RESUMO
Reinventing potato from a clonally propagated tetraploid into a seed-propagated diploid, hybrid potato, is an important innovation in agriculture. Due to deleterious mutations, it has remained a challenge to develop highly homozygous inbred lines, a prerequisite to breed hybrid potato. Here, we employed genome design to develop a generation of pure and fertile potato lines and thereby the uniform, vigorous F1s. The metrics we applied in genome design included the percentage of genome homozygosity and the number of deleterious mutations in the starting material, the number of segregation distortions in the S1 population, the haplotype information to infer the break of tight linkage between beneficial and deleterious alleles, and the genome complementarity of the parental lines. This study transforms potato breeding from a slow, non-accumulative mode into a fast-iterative one, thereby potentiating a broad spectrum of benefits to farmers and consumers.
Assuntos
Genoma de Planta , Hibridização Genética , Solanum tuberosum/genética , Cruzamentos Genéticos , Diploide , Fertilidade/genética , Genes de Plantas , Variação Genética , Genética Populacional , Heterozigoto , Homozigoto , Vigor Híbrido/genética , Mutação/genética , Linhagem , Melhoramento Vegetal , Análise de Componente Principal , Seleção GenéticaRESUMO
Lead (Pb), cadmium (Cd), and mercury (Hg) are environmentally toxic heavy metals that can be simultaneously detected at low levels in the blood of the general population. Although our previous studies have demonstrated neurodevelopmental toxicity upon co-exposure to these heavy metals at these low levels, the precise mechanisms remain largely unknown. Dendritic spines are the structural foundation of memory and undergo significant dynamic changes during development. This study focused on the dynamics of dendritic spines during brain development following Pb, Cd, and Hg co-exposure-induced memory impairment. First, the dynamic characteristics of dendritic spines in the prefrontal cortex were observed throughout the life cycle of normal rats. We observed that dendritic spines increased rapidly from birth to their peak value at weaning, followed by significant pruning and a decrease during adolescence. Dendritic spines tended to be stable until their loss in old age. Subsequently, a rat model of low-dose Pb, Cd, and Hg co-exposure from embryo to adolescence was established. The results showed that exposure to low doses of heavy metals equivalent to those detected in the blood of the general population impaired spatial memory and altered the dynamics of dendritic spine pruning from weaning to adolescence. Proteomic analysis of brain and blood samples suggested that differentially expressed proteins upon heavy metal exposure were enriched in dendritic spine-related cytoskeletal regulation and axon guidance signaling pathways and that cofilin was enriched in both of these pathways. Further experiments confirmed that heavy metal exposure altered actin cytoskeleton dynamics and disturbed the dendritic spine pruning-related LIM domain kinase 1-cofilin pathway in the rat prefrontal cortex. Our findings demonstrate that low-dose Pb, Cd, and Hg co-exposure may promote memory impairment by perturbing dendritic spine dynamics through dendritic spine pruning-related signaling pathways.
Assuntos
Cádmio , Mercúrio , Humanos , Adolescente , Animais , Ratos , Cádmio/toxicidade , Mercúrio/toxicidade , Espinhas Dendríticas , Chumbo/toxicidade , Proteômica , Fatores de Despolimerização de Actina , Encéfalo , Transtornos da Memória/induzido quimicamenteRESUMO
Heterosis is a fundamental biological phenomenon characterized by the superior performance of hybrids over their parents. Although tremendous progress has been reported in seed crops, the molecular mechanisms underlying heterosis in clonally propagated crops are largely unknown. Potato (Solanum tuberosum L.) is the most important tuber crop and an ongoing revolution is transforming potato from a clonally propagated tetraploid crop into a seed-propagated diploid hybrid potato. In our previous study, we developed the first generation of highly homozygous inbred lines of potato and hybrids with strong heterosis. Here, we integrated transcriptome, metabolome, and DNA methylation data to explore the genetic and molecular basis of potato heterosis at three developmental stages. We found that the initial establishment of heterosis in diploid potato was mainly due to dominant complementation. Flower color, male fertility, and starch and sucrose metabolism showed obvious gene dominant complementation in hybrids, and hybrids devoted more energy to primary metabolism for rapid growth. In addition, we identified ~2 700 allele-specific expression genes at each stage, which likely function in potato heterosis and might be regulated by CHH allele-specific methylation level. Our multi-omics analysis provides insight into heterosis in potato and facilitates the exploitation of heterosis in potato breeding.
Assuntos
Vigor Híbrido , Solanum tuberosum , Diploide , Vigor Híbrido/genética , Hibridização Genética , Melhoramento Vegetal , Solanum tuberosum/genética , TetraploidiaRESUMO
Distal metaphyseal tibial fractures (3-5 cm from the joint with zones of comminution or <3 cm from the joint) are challenging to fix and are associated with many complications. The study objective was to evaluate the functional outcomes and complications after treating distal metaphyseal tibial fractures using anatomical anterolateral tibia locking plates or anterolateral-medial plates. This retrospective study included 57 patients with distal metaphyseal tibial fractures. Thirty patients were treated by open reduction internal fixation with anterolateral plates; 27 patients were treated with anterolateral-medial plates. Patients were followed at regular intervals. The time to fracture union and complications were recorded. We evaluated the stage of fracture healing using the Radiographic Union Score for Tibial fractures. The patients treated with anterolateral plates had significantly higher rates of loss of reduction and malunion than those treated with anterolateral-medial plates (pâ¯=â¯.02 and pâ¯=â¯.002, respectively). There were no significant differences in the radiographic union scores (pâ¯=â¯.22), non-union (pâ¯=â¯.17), incision necrosis (pâ¯=â¯.91), or infection (pâ¯=â¯.94) between the 2 groups. The functional outcomes were assessed using the American Orthopedic Foot and Ankle Society hindfoot-ankle score at the 12-month follow-up. The mean hindfoot-ankle scores were 90.9 ± 5.0 (range 79 to 100, median 90) and 92.3 ± 5.1 (range 82 to 100, median 92) for the anterolateral plates and anterolateral-medial plates, respectively (pâ¯=â¯.29). For distal metaphyseal tibial fractures, anterolateral-medial plates may be worthwhile for reducing loss of reduction and malunion.
Assuntos
Fraturas Cominutivas , Fraturas da Tíbia , Placas Ósseas , Fixação Interna de Fraturas , Consolidação da Fratura , Humanos , Estudos Retrospectivos , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/cirurgia , Resultado do TratamentoRESUMO
PURPOSE: The aim of this study was to compare the outcomes of laparoscopic appendectomy (LA) using purse string invaginating sutures (PS) with those using intracorporeal knotting (IK) or Hem-o-lock polymeric clips (HL). METHODS: A total of 882 patients who underwent laparoscopic appendectomy from January 2015 to December 2017 were studied retrospectively. Of these, 538 patients used PS, 229 patients used IK and 115 patients used HL to close the appendiceal stump. Their demographic characteristics, intraoperative findings and postoperative complications were analysed retrospectively. RESULTS: There were similar percentages of complicated cases in all the groups (21.7% in PS vs. 21.4% in IK vs. 24.3% in HL, p = 0.803). The mean length of hospital stay was shorter in PS group when compared to IK or HL group (3.72 + 2.35 in PS vs. 4.41 + 2.40 in IK, 4.43 + 2.66 in HL, p < 0.05) as well as lower ASA scores (1.7 + 0.6 in PS vs. 1.8 + 0.6 in IK vs. 1.7 + 0.6 in HL, p < 0.05). The overall complication rates for the PS, the HL and the IK groups were 12.1, 8.7 and 9.2%, respectively. The rate of wound infection was higher in PS group for uncomplicated appendicitis (5.0% in PS vs. 2.8% in IK and 1.1% in HL, p = 0.129). Furthermore, there were no differences in the rate of intra-abdominal infection among the groups in both uncomplicated and complicated cases. CONCLUSIONS: Based on our results, purse string suture failed to demonstrate better postoperative outcome in laparoscopic appendectomy and is no longer recommended by our institution as initial approach.
Assuntos
Apendicectomia , Apendicite/cirurgia , Laparoscopia , Complicações Pós-Operatórias , Técnicas de Sutura , Adulto , Apendicectomia/efeitos adversos , Apendicectomia/instrumentação , Apendicectomia/métodos , Pesquisa Comparativa da Efetividade , Feminino , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/instrumentação , Laparoscopia/métodos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Técnicas de Sutura/efeitos adversos , Técnicas de Sutura/estatística & dados numéricosRESUMO
Influenza A virus (IAV) possesses a high infectivity and pathogenicity, and can lead to severe respiratory infection with similar symptoms caused by some other common respiratory viruses. Lateral flow assay (LFA) has been widely deployed in remote settings as a rapid and reliable approach for point-of-care detection of infectious pathogens. However, it still remains challenging to detect IAV virions using LFA from clinical samples such as nasopharyngeal or throat swabs, because their various components and high viscosity can decrease flow velocity and lead to the nonspecific adsorption of nanoparticle labels on the sensing membrane. Herein, we demonstrated a magnetic quantum dot nanobeads (MQBs) based LFA for magnetic enrichment and fluorescent detection of IAV virions in clinical specimens. In this study, MQBs were synthesized and then conjugated with IAV-specific antibody to efficiently enrich IAV virions from complex biological matrix, but also serve as highly bright fluorescent probes in lateral flow strips. This assay can achieve quantitative detection of IAV virions with a low limit of detection down to 22 pfu mL-1 within 35â¯minutes, and show good specificity between influenza B virus and two adenovirus strains. Furthermore, the presented platform was able to directly detect IAV virions spiked in nasopharyngeal swab dilution, indicating its stability and feasibility in clinical applications. Thus, this point-of-care detection platform holds great promise as a broadly applicable approach for the rapid diagnosis of influenza A.
RESUMO
Influenza A virus (IAV) is highly contagious and causes considerable mortality worldwide. TLR3, 7, 8 and 9 recognize viral nucleic acids and rapidly trigger different signaling cascades that contribute to the production of interferons (IFNs) to antiviral defense. Therefore, a host immune response induced by the activation of these receptors can be used as a new antiviral strategy. In this study, the protective effect of sodium ferulate (SF) is investigated on mice infected with influenza virus A/FM/1/47(H1N1). SF improved survival and mitigated weight loss in infected mice. SF inhibited influenza virus replication by activating TLR7 and TLR9, which resulted in the promotion of IRF7 translocation into the nucleus and the production of typeâ IFNs. Moreover, SF inhibited the NF-κB pathway by preventing p65 translocation from the cytoplasm to the nucleus. These findings demonstrate that SF plays a critical role in protection against IAV infection by activation of the TLR7/9-MyD88-IRF7 signaling pathway and inhibition of the NF-κB signaling pathway.
Assuntos
Antivirais/farmacologia , Ácidos Cumáricos/farmacologia , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/prevenção & controle , Animais , Embrião de Galinha , Cães , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H1N1/fisiologia , Fator Regulador 7 de Interferon/metabolismo , Interferon Tipo I/sangue , Pulmão/virologia , Células Madin Darby de Rim Canino , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos Endogâmicos BALB C , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Infecções por Orthomyxoviridae/mortalidade , Transdução de Sinais/efeitos dos fármacos , Receptor 7 Toll-Like/metabolismo , Receptor Toll-Like 9/metabolismo , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Pro-gastrin-releasing peptide (ProGRP) is a kind of tumor marker applied more and more commonly in recent years. This study was aimed at determining the age and gender-specific reference intervals (RIs) for ProGRP in healthy Han ethnic adults from Guangxi, China. METHODS: A total of 2,045 apparently healthy males and 1,740 apparently healthy females aged from 21 to 90 years were included in this study. The serum ProGRP values were determined by electrochemiluminescence immunoassay (ECLIA). The one-sided upper 95th percentile of ProGRP concentrations were used to define the RIs. RESULTS: The reference limits in different age groups (21 - 40, 41 - 50, 51 - 60, 61 - 70, and > 70 years) were 37.3, 39.7, 45.7, 47.3, and 61.3 pg/mL for males, and 36.3, 38.1, 42.7, 53.5, and 60.1 pg/mL for females, respectively. There was no significant difference in the levels of ProGRP between males and females. The serum ProGRP levels were positively correlated with age. CONCLUSIONS: We established the age and gender-specific RIs for ProGRP in the adults from Guangxi, China. It will be valuable for future clinical and laboratory studies.
Assuntos
Técnicas Eletroquímicas/métodos , Imunoensaio/métodos , Medições Luminescentes/métodos , Peptídeos/sangue , Precursores de Proteínas/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/estatística & dados numéricos , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto JovemRESUMO
This study investigated the roles of ERK1 and ERK2 in transforming growth factor-ß1 (TGF-ß1)-induced tissue inhibitor of metalloproteinases-3 (TIMP-3) expression in rat chondrocytes, and the specific roles of ERK1 and ERK2 in crosstalk with Smad2/3 were investigated to demonstrate the molecular mechanism of ERK1/2 regulation of TGF-ß1 signalling. To examine the interaction of specific isoforms of ERK and the Smad2/3 signalling pathway, chondrocytes were infected with LV expressing either ERK1 or ERK2 siRNA and stimulated with or without TGF-ß1. At indicated time-points, TIMP-3 expression was determined by real-time PCR and Western blotting; p-Smad3, nuclear p-Smad3, Smad2/3, p-ERK1/2 and ERK1/2 levels were assessed. And then, aggrecan, type II collagen and the intensity of matrix were examined. TGF-ß1-induced TIMP-3 expression was significantly inhibited by ERK1 knock-down, and the decrease in TIMP-3 expression was accompanied by a reduction of p-Smad3 in ERK1 knock-down cells. Knock-down of ERK2 had no effect on neither TGF-ß1-induced TIMP-3 expression nor the quantity of p-Smad3. Moreover, aggrecan, type II collagen expression and the intensity of matrix were significantly suppressed by ERK1 knock-down instead of ERK2 knock-down. Taken together, ERK1 and ERK2 have different roles in TGF-ß1-induced TIMP-3 expression in rat chondrocytes. ERK1 instead of ERK2 can regulate TGF-ß/Smad signalling, which may be the mechanism through which ERK1 regulates TGF-ß1-induced TIMP-3 expression.
Assuntos
Condrócitos/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Inibidor Tecidual de Metaloproteinase-3/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Animais , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Condrócitos/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Técnicas de Silenciamento de Genes , Isoenzimas/metabolismo , Lentivirus/metabolismo , Fosforilação/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , RatosRESUMO
PURPOSE: To investigate the serum concentrations of anti-heat shock protein 20 (anti-Hsp20) antibodies in women with ovarian cancer at different clinical stages, and the relationship between these concentrations and tumor progression. MATERIALS AND METHODS: Blood samples were obtained from 72 patients undergoing surgery for ovarian cancer, 21 women with ovarian carcinoid, and 42 healthy women. Anti-Hsp20 antibody concentrations were determined by enzyme-linked immunosorbent assay. RESULTS: Mean anti-Hsp20 antibody concentrations were significantly lower in patients with ovarian cancer than in the control group. The anti-Hsp20 antibody concentrations were negatively correlated with ovarian cancer malignancy. CONCLUSIONS: The present findings suggest that anti-Hsp20 antibodies may play a protective role against ovarian cancer progression, and that anti-Hsp20 antibodies may be a new index for the early diagnosis and treatment of ovarian cancer.
Assuntos
Autoanticorpos/sangue , Proteínas de Choque Térmico HSP20/imunologia , Neoplasias Ovarianas/imunologia , Adulto , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologiaRESUMO
The primary processing is important links and closely related to the quality of traditional Chinese medicinal materials, and is not only cleaning of remove the non-officinal parts, drying for termination the physiological status of organisms, but also retaining the most active substances, decreasing the toxic components, and promoting the transformation among chemical ingredients through primary processing. So the traditional primary processing endows with characters, quality, specifications and properties of traditional Chinese medicine, and embodies some important science truth. The traditional primary processing method and technology systems are derived from the long-term practices and experiences, which are distinctive, colorful, diverse, and scientific, which are helpful to development and utilization of traditional Chinese medicine resources. This paper systemically expounds the research status of the Chinese medicine processing method, summarizes the problems in the primary processing of traditional Chinese medicinal materials research, and prospects its bright future.
Assuntos
Química Farmacêutica/métodos , Medicamentos de Ervas Chinesas/química , Química Farmacêutica/tendências , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional ChinesaRESUMO
Tissue inhibitor of metalloproteinase-3 (TIMP-3) is an important natural inhibitor of matrix metalloproteinases (MMPs) and of a disintegrin and metalloproteinase with thrombospondin motif (ADAMTs), which can cleave cartilage extracellular matrix components to cause cartilage degradation. In this study, our data suggest TGF-ß1 induces TIMP-3 expression through activations of both the ERK1/2 and Smad2/3 signaling pathways. TGF-ß1-stimulated TIMP-3 expression was significantly inhibited by SB525334 (TGF-ß receptor I kinase inhibitor), accompanied by a reduction in ERK1/2 and Smad3 phosphorylation. We used PD98059 (MEK inhibitor) and SIS3 (inhibitor of Smad3 phosphorylation) to investigate the respective roles of ERK1/2 and Smad2/3 signaling pathways in TGF-ß1-induced TIMP-3 expression. The results show PD98059 treatment significantly suppressed TGF-ß1-induced ERK1/2 phosphorylation and TIMP-3 expression. Under these conditions, the degree of Smad3 phosphorylation correlated with ERK1/2 activation, which suggests that ERK1/2 may activate Smad3 phosphorylation. SIS3 significantly inhibited TGF-ß1-induced Smad3 phosphorylation and TIMP-3 expression. ERK1/2 phosphorylation alone had no effect on TGF-ß1-induced TIMP-3 expression, which suggests ERK1/2 via Smad3 phosphorylation regulates TGF-ß1-induced TIMP-3 expression. Here, we demonstrate that ERK1/2 may be capable of activating the Smad2/3 signaling pathway to result in TGF-ß1-induced TIMP-3 up-regulation.
Assuntos
Condrócitos/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Smad2/metabolismo , Proteína Smad3/metabolismo , Inibidor Tecidual de Metaloproteinase-3/biossíntese , Fator de Crescimento Transformador beta1/metabolismo , Regulação para Cima/fisiologia , Animais , Células Cultivadas , Condrócitos/citologia , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Flavonoides/farmacologia , Imidazóis/farmacologia , Isoquinolinas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/genética , Fosforilação/fisiologia , Inibidores de Proteínas Quinases/farmacologia , Piridinas/farmacologia , Pirróis/farmacologia , Quinoxalinas/farmacologia , Ratos , Proteína Smad2/antagonistas & inibidores , Proteína Smad2/genética , Proteína Smad3/antagonistas & inibidores , Proteína Smad3/genética , Inibidor Tecidual de Metaloproteinase-3/genética , Fator de Crescimento Transformador beta1/genética , Regulação para Cima/efeitos dos fármacosRESUMO
AIM: Androgen receptor (AR) antagonists have proven to be useful in the early control of prostate cancer. The aim of this study was to identify and characterize a novel ß-amino-carbonyl-based androgen receptor antagonist. METHODS: Different isomers of the ß-amino-carbonyl compounds were obtained by chiral separation. The bioactivities of the isomers were evaluated by AR nuclear translocation, mammalian two-hybrid, competitive receptor binding and cell proliferation assays. The expression of genes downstream of AR was analyzed with real-time PCR. The therapeutic effects on tumor growth in vivo were observed in male SCID mice bearing LNCaP xenografts. RESULTS: Compound 21 was previously identified as an AR modulator by the high-throughput screening of a diverse compound library. In the present study, the two isomers of compound 21, termed compounds 21-1 and 21-2, were characterized as partial AR agonists in terms of androgen-induced AR nuclear translocation, prostate-specific antigen expression and cell proliferation. Further structural modifications led to the discovery of a androgen receptor antagonist (compound 6012), which blocked androgen receptor nuclear translocation, androgen-responsive gene expression and androgen-dependent LNCaP cell proliferation. Four stereoisomers of compound 6012 were isolated, and their bioactivities were assessed. The pharmacological effects of 6012, including AR binding, androgen-induced AR translocation, NH2- and COOH-terminal interaction, growth inhibition of LNCaP cells in vitro and LNCaP xenograft growth in nude mice, were mainly restricted to isomer 6012-4 (1R, 3S). CONCLUSION: Compound 6012-4 was determined to be a novel androgen receptor antagonist with prostate cancer inhibitory activities comparable to bicalutamide both in vitro and in vivo.
Assuntos
Antagonistas de Receptores de Andrógenos/farmacologia , Receptores Androgênicos/metabolismo , Animais , Linhagem Celular , Linhagem Celular Tumoral , Nucléolo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Células HEK293 , Humanos , Masculino , Camundongos Nus , Camundongos SCID , Antígeno Prostático Específico/metabolismoRESUMO
OBJECTIVE: To investigate a possible correlation between expression levels of heat shock protein 20 (HSP20) and tumor progression in patients with ovarian cancer. MATERIALS AND METHODS: The study included 34 patients with ovarian cancer who were to undergo surgery, seven patients with ovarian carcinoid tumors, and five patients with normal ovaries as a control group. Ovarian tissues were obtained from patients by surgical resection and then analyzed by western blot. RESULTS: Expression levels of HSP20 were inversely correlated with the grade of malignancy. CONCLUSION: The present findings suggest that HSP20 may play a protective role against the progression of ovarian cancer. Thus, HSP20 may represent a new target for the prediction and treatment of ovarian cancer.
Assuntos
Proteínas de Choque Térmico HSP20/fisiologia , Neoplasias Ovarianas/patologia , Adulto , Progressão da Doença , Feminino , Proteínas de Choque Térmico HSP20/análise , Humanos , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
MAF bZIP transcription factor G (MAFG)-driven astrocytes have been reported to promote inflammation in the CNS. However, its function in depression, the primary cause of disability worldwide, has not been well characterized. This study investigated the possible perturbation of heme oxygenase 1 (HMOX1, also known as HO1) by the transcription factor MAFG as an underlying mechanism of the development of depression. The GSE98793 dataset was included for gene expression analysis of whole blood from donors with major depressive disorder and controls, and the target of MAFG was predicted by multiple database mining. Mouse and cellular models of depression were established by chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS) treatment of astrocytes, which were treated with MAFG and HMOX1 knockdown plasmids. MAFG was highly expressed in the hippocampal tissues of CUMS-challenged mice and LPS-induced astrocytes. MAFG knockdown alleviated depression-like behaviors in mice. MAFG bound to the HMOX1 promoter and repressed its transcription. Knockdown of HMOX1 exacerbated neuroinflammation in astrocytes and accelerated depression-like behavior in mice. In conclusion, MAFG knockdown attenuated CUMS-stimulated depression-like behaviors in mice by astrocyte-mediated neuroinflammation via restoration of HMOX1.
Assuntos
Astrócitos , Depressão , Heme Oxigenase-1 , Doenças Neuroinflamatórias , Animais , Humanos , Masculino , Camundongos , Astrócitos/metabolismo , Depressão/metabolismo , Modelos Animais de Doenças , Heme Oxigenase-1/metabolismo , Hipocampo/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias/metabolismo , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Estresse Psicológico/metabolismoRESUMO
BACKGROUND: Cinnamomum cassia Presl, a traditional Chinese medicine recorded in "Shennong's Herbal Classic," has been historically used to treat respiratory diseases and is employed to address inflammation. The essential oil derived from Cinnamomum cassia bark is a primary anti-inflammatory agent. However, there remains ambiguity regarding the chemical composition of cinnamon bark essential oil (BCEO), its principal anti-inflammatory components, and their potential efficacy in typical inflammatory respiratory conditions, such as acute lung injury (ALI). PURPOSE: This study aimed to unveil the chemical composition of BCEO. In addition, the mechanism of action of BCEO in ameliorating ALI and regulating macrophage polarization through the TLR4/MyD88/NF-κB pathway was elucidated. METHODS: BCEO was extracted using supercritical fluid extraction (SFE) and characterized through gas chromatography-mass spectrometry (GC-MS) analysis. Acute oral toxicity was observed in C57BL/6 J mice. The pharmacological effects and underlying mechanisms of BCEO were evaluated in a mouse model of ALI, which was induced by administering 5 mg/kg of lipopolysaccharide (LPS) through intratracheal instillation. RESULTS: GC-MS analysis revealed 99.08% of the constituents of BCEO. The primary components of BCEO were trans-cinnamaldehyde, o-methoxycinnamaldehyde, (+)-α-muurolene, δ-cadinene, and copaene. Oral acute toxicity tests indicated that the maximum tolerated dose of BCEO was 12 g/kg/day. BCEO treatment significantly reduced lung W/D ratio, total protein concentration in BALF, levels of TNF-α, IL-6, and IL-1ß in BALF, WBC count and NEU% in peripheral blood, and lung histological damage. Pulmonary function, IL-10 levels, and LYM% in peripheral blood also showed improvement. BCEO effectively decreased the proportion of M1 phenotype macrophages in BALF, M1/M2 ratio, and apoptotic cells in the lung tissue while increasing the proportion of M2 phenotype macrophages in BALF. Furthermore, BCEO treatment led to reduced protein and mRNA levels of TLR4, MyD88, and p-p65, alongside increased p65 expression, suggesting its potential to impede the TLR4/MyD88/NF-κB signaling pathway. CONCLUSION: SFE-extracted BCEO or its major constituents could serve as a viable treatment for ALI by reducing lung inflammation, improving pulmonary function, and protecting against LPS-induced ALI in mice. This therapeutic effect is achieved by inhibiting M1 macrophage polarization, promoting M2 macrophage polarization, and suppressing the TLR4/MyD88/NF-κB signaling pathway.
Assuntos
Lesão Pulmonar Aguda , Anti-Inflamatórios , Cinnamomum aromaticum , Macrófagos , Óleos Voláteis , Casca de Planta , Animais , Masculino , Camundongos , Acroleína/análogos & derivados , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Anti-Inflamatórios/farmacologia , Cinnamomum aromaticum/química , Modelos Animais de Doenças , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Casca de Planta/química , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismoRESUMO
Turbidity is a crucial indicator of water quality. The European Commission's Copernicus Land Monitoring Service Platform provides free turbidity data for large lakes to monitor the global water quality of lakes. However, the data were missing from April 2012 to April 2016, severely limiting long-term analysis. Based on MODIS and turbidity data, Random Forest and XGBoost models are used to invert Tonle Sap Lake's turbidity. Random Forest outperformed the XGBoost model. Based on Random Forest model, missing data were filled in to construct long-term series data of Tonle Sap Lake turbidity (2004-2021). Trend, persistence and correlation analyses were conducted to reveal spatiotemporal characteristics and driving mechanism of turbidity. The results showed that: (1) spatially, the average annual, monthly, and seasonal turbidity was higher in the north but lower in the south, with regions of higher turbidity exhibiting more significant changes; (2) temporally, the annual turbidity mean was 53.99 NTU and showed an increasing trend. Monthly, turbidity values were higher from March to August and lower from September to February, with the highest and lowest recorded in June and November at 110.06 and 5.82 NTU, respectively. Seasonally, turbidity was higher in spring and summer compared to autumn and winter, with mean turbidity values of 84.16, 93.47, 15.33 and 23.21 NTU, respectively; (3) In terms of sustainability, the Hurst exponent for annual turbidity was 0.23, indicating a reverse trend in the near future; (4) Dam construction's impact on turbidity was not significant. Compared with natural factors (permanent wetlands, grasslands, lake surface water temperature, and remote sensing ecological index), human activities (barren, urban and built-up lands, croplands and population density) had a more significant impact on turbidity. Turbidity was highly correlated with croplands (r = 0.76), followed by population density (r = 0.71), and urban and built-up lands (r = 0.69).
RESUMO
This paper introduces a solution to address the intricacy of the model employed in the deep learning-based diagnosis of musculoskeletal abnormalities and the limitations observed in the performance of a single deep learning network model. The proposed approach involves the integration of an improved EfficientNet-B2 model with MobileNetV2, resulting in the creation of FusionNet. First, EfficientNet-B2 is combined with coordinate attention (CA) to obtain CA-EfficientNet-B2. Furthermore, aiming to minimize the model parameter count, we further enhanced the mobile inverted residual bottleneck convolution module (MBConv) employed for feature extraction in EfficientNet-B2, resulting in the development of CA-MBC-EfficientNet-B2. Next, the features extracted from CA-MBC-EfficientNet-B2 and MobileNetV2 are fused. Finally, the final diagnosis of musculoskeletal abnormalities was performed by using fully connected layers. The experimental results demonstrate that, first, compared to EfficientNet-B2, CA-MBC-EfficientNet-B2 not only significantly improves the diagnostic performance of musculoskeletal abnormalities, it also reduces the parameter count and storage space by 17%. Moreover, as compared to other models, FusionNet demonstrates remarkable performance in the area of anomaly diagnosis, particularly on the elbow dataset, achieving a precision of 92.93%, an AUC of 93.89% and an accuracy of 87.10%.
Assuntos
Anormalidades Musculoesqueléticas , Humanos , Anormalidades Musculoesqueléticas/diagnóstico , Aprendizado ProfundoRESUMO
BACKGROUND: Breast cancer (BC) is one of the most prevalent malignant tumours that threatens women health worldwide. It has been reported that circular RNAs (circRNAs) play an important role in regulating tumour progression and tumour microenvironment (TME) remodelling. METHODS: Differentially expression characteristics and immune correlations of circRNAs in BC were verified using high-throughput sequencing and bioinformatic analysis. Exosomes were characterised by nanoparticle transmission electron microscopy and tracking analysis. The biological function of circ-0100519 in BC development was demonstrated both in vitro and in vivo. Western blotting, RNA pull-down, RNA immunoprecipitation, flow cytometry, and luciferase reporter were conducted to investigate the underlying mechanism. RESULTS: Circ-0100519 was significant abundant in BC tumour tissues and related to poor prognosis. It can be encapsulated into secreted exosomes, thereby promoting BC cell invasion and metastasis via inducing M2-like macrophages polarisation.Mechanistically, circ-0100519 acted as a scaffold to enhance the interaction between the deubiquitinating enzyme ubiquitin-specific protease 7 (USP7) and nuclear factor-like 2 (NRF2) in macrophages, inducing the USP7-mediated deubiquitination of NRF2. Additionally, HIF-1α could function as an upstream effector to enhance circ-0100519 transcription. CONCLUSIONS: Our study revealed that exosomal circ-0100519 is a potential biomarker for BC diagnosis and prognosis, and the HIF-1α inhibitor PX-478 may provide a therapeutic target for BC.
Assuntos
Neoplasias da Mama , Exossomos , Fator 2 Relacionado a NF-E2 , RNA Circular , Peptidase 7 Específica de Ubiquitina , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Humanos , RNA Circular/genética , RNA Circular/metabolismo , Feminino , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genética , Peptidase 7 Específica de Ubiquitina/genética , Peptidase 7 Específica de Ubiquitina/metabolismo , Exossomos/metabolismo , Exossomos/genética , Macrófagos/metabolismo , Camundongos , Progressão da Doença , Animais , Linhagem Celular TumoralRESUMO
Eelgrass beds provide a habitat for many high-value fishery resources, and provisioning services, one of the ecosystem services, need to be quantified. However, few examples have been evaluated spatially. We determined the distribution of eelgrass beds in Lake Notoro, a marine lagoon in Hokkaido, Japan, and quantified the provisioning services by the eelgrass beds in relation to Pandalus latirostris, a fishery resource. Acoustic measurement surveys of the eelgrass beds and catch surveys of the shrimp were conducted in July and August 2015. The relationship between catch per unit effort (CPUE) of shrimp and the distribution of eelgrass beds was shown. The estimated distribution area of eelgrass beds was 7.07 km2. Shrimp was frequently caught at water depths of 3-5 m, approximately 200 m from the edge of the eelgrass beds. The expected catch of shrimp in the fishing area of Lake Notoro in 2015 was 25.37 tons and US$ 463.6 thousand. Eelgrass beds were found to affect the fisheries production not only on the inside but also at the edge and outside. The entire coastal space should be evaluated, while considering the effect of the distribution of eelgrass beds, to quantify the provisioning services.