RESUMO
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by homozygous deletions or mutations in survival motor neuron gene 1 (SMN1). Currently, the primary therapeutic strategy for SMA is to increase the level of SMN via correcting SMN2 splicing (nusinersen and risdiplam). However, some patients with SMA do not respond to such treatments, thereby warranting a need to develop new therapeutic strategies. We have previously reported that SMN2 expression is epigenetically regulated by DNA methylation levels of the SMN2 promoter region. In the present study, we determined that methyl-CpG-binding protein 2 (MeCP2) may bind to this critical promoter region (nt-167 to 43). Antisense oligonucleotides (ASO-P1 and ASO-P2) were designed to target the key methylation sites in the SMN2 promoter region, which enhanced the overall transcription and functional protein expression levels in the SMA cell lines. These results were similar to those observed in nusinersen-treated SMA cells. Moreover, a combined treatment of ASO-P1 and ASO-NUS in SMA cell lines further increases fl-SMN2 transcript and SMN protein levels. The delivery of ASO-P1 to the central nervous system of severe SMA mice corrected the molecular, pathological, and functional phenotypes of this disease and increased survival rates. Our findings suggest that the key methylation regions in the SMN2 promoter region may be a novel therapeutic target for SMA.
Assuntos
Atrofia Muscular Espinal , Oligonucleotídeos Antissenso , Animais , Linhagem Celular , Modelos Animais de Doenças , Humanos , Camundongos , Neurônios Motores/metabolismo , Atrofia Muscular Espinal/metabolismo , Oligonucleotídeos Antissenso/genética , Regiões Promotoras Genéticas/genética , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Proteína 2 de Sobrevivência do Neurônio Motor/metabolismoRESUMO
Slow-light photonic crystal waveguide (PCW) gas sensors based on infrared absorption spectroscopy play a pivotal role in enhancing the on-chip interaction between light and gas molecules, thereby significantly boosting sensor sensitivity. However, two-dimensional (2D) PCWs are limited by their narrow mode bandwidth and susceptibility to polarization, which restricts their ability for multigas measurement. Due to quasi-TE and quasi-TM mode guiding characteristics in one-dimensional (1D) PCW, a novel slow-light-enhanced polarization division multiplexing infrared absorption spectroscopy was proposed for on-chip wideband multigas detection. The optimized 1D PCW gas sensor experimentally shows an impressive slow-light mode bandwidth exceeding 100 nm (TM, 1500-1550 nm; TE, 1610-1660 nm) with a group index ranging from 4 to 25 for the two polarizations. The achieved bandwidth in the 1D PCW is 2-3 times that of the reported quasi-TE polarized 2D PCWs. By targeting the absorption lines of different gas species, multigas detection can be realized by modulating the lasers and demodulating the absorption signals at different frequencies. As an example, we performed dual-gas measurements with the 1D PCW sensor operating in TE mode at 1.65 µm for methane (CH4) detection and in TM mode at 1.53 µm for acetylene (C2H2) detection. The 1 mm long sensor achieved a remarkable limit of detection (LoD) of 0.055% for CH4 with an averaging time of 17.6 s, while for C2H2, the LoD was 0.18%. This polarization multiplexing sensor shows great potential for on-chip gas measurement because of the slow-light enhancement in the light-gas interaction effect as well as the large slow-light bandwidth for multigas detection.
RESUMO
Compared to the most commonly used on-chip direct absorption spectroscopy (DAS) gas detection technique, the second harmonic (2f) based on-chip wavelength modulation spectroscopy (WMS) proposed by our group has the faculty to suppress noise and improve performance, but the accuracy of 2f WMS is easily affected by optical power variation. A mid-infrared auto-correction on-chip gas sensor based on 2f/1f WMS was proposed for decreasing the influence of the variation of optical power. The limit of detection of methane (CH4) obtained by a chalcogenide waveguide with a length of 10â mm is 0.031%. Compared with the 2f WMS, the maximum relative concentration error of the auto-correction on-chip gas sensor was decreased by â¼5.6 times. The measurement error is ≤2% in a temperature variation range of 30°C. This auto-correction sensor without a complicated manual calibration is helpful to the high accuracy measurement for on-chip integrated gas sensing.
RESUMO
BACKGROUND: Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS. METHODS: A retrospective review was conducted on a series of 12 patients diagnosed with AS. All patients sustained thoracolumbar fractures between October 2018 and October 2022 and underwent posterior robotic-assisted percutaneous fixation procedures. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union. The clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). To investigate the achieved operative correction, pre- and postoperative radiographs in the lateral plane were analyzed by measuring the Cobb angle. RESULTS: The 12 patients had a mean age of 62.8 ± 13.0 years and a mean follow-up duration of 32.7 ± 18.9 months. Mean hospital stay duration was 15 ± 8.0 days. The mean operative time was 119.6 ± 32.2 min, and the median blood loss was 50 (50, 250) ml. The VAS value improved from 6.8 ± 0.9 preoperatively to 1.3 ± 1.0 at the final follow-up (P < 0.05). The ODI value improved from 83.6 ± 6.1% preoperatively to 11.8 ± 6.6% at the latest follow-up (P < 0.05). The average Cobb angle changed from 15.2 ± 11.0 pre-operatively to 8.3 ± 7.1 at final follow-up (P < 0.05). Bone healing was consistently achieved, with an average healing time of 6 (5.3, 7.0) months. Of the 108 screws implanted, 2 (1.9%) were improperly positioned. One patient experienced delayed nerve injury after the operation, but the nerve function returned to normal upon discharge. CONCLUSION: Posterior robotic-assisted percutaneous internal fixation can be used as an ideal surgical treatment for thoracolumbar fractures in AS patients. However, while robot-assisted pedicle screw placement can enhance the accuracy of pedicle screw insertion, it should not be relied upon solely.
Assuntos
Fixação Interna de Fraturas , Vértebras Lombares , Procedimentos Cirúrgicos Robóticos , Fraturas da Coluna Vertebral , Espondilite Anquilosante , Vértebras Torácicas , Humanos , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Masculino , Pessoa de Meia-Idade , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/diagnóstico por imagem , Feminino , Estudos Retrospectivos , Espondilite Anquilosante/cirurgia , Espondilite Anquilosante/complicações , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Vértebras Lombares/diagnóstico por imagem , Procedimentos Cirúrgicos Robóticos/métodos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Resultado do Tratamento , Idoso , Duração da Cirurgia , Tempo de Internação , Parafusos Pediculares , Adulto , Perda Sanguínea Cirúrgica/estatística & dados numéricos , SeguimentosRESUMO
Taste sensors with an allostery approach have been studied to detect non-charged bitter substances, such as xanthine derivatives, used in foods (e.g., caffeine) or pharmaceuticals (e.g., etofylline). In this study, the authors modified a taste sensor with 3-bromo-2,6-dihydroxybenzoic acid and used it in conjunction with sensory tests to assess the bitterness of non-charged pharmaceuticals with xanthine scaffolds (i.e., acefylline and doxofylline), as well as allopurinol, an analogue of hypoxanthine. The results show that the sensor was able to differentiate between different levels of sample bitterness. For instance, when assessing a 30 mM sample solution, the sensor response to acefylline was 34.24 mV, which corresponded to the highest level of bitterness (τ = 3.50), while the response to allopurinol was lowest at 2.72 mV, corresponding to relatively weaker bitterness (τ = 0.50). Additionally, this study extended the application of the sensor to detect pentoxifylline, an active pharmaceutical ingredient in pediatric medicines. These results underscore the taste sensor's value as an additional tool for early-stage assessment and prediction of bitterness in non-charged pharmaceuticals.
Assuntos
Alopurinol , Paladar , Xantina , Alopurinol/química , Humanos , Xantina/química , Técnicas Biossensoriais/métodosRESUMO
Angiomatoid fibrous histiocytoma (AFH) is a soft tissue tumor of uncertain differentiation. Although its prognosis is good, its diagnosis and differential diagnosis remain a challenge, particularly for tumors with an atypical morphology. We evaluated the clinicopathological characteristics of 14 AFH cases and examined the key factors in its diagnosis or differential diagnosis. The cohort comprised 6 men and 8 women aged 9-65 years (average age: 31.2 years). Most of the tumors (11/14, 79%) were located in soft tissues, whereas 3/14 (21%) were located in the lung (1 case) and brain (2 cases). Tumor cells were spindle-shaped to epithelioid, with a visible fibrous capsule (9/14, 64%), hemorrhagic gap (9/14, 64%), lymphocyte sleeve (7/14, 50%), necrosis (3/14, 21%), and infiltrative boundary (4/14, 29%). The tumors expressed desmin (10/14, 71%) and exhibited low levels of Ki-67. 13 cases (93%) displayed ESWSR1 gene rearrangement. At follow-up, 1 case (7%) experienced local tumor recurrence. AFH is a rare intermediate tumor. Its pathological diagnosis requires a comprehensive analysis of histological, immunophenotypic, and molecular genetic features to avoid misdiagnosis. Our study has further enriched the histological features of AFH, emphasizing the importance of differential diagnosis and providing a reference for clinical practice.
RESUMO
OBJETIVE: To explore the characteristics of SMN1 gene variants and carry out functional verification for two children with Spinal muscular atrophy (SMA). METHODS: Two male children with complicated SMA diagnosed at the Children's Hospital Affiliated to Capital Institute of Pediatrics respectively in July 2021 and April 2022 due to delayed or retrograde motor development were selected as the study subjects. Clinical data of the children were collected. Primary culture of skin fibroblasts was carried out, and peripheral blood samples were collected from both children and their parents. Multiplex ligation-dependent probe amplification, combined long-range PCR and nested PCR, and Sanger sequencing were carried out to detect the copy number and variants of the SMN1 gene. Absolute quantitative real-time PCR, Western blotting and immunofluorescence were used to determine the transcriptional level of the SMN gene, expression of the SMN protein, and the number of functional SMN protein complexes (gems body), respectively. This study was approved by the Children's Hospital Affiliated to Capital Institute of Pediatrics (Ethics No. SHERLLM2021009). RESULTS: Child 1, a 1-year-old boy, was clinically diagnosed with type 1 SMA. Child 2, a 2-and-a-half-year-old boy, was clinically diagnosed with type 3 SMA. Both children were found to harbor a paternally derived SMN1 deletion and a maternally derived SMN1 gene variant, namely c.824G>T (p.Gly275Val) and c.884A>T (p.*295Leu). Compared with the normal controls and carriers, the levels of full-length SMN1 transcripts in their peripheral blood and skin fibroblast cell lines were significantly decreased (P < 0.05), and the levels of SMN protein normalized to that of ß-actin, and the numbers of gems bodies in the primary fibroblast cells were also significantly lower (P < 0.05). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were classified as likely pathogenic (PS3+PM3+PM5+PP3; PS3+PM3+PM4+PP3). Following the diagnosis, both children had received nusinersen treatment. Although their motor function was improved, child 1 still died at the age of 2 due to severe pulmonary infection. The walking ability of child 2 was significantly improved, and his prognosis appeared to be good. CONCLUSION: Two cases of clinically complicated SMA have been confirmed by genetic testing and experimental studies, which has provided a reference for their accurate treatment.
Assuntos
Atrofia Muscular Espinal , Proteína 1 de Sobrevivência do Neurônio Motor , Humanos , Masculino , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Atrofia Muscular Espinal/genética , Lactente , Pré-Escolar , Fibroblastos/metabolismo , MutaçãoRESUMO
OBJECTIVE: The objective of the study was to develop a nursing practice scale for rheumatoid arthritis treatment with biological disease-modifying anti-rheumatic drugs. METHODS: An anonymous self-administered questionnaire survey was administered to 1826 nurses, 960 of whom were Certified Nurses by Japan Rheumatism Foundation (CNJRFs) and 866 were registered nurses (RNs). Using exploratory factor analysis, criterion validity, and known-groups technique, we assessed the reliability and validity of the self-created 19-item nursing practice scale to evaluate the care provided to patients with rheumatoid arthritis receiving biological disease-modifying anti-rheumatic drugs based on the nurse's role as clarified from a literature review of relevant studies. RESULTS: A total of 698 (38.4%) responses were collected from 407 CNJRFs and 291 RNs. Exploratory factor analysis was conducted on 18 items to examine three factors: 'nursing to enhance patients' capacity for self-care', 'nursing in which patients participate in decision-making', and 'nursing in which team medical care is promoted'. Cronbach's α was .95. The Spearman's coefficient was ρ = .738 for criterion validity. Using the known-groups technique, CNJRFs had higher total scale scores than RNs (P < .05). CONCLUSIONS: The results confirmed the reliability, criterion validity, and construct validity of the scale.
Assuntos
Antirreumáticos , Artrite Reumatoide , Enfermeiras e Enfermeiros , Humanos , Reprodutibilidade dos Testes , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Papel do Profissional de Enfermagem , Inquéritos e QuestionáriosRESUMO
Herein, we report that bulky alkylphosphines such as PtBu3 can switch the roles from actor to spectator ligands to promote the FeCl2 -catalyzed N-amidation reaction of arylamines with dioxazolones, giving hydrazides in high efficiency and chemoselectivity. Mechanistic studies indicated that the phosphine ligands could facilitate the decarboxylation of dioxazolones on the Fe center, and the hydrogen bonding interactions between the arylamines and the ligands on Fe nitrenoid intermediates might play a role in modulating the delicate interplay between the phosphine ligand, arylamine, and acyl nitrene N, favoring N-N coupling over N-P coupling. The new ligand-promoted N-amidation protocols offer a convenient way to access various challenging triazane compounds via double or sequential N-amidation of primary arylamines.
RESUMO
Hierarchically structured bimetal hydroxides are promising for electrocatalytic oxygen evolution reaction (OER), yet synthetically challenging. Here, the nanoconfined hydrolysis of a hitherto unknown CoFe-bimetal-organic compound (b-MOC) is reported for the controllable synthesis of highly OER active nanostructures of CoFe layered double hydroxide (LDH). The nanoporous structures trigger the nanoconfined hydrolysis in the sacrificial b-MOC template, producing CoFe LDH core-shell octahedrons, nanoporous octahedrons, and hollow nanocages with abundant under-coordinated metal sites. The hollow nanocages of CoFe LDH demonstrate a remarkable turnover frequency (TOF) of 0.0505 s-1 for OER catalysis at an overpotential of 300 mV. It is durable in up to 50 h of electrolysis at step current densities of 10-100 mA cm-2 . Ex situ and in situ X-ray absorption spectroscopic analysis combined with theoretical calculations suggests that under-coordinated Co cations can bind with deprotonated Fe-OH motifs to form OER active Fe-O-Co dimmers in the electrochemical oxidation process, thereby contributing to the good catalytic activity. This work presents an efficient strategy for the synthesis of highly under-coordinated bimetal hydroxide nanostructures. The mechanistic understanding underscores the power of maximizing the amount of bimetal-dimer sites for efficient OER catalysis.
RESUMO
Over 70% land plants live in mutualistic symbiosis with arbuscular mycorrhizal (AM) fungi, and maintenance of symbiosis requires transcriptional and post-transcriptional regulation. The former has been widely studied, whereas the latter mediated by symbiotic microRNAs (miRNAs) remains obscure, especially in woody plants. Here, we performed high-throughput sequencing of the perennial woody citrus plant Poncirus trifoliata and identified 3750 differentially expressed genes (DEGs) and 42 miRNAs (DEmiRs) upon AM fungal colonization. By analyzing cis-regulatory elements in the promoters of the DEGs, we predicted 329 key AM transcription factors (TFs). A miRNA-mRNA regulatory network was then constructed by integrating these data. Several candidate miRNA families of P. trifoliata were identified whose members target known symbiotic genes, such as miR167h-AMT2;3 and miR156e-EXO70I, or key TFs, such as miR164d-NAC and miR477a-GRAS, thus are involved in AM symbiotic processes of fungal colonization, arbuscule development, nutrient exchange and phytohormone signaling. Finally, analysis of selected miRNA family revealed that a miR159b conserved in mycorrhizal plant species and a Poncirus-specific miR477a regulate AM symbiosis. The role of miR477a was likely to target GRAS family gene RAD1 in citrus plants. Our results not only revealed that miRNA-mRNA network analysis, especially miRNA-TF analysis, is effective in identifying miRNA family regulating AM symbiosis, but also shed light on miRNA-mediated post-transcriptional regulation of AM symbiosis in woody citrus plants.
Assuntos
MicroRNAs , Micorrizas , Poncirus , Simbiose/genética , Poncirus/genética , MicroRNAs/genética , RNA Mensageiro , Micorrizas/fisiologia , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/genéticaRESUMO
NEW FINDINGS: What is the central question of this study? Is there a risk of developing diabetes associated with statin treatment? What is the underlying mechanism of the increased incidence rate of new-onset diabetes in patients treated with rosuvastatin? What is the main finding and its importance? Rosuvastatin therapy reduced intraperitoneal glucose tolerance and changed the catabolism of branched-chain amino acid (BCAAs) in white adipose tissue and skeletal muscle. Protein phosphatase 2Cm knockdown completely abolished the effects of insulin and rosuvastatin on glucose absorption. This study provides mechanistic support for recent clinical data on rosuvastatin-related new-onset diabetes and underscores the logic for intervening in BCAA catabolism to prevent the harmful effects of rosuvastatin. ABSTRACT: Accumulating evidence indicates that patients treated with rosuvastatin have an increased risk of developing new-onset diabetes. However, the underlying mechanism remains unclear. In this study, we administered rosuvastatin (10 mg/kg body weight) to male C57BL/6J mice for 12 weeks and found that oral rosuvastatin dramatically reduced intraperitoneal glucose tolerance. Rosuvastatin-treated mice showed considerably higher serum levels of branched-chain amino acids (BCAAs) than control mice. They also showed dramatically altered expression of BCAA catabolism-related enzymes in white adipose tissue and skeletal muscle, including downregulated mRNA expression of BCAT2 and protein phosphatase 2Cm (PP2Cm) and upregulated mRNA expression of branched-chain ketoacid dehydrogenase kinase (BCKDK). The levels of BCKD in the skeletal muscle were reduced in rosuvastatin-treated mice, which was associated with lower PP2Cm protein levels and increased BCKDK levels. We also investigated the effects of rosuvastatin and insulin administration on glucose metabolism and BCAA catabolism in C2C12 myoblasts. We observed that incubation with insulin enhanced glucose uptake and facilitated BCAA catabolism in C2C12 cells, which was accompanied by elevated Akt and glycogen synthase kinase 3 ß (GSK3ß) phosphorylation. These effects of insulin were prevented by co-incubation of the cells with 25 µM rosuvastatin. Moreover, the effects of insulin and rosuvastatin administration on glucose uptake and Akt and GSK3ß signaling in C2C12 cells were abolished when PP2Cm was knocked down. Although the relevance of these data, obtained with high doses of rosuvastatin in mice, to therapeutic doses in humans remains to be elucidated, this study highlights a potential mechanism for the diabetogenic effects of rosuvastatin, and suggests that BCAA catabolism could be a pharmacological target for preventing the adverse effects of rosuvastatin.
Assuntos
Diabetes Mellitus , Resistência à Insulina , Animais , Masculino , Camundongos , Aminoácidos de Cadeia Ramificada/metabolismo , Glucose , Glicogênio Sintase Quinase 3 beta , Insulina , Camundongos Endogâmicos C57BL , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Proteínas Proto-Oncogênicas c-akt , RNA Mensageiro , Rosuvastatina Cálcica/efeitos adversosRESUMO
In this study, a novel composite material, Ni/Mn-MOF-74/CdS@Co3O4 was synthesized. This material consisted of a dual p-n heterojunction, which enabled efficient separation and transfer of charge carriers. Compared to a single p-n heterojunction, the presence of this dual heterojunction significantly enhanced the overall efficiency. The improved efficiency could be attributed to the unique properties of the constituent semiconductors. Co3O4 exhibited p-type semiconductor properties, while Ni/Mn-MOF-74 and CdS exhibited n-type semiconductor properties. By a combination of these materials to form a composite photocatalyst, a Z-type heterojunction was created at the interface of the p-n junction. This design established an internal electric field at both ends, effectively separating the photogenerated electrons and holes in each individual photocatalyst. As a result, the respective photocatalytic activities of the materials were maximized. To demonstrate the practical application of this composite material, it was utilized for the activation of peroxymonosulfate under visible light irradiation, with the aim of enhancing the photocatalytic degradation efficiency of tetracycline hydrochloride. The photocatalytic mechanism of Ni/Mn-MOF-74/CdS@Co3O4 in activating peroxymonosulfate and degrading tetracycline hydrochloride was investigated in detail. Furthermore, the toxicity of tetracycline hydrochloride and its intermediates was evaluated by using toxicity evaluation software.
RESUMO
A novel 1D/2D step-scheme Bi2O3/g-C3N4 was prepared using a simple reflux method. Bi2O3 photocatalysts showed lower photocatalytic activity for the degradation of tetracycline hydrochloride under visible light irradiation. After compositing with g-C3N4, the photocatalytic activity of Bi2O3 was enhanced obviously. The enhanced photocatalytic activity of the Bi2O3/g-C3N4 photocatalysts could be attributed to the high separation efficiency of carriers generated by the Bi2O3/g-C3N4 photocatalyst due to the formation of a step-scheme heterojunction, which inhibited the recombination of photogenerated electrons and holes. In order to further enhance the degradation efficiency of tetracycline hydrochloride, Bi2O3/g-C3N4 was used to activate peroxymonosulfate under visible-light irradiation. The influences of peroxymonosulfate dosage, pH value and tetracycline hydrochloride concentration on activating peroxymonosulfate to degrade tetracycline hydrochloride were investigated in detail. The mechanism of Bi2O3/g-C3N4 activating peroxymonosulfate was proved by radical quenching experiments and electron paramagnetic resonance analysis, which proved that the sulfate radical and hole dominated the degradation of tetracycline hydrochloride. The possible vulnerable sites and pathways of tetracycline hydrochloride were predicted via DFT calculations based on Fukui function and UPLC-MS. Toxicity Estimation Software predicts that the degradation processes of tetracycline hydrochloride could gradually reduce toxicity. This study could provide an efficient and green method for the subsequent treatment of antibiotic wastewater.
Assuntos
Espectrometria de Massas em Tandem , Tetraciclina , Domínio Catalítico , Cromatografia Líquida , Luz , CatáliseRESUMO
Retinoic acid-inducible gene I (RIG-I) is up-regulated during granulocytic differentiation of acute promyelocytic leukemia (APL) cells induced by all-trans retinoic acid (ATRA). It has been reported that RIG-I recognizes virus-specific 5'-ppp-double-stranded RNA (dsRNA) and activates the type I interferons signaling pathways in innate immunity. However, the functions of RIG-I in hematopoiesis remain unclear, especially regarding its possible interaction with endogenous RNAs and the associated pathways that could contribute to the cellular differentiation and maturation. Herein, we identified a number of RIG-I-binding endogenous RNAs in APL cells following ATRA treatment, including the tripartite motif-containing protein 25 (TRIM25) messenger RNA (mRNA). TRIM25 encodes the protein known as an E3 ligase for ubiquitin/interferon (IFN)-induced 15-kDa protein (ISG15) that is involved in RIG-I-mediated antiviral signaling. We show that RIG-I could bind TRIM25 mRNA via its helicase domain and C-terminal regulatory domain, enhancing the stability of TRIM25 transcripts. RIG-I could increase the transcriptional expression of TRIM25 by caspase recruitment domain (CARD) domain through an IFN-stimulated response element. In addition, RIG-I activated other key genes in the ISGylation pathway by activating signal transducer and activator of transcription 1 (STAT1), including the modifier ISG15 and several enzymes responsible for the conjugation of ISG15 to protein substrates. RIG-I cooperated with STAT1/2 and interferon regulatory factor 1 (IRF1) to promote the activation of the ISGylation pathway. The integrity of ISGylation in ATRA or RIG-I-induced cell differentiation was essential given that knockdown of TRIM25 or ISG15 resulted in significant inhibition of this process. Our results provide insight into the role of the RIG-I-TRIM25-ISGylation axis in myeloid differentiation.
Assuntos
Diferenciação Celular , Citocinas/metabolismo , Proteína DEAD-box 58/metabolismo , Granulócitos/fisiologia , Fatores de Transcrição/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinas/metabolismo , Linhagem Celular Tumoral , Citocinas/genética , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Estabilidade de RNA , RNA Mensageiro/metabolismo , Receptores Imunológicos , Fatores de Transcrição/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinas/genética , Regulação para CimaRESUMO
Shatangju (Citrus reticulata Blanco cv. Shatangju) belongs to genus Citrus and was cultivated extensively in southern China. In April 2022, a leaf blight-like symptom (firstly brown spots appeared on infecting leaves, then these brown spots extended, finally the whole leaves displayed blight-like symptom) was observed on 5%~10% of Shatangju seedlings (around five hundreds in total) in an orchard located in Wuhan city, Hubei, China. Diseased leaves from three seedlings were collected and cut into pieces (0.2 to 0.5 cm). These pieces were surface-sterilized using 75% ethanol for 3 min, rinsed with sterile distilled water for several times, then placed on potato dextrose agar (PDA) and incubated at 26°C with 12-h light/dark cycle. Over 20 pieces plated, wherein 30% were identified as Colletotrichum fructicola, 60% as Neopestalotiopsis spp., and 10% developed saprophytes. C. fructicola was a known pathogen on citrus, thus Neopestalotiopsis spp. was further investigated. Eight single-conidium colonies of the Neopestalotiopsis spp. were obtained, wherein STJ-8 was chosen as a representative for further study. The average growth rate of STJ-8 was 15.1±0.5 mm/day (n=5). Fungal colonies produced white cottony mycelium with abundant black acervuli distributed in concentric rings 6-8 days after planting, which ranged from 342.3 to 710.5 µm in diameter (n=100). Conidia were fusoid, five cells, four septa with average dimensions of 25.36×5.47 µm (n=100). Basal and apical cells were hyaline, wherein three middle cells were brown with darker septa. The apical cell was cylindrical with two to three transparent accessory filaments (13.7 to 30.5 µm in length, n=80). Basal cell was conic with an appendage (4.1 to 8.8 µm in length, n=40). Partial sequences of internal transcribed spacer (ITS), translation elongation factor 1-alpha (TEF-1α), and ß-tubulin (TUB2) were amplified with reported primers (White et al. 1990; Lee et al. 2006; Maharachchikumbura et al. 2014), sequenced, and submitted to GenBank (accession nos. ITS: OP236541; TEF-1α: OP250124; TUB2:OP263094). BLASTn results showed 100% identity with the corresponding sequences of Neopestalotiopsis rosae. A multilocus phylogenetic analysis showed STJ-8 was closest to N. rosae. Thus, STJ-8 was identified as N. rosae. Pathogenicity tests were performed on one-year-old Shatangju seedlings and detached primary leaves by inoculating needle-wounded leaves with seven days old 5-mm mycelial plugs/acervuli (about 5000 spores) of STJ-8. Control seedlings/leaves were inoculated with 5-mm PDA plugs/sterile water drops. All inoculated detached leaves were cultured at same the place with STJ-8 cultured, while inoculated seedlings were put in a growth chamber at 26°C under a 16-h light/dark cycle (60% humidity). Symptoms developed on all inoculated leaves (except healthy control) 2 and 4 days post-inoculation by mycelial plugs and acervuli, respectively. N. rosae was re-isolated from the inoculated leaves, confirming Koch's postulates. N. rosae has been reported to cause diseases on various plants worldwide (Rebollar-Alviter et al. 2020; Xavier et al. 2021; Lawrence et al. 2022). In China, N. rosae has been reported to cause leaf spot/blight on pecan and strawberry (Wu et al. 2021; Gao et al. 2022), which caused great loss on these crops. To our knowledge, this is the first report of N. rosae causing leaf disease on citrus. Our study is important for developing control strategies against N. rosae in future.
RESUMO
BACKGROUND: Citrus is one of the most important fresh fruit crops worldwide. Juice sac granulation is a physiological disorder, which leads to a reduction in soluble solid concentration, total sugar, and titratable acidity of citrus fruits. Pectin methylesterase (PME) catalyzes the de-methylesterification of homogalacturonans and plays crucial roles in cell wall modification during plant development and fruit ripening. Although PME family has been well investigated in various model plants, little is known regarding the evolutionary property and biological function of PME family genes in citrus. RESULTS: In this study, 53 non-redundant PME genes were identified from Citrus sinensis genome, and these PME genes were divided into four clades based on the phylogenetic relationship. Subsequently, bioinformatics analyses of gene structure, conserved domain, chromosome localization, gene duplication, and collinearity were performed on CsPME genes, providing important clues for further research on the functions of CsPME genes. The expression profiles of CsPME genes in response to juice sac granulation and low-temperature stress revealed that CsPME genes were involved in the low temperature-induced juice sac granulation in navel orange fruits. Subcellular localization analysis suggested that CsPME genes were localized on the apoplast, endoplasmic reticulum, plasma membrane, and vacuole membrane. Moreover, yeast one-hybrid screening and dual luciferase activity assay revealed that the transcription factor CsRVE1 directly bound to the promoter of CsPME3 and activated its activity. CONCLUSION: In summary, this study conducts a comprehensive analysis of the PME gene family in citrus, and provides a novel insight into the biological functions and regulation patterns of CsPME genes during juice sac granulation of citrus.
Assuntos
Citrus sinensis , Citrus , Hidrolases de Éster Carboxílico/metabolismo , Citrus/genética , Citrus/metabolismo , Citrus sinensis/genética , Citrus sinensis/metabolismo , Frutas/genética , Frutas/metabolismo , FilogeniaRESUMO
Cell death-inducing DFF45-like effector C (CIDEC) is involved in diet-induced adipose inflammation. Whether CIDEC plays a role in diabetic vascular inflammation remains unclear. A type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated its characteristics by metabolic tests, Western blot analysis of CIDEC and C1q/tumor necrosis factor-related protein-3 (CTRP3) expression, and histopathological analysis of aortic tissues. The diabetic group exhibited elevated CIDEC expression, aortic inflammation, and remodeling. To further investigate the role of CIDEC in the pathogenesis of aortic inflammation, gene silencing was used. With CIDEC gene silencing, CTRP3 expression was restored, accompanied with amelioration of insulin resistance, aortic inflammation, and remodeling in diabetic rats. Thus, the silencing of CIDEC is potent in mediating the reversal of aortic inflammation and remodeling, indicating that CIDEC may be a potential therapeutic target for vascular complications in diabetes.
Assuntos
Diabetes Mellitus Experimental , Resistência à Insulina , Animais , Morte Celular , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/genética , Inflamação/genética , Proteínas/genética , Proteínas/metabolismo , RatosRESUMO
To realize early fire identification in cotton harvesting operations, a mid-infrared carbon monoxide (CO) sensor system was developed. To match the broadband light source with a 15° divergence angle, a multipass gas cell (MPGC) with an effective path length of 180 cm was designed to improve sensor sensitivity, leading to a limit of detection (LoD) of 0.83 parts-per-million by volume (ppmv). A damping module with springs at the bottom and front/back sides was fabricated, which can effectively reduce the vibration intensity by >80%. The sensor system can operate normally from -40 °C to 85 °C by stabilizing the temperature of the optical module through heating or cooling as well as using automotive electronic components. An adaptive early fire identification algorithm based on a dual-parameter threshold alarming method was proposed to avoid false and missing alarms. Field deployments on a harvester verified the good practicability of the sensor system.
Assuntos
Monóxido de Carbono , Temperatura Baixa , Temperatura , Limite de DetecçãoRESUMO
In this paper, the ternary Bi2O3/CQDs/rGO photocatalyst was synthesized by a solvothermal method. The as-fabricated Bi2O3/CQDs/rGO composites showed stronger visible-light response and higher photocatalytic activity. In order to further enhance the degradation efficiency of tetracycline hydrochloride, Bi2O3/CQDs/rGO was used to activate peroxymonosulfate under visible-light irradiation. The degradation efficiency increased sevenfold, indicating that the synergistic effect of photocatalysis and peroxymonosulfate activated by photogenerated electrons could clearly increase the degradation efficiency of tetracycline hydrochloride. In addition, the photocatalytic mechanism was further proposed and verified by radical quenching experiments and electron paramagnetic resonance analysis. Thus, this study provides a new idea for the photocatalytic application of Bi2O3/CQDs/rGO and a contribution to the degradation of antibiotics to avoid polluting the water environment.