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This study aimed to investigate the association between serum chloride levels and all-cause mortality in critically ill patients with chronic obstructive pulmonary disease (COPD). Data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were extracted for analysis. Demographic information, laboratory results, medical histories, vital signs, and prognosis-related data were collected. Cox proportional hazard models were used to assess the relationship between serum chloride levels and 90-day and 365-day mortality. Subgroup analyses were conducted to explore potential interactions between serum chloride levels and various factors. The study included patients with a median age of 72.00 years, of whom 52.39% were male. Higher quartiles of serum chloride levels were associated with significantly lower levels of weight, RBC, platelet, hemoglobin, and other variables (P < 0.05), accompanied by lower 90-day and 365-day mortality (P < 0.05). Cox proportional hazard model indicated that the risk of death was significantly lower in the fourth quartile of serum chloride levels compared with the first quartile after adjusting for confounders (90-day HR = 0.54, 365-day HR = 0.52, both P < 0.05). An L-shape relationship was observed, with risks of death decreasing as serum chloride levels increased, although the magnitude decreased when levels reached 102 mmol/L. This study demonstrated an independent L-shaped association between serum chloride levels and all-cause mortality in critically ill patients with COPD. This finding helps us to understand the prognostic value of serum chloride levels in critically ill patients with COPD.
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Cloretos , Estado Terminal , Doença Pulmonar Obstrutiva Crônica , Humanos , Masculino , Feminino , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/mortalidade , Estado Terminal/mortalidade , Idoso , Estudos Retrospectivos , Cloretos/sangue , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Idoso de 80 Anos ou maisRESUMO
There are few studies on the relationship between dietary habits and asthma-COPD overlap (ACO). In this study, we aimed to investigate the association between dietary inflammation index (DII) score and ACO. Data from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020. The DII score was first calculated and the demographic characteristics of the grouping based on the DII quartile were assessed. The weighted logistic regression model was used to study the relationship between DII and ACO. Subgroup analysis was used to further explore the differences in different subgroups. Restricted cubic spline (RCS) plot was used to show the general trend of DII score and disease risk, and threshold effect analysis was used to determine the inflection point. In a comparison of baseline characteristics, the highest ACO prevalence was found in the fourth quartile array of people in DII. An adjusted weighted logistic regression model showed that DII was positively correlated with the incidence of ACO. Subgroup analysis showed that the association was more pronounced in women, non-Hispanics, people with cardiovascular disease, and people without diabetes. The RCS graph shows that overall, the risk of ACO increases with the increase of DII score. Threshold effect analysis showed that the inflection point was 3.779, and the risk was more significant after the DII score was greater than the inflection point value (OR 2.001, 95% CI 1.334-3.001, P < 0.001). Higher DII scores were positively associated with ACO risk. These results further support diet as an intervention strategy for ACO prevention and treatment.
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Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Feminino , Inquéritos Nutricionais , Inflamação/epidemiologia , Inflamação/diagnóstico , Dieta/efeitos adversos , Asma/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologiaRESUMO
Transient gene expression system is an important tool for rapid production of recombinant proteins in Chinese hamster ovary (CHO) cells. However, their low productivity is the main hurdle to overcome. An effective approach through which to obtain high protein yield involves targeting transcriptional, post-transcriptional events (PTEs), and culture conditions. Here, we investigated the effects of protein disulfide isomerase (PDI) and spliced X-box binding protein 1 (XBP-1s) co-overexpression combined with mild hypothermia on the transient yields of recombinant proteins in CHO cells. The results showed that the gene of interest (GOI) and the PDI/XBP-1s helper vector at a co-transfection ratio of 10:1 could obviously increase transient expression level of recombinant protein in CHO cells. However, PDI/XBP-1s overexpression had no significance effect on the mRNA levels of the recombinant protein, suggesting that it targeted PTEs. Moreover, the increased production was due to the enhancing of cell specific productivity, not related to cell growth, viability, and cell cycle. In addition, combined PDI/XBP-1s co-overexpression and mild hypothermia could further improve Adalimumab expression, compared to the control/37 °C and PDI/XBP-1s/37 °C, the Adalimumab volume yield of PDI/XBP-1s/33 °C increased by 203% and 142%, respectively. Mild hypothermia resulted in 3.52- and 2.33-fold increase in the relative mRNA levels of PDI and XBP-1s, respectively. In conclusion, the combination of PDI/XBP-1s overexpression and culture temperature optimization can achieve higher transient expression of recombinant protein, which provides a synergetic strategy to improve transient production of recombinant protein in CHO cells.
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Hipotermia , Fatores de Transcrição , Cricetinae , Animais , Células CHO , Cricetulus , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Isomerases de Dissulfetos de Proteínas/genética , Adalimumab/genética , Hipotermia/genética , Proteínas Recombinantes , Transfecção , Transgenes , RNA MensageiroRESUMO
INTRODUCTION: Psoriasis is a common skin disease, with chronic inflammation and a complex etiology. It has long been recognized that chronic skin conditions and mental health disorders are often co-morbid. Thus, the concept of the gut-brain-skin axis emphasized in mental health disorders may also regulate the health of skin. RESULTS: The gut microbiota has been found to be the bridge between the immune system and nervous system. By leveraging clinical cases and animal models of psoriasis, an important communication pathway has been identified along the gut-brain-skin axis that is associated with the modulation of neurotransmitters from the microbiota. Furthermore, mammalian neurotransmitters, including dopamine, serotonin, or γ-aminobutyric acid (GABA), can be produced and/or consumed by several types of bacteria. Other studies suggest that manipulating these neurotransmitters by bacteria may have an effect on host physiology, and the levels of neurotransmitter can be altered by microbiota-based interventions. CONCLUSIONS: Nonetheless, it is unknown whether or not the manipulation of neurotransmitter levels by bacteria can affect the occurrence and development of psoriasis. Notably, preliminary experiments found that oral consumption of probiotics improves the clinical symptoms in patients with psoriasis, perhaps correlated with the gut microbiome-mediated crosstalk between the immune system and the nervous system by secreting neurotransmitters in psoriasis. In this review, the communication along the gut-brain-skin axis is discussed.
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Diabetic nephropathy (DN) is one of the most severe complications that can occur in patients with diabetes, and without effective and timely therapeutic intervention, can gradually progress to renal failure. Previous studies have focused on investigating the pathogenesis of DN; however, the role of dualspecificity phosphatase 6 (DUSP6) in DN is not completely understood. Therefore, the present study aimed to investigate the role of dualspecificity phosphatase 6 (DUSP6) in DN. DN model mice were established and the expression levels of DUSP6 in the kidney tissues and high glucose (HG)induced murine podocytes (MPC5 cells) were determined using immunohistochemistry, reverse transcriptionquantitative PCR and western blotting. In addition, the levels of reactive oxygen species (ROS) and inflammatory cytokines in MPC5 cells were analyzed using commercial assay kits or ELISA kits, respectively, and flow cytometric analysis was performed to analyze the rate of cell apoptosis. The present study indicated that DUSP6 expression levels were significantly decreased in DN model mice compared with control mice, and in HGinduced MPC5 cells compared with normal glucoseinduced MPC5 cells. DUSP6 overexpression enhanced MPC5 cell viability and increased protein expression levels of cell markers, such as synaptopodin and nephrin, compared with the negative control group. DUSP6 overexpression also reduced the levels of ROS and inflammatory cytokines, including interleukin (IL)1ß, IL6 and tumor necrosis factorα secreted by MPC5 cells under HG conditions. Moreover, compared with the HG group, cell apoptosis was inhibited by DUSP6 overexpression under HG conditions, which was further indicated by decreased expression levels of cleaved caspase3 and Bax. Thus, these findings indicated that DUSP6 mediated the protection against HGinduced inflammatory response.
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Neuropatias Diabéticas/metabolismo , Fosfatase 6 de Especificidade Dupla/metabolismo , Glucose/efeitos adversos , Podócitos/citologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Neuropatias Diabéticas/induzido quimicamente , Modelos Animais de Doenças , Regulação para Baixo , Fosfatase 6 de Especificidade Dupla/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Podócitos/metabolismoRESUMO
BACKGROUND: C-Myc overexpression is associated with poor prognosis and aggressive progression of natural killer/T-cell lymphoma (NKTCL). Matrine, a main alkaloid of the traditional Chinese herb Sophora flavescens Ait, has been shown to inhibit cellular proliferation and induce apoptosis of various cancer cells. The present study investigated the effects and possible mechanisms of matrine inhibiting the growth of natural killer/T-cell lymphoma cells. METHODS: The effects of matrine on the proliferation, apoptosis and expression of apoptotic molecules, STAT3, LMP1, RUNX3, EZH2 and activation of CaMKIIγ/c-Myc pathway were examined in cultured NKTCL cell line NK92 cells. RESULTS: In cultured NK92 cells, matrine inhibited the proliferation in a dose and time dependent manner. The IC50 value of matrine was 1.71 mM for 72 h post exposure in NK92 cells. Matrine induced apoptosis with decreased Bcl-2 expression and the proteasome-dependent degradation of c-Myc protein in NK92 cells. c-Myc protein half-life in NK92 was reduced from 80.7 min to 33.4 min after matrine treatment, which meant the stability of c-Myc was decreased after matrine exposure. Furthermore, we found that matrine downregulated c-Myc phosphorylation at Ser62 together with the inhibition of CaMKIIγ, a key regulator of c-Myc protein in NKTCL. The downregulation of c-Myc transcription by matrine was mediated through LMP1 inhibition. We also observed that anti-proliferative activity of matrine was irrelevant to STAT3, RUNX3 and EZH2. CONCLUSIONS: The results of the present study indicated that matrine inhibits the growth of natural killer/T-cell lymphoma cells by modulating LMP1-c-Myc and CaMKIIγ-c-Myc signaling pathway.
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Alcaloides/farmacologia , Apoptose/efeitos dos fármacos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Células Matadoras Naturais/metabolismo , Linfoma de Células T/tratamento farmacológico , Quinolizinas/farmacologia , Fatores de Transcrição/metabolismo , Linhagem Celular Tumoral , Células Cultivadas , Regulação para Baixo , Humanos , Transdução de Sinais , Sophora , MatrinasRESUMO
The application of laccase-mediator-based catalysis is limited owing to the high cost of laccases and mediators and the potential toxicity of free mediators. Here, a novel biocatalyst (Im-LMS) was fabricated by immobilizing both laccase and a mediator (2,2'-azino-bis-[3-ethylbenzothiazoline]-6-sulfonic acid) on layered double hydroxide/alginate biohybrid beads. The catalytic activity of Im-LMS was evaluated for dye decolorization using malachite green. The decolorization yields of malachite green by Im-LMS and the free laccase-mediator system were 92% within 120 min and 90% within 90 min. Malachite green solution was detoxified completely after biodegradation by Im-LMS. Following eight reuse cycles of Im-LMS for dye treatment, a decolorization yield of 79% was obtained. The activity of Im-LMS was almost completely stable after being stored for 10 days. The recyclability and stability of Im-LMS will be helpful for reducing the running cost and potential toxicity associated with mediators to facilitate practical applications.
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Alginatos/química , Aspergillus oryzae/enzimologia , Enzimas Imobilizadas/química , Proteínas Fúngicas/química , Lacase/química , Corantes de Rosanilina/química , Ácidos Sulfônicos/químicaRESUMO
Hierarchical copper shells anchored on magnetic nanoparticles were designed and fabricated to selectively deplete hemoglobin from human blood by immobilized metal affinity chromatography. Briefly, CoFe2O4 nanoparticles coated with polyacrylic acid were first synthesized by a one-pot solvothermal method. Hierarchical copper shells were then deposited by immobilizing Cu2+ on nanoparticles and subsequently by reducing between the solid CoFe2O4@COOH and copper solution with NaBH4. The resulting nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectrometry, X-ray photoelectron spectroscopy, and vibrating sample magnetometry. The particles were also tested against purified bovine hemoglobin over a range of pH, contact time, and initial protein concentration. Hemoglobin adsorption followed pseudo-second-order kinetics and reached equilibrium in 90 min. Isothermal data also fit the Langmuir model well, with calculated maximum adsorption capacity 666 mg g-1. Due to the high density of Cu2+ on the shell, the nanoparticles efficiently and selectively deplete hemoglobin from human blood. Taken together, the results demonstrate that the particles with hierarchical copper shells effectively remove abundant, histidine-rich proteins, such as hemoglobin from human blood, and thereby minimize interference in diagnostic and other assays.
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Cobre/química , Hemoglobinas/análise , Hemoglobinas/isolamento & purificação , Nanopartículas de Magnetita/química , Resinas Acrílicas/química , Adsorção , Animais , Bovinos , Histidina/química , Humanos , Concentração de Íons de Hidrogênio , Cinética , Magnetismo , Magnetometria , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanocompostos/química , Espectroscopia Fotoeletrônica , Proteínas/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The Holevo bound is a keystone in many applications of quantum information theory. We propose " maximal Holevo quantity for weak measurements" as the generalization of the maximal Holevo quantity which is defined by the optimal projective measurements. The scenarios that weak measurements is necessary are that only the weak measurements can be performed because for example the system is macroscopic or that one intentionally tries to do so such that the disturbance on the measured system can be controlled for example in quantum key distribution protocols. We evaluate systematically the maximal Holevo quantity for weak measurements for Bell-diagonal states and find a series of results. Furthermore, we find that weak measurements can be realized by noise and project measurements.
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We study the local indistinguishability problem of quantum states. By introducing an easily calculated quantity, non-commutativity, we present an criterion which is both necessary and sufficient for the local indistinguishability of a complete set of pure orthogonal product states. A constructive distinguishing procedure to obtain the concrete local measurements and classical communications is given. The non-commutativity of ensembles can be also used to characterize the quantumness for classical-quantum or quantum-classical correlated states.