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Milk fat globule membrane (MFGM) is a three-layer membrane-like structure encasing natural milk fat globules (MFGs). MFGM holds promise as a nutritional supplement because of the numerous physiological functions of its constituent protein. This review summarizes and compares the differences in MFGM protein composition across various species, including bovines, goats, camels, mares, and donkeys, and different lactation periods, such as colostrum and mature milk, as assessed by techniques such as proteomics and mass spectrometry. We also discuss the health benefits of MFGM proteins throughout life. MFGM proteins promote intestinal development, neurodevelopment, and glucose and lipid metabolism by upregulating tight junction protein expression, brain function-related genes, and glucose and fatty acid biosynthesis processes. We focus on the mechanisms underlying these beneficial effects of MFGM proteins. MFGM proteins activate key substances in in signaling pathways, such as the phosphatidylinositol 3-kinase/protein kinase B, mitogen-activated protein kinase, and myosin light chain kinase signaling pathways. Overall, the consumption of MFGM proteins plays an essential role in conferring health benefits, some of which are important throughout the mammalian life cycle.
Types and amounts of MFGM proteins in mammals, as assessed by proteomic and mass spectrometry analysis, are summarized.Colostrum MFGM contains more acute phase proteins, whereas mature milk has higher levels of mucins (1 and 15), ADPH, XDH, and FABP.Health benefits of MFGM proteins, including intestinal development, neurodevelopment, and immune activity enhancement, are summarized.MFGM proteins have been shown to significantly activate the PI3K/Akt/mTOR signaling pathway, promoting cell proliferation and glycolipid metabolism.
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BACKGROUND: Self-emulsifying nano-phase of traditional Chinese medicine are a research hotspot. Xiao-Chai-Hu decoction is a commonly used compound decoction in clinical practice, which is of great research significance. The aim of this study was to isolate and characterize the self-emulsifying nano-phase and other phases of Xiao-Chai-Hu decoction, and to study the effects of each phase on acute liver injury. METHODS: The liquid medicine was prepared employing centrifugation followed by dialysis. Single- factor investigation methodology was utilized to optimize the preparation parameters for both phases. Characterization of the formulated phase involved analyses such as surface morphology assessment, measurement of nanoparticle size and Zeta potential using an analyzer, observation of the Tyndall effect, conducting diffusion and dilution tests, examination under a microscope, and structural visualization via transmission electron microscopy (TEM). Furthermore, an acute liver injury model was established in rats through intraperitoneal injection of D-Galactosamine (D-Gal- N). To assess hepatic function and oxidative stress status, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content in liver tissue were quantified. The liver coefficients for each group were calculated as an additional parameter. For histopathological evaluation, liver tissue sections from the experimental group were stained with Hematoxylin and Eosin (H&E) and examined microscopically under light conditions. These revisions aim to enhance clarity, correct minor grammatical errors (such as capitalization of "HE" to "H&E"), and ensure a smoother flow of information without altering the scientific content of your original text. RESULTS: Successful establishment and separation of four distinct phases were achieved, including the self-emulsifying nano-phase, precipitation phase, suspension phase, and true solution phase. The self-emulsifying nano-phase was characterized as spherical particles with an average diameter of approximately 100 nm. Pharmacodynamic assessments revealed that both Xiao-Chai-Hu decoction and its self-emulsifying nano-phase significantly reduced liver coefficients and alanine aminotransferase (ALT) levels compared to controls (P<0.05). However, no statistically significant differences were observed in regards to aspartate aminotransferase (AST) concentrations, malondialdehyde (MDA) content, or superoxide dismutase (SOD) activity between the treatment groups and control (P>0.05). These findings indicate that both Xiao-Chai-Hu decoction and its self-emulsifying nano-formulation ameliorated D-GalN-induced acute liver injury, albeit without statistically distinguishable efficacy between them (P>0.05). CONCLUSION: The presence of a self-emulsifying nano-phase within Xiao-Chai-Hu decoction is confirmed, and this nano-phase emerges as a therapeutically efficacious component in mitigating acute liver injury.
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With the successive release of the CONSORT extensions for acupuncture, moxibustion, cupping, and Tuina/massage, this review aims to assess the reporting characteristics and quality of randomized controlled trials (RCTs) based on these specific guidelines. A comprehensive review was conducted by searching multiple databases, including Embase, Ovid MEDLINE(R), All EBM Reviews, AMED, CNKI, VIP Chinese Medical Journal Database, and Wanfang Data, for publications from January 1 to December 31, 2022. Two reviewers independently evaluated the eligibility of the records, extracted predetermined information, and assessed the reporting based on the STRICTA, STRICTOM, STRICTOC, and STRICTOTM checklists. Among the included 387 studies (acupuncture, 213; Tuina/massage, 85; moxibustion, 73; cupping, 16), the overall reporting compliance averaged 56.0%, with acupuncture leading at 62.6%, followed by cupping (60.2%), moxibustion (53.1%), and Tuina/massage (47.9%). About half of the evaluated items showed poor reporting (compliance rate < 65%). Notably, international journals demonstrated significantly higher reporting quality than Chinese journals (P < 0.05). Although acupuncture trials had relatively higher compliance rates, deficiencies persist in reporting non-pharmacological therapies of Chinese medicine, particularly in areas like treatment environment details and provider background information.
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Protein function prediction is critical for understanding the cellular physiological and biochemical processes, and it opens up new possibilities for advancements in fields such as disease research and drug discovery. During the past decades, with the exponential growth of protein sequence data, many computational methods for predicting protein function have been proposed. Therefore, a systematic review and comparison of these methods are necessary. In this study, we divide these methods into four different categories, including sequence-based methods, 3D structure-based methods, PPI network-based methods and hybrid information-based methods. Furthermore, their advantages and disadvantages are discussed, and then their performance is comprehensively evaluated and compared. Finally, we discuss the challenges and opportunities present in this field.
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Biologia Computacional , Proteínas , Proteínas/química , Proteínas/metabolismo , Biologia Computacional/métodos , Humanos , Análise de Sequência de Proteína/métodos , AlgoritmosRESUMO
OBJECTIVE: Immunotherapy, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. However, it can also cause immune-related adverse events (irAEs). This study aimed to develop a clinically practical animal model of irAEs using BALB/c mice. METHODS: Subcutaneous tumors of mouse breast cancer 4T1 cells were generated in inbred BALB/c mice. The mice were treated with programmed death-1 (PD-1) and cytotoxic t-lymphocyte antigen 4 (CTLA-4) inhibitors once every 3 days for five consecutive administration cycles. Changes in tumor volume and body weight were recorded. Lung computed tomography (CT) scans were conducted. The liver, lungs, heart, and colon tissues of the mice were stained with hematoxylin-eosin (H&E) staining to observe inflammatory infiltration and were scored. Serum samples were collected, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ferritin, glutamic-pyruvic transaminase (ALT), tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). Mouse liver and lung cell suspensions were prepared, and changes in macrophages, T cells, myeloid-derived suppressor cells (MDSCs), and regulatory (Treg) cells were detected by flow cytometry. RESULTS: Mice treated with PD-1 and CTLA-4 inhibitors showed significant reductions in tumor volume and body weight. The tissue inflammatory scores in the experimental group were significantly higher than those in the control group. Lung CT scans of mice in the experimental group showed obvious inflammatory spots. Serum levels of ferritin, IL-6, TNF-α, IFN-γ, and ALT were significantly elevated in the experimental group. Flow cytometry analysis revealed a substantial increase in CD3+T cells, Treg cells, and macrophages in the liver and lung tissues of mice in the experimental group compared with the control group, and the change trend of MDSCs was opposite. CONCLUSIONS: The irAE-related animal model was successfully established in BALB/c mice using a combination of PD-1 and CTLA-4 inhibitors through multiple administrations with clinical translational value and practical. This model offers valuable insights into irAE mechanisms for further investigation.
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Modelos Animais de Doenças , Inibidores de Checkpoint Imunológico , Camundongos Endogâmicos BALB C , Animais , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/farmacologia , Camundongos , Feminino , Antígeno CTLA-4/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Linhagem Celular TumoralRESUMO
Plastid retrograde signaling plays a key role in coordinating the expression of plastid genes and photosynthesis-associated nuclear genes (PhANGs). Although plastid retrograde signaling can be substantially compromised by mitochondrial dysfunction, it is not yet clear whether specific mitochondrial factors are required to regulate plastid retrograde signaling. Here, we show that mitochondrial ATP synthase beta-subunit mutants with decreased ATP synthase activity are impaired in plastid retrograde signaling in Arabidopsis thaliana. Transcriptome analysis revealed that the expression levels of PhANGs were significantly higher in the mutants affected in the AT5G08670 gene encoding the mitochondrial ATP synthase beta-subunit, compared to wild-type (WT) seedlings when treated with lincomycin (LIN) or norflurazon (NF). Further studies indicated that the expression of nuclear genes involved in chloroplast and mitochondrial retrograde signaling was affected in the AT5G08670 mutant seedlings treated with LIN. These changes might be linked to the modulation of some transcription factors (TFs), such as LHY (Late Elongated Hypocotyl), PIF (Phytochrome-Interacting Factors), MYB, WRKY, and AP2/ERF (Ethylene Responsive Factors). These findings suggest that the activity of mitochondrial ATP synthase significantly influences plastid retrograde signaling.
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Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , ATPases Mitocondriais Próton-Translocadoras , Plastídeos , Transdução de Sinais , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , ATPases Mitocondriais Próton-Translocadoras/genética , Plastídeos/metabolismo , Plastídeos/genética , Mitocôndrias/metabolismo , Plântula/genética , Plântula/metabolismo , Mutação , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Lincomicina/farmacologia , Perfilação da Expressão GênicaRESUMO
BACKGROUND: Canine circovirus (CanineCV), a non-enveloped virus with a circular DNA genome, has been identified in various avian and mammalian species, including domestic and wild canids. This study aimed to comprehensively analyze the prevalence of CanineCV across diverse animal species in 11 provinces of China. RESULTS: A total of 1,666 serum samples were collected, revealing a 5.82% prevalence of CanineCV in dogs, with the highest rates being observed in southern and eastern China. Phylogenetic analysis of 266 global CanineCV genomes sourced from the NCBI identified six distinct genotypes, elucidating the complex dynamics of their evolution. Evidence suggested a potential bat origin for CanineCV, with positive selection and high rates of evolution being observed. Recombination analysis revealed dynamic genetic exchange, highlighting the intricate nature of CanineCV evolution. Mutational analysis identified key amino acid substitutions likely to influence the virus's adaptation. Additionally, glycosylation, palmitoylation, and SUMOylation sites were predicted, shedding light on crucial functional properties of the virus. CONCLUSIONS: This study provides a global perspective on the origin, genetic diversity, and evolutionary dynamics of CanineCV. Understanding these factors is crucial for elucidating its epidemiology and potential health risks.
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Infecções por Circoviridae , Circovirus , Doenças do Cão , Filogenia , Animais , Circovirus/genética , Circovirus/classificação , Cães , Doenças do Cão/virologia , Doenças do Cão/epidemiologia , China/epidemiologia , Infecções por Circoviridae/veterinária , Infecções por Circoviridae/epidemiologia , Infecções por Circoviridae/virologia , Evolução Molecular , Genoma Viral , Variação Genética , Prevalência , GenótipoRESUMO
Xiaochaihu Decoctionï¼XCHDï¼is a classic prescription for the treatment of fever, but the mechanism is not clear. In this study, We elucidated the mechanism of action through network pharmacology and molecular docking. A rat fever model was established to verify the prediction results of network pharmacology. The analysis revealed that 120 intersection targets existed between XCHD and fever. The TP53, STAT3, RELA, MAPK1, AKT1, TNF and MAPK14 as potential core targets of XCHD in fever treatment. GO and KEGG pathway enrichment analyses indicated that XCHD may act through pathways such as the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, IL-17 signaling pathway. Molecular docking results demonstrated that quercetin, kaempferol, ß-sitosterol, stigmasterol and baicalein exhibited strong binding activity to key targets. Animal experiments showed that XCHD significantly reduced body temperature and levels of IL-1ß, IL-6, TNF-α, NO, PGE2, and cAMP in rats with fever. Importantly, no significant difference was observed between the XCHD self-emulsifying nano phase plus suspension phase and XCHD group. XCHD exerts its therapeutic effects on fever through a multi-ingredient, multi-target, and multi-pathway approach.
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The CO preferential oxidation reaction (CO-PROX) is an effective strategy to remove residual poisonous CO in proton exchange membrane fuel cells, in which oxygen vacancies play a critical role in CO adsorption and activation. Herein, a series of CuO/CeO2 catalysts derived from Ce-MOFs precursors were synthesized using different organic ligands via the hydrothermal method and the CO-PROX performance was investigated. The CuO/CeO2-135 catalyst derived from homophthalic tricarboxylic acid (1,3,5-H3BTC) exhibited superior catalytic performance with 100 % CO conversion at a relatively low temperature (T100% = 100 °C), with a wide reaction temperature range and excellent stability. The superior catalytic properties were attributed to the structural improvements provided by the 1,3,5-H3BTC precursors and the promotional effects of oxygen vacancies. Additionally, in-situ Raman spectroscopy was performed to verify the dynamic roles of oxygen vacancies for CO adsorption and activation, while in-situ DRIFTS analysis revealed key intermediates in the CO-PROX reaction, shedding light on the mechanistic aspects of the catalytic process. This work not only demonstrates insights into the effective CuO/CeO2 catalysts for CO preferential oxidation, but also provides a feasible way to synthesize MOF-derived catalysts.
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Mo4/3B2-x nanosheets are newly developed, and 2D transition metal borides (MBene) were reported in 2021, but there is no report on their further applications and modification; hence, this article sheds light on the significance of potential biological prospects for future biomedical applications. Therefore, elucidation of the biocompatibility, biotoxicology, and bioactivity of Mo4/3B2-x nanosheets has been an urgent need to be fulfilled. Nanometabolomics (also referred as nanomaterials-based metabolomics) was first proposed and utilized in our previous work, which specialized in interpreting nanomaterials-induced metabolic reprogramming through aqueous metabolomics and lipidomics approach. Hence, nanometabolomics could be considered as a novel concept combining nanoscience and metabolomics to provide bioinformation on nanomaterials' biomedical applications. In this work, the safe range of concentration (<50 mg/L) with good biosafety toward human umbilical vein endothelial cells (HUVECs) was discovered. The low concentration (5 mg/L) and high concentration (50 mg/L) of Mo4/3B2-x nanosheets were utilized for the in vitro Mo4/3B2-x-cell interaction. Nanometabolomics has elucidated the biological prospective of Mo4/3B2-x nanosheets via monitoring its biocompatibility and metabolic shift of HUVECs. The results revealed that 50 mg/L Mo4/3B2-x nanosheets could lead to a stronger alteration of amino acid metabolism with disturbance of the corresponding amino acid-related pathways (including amino acid metabolism, amino acid degradation, fatty acid biosynthesis, and lipid biosynthesis and metabolism). These interesting results were closely involved with the oxidative stress and production of excess ROS. This work could be regarded as a pathbreaking study on Mo4/3B2-x nanosheets at a biological level, which also designates their further biochemical, medical, and industrial application and development based on nanometabolomics bioinformation.
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Aminoácidos , Células Endoteliais da Veia Umbilical Humana , Nanoestruturas , Humanos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Aminoácidos/química , Aminoácidos/metabolismo , Nanoestruturas/química , Nanoestruturas/toxicidade , Metabolômica , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Compostos de Boro/química , Compostos de Boro/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Reprogramação MetabólicaRESUMO
Introduction: Continuous positive airway pressure (CPAP) therapy improves clinical symptoms in patients with obstructive sleep apnea (OSA); however, the mechanism of this clinical improvement and how it may be associated with the restoration of white matter (WM) structures in the brain is unclear. Therefore, this study investigated the relationship between the structural recovery of brain WM and improvements in cognitive function and emotion after long-term (12 months) CPAP treatment in patients with OSA. Methods: We collected data from 17 patients with OSA before and 12 months after CPAP treatment, including sleep monitoring, clinical assessment, and diffusion tensor imaging (DTI) magnetic resonance imaging. Results: We observed a partial reversible recovery of brain WM (mean and radial diffusion coefficients) after treatment. This recovery involved the commissural fibers (cingulum, body of corpus callosum), projection fibers (retrolenticular part of the internal capsule, posterior thalamic radiation, posterior limb of the internal capsule, superior corona radiata, posterior corona radiata), association fibers (external capsule, superior longitudinal fasciculus, inferior longitudinal fasciculus), and other regions. In addition, the improvements in WM fibers in one part of the brain significantly were correlated with the Hamilton Anxiety Scale and Hamilton Depression Scale scores. Discussion: Our results suggest that reversible recovery of reduced brain WM integrity due to OSA may require longer CPAP treatment. Moreover, changes in the integrity of the commissural fibers were associated with emotion regulation. These restored WM areas may explain the cognitive and mood improvements observed after OSA treatment.
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PURPOSE: To investigate dynamic functional connectivity (dFC) within the cerebellar-whole brain network and dynamic topological properties of the cerebellar network in obstructive sleep apnea (OSA) patients. METHODS: Sixty male patients and 60 male healthy controls were included. The sliding window method examined the fluctuations in cerebellum-whole brain dFC and connection strength in OSA. Furthermore, graph theory metrics evaluated the dynamic topological properties of the cerebellar network. Additionally, hidden Markov modeling validated the robustness of the dFC. The correlations between the abovementioned measures and clinical assessments were assessed. RESULTS: Two dynamic network states were characterized. State 2 exhibited a heightened frequency, longer fractional occupancy, and greater mean dwell time in OSA. The cerebellar networks and cerebrocerebellar dFC alterations were mainly located in the default mode network, frontoparietal network, somatomotor network, right cerebellar CrusI/II, and other networks. Global properties indicated aberrant cerebellar topology in OSA. Dynamic properties were correlated with clinical indicators primarily on emotion, cognition, and sleep. CONCLUSION: Abnormal dFC in male OSA may indicate an imbalance between the integration and segregation of brain networks, concurrent with global topological alterations. Abnormal default mode network interactions with high-order and low-level cognitive networks, disrupting their coordination, may impair the regulation of cognitive, emotional, and sleep functions in OSA.
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Cerebelo , Rede Nervosa , Apneia Obstrutiva do Sono , Humanos , Masculino , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Pessoa de Meia-Idade , Adulto , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Imageamento por Ressonância Magnética , Conectoma , Vias Neurais/fisiopatologia , Vias Neurais/diagnóstico por imagem , Rede de Modo Padrão/fisiopatologia , Rede de Modo Padrão/diagnóstico por imagemRESUMO
Background: Glycyrrhetinic acid-mediated brucine self-assembled nanomicelles enhance the anti-hepatitis B properties of brucine by improving its water solubility, short half-life, toxicity, and side effects. Brucine (B) is an indole alkaloid extracted from the seeds of Strychnos nux-vomica (Loganiaceae). Purpose: To assess the efficacy of the Brucine-Glycyrrhetnic acid-Polyethylene glycol-3,3'-dithiodipropionic acid-Glycerin monostearate (B-GPSG) in treating hepatitis B, its potential to protect against acute liver injury caused by d-galactosamine and its anti-hepatoma activities were studied. Research Design: The concentration of B-GPSG used in the in vivo and in vitro experiments was 0.63 mg/mL. The rats injected with d-GalN (450 mg/kg) were used as liver injury models. The rats were separated into normal, model, positive, positive control, B-PSG and B-GPSG groups. Hepatoma cells expressing HBV HepG2.2.15 were used for in vitro experiments. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate cloning, Hoechst staining and flow cytometry were conducted to explore the mechanism of B-GPSG against hepatitis B. Results: Compared with the model group, the liver coefficient of B-GPSG group decreased (4.59 ± 0.17 vs 5.88 ± 0.42), the content of MDA in rat liver homogenate decreased (12.54 ± 1.81 vs 23.05 ± 2.98), the activity of SOD increased, the activity of ALT and AST in rat serum decreased. In vitro, the IC50 values of B-GPSG group decreased. B-GPSG group effectively inhibited the proliferation and migration of HepG2.2.15 cells. Conclusions: The hepatoprotective effects of B-GPSG nanomicelles, which are attributed to their GA-mediated liver targeting and synergistic actions with brucine, suggest their therapeutic potential against hepatitis B. This development opens up new possibilities for the application of traditional Chinese medicine and nanomedicine in anti-hepatitis B.
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Ácido Glicirretínico , Hepatite B , Estricnina , Animais , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/química , Ácido Glicirretínico/farmacologia , Humanos , Células Hep G2 , Hepatite B/tratamento farmacológico , Estricnina/análogos & derivados , Estricnina/farmacologia , Estricnina/administração & dosagem , Estricnina/química , Ratos , Masculino , Ratos Sprague-Dawley , Antivirais/farmacologia , Antivirais/química , Antivirais/administração & dosagem , Fígado/metabolismo , Fígado/efeitos dos fármacos , Sistemas de Liberação de Fármacos por Nanopartículas/químicaRESUMO
Photodynamic therapy (PDT) using aggregation-induced emission photosensitizer (AIE-PS) holds tremendous potential but is limited by its inherent disadvantages and the high concentrations of reduced glutathione (GSH) in tumor cells that can neutralize ROS to weaken PDT. Herein, we designed a nanodelivery system (CM-HSADSP@[PS-Sor]) in which albumin was utilized as a carrier for hydrophobic drug AIE-PS and Sorafenib, cross-linkers with disulfide bonds were introduced to form a nanogel core, and then cancer cell membranes were wrapped on its surface to confer homologous tumor targeting ability. A two-way strategy was employed to disturb redox-homeostasis through blocking GSH synthesis by Sorafenib and consuming excess GSH via abundant disulfide bonds, thereby promoting the depletion of GSH, which in turn increased the ROS levels in cancer cells to amplify the efficacy of ferroptosis and PDT, achieving an efficient in vivo antibreast cancer effect. This study brings a new strategy for ROS-based cancer therapy and expands the application of an albumin-based drug delivery system.
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Ferroptose , Oxirredução , Fotoquimioterapia , Fármacos Fotossensibilizantes , Ferroptose/efeitos dos fármacos , Fotoquimioterapia/métodos , Humanos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Fármacos Fotossensibilizantes/química , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Linhagem Celular Tumoral , Glutationa/metabolismo , Homeostase/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Camundongos Endogâmicos BALB C , Sistemas de Liberação de Medicamentos/métodos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Sorafenibe/químicaRESUMO
Rhenium (Re) and uranium (U) are essential proxies in reconstructing past oceanic oxygenation evolution. However, their removal in continental shelf sediments, hotspots of early diagenesis, were previously treated as quantitatively unimportant sinks in the ocean. Here we examine the sedimentary reductive removal of Re and U and their coupling with organic carbon decomposition, utilizing the 224Ra/228Th disequilibria within the East China Sea shelf. We identified positive correlations between their removal fluxes and the rates of sediment oxygen consumption or organic carbon decomposition. These correlations enable an evaluation of global shelf reductive sinks that are comparable to (for Re) or higher than (~4-fold for U) previously established suboxic/anoxic sinks. These findings suggest potential imbalances in the modern budgets of Re and U, or perhaps a substantial underestimation of their sources. Our study thus highlights shelf sedimentary reductive removal as critical yet overlooked sinks for Re and U in the modern ocean.
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The interplay between nitrogen and sulfur assimilation synergistically supports and sustains plant growth and development, operating in tandem to ensure coordinated and optimal outcomes. Previously, we characterized Arabidopsis CHLOROPHYLL A/B-BINDING (CAB) overexpression 2 (COE2) mutant, which has a mutation in the NITRIC OXIDE-ASSOCIATED (NOA1) gene and exhibits deficiency in root growth under low nitrogen (LN) stress. This study found that the growth suppression in roots and shoots in coe2 correlates with decreased sensitivity to low sulfur stress treatment compared to the wild-type. Therefore, we examined the regulatory role of COE2 in nitrogen and sulfur interaction by assessing the expression of nitrogen metabolism-related genes in coe2 seedlings under low sulfur stress. Despite the notable upregulation of nitrate reductase genes (NIA1 and NIA2), there was a considerable reduction in nitrogen uptake and utilization, resulting in a substantial growth penalty. Moreover, the elevated expression of miR396 perhaps complemented growth stunting by selectively targeting and curtailing the expression levels of GROWTH REGULATING FACTOR 2 (GRF2), GRF4, and GRF9. This study underscores the vital role of COE2-mediated nitrogen signaling in facilitating seedling growth under sulfur deficiency stress.
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Proteínas de Arabidopsis , Arabidopsis , Regulação da Expressão Gênica de Plantas , Nitrogênio , Enxofre , Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/fisiologia , Nitrogênio/metabolismo , Enxofre/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Estresse Fisiológico , Plântula/metabolismo , Plântula/crescimento & desenvolvimento , Plântula/genética , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/genética , Nitrato Redutase/metabolismo , Nitrato Redutase/genéticaRESUMO
BACKGROUND: The optimal revascularization strategy for non-culprit vessels is still up for debate nowadays, particularly when it comes to individuals with different Killip classes. Therefore, the aim of our study was to investigate whether multivessel revascularization, as compared with infarct-related artery (IRA) alone revascularization, improves long-term prognosis in patients who have experienced an acute myocardial infarction (AMI) and have multivessel coronary artery disease (CAD). METHODS: A retrospective analysis was conducted on clinical data from 646 patients who presented with AMI and multivessel CAD at Beijing Chaoyang hospital between November 2014 and November 2020. Based on various revascularization strategies, patients were categorised into two groups: IRA-only revascularization (n = 416) and multivessel revascularization (n = 230). The primary endpoint was cardiovascular death. RESULTS: In the following 60.6 months (60.6 ± 23.9), the primary endpoint occurred in 3% of the multivessel revascularization group versus 9.6% in the IRA-only revascularization group (HR 0.284, CI 0.120-0.669, p = 0.002). For the Killip I-II patients (n = 533), the primary endpoint occurred in 2.6% of the multivessel revascularization group versus 9.5% in the IRA-only revascularization group (HR 0.236, CI 0.083-0.667, p = 0.003). For Killip III-IV patients (n = 113), there was no significance differences in the primary endpoint. After using the inverse probability weighted method, the benefit of complete revascularization was consistently observed. CONCLUSIONS: Multivessel revascularization significantly reduced the incidence of cardiovascular death for patients presenting with AMI and multivessel CAD, particularly for Killip I-II patients. There were no significant differences in the primary outcome across the groups of patients with Killip III-IV.
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Doença da Artéria Coronariana , Infarto do Miocárdio , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/complicações , Infarto do Miocárdio/cirurgia , Infarto do Miocárdio/diagnóstico , Idoso , Intervenção Coronária Percutânea/métodos , Revascularização Miocárdica/métodos , Resultado do Tratamento , Angiografia Coronária , Vasos Coronários/cirurgia , Vasos Coronários/diagnóstico por imagem , Seguimentos , Taxa de Sobrevida/tendências , PrognósticoRESUMO
PURPOSE: Previous studies have demonstrated impaired cerebellar function in patients with obstructive sleep apnea (OSA), which is associated with impaired cognition. However, the effects of OSA on resting-state functional connectivity (FC) in the cerebellum has not been determined. The purpose of this study was to investigate resting-state FC of the cerebellar subregions and its relevance to clinical symptoms in patients with OSA. METHODS: Sixty-eight patients with OSA and seventy-two healthy controls (HCs) were included in the study. Eight subregions of the cerebellum were selected as regions of interest, and the FC values were calculated for each subregion with other voxels. A correlation analysis was performed to examine the relationship between clinical and cognitive data. RESULTS: Patients with OSA showed higher FC in specific regions, including the right lobule VI with the right posterior middle temporal gyrus and right angular gyrus, the right Crus I with the bilateral precuneus/left superior parietal lobule, and the right Crus II with the precuneus/right posterior cingulate cortex. Furthermore, the oxygen depletion index was negatively correlated with aberrant FC between the right Crus II and the bilateral precuneus / right posterior cingulate cortex in OSA patients (p = 0.004). CONCLUSION: The cerebellum is functionally lateralized and closely linked to the posterior default mode network. Higher FC is related to cognition, emotion, language, and sleep in OSA. Abnormal FC may offer new neuroimaging evidence and insights for a deeper comprehension of OSA-related alterations.
Assuntos
Cerebelo , Imageamento por Ressonância Magnética , Apneia Obstrutiva do Sono , Humanos , Masculino , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Pessoa de Meia-Idade , Adulto , Estudos de Casos e Controles , Mapeamento Encefálico/métodos , DescansoRESUMO
Objectives: This study aims to assess the efficacy of narrow band imaging (NBI) endoscopy in utilizing radiomics for predicting radiosensitivity in nasopharyngeal carcinoma (NPC), and to explore the associated molecular mechanisms. Materials: The study included 57 NPC patients who were pathologically diagnosed and underwent RNA sequencing. They were categorized into complete response (CR) and partial response (PR) groups after receiving radical concurrent chemoradiotherapy. We analyzed 267 NBI images using ResNet50 for feature extraction, obtaining 2048 radiomic features per image. Using Python for deep learning and least absolute shrinkage and selection operator for feature selection, we identified differentially expressed genes associated with radiomic features. Subsequently, we conducted enrichment analysis on these genes and validated their roles in the tumor immune microenvironment through single-cell RNA sequencing. Results: After feature selection, 54 radiomic features were obtained. The machine learning algorithm constructed from these features showed that the random forest algorithm had the highest average accuracy rate of 0.909 and an area under the curve of 0.961. Correlation analysis identified 30 differential genes most closely associated with the radiomic features. Enrichment and immune infiltration analysis indicated that tumor-associated macrophages are closely related to treatment responses. Three key NBI differentially expressed immune genes (NBI-DEIGs), namely CCL8, SLC11A1, and PTGS2, were identified as regulators influencing treatment responses through macrophages. Conclusion: NBI-based radiomics models introduce a novel and effective method for predicting radiosensitivity in NPC. The molecular mechanisms may involve the functional states of macrophages, as reflected by key regulatory genes.
RESUMO
As a potential material to solve rampant dendrites and hydrogen evolution reaction (HER) problem of aqueous zinc metal batteries (AZMB), hydrogel electrolytes usually require additional additives or multi-molecular network strategies to solve existing problems of ionic conductivity, mechanical properties and interface stability. However, the intrinsic zincophilic properties of the gel itself are widely neglected leading to the addition of additional molecules and the complexity of the preparation process. In this work, we innovatively utilize the characteristics of acrylamide's high zincophilic group density, activating the intrinsic zincophilic properties of PAM gel through a simple concentration control strategy which reconstructs a novel zinc-electrolyte interface different from conventional PAM electrolyte. The activated novel gel electrolyte with intrinsic zincophilic properties has high ionic conductivity and effectively suppresses water activity, thereby inhibiting HER corrosion. Meanwhile, it induces uniform deposition of (002) crystal planes, leading to excellent deposition kinetics and long cycle life, thereby ensuring high interfacial stability. Compared with conventional PAM gel electrolytes, the activated zincophilic group-rich hydrogel maintained excellent cycling stability (1â mA/cm2, 1â mAh/cm2) over 2250â hours; The Zn//MnO2 coin cell using novel zincophilic group -rich hydrogel still retains a high specific capacity of more than 170â mAh/g at 0.5â A/g after 1000 cycles.