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Gemcitabine resistance is one of the leading causes of bladder cancer (BCa) recurrence and progression. The dysregulation of ferroptosis is involved in this process; however, the underlying mechanisms remain unclear. In the current study, we found a prominent increase in long non-coding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) in tumor samples, which was related to advanced tumor grade and poor prognosis. SNHG16 is overexpressed in the starving tumor microenvironment (STME) and induces gemcitabine resistance by inhibiting ferroptosis in BCa. SNHG16 knockdown promotes ferroptosis and increases chemosensitivity to gemcitabine. Mechanistically, the transcription factor MEF2A was markedly upregulated in the STME, facilitating SNHG16 expression. SNHG16 acts as a competing endogenous RNA that sponges miR-425-5p and promotes NOTCH2 expression. SNHG16/miR-425-5p/NOTCH2 is demonstrated, for the first time, to suppress ferroptosis by inducing SLC7A11 and GPX4 expression in vitro and in vivo. Upregulation of miR-425-5p reverses NOTCH2-mediated inhibition of ferroptosis, thereby mitigating gemcitabine resistance. In conclusion, these findings reveal that the STME-activated MEF2A/SNHG16/miR-425-5p/NOTCH2 axis induces gemcitabine resistance by inhibiting ferroptosis and implicate SNHG16 as a potential therapeutic target for chemoresistance.
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In the postantibiotic era, the pathogenicity and resistance of pathogens have increased, leading to an increase in intestinal inflammatory disease. Bacterial infections remain the leading cause of animal mortality. With increasing resistance to antibiotics, there has been a significant decrease in resistance to both inflammation and disease in animals, thus decreasing production efficiency and increasing production costs. These side effects have serious consequences and have detracted from the development of China's pig industry. Microcin C7 (McC7) demonstrates potent antibacterial activity against a broad spectrum of pathogens, stable physicochemical properties, and low toxicity, reducing the likelihood of resistance development. Thus, McC7 has received increasing attention as a potential clinical antibacterial and immunomodulatory agent. McC7 has the potential to serve as a new generation of antibiotic substitutes; however, its commercial applications in the livestock and poultry industry have been limited. In this review, we summarize and discuss the biosynthesis, biochemical properties, structural characteristics, mechanism of action, and immune strategies of McC7. We also describe the ability of McC7 to improve intestinal health. Our aim in this study was to provide a theoretical basis for the application of McC7 as a new feed additive or new veterinary drug in the livestock and poultry breeding industry, thus providing a new strategy for alleviating resistance through feed and mitigating drug resistance. Furthermore, this review provides insight into the new functions and anti-infection mechanisms of bacteriocin peptides and proposes crucial ideas for the research, product development, and application of bacteriocin peptides in different fields, such as the food and medical industries.
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Antibacterianos , Bacteriocinas , Bacteriocinas/farmacologia , Bacteriocinas/química , Bacteriocinas/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Animais , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/uso terapêutico , Suínos , HumanosRESUMO
Acupuncture is an important therapeutic method of traditional Chinese medicine and can effectively modulate brain disorders. The therapeutic efficacy of acupuncture is hard to evaluate due to lacking of effective measurements of brain activity. In this work, we design an EEG-based monitoring system to evaluate therapeutic effect of acupuncture on human brain by extracting periodic-aperiodic features. Power spectral density is estimated to compute the adjusted power of periodic oscillatory rhythm in EEG under acupuncture stimulation. It is exhibited that the brain activity in alpha band (8-12 Hz) is significantly enhanced during acupuncture, especially in parietal and occipital lobe regions. To probe the modulatory effect of acupuncture on aperiodic brain activity, we calculate the aperiodic exponent based on the parameterization of EEG power spectra. The aperiodic exponent decreases along with acupuncture process, which is more significant in central and frontal lobe regions. Furthermore, sensitivity of different brain regions to acupuncture is assessed by the integration of adjusted power and aperiodic exponent. Experimental results demonstrate the effectiveness of proposed periodic-aperiodic measurements of EEG signals, by which different effects of four acupuncture manipulations are precisely evaluated and a knowledge graph is established. The monitoring system provides a new perspective to quantitatively evaluate acupuncture effect on human brain and improve its therapeutic efficacy in clinical applications for neural disorders.
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Terapia por Acupuntura , Algoritmos , Encéfalo , Eletroencefalografia , Humanos , Eletroencefalografia/métodos , Terapia por Acupuntura/métodos , Encéfalo/fisiologia , Masculino , Adulto , Ritmo alfa , Adulto Jovem , Reprodutibilidade dos Testes , Feminino , Resultado do Tratamento , Sensibilidade e EspecificidadeRESUMO
The presence of minute quantities of water in organic solvents can affect the progress of many reactions and cause unnecessary losses and even safety accidents in the chemical industry, especially in the productions process of organic fine chemicals. Therefore, it is necessary to carry out high-performance strategies for trace water detections in commonly used organic solvents. In this work, a fluorescent sensing system based on competitive binding of protons has been developed, demonstrating remarkable responses by UV-vis absorption and fluorescence two-modes toward a trace amount of water in organic solvents including 1,4-dioxane (Diox), tetrahydrofuran (THF), acetonitrile (MeCN), acetone (ACE), dimethylsulfoxide (DMSO) and mixed organic solvents (THF: MeCN=1: 1). The key component of the sensing system is a newly designed fluorophore NBD-PMA, which can be deprotonated to form a dynamic non-luminescent adduct, namely NBD-PMA-F, by an organic fluoride salt tetrabutylammonium fluoride (TBAF). NBD-PMA-F can be reprotonated via using trace water, exhibiting fluorescence turn on of the system. The as-prepared sensing system shows superior sensitivity, low detection limits (v/v, 0.0007 %), quick response speed (≤1.2 s) and good reversibility. Moreover, naked-eye visual rapid detection has also been successfully realized at ambient temperature, which demonstrated their practical applications value for trace water determinations.
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Fluorescence sensing and imaging techniques are being widely studied for detecting carbon monoxide (CO) in living organisms due to their speed, sensitivity, and ease of use to biological systems. Most fluorescent probes used for this purpose are based on heavy metal ions like Pd, with a few using elements like Ru, Rh, Ir, Os, Tb, and Eu. However, these metals can be expensive and toxic to cells. There is a need for more affordable and biologically safe fluorescent probes for CO detection. Drawing inspiration from the robust affinity exhibited by heme iron toward CO, in this work, a rhodamine derivative called RBF was developed for imaging CO in living cells by binding to Fe(III) and could be used for CO sensing. A Fe(III)-based fluorescent probe for CO imaging in living cells offers advantages of cost effectiveness, low toxicity, and ease of use. The fluorescence detection using the RBF-Fe system showed a direct correlation with increasing levels of CORM-3 (LOD = 146 nM) or the exposure time of CO gas, displaying reduced fluorescence. A CO test paper based on RBF-Fe was created for simple on-site CO detection, where fluorescence would diminish in response to CO exposure, allowing rapid (2 min) visual identification. Imaging of CO in living cells was successfully conducted using the probe system, showing a decrease in fluorescence intensity as CORM-3 concentrations increased, indicating its effectiveness in monitoring CO levels accurately within living cells.
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Monóxido de Carbono , Compostos Férricos , Corantes Fluorescentes , Monóxido de Carbono/análise , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Humanos , Compostos Férricos/química , Compostos Férricos/análise , Imagem Óptica , Rodaminas/química , Células HeLaRESUMO
Breast cancer (BC) is currently the most prevalent malignancy worldwide, and finding effective non-invasive biomarkers for routine clinical detection of BC remains a significant challenge. Here, we performed non-targeted and targeted metabolomics analysis on the screening, training and validation cohorts of serum samples from 1,947 participants. A metabolite biomarker model including glutamate, erythronate, docosahexaenoate, propionylcarnitine, and patient's age was established for detecting BC. This model demonstrated better diagnostic performance than carbohydrate antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) alone in discriminating BC from healthy controls both in the training and validation cohorts [area under the curve (AUC), 0.954; sensitivity, 87.1% and specificity, 93.5% for the training cohort and 0.834, 68.3%, and 85.2%, respectively, for the validation cohort 1]. This study has established a noninvasive approach for the detection of BC, which shows potential as a suitable supplement to the clinical screening methods currently employed for BC.
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Diabetic cardiomyopathy (DCM) is a prevalent myocardial microvascular complication of the myocardium with a complex pathogenesis. Investigating the pathogenesis of DCM can significantly contribute to enhancing its prevention and treatment strategies. Our study revealed an upregulation of lysine acetyltransferase 2 A (Kat2a) expression in DCM, accompanied by a decrease in N6-methyladenosine (m6A) modified Kat2a mRNA levels. Our study revealed an upregulation of lysine acetyltransferase 2 A (Kat2a) expression in DCM, accompanied by a decrease in N6-methyladenosine (m6A) modified Kat2a mRNA levels. Functionally, inhibition of Kat2a effectively ameliorated high glucose-induced cardiomyocyte injury both in vitro and in vivo by suppressing ferroptosis. Mechanistically, Demethylase alkB homolog 5 (Alkbh5) was found to reduce m6A methylation levels on Kat2a mRNA, leading to its upregulation. YTH domain family 2 (Ythdf2) played a crucial role as an m6A reader protein mediating the degradation of Kat2a mRNA. Furthermore, Kat2a promoted ferroptosis by increasing Tfrc and Hmox1 expression via enhancing the enrichment of H3K27ac and H3K9ac on their promoter regions. In conclusion, our findings unveil a novel role for the Kat2a-ferroptosis axis in DCM pathogenesis, providing valuable insights for potential clinical interventions.
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Cardiomiopatias Diabéticas , Ferroptose , Heme Oxigenase-1 , Histona Acetiltransferases , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Cardiomiopatias Diabéticas/genética , Animais , Ferroptose/genética , Humanos , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/genética , Camundongos , Histona Acetiltransferases/metabolismo , Histona Acetiltransferases/genética , Masculino , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Adenosina/análogos & derivados , Adenosina/metabolismoRESUMO
Electrocoagulation technology, due to its simplicity and ease of operation, is often considered for treating arsenic-contaminated groundwater. However, challenges such as anode wear have hindered its development and application. This study aims to develop a siderite-filled anode electrocoagulation system for efficient removal of As(iii) and investigate its effectiveness. The impact of operational parameters on the removal rate of As(iii) was analyzed through single-factor tests, and the stability and superiority of the device were evaluated. The response surface methodology was employed to analyze the interactions between various factors and determine the optimal operational parameters by integrating data from these tests. Under conditions where the removal rate of As reached 99.3 ± 0.37%, with an initial concentration of As(iii) at 400 µg L-1, current intensity at 30 mA, initial solution pH value at 7, and Na2SO4 concentration at 10 mM. The flocculant used was subjected to characterization analysis to examine its structure, morphology, and elemental composition under these optimal operational parameters. The oxidation pathway for As(iii) within this system relies on integrated results from direct electrolysis as well as ËO2 -, ËOH, and Fe(iv) mediated oxidation processes. The elimination of arsenic encompasses two fundamental mechanisms: firstly, the direct adsorption of As(iii) by highly adsorbent flocculants like γ-FeOOH and magnetite (Fe3O4); secondly, the oxidation of As(iii) into As(v), followed by its reaction with siderite or other compounds to generate a dual coordination complex or iron arsenate, thus expediting its eradication. The anodic electrocoagulation system employing siderite as a filler exhibits remarkable efficiency and cost-effectiveness, while ensuring exceptional stability, thereby providing robust theoretical underpinnings for the application of electrocoagulation technology in arsenic removal.
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BACKGROUND: This study aimed to evaluate the effectiveness and safety of 2D laparoscopy vs 3D laparoscopy for the treatment of colorectal cancer. METHODS: A literature search was conducted through PubMed, Web of Science, and Embase from their inception to January 2024. Studies investigating different outcomes of colorectal surgery were included. Results are presented as odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs). The protocol for this review has been registered on PROSPERO (CRD42024504902). RESULTS: A total of 10 publications were retrieved in this article. The 3D group is associated with a significant improvement in intraoperative blood loss (MD = -8.04, 95% CI = -14.18 to -1.89, P = 0.01, I2 = 55%), operative time (MD = -17.33, 95% CI = -29.15 to -5.51, P = 0.004, I2 = 90%), and postoperative hospital stay (MD = -0.23, 95% CI = -0.43 to -0.04, P = 0.02, I2 = 48%) compared to that of patients treated in the 2D group, particularly for rectal cancer patients above three results (MD = -10.36, 95% CI = -15.00 to -5.73, P < 0.001, I2 = 0%), (MD = -18.85, 95% CI = -34.88 to -2.82, P = 0.02, I2 = 57%), and (MD = -0.93, 95% CI = -1.53 to -0.34, P = 0.002, I2 = 0%), respectively. There was no significant statistical difference in the time of pass flatus (MD = -0.14, 95% CI = -0.49 to 0.21, P = 0.44, I2 = 79%) and the number of dissected lymph nodes (MD = 0.36, 95% CI = -0.49 to 1.21, P = 0.41, I2 = 45%), but the 3D group had an earlier postoperative pass flatus for rectal cancer patients (MD = -0.46, 95% CI = -0.66 to -0.27, P<0.001, I2 = 0%) and the more number of dissected lymph nodes for colon cancer patients (MD = 1.54, 95% CI = 0.05 to 3.03, P = 0.04, I2 = 69%) than the 2D group. There was no significant difference in postoperative overall complication (OR = 0.94, 95% CI = 0.67 to 1.31, P = 0.71, I2 = 0%) and anastomotic leakage (OR = 0.93, 95% CI = 0.48 to 1.80, P = 0.83, I2 = 0%) in the two groups, regardless of rectal cancer and colon surgery patients. CONCLUSION: This meta-analysis demonstrates that 3D laparoscopy could reduce the amount of blood loss, accelerate postoperative pass flatus, and shorten the operation time and postoperative hospital stay over 2D for radical rectal cancer surgery, without obvious advantage for radical colon cancer surgery. Moreover, 3D laparoscopy increases the number of dissected lymph nodes for radical colon cancer surgery but may not be observed in rectal cancer surgery.
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Epidemiological findings have determined the linkage of fine particulate matter (PM2.5) and the morbidity of hypertension. However, the mode of action and specific contribution of PM2.5 component in the blood pressure elevation remain unclear. Platelets are critical for vascular homeostasis and thrombosis, which may be involved in the increase of blood pressure. Among 240 high-PM2.5 exposed, 318 low-PM2.5 exposed workers in a coking plant and 210 workers in the oxygen plant and cold-rolling mill enrolled in present study, both internal and external exposure characteristics were obtained, and we performed linear regression, adaptive elastic net regression, quantile g-computation and mediation analyses to analyze the relationship between urine metabolites of polycyclic aromatic hydrocarbons (PAHs) and metals fractions with platelets indices and blood pressure indicators. We found that PM2.5 exposure leads to increased systolic blood pressure (SBP) and pulse pressure (PP). Specifically, for every 10 µg/m3 increase in PM2.5, there was a 0.09 mmHg rise in PP. Additionally, one IQR increase in urinary 1-hydroxypyrene (1.06 µmol/mol creatinine) was associated with a 3.43 % elevation in PP. Similarly, an IQR increment of urine cobalt (2.31 µmol/mol creatinine) was associated with a separate 1.77 % and 4.71 % elevation of SBP and PP. Notably, platelet-to-lymphocyte ratio (PLR) played a mediating role in the elevation of SBP and PP induced by cobalt. Our multi-pollutants results showed that PAHs and cobalt were deleterious contributors to the elevated blood pressure. These findings deepen our understanding of the cardiovascular effects associated with PM2.5 constituents, highlighting the importance of increased vigilance in monitoring and controlling the harmful components in PM2.5.
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Poluentes Atmosféricos , Pressão Sanguínea , Material Particulado , Hidrocarbonetos Policíclicos Aromáticos , Material Particulado/análise , Humanos , Pressão Sanguínea/efeitos dos fármacos , Masculino , Plaquetas/efeitos dos fármacos , Adulto , Metais/urina , Feminino , Exposição Ocupacional/estatística & dados numéricos , Pessoa de Meia-Idade , Hipertensão/epidemiologiaRESUMO
Starch based carbon aerogel has attracted significant attention due to the wide source, environmental friendliness and low price of raw materials. Here, starch based carbon aerogel was fabricated by graft reaction and cross-linking reaction of starch. The network structure of starch hydrogel was optimized through graft and cross-linking reaction. After freeze drying and high temperature carbonization, the obtained carbon aerogel that carbonized at 800 °C showed a specific surface area of 1508 m2·g-1 without activation which is far higher than that of other unactivated carbon aerogels. The starch based carbon aerogel carbonized at 800 °C exhibited superior methylene blue adsorption ability with a maximum adsorption capacity of 963.5 mg·g-1 as a result of its rich surface functional groups, high specific surface area, and reasonable pore size distribution. Furthermore, the carbon aerogel carbonized at 700 °C exhibited excellent electrochemical performance with a specific capacitance of 180.1 F·g-1 at a current density of 1 A·g-1as electrode materials for supercapacitors. Overall, this work provides a new method to prepare high performance starch based carbon aerogel.
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Carbono , Capacitância Elétrica , Géis , Azul de Metileno , Amido , Amido/química , Azul de Metileno/química , Carbono/química , Adsorção , Géis/química , Propriedades de Superfície , PorosidadeRESUMO
Low discovery rates for new antibiotics, commercial disincentives to invest, and inappropriate use of existing drugs have created a perfect storm of antimicrobial resistance (AMR). This "silent pandemic" of AMR looms as an immense, global threat to human health. In tandem, many potential novel drug candidates are not progressed due to elevated hydrophobicity, which may result in poor intracellular internalization and undesirable serum protein binding. With a reducing arsenal of effective antibiotics, enabling technology platforms that improve the outcome of treatments, such as repurposing existing bioactive agents, is a prospective option. Nanocarrier (NC) mediated drug delivery is one avenue for amplifying the therapeutic outcome. Here, the performance of several antibiotic classes encapsulated within the lipid-based cubosomes is examined. The findings demonstrate that encapsulation affords significant improvements in drug concentration:inhibition outcomes and assists in other therapeutic challenges associated with internalization, enzyme degradation, and protein binding. We emphasize that a currently sidelined compound, novobiocin, became active and revealed a significant increase in inhibition against the pathogenic Gram-negative strain, Pseudomonas aeruginosa. Encapsulation affords co-delivery of multiple bioactives as a strategy for mitigating failure of monotherapies and tackling resistance. The rationale in optimized drug selection and nanocarrier choice is examined by transport modeling which agrees with experimental inhibition results. The results demonstrate that lipid nanocarrier encapsulation may alleviate a range of challenges faced by antibiotic therapies and increase the range of antibiotics available to treat bacterial infections.
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Antibacterianos , Portadores de Fármacos , Lipídeos , Pseudomonas aeruginosa , Antibacterianos/química , Antibacterianos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Portadores de Fármacos/química , Lipídeos/química , Nanopartículas/química , Testes de Sensibilidade Microbiana , Humanos , Sistemas de Liberação de MedicamentosRESUMO
Toxic gases are used in different types of industries and thus, present a potential health hazard. Therefore, highly sensitive gas sensing materials are essential for the safety of those operating in their environments. A process involving electrospinning polymer solutions impregnated with transition metal ions are developed to yield nanofibers that are annealed to form graphitic carbon / nickel nanoparticle-based fibers for gas sensing applications. The performance of these gas sensors is strongly related to the ability to control the material parameters of the active material. As the formation of these nanostructures, which nucleate within solid carbon scaffolds, have not been investigated, the growth mechanisms are look to understand in order to exert control over the resulting material. Evaluation of these growth mechanisms are conducted through a combination of thermogravimetric analysis with mass spectrometry (TGA-MS), x-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and x-ray photoelectron spectroscopy (XPS) and reveal nucleation of nickel at the onset of the polymer scaffold decomposition with subsequent growth processes, including surface diffusion, aggregation, coalescence and evaporation condensation, that are activated at different temperatures. Gas sensing experiments conducted on analyte gases demonstrate good sensitivity and response times, and significant potential for use in other energy and environmental applications.
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BACKGROUND: The energy supply of certain cancer cells depends on aerobic glycolysis rather than oxidative phosphorylation. Our previous studies have shown that withaferin A (WA), a lactone compound derived from Withania somnifera, suppresses skin carcinogenesis at least partially by stabilizing IDH1 and promoting oxidative phosphorylation. Here, we have extended our studies to evaluate the anti-tumor effect of WA in liver cancer. METHODS: Differential expression of glycolysis-related genes between liver cancer tissues and normal tissues and prognosis were verified using an online database. Glycolysis-related protein expression was detected using western blot after overexpression and knockdown of IDH1 and mitochondrial membrane potential assay based on JC-1, and mitochondrial complex I activity was also detected. The inhibitory effect of WA on the biological functions of HepG2 cells was detected along with cell viability using MTT assay, scratch assay, clone formation assay, glucose consumption and lactate production assay. Western blot and qRT-PCR were used to detect the expression of proteins and genes related to IDH1, p53 and HIF1α signaling pathways. RESULTS: We first identified that IDH1 expression was downregulated in human liver cancer cells compared to normal liver cells. Next, we found that treatment of HepG2 cells with WA resulted in significantly increased protein levels of IDH1, accompanied by decreased levels of several glycolytic enzymes. Furthermore, we found that WA stabilized IDH1 proteins by inhibiting the degradation by the proteasome. The tumor suppressor p53 was also upregulated by WA treatment, which played a critical role in the upregulation of IDH1 and downregulation of the glycolysis-related genes. Under hypoxic conditions, glycolysis-related genes were induced, which was suppressed by WA treatment, and IDH1 expression was still maintained at higher levels under hypoxia. CONCLUSION: Taken together, our results indicated that WA suppresses liver cancer tumorigenesis by p53-mediated IDH1 upregulation, which promotes mitochondrial respiration, thereby inhibiting the HIF-1α pathway and blocking aerobic glycolysis.
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Glicólise , Subunidade alfa do Fator 1 Induzível por Hipóxia , Isocitrato Desidrogenase , Neoplasias Hepáticas , Transdução de Sinais , Proteína Supressora de Tumor p53 , Vitanolídeos , Humanos , Vitanolídeos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Glicólise/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Transdução de Sinais/efeitos dos fármacos , Isocitrato Desidrogenase/genética , Isocitrato Desidrogenase/metabolismo , Proliferação de Células/efeitos dos fármacos , Células Hep G2 , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Carcinogênese/efeitos dos fármacosRESUMO
Background: Anxiety and social withdrawal are highly prevalent among patients with Alzheimer's disease (AD). However, the neural circuit mechanisms underlying these symptoms remain elusive, and there is a need for effective prevention strategies. Objective: This study aims to elucidate the neural circuitry mechanisms underlying social anxiety in AD. Methods: We utilized 5xFAD mice and conducted a series of experiments including optogenetic manipulation, Tandem Mass Tag-labeled proteome analysis, behavioral assessments, and immunofluorescence staining. Results: In 5xFAD mice, we observed significant amyloid-ß (Aß) accumulation in the anterior part of basolateral amygdala (aBLA). Behaviorally, 6-month-old 5xFAD mice displayed excessive social avoidance during social interaction. Concurrently, the pathway from aBLA to ventral hippocampal CA1 (vCA1) was significantly activated and exhibited a disorganized firing patterns during social interaction. By optogenetically inhibiting the aBLA-vCA1 pathway, we effectively improved the social ability of 5xFAD mice. In the presence of Aß accumulation, we identified distinct changes in the protein network within the aBLA. Following one month of administration of Urolithin A (UA), we observed significant restoration of the abnormal protein network within the aBLA. UA treatment also attenuated the disorganized firings of the aBLA-vCA1 pathway, leading to an improvement in social ability. Conclusions: The aBLA-vCA1 circuit is a vulnerable pathway in response to Aß accumulation during the progression of AD and plays a crucial role in Aß-induced social anxiety. Targeting the aBLA-vCA1 circuit and UA administration are both effective strategies for improving the Aß-impaired social ability.
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Peptídeos beta-Amiloides , Complexo Nuclear Basolateral da Amígdala , Região CA1 Hipocampal , Cumarínicos , Camundongos Transgênicos , Animais , Camundongos , Peptídeos beta-Amiloides/metabolismo , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/efeitos dos fármacos , Complexo Nuclear Basolateral da Amígdala/metabolismo , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Cumarínicos/farmacologia , Doença de Alzheimer/metabolismo , Masculino , Comportamento Social , Modelos Animais de Doenças , Ansiedade/metabolismo , Interação Social/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , OptogenéticaRESUMO
The prevalence of cardiovascular diseases continues to be a challenge for global health, necessitating innovative solutions. The potential of high-density lipoprotein (HDL) mimetic nanotherapeutics in the context of cardiovascular disease and the intricate mechanisms underlying the interactions between monocyte-derived cells and HDL mimetic showing their impact on inflammation, cellular lipid metabolism, and the progression of atherosclerotic plaque. Preclinical studies have demonstrated that HDL mimetic nanotherapeutics can regulate monocyte recruitment and macrophage polarization towards an anti-inflammatory phenotype, suggesting their potential to impede the progression of atherosclerosis. The challenges and opportunities associated with the clinical application of HDL mimetic nanotherapeutics, emphasize the need for additional research to gain a better understanding of the precise molecular pathways and long-term effects of these nanotherapeutics on monocytes and macrophages to maximize their therapeutic efficacy. Furthermore, the use of nanotechnology in the treatment of cardiovascular diseases highlights the potential of nanoparticles for targeted treatments. Moreover, the concept of theranostics combines therapy and diagnosis to create a selective platform for the conversion of traditional therapeutic medications into specialized and customized treatments. The multifaceted contributions of HDL to cardiovascular and metabolic health via highlight its potential to improve plaque stability and avert atherosclerosis-related problems. There is a need for further research to maximize the therapeutic efficacy of HDL mimetic nanotherapeutics and to develop targeted treatment approaches to prevent atherosclerosis. This review provides a comprehensive overview of the potential of nanotherapeutics in the treatment of cardiovascular diseases, emphasizing the need for innovative solutions to address the challenges posed by cardiovascular diseases.
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Doenças Cardiovasculares , Lipoproteínas HDL , Macrófagos , Monócitos , Humanos , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Animais , Doenças Cardiovasculares/tratamento farmacológico , Monócitos/efeitos dos fármacos , Nanopartículas/química , Aterosclerose/tratamento farmacológico , Placa Aterosclerótica/tratamento farmacológico , Nanomedicina/métodos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologiaRESUMO
Acute sleep deprivation has aroused widespread concern and the relationship between acute sleep deprivation and cortisol levels is inconsistent. This study aimed to explore additional evidence and details. The PubMed, Web of Science, EMBASE, CLINAHL and Cochrane databases were searched for eligible studies published up to June 7, 2023. All analyses were performed using Review Manager 5.4 and Stata/SE 14.0. A total of 24 studies contributed to this meta-analysis. There was no significant difference in cortisol levels between participants with acute sleep deprivation and normal sleep in 21 crossover-designed studies (SMD = 0.18; 95% CI: -0.11, 0.45; p = 0.208) or 3 RCTs (SMD = 0.26; 95% CI: -0.22, 0.73; p = 0.286). Subgroup analysis revealed that the pooled effects were significant for studies using serum as the sample (SMD = 0.46; 95%CI: 0.11, 0.81; p = 0.011). Studies reporting cortisol levels in the morning, in the afternoon and in the evening did not show significant difference (p > 0.05). The pooled effects were statistically significant for studies with multiple measurements (SMD = 0.28; 95%CI: 0.03, 0.53; p = 0.027) but not for studies with single cortisol assessments (p = 0.777). When the serum was used as the test sample, the cortisol levels of individuals after acute sleep deprivation were higher than those with normal sleep.
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Hidrocortisona , Privação do Sono , Privação do Sono/sangue , Hidrocortisona/sangue , HumanosRESUMO
Leveraging solar energy through photocatalytic hydrogen production from water stands out as one of the most promising approaches to address the energy and environmental challenges. The choice of catalyst profoundly influences the outcomes of photocatalytic reactions, and constructing heterojunctions has emerged as a widely applied strategy to overcome the limitations associated with single-phase photocatalysts. MoO3, renowned for its high chemical stability, encounters issues such as low photocatalytic efficiency and fast recombination of photogenerated electrons and holes. To tackle these challenges, the morphology of MoO3 has been controlled to form nanorods, simultaneously suppressing the aggregation of the catalyst and increasing the number of surface-active sites. Moreover, to facilitate the separation of photogenerated charge carriers, Cd0.9Zn0.1S nanoparticles with a twin crystal structure are deposited on the surface of MoO3, establishing an S-scheme heterojunction. Experimental findings demonstrate that the synergistic effects arising from the well-defined morphology and interface interactions extend the absorption range to visible light response, improve charge transfer activity, and prolong the lifetime of charge carriers. Consequently, Cd0.9Zn0.1S/MoO3 S-scheme heterojunctions exhibit outstanding photocatalytic hydrogen production performance (3909.79 µmol g-1 h-1) under visible light irradiation, surpassing that of MoO3 by nearly nine fold.
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Micromechanical resonators have aroused growing interest as biological and chemical sensors, and microcantilever beams are the main research focus. Recently, a resonant microcantilever with an integrated heater has been applied in on-chip thermogravimetric analysis (TGA). However, there is a strong relationship between the mass sensitivity of a resonant microcantilever and the location of adsorbed masses. Different sampling positions will cause sensitivity differences, which will result in an inaccurate calculation of mass change. Herein, an integrated H-shaped resonant beam with uniform mass sensitivity and temperature distribution is proposed and developed to improve the accuracy of bio/chemical sensing and TGA applications. Experiments verified that the presented resonant beam possesses much better uniformity of sensitivity and temperature distribution compared with resonant microcantilevers. Gas-sensing and TGA experiments utilizing the integrated resonant beam were also carried out and exhibited good measurement accuracy.