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OBJECTIVE: To explore the role of HIF-1α in hypercoagulable state of COPD induced by lipopolysaccharide plus smoking in rats. It also has to explore the regulatory mechanism of HIF-1α-EPO/EDN-1/VEGF pathway by using its activator and inhibitor. METHODS: 60 Sprague-Dawley rats (SD rats) were randomly divided into healthy control group, COPD hypercoagulable control group, activator group, and inhibitor group with 15 rats in each group. The healthy control group was fed freely. The other groups were given smoke and lipopolysaccharide by tracheal instillation to establish the experimental animal model of COPD hypercoagulability. After successful modeling, each experimental group was given 0.9 % sodium chloride solution and corresponding drugs by intraperitoneal injection for 7 days. Lung function was detected after drug administration. Hematoxylin-eosin staining was used to observe the pathological changes of lung tissue. Enzyme-linked immunosorbent assay was used to detect serum D-D,F (1 + 2),IL-6,TNF-α. The mRNA expressions of HIF-1α, EPO, EDN-1, and VEGF were detected by RT-PCR. Western-Blot and IHC were used to detect the expression of HIF-1α, EPO, EDN-1, and VEGF in lung tissue of rats. RESULTS: Compared with the healthy control group, rats in COPD hypercoagulable control group had COPD symptoms/signs, decreased lung function, increased the expression of serum D-D and F (1 + 2), increased the expression of inflammatory factors IL-6,TNF-α, and increased the expression of proteins HIF-1α, EPO, EDN-1 and VEGF. Compared with COPD hypercoagulable control group, lung function in activator group and inhibitor group had no obvious changes. The expressions of serum D-D,F (1 + 2),IL-6,TNF-α in activator group have increased noticeably. The expressions of proteins HIF-1α, EPO, EDN-1, and VEGF have further increased. Compared with COPD hypercoagulable control group, the expression of serum D-D, F (1 + 2), HIF-1α, EPO, EDN-1, and VEGF in the inhibitor group decreased. CONCLUSION: HIF-1α-EPO/EDN-1/VEGF pathway plays an important role in the hypercoagulable state of COPD. HIF-1α inhibitor can improve airway inflammation and reduce hypercoagulability in COPD model rats.
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Doença Pulmonar Obstrutiva Crônica , Trombofilia , Animais , Ratos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Interleucina-6 , Lipopolissacarídeos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/metabolismo , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Staphylococcus epidermidis is an opportunistic pathogen commonly implicated in medical device-related infections. Its propensity to form biofilms not only leads to chronic infections but also exacerbates the issue of antibiotic resistance, necessitating high-dose antimicrobial treatments. In this study, we explored the use of diclofenac sodium, a non-steroidal anti-inflammatory drug, as an anti-biofilm agent against S. epidermidis. In this study, crystal violet staining and confocal laser scanning microscope analysis showed that diclofenac sodium, at subinhibitory concentration (0.4 mM), significantly inhibited biofilm formation in both methicillin-susceptible and methicillin-resistant S. epidermidis isolates. MTT assays demonstrated that 0.4 mM diclofenac sodium reduced the metabolic activity of biofilms by 25.21-49.01% compared to untreated controls. Additionally, the treatment of diclofenac sodium resulted in a significant decrease (56.01-65.67%) in initial bacterial adhesion, a crucial early phase of biofilm development. Notably, diclofenac sodium decreased the production of polysaccharide intercellular adhesin (PIA), a key component of the S. epidermidis biofilm matrix, in a dose-dependent manner. Real-time quantitative PCR analysis revealed that diclofenac sodium treatment downregulated biofilm-associated genes icaA, fnbA, and sigB and upregulated negative regulatory genes icaR and luxS, providing potential mechanistic insights. These findings indicate that diclofenac sodium inhibits S. epidermidis biofilm formation by affecting initial bacterial adhesion and the PIA synthesis. This underscores the potential of diclofenac sodium as a supplementary antimicrobial agent in combating staphylococcal biofilm-associated infections.
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Antibacterianos , Biofilmes , Diclofenaco , Staphylococcus epidermidis , Biofilmes/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos , Staphylococcus epidermidis/fisiologia , Diclofenaco/farmacologia , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Anti-Inflamatórios não Esteroides/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Humanos , Polissacarídeos Bacterianos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacosRESUMO
Ulcerative colitis (UC) is an inflammatory bowel disorder (IBD) characterized by relapsing chronic inflammation of the colon that causes continuous mucosal inflammation. The global incidence of UC is steadily increasing. Immune mechanisms are involved in the pathogenesis of UC, of which complement is shown to play a critical role by inducing local chronic inflammatory responses that promote tissue damage. However, the function of various complement components in the development of UC is complex and even paradoxical. Some components (e.g. C1q, CD46, CD55, CD59, and C6) are shown to safeguard the intestinal barrier and reduce intestinal inflammation, while others (e.g. C3, C5, C5a) can exacerbate intestinal damage and accelerate the development of UC. The complement system was originally thought to function primarily in an extracellular mode; however, recent evidence indicates that it can also act intracellularly as the complosome. The current study provides an overview of current studies on complement and its role in the development of UC. While there are few studies that describe how intracellular complement contributes to UC, we discuss potential future directions based on related publications. We also highlight novel methods that target complement for IBD treatment.
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Colite Ulcerativa , Doenças Inflamatórias Intestinais , Humanos , Proteínas do Sistema Complemento , Inflamação , Fatores de TranscriçãoRESUMO
Photocatalysis technology has the advantages of being green, clean, and environmentally friendly, and has been widely used in CO2 reduction, hydrolytic hydrogen production, and the degradation of pollutants in water. Cu2O has the advantages of abundant reserves, a low cost, and environmental friendliness. Based on the narrow bandgap and strong visible light absorption ability of Cu2O, Cu2O-based composite materials show infinite development potential in photocatalysis. However, in practical large-scale applications, Cu2O-based composites still pose some urgent problems that need to be solved, such as the high composite rate of photogenerated carriers, and poor photocatalytic activity. This paper introduces a series of Cu2O-based composites, based on recent reports, including pure Cu2O and Cu2O hybrid materials. The modification strategies of photocatalysts, critical physical and chemical parameters of photocatalytic reactions, and the mechanism for the synergistic improvement of photocatalytic performance are investigated and explored. In addition, the application and photocatalytic performance of Cu2O-based photocatalysts in CO2 photoreduction, hydrogen production, and water pollution treatment are discussed and evaluated. Finally, the current challenges and development prospects are pointed out, to provide guidance in applying Cu2O-based catalysts in renewable energy utilization and environmental protection.
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The pollution of phenol wastewater is becoming worse. In this paper, a 2D/2D nanosheet-like ZnTiO3/Bi2WO6 S-Scheme heterojunction was synthesized for the first time through a two-step calcination method and a hydrothermal method. In order to improve the separation efficiency of photogenerated carriers, the S-Scheme heterojunction charge-transfer path was designed and constructed, the photoelectrocatalytic effect of the applied electric field was utilized, and the photoelectric coupling catalytic degradation performance was greatly enhanced. When the applied voltage was +0.5 V, the ZnTiO3/Bi2WO6 molar ratio of 1.5:1 had highest degradation rate under visible light: the degradation rate was 93%, and the kinetic rate was 3.6 times higher than that of pure Bi2WO6. Moreover, the stability of the composite photoelectrocatalyst was excellent: the photoelectrocatalytic degradation rate of the photoelectrocatalyst remained above 90% after five cycles. In addition, through electrochemical analysis, XRD, XPS, TEM, radical trapping experiments, and valence band spectroscopy, we found that the S-scheme heterojunction was constructed between the two semiconductors, which effectively retained the redox ability of the two semiconductors. This provides new insights for the construction of a two-component direct S-scheme heterojunction as well as a feasible new solution for the treatment of phenol wastewater pollution.
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Crop diseases are one of the important factors affecting crop yield and quality and are also an important research target in the field of agriculture. In order to quickly and accurately identify crop diseases, help farmers to control crop diseases in time, and reduce crop losses. Inspired by the application of convolutional neural networks in image identification, we propose a lightweight crop disease image identification model based on attentional feature fusion named DSGIResNet_AFF, which introduces self-built lightweight residual blocks, inverted residuals blocks, and attentional feature fusion modules on the basis of ResNet18. We apply the model to the identification of rice and corn diseases, and the results show the effectiveness of the model on the real dataset. Additionally, the model is compared with other convolutional neural networks (AlexNet, VGG16, ShuffleNetV2, MobileNetV2, MobileNetV3-Small and MobileNetV3-Large), and the experimental results show that the accuracy, sensitivity, F1-score, AUC of the proposed model DSGIResNet_AFF are 98.30%, 98.23%, 98.24%, 99.97%, respectively, which are better than other network models, while the complexity of the model is significantly reduced (compared with the basic model ResNet18, the number of parameters is reduced by 94.10%, and the floating point of operations(FLOPs) is reduced by 86.13%). The network model DSGIResNet_AFF can be applied to mobile devices and become a useful tool for identifying crop diseases.
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Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Processamento de Imagem Assistida por Computador/métodosRESUMO
Cerebral ischaemia/reperfusion (I/R) injury-induced irreversible brain injury is a major cause of mortality and functional impairment in ageing people. Gastrodin (GAS), derived from the traditional Chinese herbal medicine Tianma, has been reported to inhibit the progression of stroke, but the mechanism whereby GAS modulates the progression of cerebral I/R remains unclear. The middle cerebral artery occlusion method was used as a model of I/R in vivo. Rats were pretreated with GAS by intraperitoneal injection 7 days before I/R surgery and were then treated with GAS for 7 days after I/R surgery. Additionally, an oxygen-glucose deprivation/reoxygenation model using neuronal cells was established in vitro to simulate I/R injury. 2,3,5-Triphenyltetrazolium chloride and Nissl staining were used to evaluate infarct size and neuronal damage, respectively. Lactate dehydrogenase release and cell counting kit-8 assays were used to assess neuronal cell viability. Enzyme-linked immunosorbent assay, qPCR, flow cytometry and western blotting were performed to analyse the expression levels of inflammatory factors (IL-1ß, IL-18), lncRNA NEAT1, miR-22-3p, NLRP3 and cleaved caspase-1. Luciferase reporter experiments were performed to verify the association between lncRNA NEAT1 and miR-22-3p. The results indicated that GAS could significantly improve the neurological scores of rats and reduce the area of cerebral infarction. Meanwhile, GAS inhibited pyroptosis by downregulating NLRP3, inflammatory factors (IL-1ß, IL-18) and cleaved caspase-1. In addition, GAS attenuated I/R-induced inflammation in neuronal cells through the modulation of the lncRNA NEAT1/miR-22-3p axis. GAS significantly attenuated cerebral I/R injury via modulation of the lncRNA NEAT1/miR-22-3p axis. Thus, GAS might serve as a new agent for the treatment of cerebral I/R injury.
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Álcoois Benzílicos/uso terapêutico , Glucosídeos/uso terapêutico , MicroRNAs/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Piroptose/efeitos dos fármacos , RNA Longo não Codificante/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Encéfalo/patologia , Hipóxia Celular/fisiologia , Glucose/deficiência , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Inflamação/tratamento farmacológico , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oxigênio/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologiaRESUMO
BACKGROUND: Scrub typhus is caused by O. tsutsugamushi and spreads through mite larvae biting the skin. Classic symptoms of the disease are eschar and lymphadenopathy. Previous reports have revealed clinical manifestations of scrub typhus, including gastrointestinal symptoms, meningoencephalitis, ocular flutter, pneumonitis, acute respiratory distress syndrome, and acute kidney injury. However, cases of scrub typhus presenting as a urinary tract infection (UTI) with high D-dimer levels could be easily misdiagnosed when clinical attention is insufficient, resulting in difficulty in making a timely diagnosis of the infection. Metagenomics next-generation sequencing (mNGS) is a revolutionary and highly sensitive method that may help in diagnosing atypical cases, even when trace amounts of pathogens are present. CASE PRESENTATION: A 52-year-old female presented with a 10-day history of fever, chills, headache and myalgia. She was initially diagnosed with influenza at a local clinic. Various antibacterials were used on the 2nd-12th day onwards; however, her symptoms persisted and were followed by increased urination duration, frequency, urgency and dysuria for 2 days. Orientia tsutsugamushi was confirmed as the pathogen responsible for the infection through mNGS analysis of her blood samples from Day 13 onwards. The patient's temperature changed remarkably 24 h after the initiation of doxycycline. Over the next 48 h (i.e., Day 15 onwards), the patient showed clinical improvement. She recovered and was discharged from the hospital. CONCLUSIONS: Scrub typhus can present atypical clinical symptoms, such as UTIs, in a febrile patient. mNGS may be a useful method for identifying O. tsutsugamushi infection in patients with atypical clinical manifestations.
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Orientia tsutsugamushi , Tifo por Ácaros , Infecções Urinárias , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Metagenômica , Pessoa de Meia-Idade , Orientia tsutsugamushi/genética , Tifo por Ácaros/diagnóstico , Tifo por Ácaros/tratamento farmacológico , Infecções Urinárias/diagnósticoRESUMO
PURPOSE: Visual outcomes after cataract surgery in diabetic patients with retinal or visual pathway disease are difficult to predict as the fundus may be obscured, and assessment of visual potential is challenging. This study assessed the value of visual electrophysiology as a prognostic indicator of visual recovery in diabetic patients with cataract, prior to cataract surgery. METHODS: Forty-one diabetic patients (aged 52-80; 74 eyes) and 13 age-matched non-diabetic control patients (21 eyes) were examined prior to cataract surgery. Pre-surgical examinations included best-corrected visual acuity (BCVA), slit-lamp bio-microscopy, ISCEV-standard full-field electroretinography (ffERG), and flash visual evoked potential (flash VEP) testing. Electrophysiological assessments included quantification of the DA and LA ERG, oscillatory potentials (OPs; OP1, OP2, OP3, OP4) and flash VEP P1, P2, and P3 components. Post-operative BCVA was measured in all cases and the diabetic patients grouped according to the severity of visual acuity loss: mild (logMAR ≤ 0.1), moderate (0.1 < logMAR < 0.5), or severe (logMAR ≥ 0.5). A fourth group included those without diabetes. The pre-surgical electrophysiological data was compared between the four groups by analysis of variance. RESULTS: The severity of post-surgical visual acuity loss in the diabetic patients was classified as mild (N=22 eyes), moderate (N=31 eyes), or severe (N=21 eyes). In the group without diabetes, post-surgical visual impairment was classified as mild (N=21 eyes). The pre-operative DA 10.0 ERG a-wave amplitudes, DA 3.0 ERG OP2 amplitudes, and the LA 3.0 a- and b-wave amplitudes showed best significant differences among the four groups. The flash VEP did not show significant difference between groups. CONCLUSION: Electrophysiological assessment of diabetic patients with cataract can provide a useful measure of retinal function. Full-field ERG components, including the DA 10.0 ERG a-wave, DA 3.0 ERG OP2 component, and the LA 3.0 a- and b-wave amplitudes, are of prognostic value in predicting post-surgical visual acuity, and may inform the surgical management of cataract patients with diabetes.
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Catarata , Diabetes Mellitus , Catarata/complicações , Catarata/diagnóstico , Eletrofisiologia , Eletrorretinografia , Potenciais Evocados Visuais , Humanos , Prognóstico , RetinaRESUMO
Orexin is a peptide neurotransmitter released in the globus pallidus. Morphological evidence reveals that both orexin 1 receptor (OX1R) and orexin 2 receptor (OX2R) exist in the globus pallidus. Here we showed that bilateral microinjection of both orexin-A and orexin-B into the globus pallidus alleviated motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian mice. Further in vivo extracellular single-unit recording revealed that the basal spontaneous firing rate of the globus pallidus neurons in MPTP parkinsonian mice was slower than that of normal mice. Application of orexin-A or orexin-B significantly increased the spontaneous firing rate of pallidal neurons. The influx of Ca2+ through the L-type Ca2+ channel is the major mechanism involved in orexin-induced excitation in the globus pallidus. Orexin-A-induced increase in firing rate of pallidal neurons in MPTP parkinsonian mice was stronger than that of normal mice. Orexin-A exerted both electrophysiological and behavioral effects mainly via OX1R, and orexin-B exerted the effects via OX2R. Endogenous orexins modulated the excitability of globus pallidus neurons mainly through OX1R. The present behavioral and electrophysiological results suggest that orexins ameliorate parkinsonian motor deficits through increasing the spontaneous firing of globus pallidus neurons.
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Potenciais de Ação/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Orexinas/farmacologia , Animais , Modelos Animais de Doenças , Globo Pálido/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Doença de Parkinson/tratamento farmacológicoRESUMO
Via Bischler-Napieralski cyclization of amide precursors as the key step, a series of diazapyrene derivatives were designed and successfully synthesized. Their crystal structures, optoelectronic properties, and acid-responsive feature were investigated, which demonstrated that the doping of nitrogen atoms to the pyrene framework remarkably modulates their physical and chemical properties.
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TLRs are key sensors for conserved bacterial molecules and play a critical role in host defense against invading pathogens. Although the roles of TLRs in defense against pathogen infection and in maintaining gut immune homeostasis have been studied, the precise functions of different TLRs in response to pathogen infection in the gut remain elusive. The present study investigated the role of TLR signaling in defense against the Gram-negative bacterial pathogen Salmonella typhimurium The results indicated that TLR9-deficient mice were more susceptible to S. typhimurium infection compared with wild-type and TLR2- or TLR4-deficient mice, as indicated by more severe intestinal damage and the highest bacterial load. TLR9 deficiency in intestinal epithelial cells (IECs) augmented the activation of NF-κB and NLRP3 inflammasomes significantly, resulting in increased secretion of IL-1ß. IL-1ß increased the expression of NKG2D on intestinal intraepithelial lymphocytes and NKG2D ligands on IECs, resulting in higher susceptibility of IECs to cytotoxicity of intestinal intraepithelial lymphocytes and damage to the epithelial barrier. We proposed that TLR9 regulates the NF-κB-NLRP3-IL-1ß pathway negatively in Salmonella-induced NKG2D-mediated intestinal inflammation and plays a critical role in defense against S. typhimurium infection and in the protection of intestinal integrity.
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Gastroenterite/imunologia , Interleucina-1beta/metabolismo , Intestinos/imunologia , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Salmonelose Animal/imunologia , Salmonella typhimurium/imunologia , Receptor Toll-Like 9/metabolismo , Animais , Células Epiteliais/imunologia , Gastroenterite/microbiologia , Regulação da Expressão Gênica , Inflamassomos/metabolismo , Inflamação , Interleucina-1beta/imunologia , Intestinos/citologia , Intestinos/patologia , Camundongos , NF-kappa B/metabolismo , Subfamília K de Receptores Semelhantes a Lectina de Células NK/genética , Subfamília K de Receptores Semelhantes a Lectina de Células NK/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Espécies Reativas de Oxigênio/metabolismo , Salmonelose Animal/microbiologia , Transdução de Sinais , Receptor 2 Toll-Like/deficiência , Receptor 2 Toll-Like/imunologia , Receptor 3 Toll-Like/deficiência , Receptor 3 Toll-Like/imunologia , Receptor Toll-Like 9/deficiência , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/imunologiaRESUMO
Adipose tissue is the main energy reserve of the body. When energy is required, adipocyte triglycerides stored in lipid droplets (LDs) are broken down by lipase, and free fatty acids are released to supply the physiological need. Intracellular LDs are active metabolic organelles in mammalian cells, particularly in adipocytes. The present study was aimed to investigate the morphological changes of LDs and the alternation of LD-associated perilipin family proteins during long-term lipolysis stimulated by forskolin. Primary differentiated adipocytes derived from epididymal fat pads of Sprague-Dawley (SD) rats were incubated in the presence or absence of 1 µmol/L forskolin for 24 h. Content of glycerol released to the culture medium was determined by a colorimetric assay and served as an index of lipolysis. Morphological changes of LDs were observed by Nile red staining. The mRNA level of perilipin family genes was detected by quantitative real-time PCR. The protein level and subcellular localization were examined by immunoblotting and immunofluorescence staining, respectively. The results showed that forskolin induced sustained lipolysis in differentiated adipocytes. The morphology of LDs changed in a time-dependent manner. Large clustered LDs became gradually smaller in size and eventually disappeared; in contrast, peripheral micro-LDs increased gradually in number until the cytoplasm was filled with numerous micro-LDs. The protein level of the perilipin family proteins showed obvious alternation. Mature adipocytes physiologically expressed a very low level of Plin2 protein, whereas in adipocytes stimulated with lipolytic forskolin, the protein and mRNA levels of Plin2 were significantly increased, and the increased Plin2 was specifically bound to the surface of LDs. During chronic stimulation of forskolin, the mRNA level of Plin3 was unchanged, but the mRNA levels of Plin1, Plin4 and Plin5 were significantly decreased. These results suggest that the morphology of LDs and perilipin family proteins on the surface of LDs are significantly altered during long-term lipolysis stimulated by forskolin, representing a dynamic process of the remodeling of LDs.
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Adipócitos/efeitos dos fármacos , Colforsina/farmacologia , Gotículas Lipídicas , Lipólise , Perilipinas/metabolismo , Animais , Células Cultivadas , Perilipina-2/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
The intestinal immune system is crucial for protection from pathogenic infection and maintenance of mucosal homeostasis. We studied the intestinal immune microenvironment in a Salmonella enterica serovar Typhimurium intestinal infection mouse model. Intestinal lamina propria macrophages are the main effector cells in innate resistance to intracellular microbial pathogens. We found that S Typhimurium infection augmented Tim-3 expression on intestinal lamina propria CD4+ T cells and enhanced galectin-9 expression on F4/80+ CD11b+ macrophages. Moreover, CD4+ T cells promoted the activation and bactericidal activity of intestinal F4/80+ CD11b+ macrophages via the Tim-3/galectin-9 interaction during S Typhimurium infection. Blocking the Tim-3/galectin-9 interaction with α-lactose significantly attenuated the bactericidal activity of intracellular S Typhimurium by macrophages. Furthermore, the Tim-3/galectin-9 interaction promoted the formation and activation of inflammasomes, which led to caspase-1 cleavage and interleukin 1ß (IL-1ß) secretion. The secretion of active IL-1ß further improved bactericidal activity of macrophages and galectin-9 expression on macrophages. These results demonstrated the critical role of the cross talk between CD4+ T cells and macrophages, particularly the Tim-3/galectin-9 interaction, in antimicrobial immunity and the control of intestinal pathogenic infections.
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Linfócitos T CD4-Positivos/imunologia , Galectinas/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Mucosa Intestinal/imunologia , Macrófagos/imunologia , Mucosa/imunologia , Infecções por Salmonella/imunologia , Salmonella typhimurium/imunologia , Animais , Linfócitos T CD4-Positivos/metabolismo , Modelos Animais de Doenças , Imunidade Inata , Imunidade nas Mucosas , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Viabilidade Microbiana , Ligação Proteica , Mapas de Interação de Proteínas , Salmonella typhimurium/fisiologiaRESUMO
Orexin is a member of neuropeptides which is involved in the central motor control. The substantia nigra pars compacta (SNc) is an important nucleus participating in motor control under both physiological and pathological conditions. Morphological studies reveal that orexinergic neurons located in lateral hypothalamus innervate the SNc. Both orexin-1 receptors (OX1 R) and orexin-2 receptors (OX2 R) are expressed in the SNc. To investigate the effects of orexins on SNc, single unit in vivo extracellular recordings and behavioral tests were performed in this study. Micro-pressure administration of orexin A and orexin B significantly increased the spontaneous firing rate of nigral DAergic neurons by 65.87 ± 7.73% and 90.49 ± 17.83%, respectively. The excitatory effects of orexin A on nigral DAergic neurons were mainly mediated by OX1 R, while OX2 R were involved in the increase in firing rate induced by orexin B. Selectively blocking OX1 R and OX2 R significantly decreased the firing rate of nigral DAergic neurons by 36.77 ± 6.26% and 32.04 ± 6.12%, respectively, which suggested that endogenous orexins modulated the spontaneous firing activity of nigral DAergic neurons. Finally, both elevated body swing test and haloperidol-induced postural behavioral test showed that unilateral microinjection of orexin A and orexin B induced significantly contralateral-biased swing and deflection behavior. Meanwhile, the specific OX1 R and OX2 R antagonists produced opposite effects. The present electrophysiological and behavioral studies suggested that orexins increased the firing activity of nigral DAergic neurons and participated in central motor control. Open Practices Open Science: This manuscript was awarded with the Open Materials Badge. For more information see: https://cos.io/our-services/open-science-badges/.
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Neurônios Dopaminérgicos/efeitos dos fármacos , Orexinas/farmacologia , Substância Negra/efeitos dos fármacos , Animais , Comportamento Animal , Antagonistas de Dopamina/farmacologia , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Haloperidol/farmacologia , Masculino , Microinjeções , Atividade Motora/efeitos dos fármacos , Receptores de Orexina/biossíntese , Receptores de Orexina/genética , Orexinas/administração & dosagem , Equilíbrio Postural/efeitos dos fármacos , Ratos , Ratos Wistar , Substância Negra/citologiaRESUMO
Two aryl-substituted tetraphenylfurans (TPF-1 and TPF-2) and the corresponding ring-opened (Z)-1,4-enedione derivatives (TPBD-1 and TPBD-2) have been successfully synthesized. Although all the molecules adopt propeller-like configurations, experimental results revealed that the tetraphenylfurans (TPFs) were aggregation-caused quenching (ACQ) fluorophores whereas the 1,4-enediones (TPBDs) were aggregation-induced emission (AIE) active. Additionally, the TPFs and TPBDs exhibited contrasting "turn-on" mechanochromic behavior, with an unusual blueshift of mechanochromic fluorescence for the TPFs and a remarkable redshifted mechanochromism for the TPBDs. Both of these solid-state optical properties were proven to be highly dependent on the mode of molecular packing and substituent effects. In particular, in addition to the tunability of the fluorescent properties through aggregation and mechanical force, ground TPF-1 was found to be efficiently sensitive to light. On the basis of these findings we constructed a smart film with ground TPF-1 and demonstrated its utility in data encryption and decryption well controlled by UV light. Therefore, this work not only provides an insight into the mechanism of AIE as well as mechanochromic effects, but also paves the way towards the development of multifunctional stimuli-responsive materials and devices.
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Botryosphaeria dieback, caused by species of Botryosphaeriaceae, is an important grapevine trunk disease in Australia. Inocula produced by the pathogens are primarily dispersed by rain splash and wind and infect pruning wounds leading to cankers, dieback, and eventually death of vines. The objective of this study was to develop molecular tools to detect and quantify Botryosphaeriaceae inocula from the environment. These tools are essential for investigating spore dispersal patterns of Botryosphaeriaceae pathogens in Australian vineyards. DNA extraction protocols were evaluated and one modified protocol was found suitable for extracting Botryosphaeriaceae DNA from artificially and naturally inoculated Burkard volumetric spore sampler tapes. Multispecies primers and a hydrolysis probe for quantitative PCR (qPCR) were further developed to detect and quantify Botryosphaeriaceae inocula from environmental samples. Specificity tests showed that the multispecies primers were able to amplify the DNA of 10 Botryosphaeriaceae species (58 isolates) found in Australia while none of the 27 nontarget fungal species (90 isolates) tested were amplified. The qPCR assay was suitable for amplifying purified DNA, synthetic DNA fragments (gBlocks), and mixed DNA from spore trap tapes. The qPCR method developed in this study was shown to be rapid and sensitive in detecting Botryosphaeriaceae inocula from the environment using spore traps.
Assuntos
Ascomicetos/genética , DNA Fúngico/genética , Esporos Fúngicos/genética , Vitis/crescimento & desenvolvimento , Ascomicetos/classificação , Ascomicetos/fisiologia , Austrália , Primers do DNA/genética , DNA Fúngico/isolamento & purificação , Doenças das Plantas/microbiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reprodutibilidade dos Testes , Especificidade da Espécie , Esporos Fúngicos/fisiologia , Vitis/microbiologiaRESUMO
Boron carbide is one of the hardest materials known, with diamond-like mechanical properties and excellent chemical stability. It is wildly used in military defense area, nuclear industry, aerospace technology, etc. Precursor-derived ceramics have made it easier to produce pure boron carbide in processed forms and expand its applications. The challenge of this method is the synthesis of precursor polymer with high-ceramic-yield. The aim of the present work is to develop a new poly(6-norbornenyldecaborane-co-decaborane) [P(ND-co-D)] copolymer, which was successfully synthesized via ring-opening metathesis polymerization of 6-norbornenyldecaborane and tandem hydroboration with decaborane. The obtained light-yellow powder displayed good solubility, and was fully characterized by NMR, FT-IR and GPC analysis. Thermogravimetric analysis demonstrated that the char yield was up to 79%. The polymer-to-ceramic transformation process and pyrolysis mechanism has shown that the rearrangement of carbon chains of P(ND-co-D) mainly occurred in the temperature range of 350 °C~470 °C. Furthermore, the crystallization behavior and microstructures of derived ceramics were studied by XRD and SEM. Nano-sized boron carbide powders were prepared by pyrolysis of P(ND-co-D) under argon at 1400 °C for 2 h, while the structure and morphologies of the obtained rhombohedral B4C were investigated.
Assuntos
Compostos de Boro/química , Cerâmica/química , Dureza , Polímeros/química , Cristalização , PolimerizaçãoRESUMO
Grassland fire is one of the most important disturbance factors of the natural ecosystem. Climate factors influence the occurrence and development of grassland fire. An analysis of the climate conditions of fire occurrence can form the basis for a study of the temporal and spatial variability of grassland fire. The purpose of this paper is to study the effects of monthly time scale climate factors on the occurrence of grassland fire in HulunBuir, located in the northeast of the Inner Mongolia Autonomous Region in China. Based on the logistic regression method, we used the moderate-resolution imaging spectroradiometer (MODIS) active fire data products named thermal anomalies/fire daily L3 Global 1km (MOD14A1 (Terra) and MYD14A1 (Aqua)) and associated climate data for HulunBuir from 2000 to 2010, and established the model of grassland fire climate index. The results showed that monthly maximum temperature, monthly sunshine hours and monthly average wind speed were all positively correlated with the fire climate index; monthly precipitation, monthly average temperature, monthly average relative humidity, monthly minimum relative humidity and the number of days with monthly precipitation greater than or equal to 5 mm were all negatively correlated with the fire climate index. We used the active fire data from 2011 to 2014 to validate the fire climate index during this time period, and the validation result was good (Pearson's correlation coefficient was 0.578), which showed that the fire climate index model was suitable for analyzing the occurrence of grassland fire in HulunBuir. Analyses were conducted on the temporal and spatial distribution of the fire climate index from January to December in the years 2011-2014; it could be seen that from March to May and from September to October, the fire climate index was higher, and that the fire climate index of the other months is relatively low. The zones with higher fire climate index are mainly distributed in Xin Barag Youqi, Xin Barag Zuoqi, Zalantun Shi, Oroqen Zizhiqi, and Molidawa Zizhiqi; the zones with medium fire climate index are mainly distributed in Chen Barag Qi, Ewenkizu Zizhiqi, Manzhouli Shi, and Arun Qi; and the zones with lower fire climate index are mainly distributed in Genhe Shi, Ergun city, Yakeshi Shi, and Hailar Shi. The results of this study will contribute to the quantitative assessment and management of early warning and forecasting for mid-to long-term grassland fire risk in HulunBuir.
RESUMO
BACKGROUND: Astragalus membranaceus (AM) shows potential therapeutic benefits for managing diabetic kidney disease (DKD), a leading cause of kidney failure with no cure. However, its comprehensive effects on renal outcomes and plausible mechanisms remain unclear. PURPOSE: This systematic review and meta-analysis aimed to synthesize the effects and mechanisms of AM on renal outcomes in DKD animal models. METHODS: Seven electronic databases were searched for animal studies until September 2023. Risk of bias was assessed based on SYRCLE's Risk of Bias tool. Standardized mean difference (SMD) or mean difference (MD) were estimated for the effects of AM on serum creatinine (SCr), blood urea nitrogen (BUN), albuminuria, histological changes, oxidative stress, inflammation, fibrosis and glucolipids. Effects were pooled using random-effects models. Heterogeneity was presented as I2. Subgroup analysis investigated treatment- and animal-related factors for renal outcomes. Publication bias was assessed using funnel plots and Egger's test. Sensitivity analysis was performed to assess the results' robustness. RevMan 5.3 and Stata MP 15 software were used for statistical analysis. RESULTS: Forty studies involving 1543 animals were identified for analysis. AM treatment significantly decreased SCr (MD = -19.12 µmol/l, 95 % CI: -25.02 to -13.23), BUN (MD = -6.72 mmol/l, 95 % CI: -9.32 to -4.12), urinary albumin excretion rate (SMD = -2.74, 95 % CI: -3.57, -1.90), histological changes (SMD = -2.25, 95 % CI: -3.19 to -1.32). AM treatment significantly improved anti-oxidative stress expression (SMD = 1.69, 95 % CI: 0.97 to 2.41), and decreased inflammation biomarkers (SMD = -3.58, 95 % CI: -5.21 to -1.95). AM treatment also decreased fibrosis markers (i.e. TGF-ß1, CTGF, collagen IV, Wnt4 and ß-catenin) and increased anti-fibrosis marker BMP-7. Blood glucose, lipids and kidney size were also improved compared with the DM control group. CONCLUSION: AM could improve renal outcomes and alleviate injury through multiple signaling pathways. This indicates AM may be an option to consider for the development of future DKD therapeutics.