and high UPF consumption, compared with those with low genetic predisposition and low UPF consumption. CONCLUSION: In summary, UPF consumption was found to be associated with a higher risk of gout, particularly in those participants with genetic predisposition to gout. Our study indicated that reducing UPF consumption is crucial for gout prevention.
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Bancos de Espécimes Biológicos , Gota , Humanos , Estudos Prospectivos , Biobanco do Reino Unido , Predisposição Genética para Doença , Gota/epidemiologia , Gota/genética , DietaRESUMO
Early diagnosis of post-traumatic osteoarthritis (PTOA) is critical for designing better treatments before the degradation becomes irreversible. We utilized multimodal high-resolution imaging to investigate early-stage deterioration in articular cartilage and the subchondral bone plate from a sub-critical impact to the knee joint, which initiates PTOA. The knee joints of 12 adult rabbits were mechanically impacted once on the femoral articular surface to initiate deterioration. At 2- and 14-week post-impact surgery, cartilage-bone blocks were harvested from the impact region in the animals (N = 6 each). These blocks were assessed for deterioration using polarized light microscopy (PLM), microcomputed tomography (µCT), and biochemical analysis. Statistically significant changes were noted in the impact tissues across the calcified zone (CZ) at 14 weeks post-impact: the optical retardation values in the CZ of impact cartilage had a drop of 29.0% at 14 weeks, while the calcium concentration in the CZ of impact cartilage also had a significant drop at 14 weeks. A significant reduction of 6.3% in bone mineral density (BMD) was noted in the subchondral bone plate of the impact samples at 14 weeks. At 2 weeks post-impact, only minor, non-significant changes were measured. Furthermore, the impact knees after 14 weeks had greater structural changes compared with the 2-week impact knees, indicating progressive degradation over time. The findings of this study facilitated a connection between mineralization alterations and the early deterioration of knee cartilage after a mechanical injury. In a broader context, these findings can be beneficial in improving clinical strategies to manage joint injuries.
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"Carbon Peak and Carbon Neutrality" is an important strategic goal for the sustainable development of human society. Typically, a key means to achieve these goals is through electrochemical energy storage technologies and materials. In this context, the rational synthesis and modification of battery materials through new technologies play critical roles. Plasma technology, based on the principles of free radical chemistry, is considered a promising alternative for the construction of advanced battery materials due to its inherent advantages such as superior versatility, high reactivity, excellent conformal properties, low consumption and environmental friendliness. In this perspective paper, we discuss the working principle of plasma and its applied research on battery materials based on plasma conversion, deposition, etching, doping, etc. Furthermore, the new application directions of multiphase plasma associated with solid, liquid and gas sources are proposed and their application examples for batteries (e. g. lithium-ion batteries, lithium-sulfur batteries, zinc-air batteries) are given. Finally, the current challenges and future development trends of plasma technology are briefly summarized to provide guidance for the next generation of energy technologies.
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BACKGROUND: Psoriatic disease (PsD) is closely associated with cardiovascular diseases. The Life's Essential 8 (LE8) score is a new metric for assessing cardiovascular health (CVH), where a higher score indicates better CVH. However, the longitudinal association between LE8 score and the risk of PsD remains uncertain. The main aim of the present study was to explore the association between LE8 scores and the risk of PsD. OBJECTIVE: To investigate the associations between LE8 score, genetic susceptibility, and the risk of PsD within a cohort design. METHODS: This cohort study included 261,642 participants from the UK Biobank without PsD at baseline. LE8 comprises eight indicators: diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. Cox proportional hazard models were employed to examine the association between the participants' LE8 scores, PsD genetic risk, and the risk of PsD. Hazard ratios (HRs) and 95% confidential intervals (CIs) were calculated. RESULTS: During an average follow-up of 12.32 years, 1,501 participants developed PsD. Compared to participants with low LE8 scores, the HRs (95% CIs) of developing PsD for those with moderate and high LE8 scores were 0.51 (0.43, 0.59) and 0.34 (0.27, 0.42) after adjustments, respectively. Dose-response analysis revealed a linear negative association between continuous LE8 score and the risk of developing PsD (P < 0.001), with no evidence of non-linear association detected. The genetic susceptibility to PsD did not modify this association (P for interaction = 0.63). Subgroup analyses revealed that women demonstrated a more pronounced beneficial association between LE8 scores and PsD risk (P for interaction = 0.02). CONCLUSIONS: Our study suggests that a higher LE8 score, regardless of genetic risk, was associated with a lower risk of PsD, particularly among women. Consequently, maintaining a high CVH status is recommended to prevent PsD and assess associated risks.
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Hypoxia drives aging and promotes age-related cognition and hearing functional decline. Despite the role of erythrocytes in oxygen (O2) transport, their role in the onset of aging and age-related cognitive decline and hearing loss (HL) remains undetermined. Recent studies revealed that signaling through the erythrocyte adenosine A2B receptor (ADORA2B) promotes O2 release to counteract hypoxia at high altitude. However, nothing is known about a role for erythrocyte ADORA2B in age-related functional decline. Here, we report that loss of murine erythrocyte-specific ADORA2B (eAdora2b-/-) accelerates early onset of age-related impairments in spatial learning, memory, and hearing ability. eAdora2b-/- mice display the early aging-like cellular and molecular features including the proliferation and activation of microglia and macrophages, elevation of pro-inflammatory cytokines, and attenuation of hypoxia-induced glycolytic gene expression to counteract hypoxia in the hippocampus (HIP), cortex, or cochlea. Hypoxia sufficiently accelerates early onset of cognitive and cochlear functional decline and inflammatory response in eAdora2b-/- mice. Mechanistically, erythrocyte ADORA2B-mediated activation of AMP-activated protein kinase (AMPK) and bisphosphoglycerate mutase (BPGM) promotes hypoxic and metabolic reprogramming to enhance production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific metabolite triggering O2 delivery. Significantly, this finding led us to further discover that murine erythroblast ADORA2B and BPGM mRNA levels and erythrocyte BPGM activity are reduced during normal aging. Overall, we determined that erythrocyte ADORA2B-BPGM axis is a key component for anti-aging and anti-age-related functional decline.
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Vias Auditivas/fisiopatologia , Disfunção Cognitiva/metabolismo , Eritrócitos/metabolismo , Hipóxia/metabolismo , Receptor A2B de Adenosina/metabolismo , 2,3-Difosfoglicerato/metabolismo , Envelhecimento/patologia , Animais , Bisfosfoglicerato Mutase/genética , Bisfosfoglicerato Mutase/metabolismo , Encéfalo/patologia , Encéfalo/fisiopatologia , Cóclea/fisiopatologia , Disfunção Cognitiva/complicações , Disfunção Cognitiva/genética , Disfunção Cognitiva/fisiopatologia , Ativação Enzimática , Deleção de Genes , Glicólise , Hipóxia/complicações , Hipóxia/genética , Hipóxia/fisiopatologia , Inflamação/complicações , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , Receptor A2B de Adenosina/deficiênciaRESUMO
PURPOSE: Degradation of articular cartilage (AC) due to injury to the knee joint may initiate post-traumatic osteoarthritis (PTOA). Failure to diagnose the onset of the disease at an early stage makes the cure ineffective for PTOA. This study investigated the consequences of a mechanical injury to the knee in a rabbit model using microscopic magnetic resonance imaging (µMRI) at high resolution. MATERIALS AND METHODS: A mechanical injury was induced to the knee joints of 12 rabbits. Cartilage blocks were extracted from the non-impacted and impacted knee joints after 2 and 14 weeks post-impact. The specimens were studied using µMRI T2 relaxation and inductively coupled plasma analysis to determine the early degradation of the articular cartilage. RESULTS: The data established a connection between T2 relaxation time and the early progression of knee PTOA after an impact injury. T2 values were found to be higher in the impacted cartilage at both 2 and 14 weeks, in particular, T2-55° values in the impacted samples displayed a significant rise of 6.93% after 2 weeks and 20.02% after 14 weeks. Lower glycosaminoglycan measurement and higher water content in the impacted cartilage confirmed the µMRI results. CONCLUSIONS: This µMRI T2 study was able to detect cartilage damage in the impacted knees. In addition, greater degradation in the affected knees at 14 weeks than at 2 weeks indicated the progressive nature of cartilage deterioration over time. The µMRI results were in accord with the biochemical analysis, indicating the detection of early structural damage in the cartilage.
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Cartilagem Articular , Osteoartrite , Animais , Coelhos , Cartilagem Articular/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Modelos Animais de DoençasRESUMO
AIM: To investigate the effect of metabolic syndrome (MetS), genetic predisposition, and their interactions, on the risk of developing chronic obstructive pulmonary disease (COPD). METHODS: Cohort analyses included 287 868 participants from the UK Biobank Study. A genetic risk score for COPD was created using 277 single nucleotide polymorphisms. Cox proportional hazard models were used to evaluate the hazard ratios (HRs) with 95% confidence intervals (CIs) for COPD in relation to exposure factors. RESULTS: During 2 658 936 person-years of follow-up, 5877 incident cases of COPD were documented. Compared with participants without MetS, those with MetS had a higher risk of COPD (HR 1.24, 95% CI 1.17-1.32). Compared to participants with low genetic predisposition, those with high genetic predisposition had a 17% increased risk of COPD. In the joint analysis, compared with participants without MetS and low genetic predisposition, the HR for COPD for those with MetS and high genetic predisposition was 1.50 (95% CI 1.36-1.65; P < 0.001). However, no significant interaction between MetS and genetic risk was found. CONCLUSIONS: Metabolic syndrome was found to be associated with an increased risk of COPD, regardless of genetic risk. It is crucial to conduct further randomized control trials to determine whether managing MetS and its individual components can potentially reduce the likelihood of developing COPD.
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Síndrome Metabólica , Doença Pulmonar Obstrutiva Crônica , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Bancos de Espécimes Biológicos , Biobanco do Reino Unido , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/complicações , Fatores de Risco , Predisposição Genética para DoençaRESUMO
BACKGROUND: Evidence has shown that the individual metrics in Life's Essential 8 (LE8), an updated cardiovascular health (CVH) concept proposed by the American Heart Association, play a role in the development of inflammatory bowel disease (IBD). However, epidemiological evidence on the overall LE8 on IBD risk remains limited. We aimed to assess the longitudinal associations of LE8-defined CVH and the risks of IBD and its subtypes, ulcerative colitis (UC) and Crohn's disease (CD). We also tested whether genetic susceptibility could modify these associations. METHODS: A total of 260,836 participants from the UK Biobank were included. LE8 scores were determined by 8 metrics (physical activity, diet, nicotine exposure, sleep, body mass index, blood pressure, blood glucose, and blood lipids), and were divided into three levels: low CVH (0-49), moderate CVH (50-79), and high CVH (80-100). Cox proportional hazards models were used to calculate the hazard ratios (HRs) and confidence intervals (CIs) of the risk of IBD in relation to CVH status. RESULTS: Over a median follow-up 12.3 years, we documented 1,500 IBD cases (including 1,070 UC and 502 CD). Compared to participants with low CVH, the HRs (95% CIs) of those with high CVH for IBD, UC, and CD were 0.67 (0.52, 0.83), 0.70 (0.52, 0.93), and 0.55 (0.38, 0.80), respectively. These associations were not modified by genetic susceptibility (all P for interactions > 0.05). The lowest HR (UC: 0.30, 95% CI: 0.20-0.45; CD: 0.33, 95% CI: 0.20-0.57) was observed in participants with both high CVH and low genetic risk. CONCLUSIONS: Better CVH, defined by LE8, was associated with significantly lower risks of IBD, UC, and CD, irrespective of genetic predisposition. Our results underscore the importance of adherence to LE8 guidelines for maintaining CVH as a potential strategy in the prevention of IBD.
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Doença de Crohn , Dieta , Predisposição Genética para Doença , Doenças Inflamatórias Intestinais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Reino Unido , Adulto , Doenças Inflamatórias Intestinais/genética , Doença de Crohn/genética , Exercício Físico , Idoso , Índice de Massa Corporal , Colite Ulcerativa/genética , Estudos de Coortes , Modelos de Riscos Proporcionais , Estudos Longitudinais , Pressão Sanguínea , Sono , Glicemia/metabolismoRESUMO
The multicomponent relaxation observed in nuclear magnetic resonance experiments in biological tissues makes it difficult to establish a correlation between specific relaxation times and tissue structural parameters. The analysis of a nanostructure (the characteristic size of 10-1000 nm) is usually based on formulas for relaxation times which depend on structural parameters at the atomic or molecular levels in the size range of 0.1-5 nm. We have recently developed an analysis method in which relaxation times' anisotropy in a sample is explicitly related to its structure of nanocavities containing a liquid or gas. However, the method is based on the analysis of experimental data on the anisotropy of relaxation times obtained by using the standard NMR technique and rotating the sample relative to a magnetic field and requires a series of experiments. In the present study, to address this challenge, we develop a new method of analysis of a multi-exponential magnetic resonance signal that does not require determining relaxation times and eliminates the sample rotation and the necessity of a series of experiments. Using the magnetic resonance imaging (MRI) technique, the total signal from the whole sample was obtained as a sum of the signals (echo decays) from all voxels. In contrast to previous research, the volumes of nanocavities and their angular distribution can be obtained by analyzing a single total signal for the entire cartilage. In addition, within the framework of this approach, it is possible to identify the reason for the multicomponent nature of relaxation. The proposed method for analyzing a single multi-exponential signal (transverse relaxation) was implemented on cartilage. Using the signal, three anatomical zones of cartilage were studied, revealing significant structural differences between them. The proposed method not only avoids the need for sample rotation but also enables repeated application of layer-by-layer magnetic resonance imaging with micron resolution. The study results allow us to suggest that water molecules contributing to the echo decay are more likely located in nanocavities formed by the fibrillar structure rather than inside the fibrils.
Assuntos
Colágeno , Imageamento por Ressonância Magnética , Nanoestruturas , Imageamento por Ressonância Magnética/métodos , Nanoestruturas/química , Colágeno/química , Animais , Anisotropia , BovinosRESUMO
OBJECTIVE: Pulmonary function is associated with the development of chronic liver disease. However, evidence of the association between pulmonary function and cirrhosis risk is still lacking. This study aimed to investigate the longitudinal associations of pulmonary function with the development of cirrhosis, and to explore whether genetic predisposition to cirrhosis could modify these associations. METHODS: Of 294,835 participants free of cirrhosis and had undergone spirometry at baseline from the UK Biobank were included. Cirrhosis diagnoses were ascertained through linked hospital records and death registries. Cox proportional hazard models were employed to investigate the longitudinal associations between pulmonary function, genetic predisposition, and cirrhosis risk. RESULTS: During a median follow-up of 12.0 years, 2598 incident cirrhosis cases were documented. Compared to individuals with normal spirometry findings, those with preserved ratio impaired spirometry (PRISm) findings (hazard ratio [HR] and 95% confidence interval [CI]: 1.32 [1.18, 1.48]) and airflow obstruction (HR [95%CI]: 1.19 [1.07, 1.31]) had a higher risk of developing cirrhosis after adjustments. These associations were consistent across all categories of genetic predisposition, with no observed modifying effect of genetic predisposition. In joint exposure analyses, the highest risk was observed in individuals with both a high genetic predisposition for cirrhosis and PRISm findings (HR [95% CI]: 1.74 [1.45, 2.08]). CONCLUSIONS: Our findings indicate that worse pulmonary function is a significant risk factor of cirrhosis, irrespective of genetic predisposition. Early identification and appropriate intervention for pulmonary function may lead to more effective healthcare resource utilization and reduce the burden associated with cirrhosis.