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Various natural polymers offer sustainable alternatives to petroleum-based adhesives, enabling the creation of high-performance engineered materials. However, additional chemical modifications and complicated manufacturing procedures remain unavoidable. Here, a sustainable high-performance engineered composite that benefits from bonding strategies with multiple energy dissipation mechanisms dominated by chemical adhesion and mechanical interlocking is demonstrated via the fungal smart creative platform. Chemical adhesion is predominantly facilitated by the extracellular polymeric substrates and glycosylated proteins present in the fungal outer cell walls. The dynamic feature of non-covalent interactions represented by hydrogen bonding endows the composite with extensive unique properties including healing, recyclability, and scalable manufacturing. Mechanical interlocking involves multiple mycelial networks (elastic modulus of 2.8 GPa) binding substrates, and the fungal inner wall skeleton composed of chitin and ß-glucan imparts product stability. The physicochemical properties of composite (modulus of elasticity of 1455.3 MPa, internal bond strength of 0.55 MPa, hardness of 82.8, and contact angle of 110.2°) are comparable or even superior to those of engineered lignocellulosic materials created using petroleum-based polymers or bioadhesives. High-performance composite biofabrication using fungi may inspire the creation of other sustainable engineered materials with the assistance of the extraordinary capabilities of living organisms.
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Hongos , Quitina/química , Módulo de ElasticidadRESUMEN
Dexamethasone is widely used in pregnant women at risk of preterm birth to reduce the occurrence of neonatal respiratory distress syndrome and subsequently reduce neonatal mortality. Studies have suggested that dexamethasone has developmental toxicity, but there is a notable absence of systematic investigations about its characteristics. In this study, we examined the effects of prenatal dexamethasone exposure (PDE) on mother/fetal mice at different doses (0.2, 0.4, or 0.8 mg/kg b.i.d), stages (gestational day 14-15 or 16-17) and courses (single- or double-course) based on the clinical practice. Results showed that PDE increased intrauterine growth retardation rate, and disordered the serum glucose, lipid and cholesterol metabolic phenotypes, and sex hormone level of mother/fetal mice. PDE was further discovered to interfere with the development of fetal lung, hippocampus and bone, inhibits steroid synthesis in adrenal and testis, and promotes steroid synthesis in the ovary and lipid synthesis in the liver, with significant effects observed at high dose, early stage and double course. The order of severity might be: ovary > lung > hippocampus/bone > others. Correlation analysis revealed that the decreased serum corticosterone and insulin-like growth factor 1 (IGF1) levels were closely related to PDE-induced low birth weight and abnormal multi-organ development in offspring. In conclusion, this study systematically confirmed PDE-induced multi-organ developmental toxicity, elucidated its characteristics, and proposed the potential "glucocorticoid (GC)-IGF1" axis programming mechanism. This research provided an experimental foundation for a comprehensive understanding of the effect and characteristics of dexamethasone on fetal multi-organ development, thereby guiding the application of "precision medicine" during pregnancy.
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Dexametasona , Relación Dosis-Respuesta a Droga , Desarrollo Fetal , Animales , Femenino , Embarazo , Dexametasona/toxicidad , Dexametasona/administración & dosificación , Masculino , Desarrollo Fetal/efectos de los fármacos , Ratones , Retardo del Crecimiento Fetal/inducido químicamente , Factor I del Crecimiento Similar a la Insulina/metabolismo , Glucocorticoides/toxicidad , Glucocorticoides/administración & dosificación , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal/inducido químicamenteRESUMEN
BACKGROUND: Perioperative neurocognitive disorders (PND) are a common central nervous system complication that predominantly affects the elderly. PND after surgery includes postoperative delirium (POD), delayed neurocognitive recovery up to 30 days (DNR), and postoperative neurocognitive disorder up to 12 months. Diabetes is an important independent risk factor for PND. Over the years, few studies have assessed the incidence of PND and the difference in serum biomarkers between diabetic and non-diabetic patients. We sought to examine the difference in the incidence of PND between elderly diabetic and non-diabetic patients in China and identify the risk factors of PND in elderly diabetics. METHODS: We conducted a secondary and exploratory data analysis from our prior studies, including patients aged 65 years or older who underwent non-cardiac elective surgery with general anesthesia. We used the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) and Montreal Cognitive Assessment (MoCA) to assess patient cognition. RESULTS: A total of 236 patients were analyzed; the incidence of PND was significantly higher in diabetic than in non-diabetic patients within 30 days (59.2% vs. 36.8%) (P = 0.022). Multivariate logistic regression analysis showed that the preoperative MoCA was an independent risk factor for PND (odds ratio, 0.88 [0.8 to 0.97]; P = 0.014), and Hosmer-Lemeshow tests showed that it could predict PND in diabetic patients (P = 0.360). According to the maximum Youden index, the optimal cutoff for preoperative MoCA was 21.5 points, yielding a specificity and sensitivity of 88.0% and 55.2% for PND. The levels of glial fibrillary acidic protein (GFAP) and Tau in diabetic patients before and after surgery were significantly higher than in non-diabetic patients among cases of PND (P = 0.002 and 0.011, respectively). CONCLUSION: The incidence of PND is higher in diabetic than in non-diabetic patients in China, and preoperative MoCA is an independent risk factor for PND in diabetics. Meanwhile, the changes in GFAP and p-Tau in diabetic patients who experienced PND were significantly higher than in non-diabetic ones.
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Diabetes Mellitus , Trastornos Neurocognitivos , Anciano , Humanos , Estudios Retrospectivos , Cognición , Factores de Riesgo , Diabetes Mellitus/epidemiologíaRESUMEN
Oridonin, a well-known traditional Chinese herbal medicinal product isolated from Isodon rubescens (Hemsl.) H.Hara, has many potential properties, including anti-inflammatory and antioxidant activities. However, there is no evidence whether oridonin have a protective effect on atherosclerosis. This study focused on the effects of oridonin on oxidative stress and inflammation generated from atherosclerosis. The therapeutic effect on atherosclerosis was evaluated by intraperitoneal injection of oridonin in a high-fat fed ApoE-/- mouse model. We isolated mouse peritoneal macrophages and detected the effect of oridonin on oxidized low-density lipoprotein-induced lipid deposition. Oil red O staining, Masson's staining, dihydroethidium fluorescence staining, immunohistochemical staining, western blotting analysis, immunofluorescence, enzyme-linked immunosorbent assay and quantitative real-time PCR were used to evaluate the effect on atherosclerosis and explore the mechanisms. Oridonin treatment significantly alleviated the progression of atherosclerosis, reduced macrophage infiltration and stabilized plaques. Oridonin could significantly inhibit inflammation associated with NLRP3 activation. Oridonin significantly reduced oxidative stress by blocking Nrf2 ubiquitination and degradation. We also found that oridonin could prevent the formation of foam cells by increasing lipid efflux protein and reducing lipid uptake protein in macrophages. Oridonin has a protective effect on atherosclerosis in ApoE-/- mice, which may be related to the inhibition of NLRP3 and the stabilization of Nrf2. Therefore, oridonin may be a potential therapeutic agent for atherosclerosis.
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Aterosclerosis , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratones Noqueados , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Inflamación/tratamiento farmacológico , Apolipoproteínas E , Apolipoproteínas/uso terapéutico , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: Lumbar puncture in the lateral decubitus position will make the neonates uncomfortable and is likely to cause position change and unstable vital signs, and the application of sedative drugs will cause adverse effects. This study explored a novel method for lumbar puncture in the prone position for low weight neonates. METHODS: The neonates were randomly assigned into the standard position group receiving lumbar puncture in the lateral decubitus position; and the improved position group receiving lumbar puncture in the prone position. The success rate of first time attempts and the overall success rate of lumbar puncture, incidence of adverse effects, NIAPAS scores were collected and compared between these two groups. The difference in success rate and adverse effects incidence rate was analysed through Chi-square. Student's t-test was used for the test of NIAPAS rating. RESULTS: The improved position group had a higher success rate of first attempt and overall success rate, significantly lower incidence of adverse effect and lower NIAPAS scores than those of the standard position group (P<0.05). CONCLUSION: This lumbar puncture in the prone position is safer, more effective, and more comfortable for preterm neonates and those with low birth weight. Thus, this method is worth of further promotion. TRIAL REGISTRATION: Registration number, ChiCTR2100049923; Date of Registration, August 11, 2021; Retrospectively registered.
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Posicionamiento del Paciente , Punción Espinal , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Posición Prona , Punción Espinal/efectos adversos , Punción Espinal/métodosRESUMEN
During quantitative real-time polymerase chain reaction (RT-qPCR) data analysis, the selection of optimal housekeeping gene is necessary to ensure the accuracy of results. It is noteworthy that housekeeping genes commonly used in adult studies may not be applicable for fetus. However, the stability analysis of housekeeping gene in fetal kidney has not been reported. This study intends to screen the applicable compound housekeeping genes in rat fetal kidney. In this study, eight housekeeping genes used in kidney studies based on literature reports (GAPDH, ACTB, 18S, HPRT, YWHAZ, HMBS, PPIA, and TBP) were selected as the research object. Their expression levels in the rat fetal kidney in physiological condition and the intrauterine growth retardation (IUGR) model induced by prenatal dexamethasone exposure (PDE) (0.2 mg/kg·day from gestation Days 9 to 20) was measured. Furthermore, these eight housekeeping genes were used to conduct relative quantitative analysis of nephrin expression in the fetal kidney in PDE-induced IUGR model, to compare the influence of choosing different housekeeping gene on data analysis of nephrin expression and to verify the reliability of selected compound housekeeping genes. In this study, stable housekeeping genes of fetal kidney tissues in PDE-induced IUGR model were identified: ACTB, GAPDH, TBP, and HMBS for males; ACTB, YWHAZ, and GAPDH for females. Besides, our results suggest that ACTB + GAPDH were the best compound housekeeping genes for normalization analysis in male fetal kidney studies, and ACTB + YWHAZ in females. This study will provide an experimental evidence basis for the selection of housekeeping genes in the RT-qPCR experiment in renal development toxicology-related models.
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Exactitud de los Datos , Expresión Génica , Genes Esenciales , Genética/instrumentación , Riñón/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa/instrumentación , Animales , Feto , RatasRESUMEN
Growth performance and meat quality are important traits for pig production. The aim of the present study was to investigate the molecular mechanisms underlying growth performance and meat quality, and to identify novel target molecules for predicting the growth performance and meat quality. The differentially expressed genes (DEGs) in Diannan small ears pigs (DSP) and Landrace pigs (LP) were assessed by RNA-sequencing analyzing technology. A total of 339 DEGs were obtained between DSP and LP. 146 DEGs were upregulated in LP compared with DSP and 193 DEGs were upregulated in DSP compared with LP. The DEGs were significantly enriched in 26 GO and 3 KEGG pathways. The protein-protein interaction (PPI) network with 201 nodes and 382 edges was constructed and 5 modules were extracted from the entire network. The identified upregulated expression of genes involved in glycolysis and myogenesis as well as extracellular matrix may be associated with fast body and muscle deposition rates in LP. Increased expression of genes involved in PPAR signaling pathway and fatty acid metabolism as well as oxidative phosphate processes could be related to the intramuscular fat deposition and meat quality in DSP. The present study may provide an improved understanding of the growth performance and meat quality.
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Perfilación de la Expresión Génica , Transcriptoma , Porcinos , Animales , Perfilación de la Expresión Génica/veterinaria , Músculo Esquelético/metabolismo , Carne/análisis , Desarrollo de Músculos/genéticaRESUMEN
Hepatocellular carcinoma (HCC) is one of the most frequent malignancies in the world. Although increasing evidence supports the role of heterogeneous ribonucleoprotein particle A1 (HNRNP A1) in tumor progression, the function of HNRNP A1 in HCC remains unclear. Here, we focused on the role of HNRNP A1 in the development of HCC. In this study, we found HNRNP A1 participates in many aspects of HCC, such as progression and prognosis. Our results showed that HNRNP A1 is upregulated in human HCC tissues and cell lines. High expression of HNRNP A1 can promote the proliferation, migration, and invasion in HCC cells and accelerate tumor progression in mice. Moreover, we found that HNRNP A1 prevents the senescence process of HCC cells. Knocking down of HNRNP A1 promotes the expression of P16INK4, which arrests the cell cycle and then induces the senescence phenotype in HCC cells. Furthermore, we found that HNRNP A1 regulated necroptosis and mitochondrial dynamics. In summary, our study indicates that HNRNP A1 promotes the development of HCC, which suggests a potential therapeutic target for HCC.
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Carcinoma Hepatocelular , Ribonucleoproteína Nuclear Heterogénea A1/metabolismo , Neoplasias Hepáticas , Animales , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Ribonucleoproteína Heterogénea-Nuclear Grupo A-B/genética , Humanos , Neoplasias Hepáticas/metabolismo , Ratones , Dinámicas Mitocondriales , Necroptosis , RibonucleoproteínasRESUMEN
Exopolysaccharides produced by edible microorganisms exhibit excellent constructive physicochemical and significant biological activity, which provide advantages for the food or pharmaceutical industries. Two novel exopolysaccharides produced by Debaryomyces hansenii DH-1 were characterized, named S1 and S2, respectively. S1, with a molecular weight of 34.594 kDa, primarily consisted of mannose and glucose in a molar ratio of 12.19:1.00, which contained a backbone fragment of α-D-Manp-(1â4)-α-D-Manp-(1â2)-α-D-Glcp-(1â3)-α-D-Manp-(1â3)-ß-D-Glcp-(1â4)-ß-D-Manp-(1â. S2, with a molecular weight of 24.657 kDa, was mainly composed of mannose and galactose in a molar ratio of 4.00:1.00, which had a backbone fragment of α-D-Manp-(1â6)-ß-D-Manp-(1â2)-α-D-Manp-(1â4)-α-D-Galp-(1â3)-ß-D-Manp-(1â6)-α-D-Manp-(1â. Both S1 and S2 exhibited good thermal stability and potent hydroxyl radical scavenging activity, with ~98%. Moreover, S1 possessed an additional strong iron-reducing capacity. In vitro antitumor assays showed that S1 and S2 significantly inhibited the proliferation of Hela, HepG2, and PC-9 cancer cells. Moreover, PC-9 was more sensitive to S1 compared with S2. The above results indicate that S1 and S2 have great potential to be utilized as natural antioxidants and candidates for cancer treatment in the food and pharmaceutical industries.
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Antioxidantes , Debaryomyces , Antioxidantes/farmacología , Antioxidantes/química , Manosa , Peso Molecular , Galactosa , Polisacáridos/químicaRESUMEN
Interleukin (IL)-10 is an essential anti-inflammatory cytokine that plays important roles as a negative regulator of immune responses to microbial antigens. c-Maf has been suggested as an essential transcriptional factor for IL-10 production in CD4+ T cells and macrophages. However, it remains unclear whether c-Maf participates in IL-10 expression in B cells. In this study, we investigated the role of c-Maf in the transcriptional regulation of IL-10 in regulatory B cells, as well as the underlying molecular mechanism. We found that c-Maf was constitutively expressed in resting B cells. c-Maf expression was upregulated in the presence of LPS and dose-dependently enhanced IL-10 production following binding to the IL-10 promoter. Moreover, a lower expression of c-Maf and decreased production of regulatory B (Breg) cells were detected in mice with collagen-induced arthritis (CIA), which may contribute to the pathological changes. Taken together, these data demonstrate that c-Maf is an indispensable yet constitutive transcription factor for IL-10 gene expression in LPS-activated B cells.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Artritis Experimental/metabolismo , Artritis Reumatoide/metabolismo , Subgrupos de Linfocitos B/inmunología , Linfocitos B Reguladores/inmunología , Interleucina-10/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Artritis Experimental/genética , Artritis Reumatoide/genética , Células Cultivadas , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Humanos , Interleucina-10/genética , Lipopolisacáridos/inmunología , Ratones , Ratones Endogámicos C57BL , Regiones Promotoras Genéticas/genéticaRESUMEN
Necrotizing enterocolitis (NEC) is a severe gastrointestinal inflammatory disease in neonates, particularly in preterm infants. The interleukin (IL) 23/IL17 axis has been shown to play an important role in the gastrointestinal inflammation. However, the association of gene polymorphisms in the IL23/IL17 axis and the development of NEC remains unknown. In this study, we aimed to explore a possible genetic role of IL23R and IL17 in the development of NEC. We identified single nucleotide polymorphisms (SNPs) in IL23R (rs10889677), IL17A (rs2275913), and IL17F (rs763780) by polymerase chain reaction and Sanger sequencing. A total of 102 NEC patients (stage II, n = 75; and stage III, n = 27) and 120 control subjects were recruited for the study. All of the participants were premature (gestational age < 37 weeks). Our results revealed that the combination of the IL17F rs763780 (TC + CC) genotype and the C allele both significantly increased the risk of NEC [odds ratio (OR) 1.89, 95% confidence interval (CI) 1.04-3.43, P = 0.035; OR 1.82, 95% CI 1.06-3.13, P = 0.028, respectively]. Furthermore, the rs763780 (TC + CC) genotype was associated with increased severity of NEC and the incidence of NEC-related perforation [OR 2.80, 95% CI 1.10-7.12, P = 0.031; OR 3.86, 95% CI 1.10-13.53, P = 0.035, respectively]. However, IL23R rs10889677 and IL17A rs2275913 were not associated with the susceptibility to NEC. In conclusion, our data suggest that a variant of IL17F (rs763780) may contribute to the development of NEC.
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Enterocolitis Necrotizante/genética , Enfermedades del Recién Nacido/genética , Interleucina-17/genética , Polimorfismo de Nucleótido Simple , Receptores de Interleucina/genética , Femenino , Humanos , Recién Nacido , MasculinoRESUMEN
Yb(3+)/Er(3+)-ion co-doped Na2Ln2Ti3O10 (Ln = Gd, La) up-conversion (UC) phosphors were successfully synthesized by a sol-gel method, and their crystal structures were characterized by powder X-ray diffraction. Dazzling yellow-greenish light was emitted under the excitation of 980 nm near-infrared (NIR) light, composing green and red emission bands from the (2)H11/2/(4)S3/2â(4)I15/2 and (4)F9/2â(4)I15/2 transitions of Er(3+), respectively. The optimal composition and synthesis parameters were determined according to their UC emission intensity. The photon absorption and emission processes were illustrated based on the UC mechanism, in which energy transfer (ET) from Yb(3+) to Er(3+) plays a pivotal role and has been proved by the variation of green emission lifetime in Er(3+) singly and Yb(3+)/Er(3+) co-doped Na2Ln2Ti3O10 samples. The temperature-dependent fluorescence intensity ratios (FIR) of the two thermal coupled energy level (TCL) emission from (2)H11/2â(4)I15/2 (526 nm) and (4)S3/2â(4)I15/2 (549 nm) were calculated in the range of 290-490 K, and their sensitivity values were approximately 0.0058 K(-1) for Na2Gd2Ti3O10 at 490 K and 0.0061 K(-1) for Na2La2Ti3O10 at 470 K, as potential optical temperature sensor.
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BACKGROUND: Accumulating evidence shows that the pathological autoreactive immune response is responsible for plaque rupture and the subsequent onset of acute coronary syndrome (ACS). Naturally occurring CD4(+)CD25(+)regulatory T cells (nTregs) are indispensable in suppressing the pathological autoreactive immune response and maintaining immune homeostasis. However, the number and the suppressive function of glycoprotein-A repetitions predominant (GARP) (+) CD4(+) CD25(+) activated nTregs were impaired in patients with ACS. Recent evidence suggests that heme oxygenase-1 (HO-1) can regulate the adaptive immune response by promoting the expression of Foxp3. We therefore hypothesized that HO-1 may enhance the function of GARP(+) CD4(+) CD25(+)Tregs in patients with ACS and thus regulate immune imbalance. METHODS: T lymphocytes were isolated from healthy volunteers (control, n=30) and patients with stable angina (SA, n=40) or ACS (n=51). Half of these cells were treated with an HO-1 inducer (hemin) for 48 h, and the other half were incubated with complete RPMI-1640 medium. The frequencies of T-helper 1 (Th1), Th2, Th17 and latency-associated peptide (LAP) (+)CD4(+) T cells and the expression of Foxp3 and GARP by CD4(+)CD25(+)T cells were then assessed by measuring flow cytometry after stimulation in vitro. The suppressive function of activated Tregs was measured by thymidine uptake. The levels of transforming growth factor-1 (TGF-ß1) in the plasma were measured using enzyme-linked immunosorbent assay (ELISA). The expression levels of the genes encoding these proteins were analyzed by real-time polymerase chain reaction. RESULTS: Patients with ACS exhibited an impaired number and suppressive function of GARP(+) CD4(+) CD25(+)Tregs and a mixed Th1/Th17-dominant T cell response when compared with the SA and control groups. The expression of LAP in T cells was also lower in patients with ACS compared to patients with SA and the control individuals. Treatment with an HO-1 inducer enhanced the biological activity of GARP(+) CD4(+) CD25(+)Tregs and resulted in increased expression of LAP and GARP by activated T cells. CONCLUSIONS: The reduced number and impaired suppressive function of GARP(+) CD4(+) CD25(+)Tregs result in excess effector T cell proliferation, leading to plaque instability and the onset of ACS. HO-1 can effectively restore impaired GARP(+) CD4(+) CD25(+)Tregs from patients with ACS by promoting LAP and GARP expression on activated T cells.
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Síndrome Coronario Agudo/inmunología , Angina Estable/inmunología , Hemo-Oxigenasa 1/metabolismo , Linfocitos T Reguladores/inmunología , Factor de Crecimiento Transformador beta1/metabolismo , Células Cultivadas , Femenino , Factores de Transcripción Forkhead/metabolismo , Hemina , Humanos , Activación de Linfocitos , Masculino , Proteínas de la Membrana/metabolismo , Persona de Mediana Edad , Linfocitos T Reguladores/citología , Regulación hacia ArribaRESUMEN
Regulatory T cells play an important role in the progression of atherosclerosis. GARP is a newly biological membrane molecule existed on activated Tregs, which is related to the release of TGF-ß. The antiatherosclerosis effects of statins partly depend on their multiple immune modulatory potencies. In this paper, we present that atorvastatin could upregulate the expression of GARP and TGF-ß in CD4+ T cells and increase the numbers of CD4+LAP+ and CD4+Foxp3+ regulatory T cells in ApoE-/- mice. Also, we indicate that atorvastatin promotes the aggregation of GARP+ and Foxp3+ cells and secretory of the TGF-ß1 in atherosclerotic plaques. Furthermore, we prove that atorvastatin could delay the procession of atherosclerosis and improve the stability of atherosclerotic plaques. Interestingly, we report that inhibition of GARP distinctly inhibits the anti-inflammatory effects of atorvastatin. We conclude that atorvastatin improves the inflammatory response in atherosclerosis partly by upregulating the expression of GARP on regulatory T cells.
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Aterosclerosis/tratamiento farmacológico , Aterosclerosis/inmunología , Atorvastatina/uso terapéutico , Proteínas de la Membrana/metabolismo , Animales , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Apoptosis/efectos de los fármacos , Aterosclerosis/metabolismo , Western Blotting , Células Cultivadas , Citometría de Flujo , Inmunohistoquímica , Masculino , Proteínas de la Membrana/genética , Ratones , Linfocitos T ReguladoresRESUMEN
BACKGROUND: Atherosclerosis (AS) is an inflammatory and immune disease. Regulatory T cells (Tregs) suppress the activation of T cells and have been shown to play a protective role during the pathogenesis of AS. However, specific markers for Tregs are lacking. Recently, glycoprotein A repetitions predominant (GARP) was discovered as a specific marker of activated Tregs, and we therefore utilized GARP as a specific surface marker for Tregs in the current study. METHODS: To assess whether GARP(+) Tregs are downregulated in patients with acute coronary syndrome (ACS), we examined CD4(+)CD25(+)GARP(+) T cell frequencies as well as their associated cytokines and suppressive function. Additionally, we compared GARP expression to that of FOXP3, which may be more sensitive as a marker of activated Tregs in patients with ACS. RESULTS: Patients with ACS demonstrated a significant decrease in circulating CD4(+)CD25(+)GARP(+) Tregs. Moreover, the suppressive function of Tregs and levels of related cytokines were also impaired in ACS patients compared to those with stable angina (SA) or normal coronary artery (NCA). Additionally, after TCR stimulation, peripheral blood mononuclear cells (PBMCs) from patients with ACS exhibited a decrease in CD4(+)CD25(+)GARP(+) Tregs. CONCLUSIONS: These fnding indicate that circulating CD4(+)CD25(+)GARP(+) Tregs are impaired in patients withACS. Thus, targeting GARP may promote the protective function of Tregs in ACS.
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Síndrome Coronario Agudo/inmunología , Proteínas de la Membrana/inmunología , Linfocitos T Reguladores/inmunología , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/patología , Anciano , Femenino , Factores de Transcripción Forkhead/sangre , Factores de Transcripción Forkhead/inmunología , Regulación de la Expresión Génica/inmunología , Humanos , Subunidad alfa del Receptor de Interleucina-2/sangre , Subunidad alfa del Receptor de Interleucina-2/inmunología , Masculino , Proteínas de la Membrana/sangre , Persona de Mediana Edad , Linfocitos T Reguladores/metabolismo , Linfocitos T Reguladores/patologíaRESUMEN
Two new lanthanide complexes with general formula [Ln2(carprofen)6(DMF)2] (Ln = Eu (1), Tb (2), DMF = N,N-dimethylformamide, carprofen = 6-chloro-α-methylcarbazole-2-acetic acid) have been synthesized by a hydrothermal method. Complex 1 was characterized by single-crystal X-ray diffraction (XRD), and it was found to crystallize in the monoclinic space group C2/c. The coordination of the ligand to the lanthanide ion has been investigated by Fourier-transform infrared (FTIR) spectra and ultraviolet-visible (UV-vis) absorption spectra. Complex 1 emits red light, but the antenna effect of the ligand is not effective, whereas complex 2 presents intense green emission with effective energy transfer from the ligand. The different performance of the two complexes is related to the energy matching between the excited states of the lanthanide ion and the triplet state of the ligand. The intramolecular energy transfer mechanisms are also discussed.
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Antiinflamatorios no Esteroideos/química , Carbazoles/química , Europio/química , Terbio/química , Cristalografía por Rayos X , Modelos Moleculares , Estructura Molecular , Difracción de Rayos XRESUMEN
The present dosage of Dexamethasone (DEX) administered to pregnant women may pose a risk of toxicity to their unborn offspring. We aimed to develop a maternal-fetal physiologically based toxicokinetic (PBTK) model for DEX in pregnant rats, with a specific focus on the role of the P-glycoprotein (P-gp) transporter in placenta perfusion, and finally facilitate the optimization of clinical DEX dosage. We conducted animal experiments to determine DEX concentrations in various rat tissues, and constructed the PBTK model using MATLAB software. Sensitivity analysis was performed to assess input parameters and the model stability, with fold error (FE) values serving as evaluation indices. Our results indicate the successful construction of the PBTK model, with the fitting key parameters such as the absorption rate constant (Ka), intrinsic hepatic clearance (CLh,int) and intrinsic P-gp clearance (CLint,P-gp). The median concentration of DEX in maternal plasma, fetal plasma, fetal lung, and fetal brain were determined, which allowed us to fit the tissue-to-plasma partition coefficients for the fetal lung (Kp,lung,f) and fetal brain (Kp,brain,f). After making adjustments, all calculated FE values were found to be less than 2, demonstrating the acceptability and accuracy of our model's predictions. Our model integrated external literature data and internal animal experimentation to comprehensively evaluate the maternal-fetal PK characteristics of DEX. These findings provide valuable support for the optimization of clinical DEX dosing.
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Dexametasona , Placenta , Humanos , Ratas , Embarazo , Femenino , Animales , Dexametasona/toxicidad , Toxicocinética , Placenta/metabolismo , Perfusión , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismoRESUMEN
Recent camouflaged object detection (COD) attempts to segment objects visually blended into their surroundings, which is extremely complex and difficult in real-world scenarios. Apart from the high intrinsic similarity between camouflaged objects and their background, objects are usually diverse in scale, fuzzy in appearance, and even severely occluded. To this end, we propose an effective unified collaborative pyramid network that mimics human behavior when observing vague images and videos, i.e. zooming in and out. Specifically, our approach employs the zooming strategy to learn discriminative mixed-scale semantics by the multi-head scale integration and rich granularity perception units, which are designed to fully explore imperceptible clues between candidate objects and background surroundings. The former's intrinsic multi-head aggregation provides more diverse visual patterns. The latter's routing mechanism can effectively propagate inter-frame differences in spatiotemporal scenarios and be adaptively deactivated and output all-zero results for static representations. They provide a solid foundation for realizing a unified architecture for static and dynamic COD. Moreover, considering the uncertainty and ambiguity derived from indistinguishable textures, we construct a simple yet effective regularization, uncertainty awareness loss, to encourage predictions with higher confidence in candidate regions. Our highly task-friendly framework consistently outperforms existing state-of-the-art methods in image and video COD benchmarks.
RESUMEN
Calcium (Ca) is required for the growth and development of sheep, but the requirement of Yunnan semi-fine wool (YSW) rams remains uncovered. The current study aims to estimate the Ca requirement of growing YSW rams based on their growth performance, Ca utilization, and serum biochemical indexes. Forty-five YSW rams (10-month-olds) were randomly allocated to five dietary treatments with varying Ca levels of 0.50% (D1), 0.68% (D2), 0.73% (D3), 0.89% (D4), and 0.98% (D5). A higher value for average daily gain and a lower value for the feed conversion ratio were observed in the D3 group compared to the D5 group (p < 0.05). The dry matter intake amount changed quadratically with the increased Ca levels (p < 0.05). The levels of Ca intake, fecal Ca, and excreted Ca were significantly higher in the D5 group than those in the D1 group (p < 0.05). The apparent Ca digestibility rate and the Ca retention rate were significantly higher in the D4 group than in the D1 group (p < 0.05). The serum Ca concentration increased linearly with the incremental levels of dietary Ca (p < 0.05). The activity of alkaline phosphatase was significantly higher in the D1 group than in the D2 group (p < 0.05). The serum levels of hydroxyproline, osteocalcin, and calcitonin decreased from the D1 group to the D2 group, and then significantly ascended (p < 0.05) with the dietary Ca levels from the D3 group to the D5 group. The serum parathyroid hormone content was elevated from the D1 group to the D3 group and then decreased from the D4 group to the D5 group. After calculation, the daily net Ca requirement for the maintenance of YSW rams was 0.073 g/kg of BW0.75, and the daily total Ca requirement was 0.676 g/kg of BW0.75. To optimize the growth performance and the Ca utilization of YSW rams, the recommended dietary Ca level ranges from 0.73% to 0.89% based on this study.