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mTORC1 is a signal integrator and master regulator of cellular anabolic processes linked to cell growth and survival. Here, we demonstrate that mTORC1 promotes lipid biogenesis via SRPK2, a key regulator of RNA-binding SR proteins. mTORC1-activated S6K1 phosphorylates SRPK2 at Ser494, which primes Ser497 phosphorylation by CK1. These phosphorylation events promote SRPK2 nuclear translocation and phosphorylation of SR proteins. Genome-wide transcriptome analysis reveals that lipid biosynthetic enzymes are among the downstream targets of mTORC1-SRPK2 signaling. Mechanistically, SRPK2 promotes SR protein binding to U1-70K to induce splicing of lipogenic pre-mRNAs. Inhibition of this signaling pathway leads to intron retention of lipogenic genes, which triggers nonsense-mediated mRNA decay. Genetic or pharmacological inhibition of SRPK2 blunts de novo lipid synthesis, thereby suppressing cell growth. These results thus reveal a novel role of mTORC1-SRPK2 signaling in post-transcriptional regulation of lipid metabolism and demonstrate that SRPK2 is a potential therapeutic target for mTORC1-driven metabolic disorders.
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Regulação da Expressão Gênica , Lipogênese , Processamento Pós-Transcricional do RNA , Transdução de Sinais , Animais , Núcleo Celular/metabolismo , Colesterol/metabolismo , Ácidos Graxos/metabolismo , Feminino , Xenoenxertos , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Camundongos Nus , Transplante de Neoplasias , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismoRESUMO
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that stimulates macromolecule synthesis through transcription, RNA processing, and post-translational modification of metabolic enzymes. However, the mechanisms of how mTORC1 orchestrates multiple steps of gene expression programs remain unclear. Here, we identify family with sequence similarity 120A (FAM120A) as a transcription co-activator that couples transcription and splicing of de novo lipid synthesis enzymes downstream of mTORC1-serine/arginine-rich protein kinase 2 (SRPK2) signaling. The mTORC1-activated SRPK2 phosphorylates splicing factor serine/arginine-rich splicing factor 1 (SRSF1), enhancing its binding to FAM120A. FAM120A directly interacts with a lipogenic transcription factor SREBP1 at active promoters, thereby bridging the newly transcribed lipogenic genes from RNA polymerase II to the SRSF1 and U1-70K-containing RNA-splicing machinery. This mTORC1-regulated, multi-protein complex promotes efficient splicing and stability of lipogenic transcripts, resulting in fatty acid synthesis and cancer cell proliferation. These results elucidate FAM120A as a critical transcription co-factor that connects mTORC1-dependent gene regulation programs for anabolic cell growth.
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Arginina , Lipogênese , Proteína de Ligação a Elemento Regulador de Esterol 1 , Lipogênese/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Fatores de Processamento de RNA , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Humanos , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismoRESUMO
Dysregulated mTORC1 signaling alters a wide range of cellular processes, contributing to metabolic disorders and cancer. Defining the molecular details of downstream effectors is thus critical for uncovering selective therapeutic targets. We report that mTORC1 and its downstream kinase S6K enhance eIF4A/4B-mediated translation of Wilms' tumor 1-associated protein (WTAP), an adaptor for the N6-methyladenosine (m6A) RNA methyltransferase complex. This regulation is mediated by 5' UTR of WTAP mRNA that is targeted by eIF4A/4B. Single-nucleotide-resolution m6A mapping revealed that MAX dimerization protein 2 (MXD2) mRNA contains m6A, and increased m6A modification enhances its degradation. WTAP induces cMyc-MAX association by suppressing MXD2 expression, which promotes cMyc transcriptional activity and proliferation of mTORC1-activated cancer cells. These results elucidate a mechanism whereby mTORC1 stimulates oncogenic signaling via m6A RNA modification and illuminates the WTAP-MXD2-cMyc axis as a potential therapeutic target for mTORC1-driven cancers.
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Adenosina/análogos & derivados , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Estabilidade de RNA , Adenosina/metabolismo , Animais , Sequência de Bases , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Fatores de Iniciação em Eucariotos/metabolismo , Células HEK293 , Humanos , Masculino , Camundongos , Modelos Biológicos , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas c-myc/metabolismo , Fatores de Processamento de RNA/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas Quinases S6 Ribossômicas/metabolismo , Transdução de SinaisRESUMO
The mammalian Target of Rapamycin Complex 1 (mTORC1)-signaling system plays a critical role in the maintenance of cellular homeostasis by sensing and integrating multiple extracellular and intracellular cues. Therefore, uncovering the effectors of mTORC1 signaling is pivotal to understanding its pathophysiological effects. Here we report that the transcription factor forkhead/winged helix family k1 (Foxk1) is a mediator of mTORC1-regulated gene expression. Surprisingly, Foxk1 phosphorylation is increased upon mTORC1 suppression, which elicits a 14-3-3 interaction, a reduction of DNA binding, and nuclear exclusion. Mechanistically, this occurs by mTORC1-dependent suppression of nuclear signaling by the Foxk1 kinase, Gsk3. This pathway then regulates the expression of multiple genes associated with glycolysis and downstream anabolic pathways directly modulated by Foxk1 and/or by Foxk1-regulated expression of Hif-1α. Thus, Foxk1 mediates mTORC1-driven metabolic rewiring, and it is likely to be critical for metabolic diseases where improper mTORC1 signaling plays an important role.
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Reprogramação Celular , Metabolismo Energético , Fatores de Transcrição Forkhead/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas 14-3-3/metabolismo , Transporte Ativo do Núcleo Celular , Animais , Sítios de Ligação , Proliferação de Células , Regulação para Baixo , Fatores de Transcrição Forkhead/genética , Quinase 3 da Glicogênio Sintase/genética , Células HEK293 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Camundongos , Fosforilação , Ligação Proteica , Transdução de SinaisRESUMO
Dysregulation of pain-associated genes in the dorsal root ganglion (DRG) is considered to be a molecular basis of neuropathic pain genesis. Fused in sarcoma (FUS), a DNA/RNA-binding protein, is a critical regulator of gene expression. However, whether it contributes to neuropathic pain is unknown. This study showed that peripheral nerve injury caused by the fourth lumbar (L4) spinal nerve ligation (SNL) or chronic constriction injury (CCI) of the sciatic nerve produced a marked increase in the expression of FUS protein in injured DRG neurons. Blocking this increase through microinjection of the adeno-associated virus (AAV) 5-expressing Fus shRNA into the ipsilateral L4 DRG mitigated the SNL-induced nociceptive hypersensitivities in both male and female mice. This microinjection also alleviated the SNL-induced increases in the levels of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and glial fibrillary acidic protein (GFAP) in the ipsilateral L4 dorsal horn. Furthermore, mimicking this increase through microinjection of AAV5 expressing full-length Fus mRNA into unilateral L3/4 DRGs produced the elevations in the levels of p-ERK1/2 and GFAP in the dorsal horn, enhanced responses to mechanical, heat and cold stimuli, and induced the spontaneous pain on the ipsilateral side of both male and female mice in the absence of SNL. Mechanistically, the increased FUS activated the NF-κB signaling pathway by promoting the translocation of p65 into the nucleus and phosphorylation of p65 in the nucleus from injured DRG neurons. Our results indicate that DRG FUS contributes to neuropathic pain likely through the activation of NF-κB in primary sensory neurons.SIGNIFICANCE STATEMENT In the present study, we reported that fused in sarcoma (FUS), a DNA/RNA-binding protein, is upregulated in injured dorsal root ganglion (DRG) following peripheral nerve injury. This upregulation is responsible for nerve injury-induced translocation of p65 into the nucleus and phosphorylation of p65 in the nucleus from injured DRG neurons. Because blocking this upregulation alleviates nerve injury-induced nociceptive hypersensitivity, DRG FUS participates in neuropathic pain likely through the activation of NF-κB in primary sensory neurons. FUS may be a potential target for neuropathic pain management.
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Neuralgia , Traumatismos dos Nervos Periféricos , Sarcoma , Feminino , Ratos , Camundongos , Masculino , Animais , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Traumatismos dos Nervos Periféricos/complicações , Traumatismos dos Nervos Periféricos/metabolismo , Hiperalgesia/metabolismo , Nociceptividade , Neuralgia/metabolismo , Células Receptoras Sensoriais/metabolismo , Sarcoma/complicações , Sarcoma/metabolismo , DNA/metabolismo , Gânglios Espinais/metabolismoRESUMO
While monoradical emitters have emerged as a new route toward efficient organic light-emitting diodes, the luminescence property of organic diradicaloids is still scarcely explored. Herein, by devising a novel radical-radical coupling-based synthetic approach, we report a new class of sulfone-functionalized Chichibabin's hydrocarbon derivatives, SD-1-3, featuring varied substituent patterns and moderate to high diradical characters of 0.44-0.70, as highly stable diradicaloids with rarely seen NIR emission beyond 900 nm. Via comprehensive experimental and theoretical investigations, we reveal that the optoelectronic and magnetic properties of these materials are significantly tuned by the variations of substitutions (H/CF3/OMe) on the molecular skeletons. More importantly, quantum chemical computations indicate that the embedding of sulfone groups has contributed to a breaking of their quasi-C2 symmetry of these diradicaloid molecules and results in an excited-state charge transfer character. Therefore, a remarkably deep NIR emissive wavelength of up to 998 nm, together with a large Stokes shift (â¼386 nm), is achieved for the CF3-based SD-2 molecule in tetrahydrofuran. To the best of our knowledge, such a luminescent wavelength of SD-2 has represented the longest wavelengths among the currently reported organic fluorescent radicals. Overall, our work not only establishes a new synthetic approach toward stable Chichibabin's hydrocarbons but also paves the way for designing NIR emissive open-shell materials with both fundamental understanding and feasible control of their luminescent properties.
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BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal lung disorder for which effective treatments remain limited. Recent investigations revealed a potential link between altered glucose metabolism and the activation of fibroblasts, the key cells responsible for generating and depositing extracellular matrix proteins within the lung interstitium during IPF development. METHOD: In this study, we aimed to investigate the potential therapeutic impact of albendazole on fibroblast to myofibroblast transition in IPF. We assess albendazole's effectiveness in attenuating the activation of fibroblasts. We focused on elucidating the mechanism underlying albendazole's impact on TGF-ß1-induced aerobic glycolysis in both lung tissues and fibroblasts obtained from patients with IPF and other lung fibrosis types. Furthermore, the antifibrotic effects of oral administration of albendazole were investigated in mouse models of pulmonary fibrosis induced by BLM or SiO2. Human precision-cut lung slices were employed to evaluate the impact of albendazole following TGF-ß1 stimulation. RESULT: In this work, we demonstrated that albendazole, a first-line broad-spectrum anthelmintic drug, effectively attenuated fibroblast to myofibroblast transition through alleviating TGF-ß1-induced aerobic glycolysis dependent on the LRRN3/PFKFB3 signaling pathway. Additionally, LRRN3 expression was downregulated in both lung tissues and fibroblasts from patients with IPF and other types of lung fibrosis. Importantly, the levels of LRRN3 correlated with the progression of the disease. Notably, oral administration of albendazole exerted potent antifibrotic effects in mouse models of pulmonary fibrosis induced by BLM or SiO2, and in human precision-cut lung slices after TGF-ß1 stimulation, as evidenced by improvements in lung morphology, reduced myofibroblast formation, and downregulation of α-SMA, collagen type 1 and Fibronectin expression in the lungs. CONCLUSION: Our study implies that albendazole can act as a potent agonist of LRRN3 during fibroblast to myofibroblast differentiation and its oral administration shows potential as a viable therapeutic approach for managing IPF.
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Albendazol , Glicólise , Miofibroblastos , Fibrose Pulmonar , Fator de Crescimento Transformador beta1 , Animais , Albendazol/farmacologia , Albendazol/uso terapêutico , Humanos , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Glicólise/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/patologia , Fibrose Pulmonar/metabolismo , Camundongos Endogâmicos C57BL , Pulmão/patologia , Pulmão/efeitos dos fármacos , Masculino , Camundongos , Transdução de Sinais/efeitos dos fármacos , Modelos Animais de Doenças , Bleomicina , FemininoRESUMO
Successful pathogen infection in plant depends on a proper interaction between the invading pathogen and its host. Post-translational modification (PTM) plays critical role(s) in plant-pathogen interaction. However, how PTM of viral protein regulates plant immunity remains poorly understood. Here, we found that S162 and S165 of Chinese wheat mosaic virus (CWMV) cysteine-rich protein (CRP) are phosphorylated by SAPK7 and play key roles in CWMV infection. Furthermore, the phosphorylation-mimic mutant of CRP (CRPS162/165D) but not the non-phosphorylatable mutant of CRP (CRPS162/165A) interacts with RNA-binding protein UBP1-associated protein 2C (TaUBA2C). Silencing of TaUBA2C expression in wheat plants enhanced CWMV infection. In contrast, overexpression of TaUBA2C in wheat plants inhibited CWMV infection. TaUBA2C inhibits CWMV infection through recruiting the pre-mRNA of TaNPR1, TaPR1 and TaRBOHD to induce cell death and H2O2 production. This effect can be supressed by CRPS162/165D through changing TaUBA2C chromatin-bound status and attenuating it's the RNA- or DNA-binding activities. Taken together, our findings provide new knowledge on how CRP phosphorylation affects CWMV infection as well as the arms race between virus and wheat plants.
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Doenças das Plantas , Proteínas Virais , Peróxido de Hidrogênio/metabolismo , Imunidade Vegetal , Vírus de Plantas , Proteínas de Ligação a RNA/genética , Triticum/genética , Proteínas Virais/metabolismoRESUMO
Tumor metastasis is a continuous and dynamic process and is a major cause of tumor-related death in triple-negative breast cancer. However, this biological process remains largely unknown in triple-negative breast cancer. The emergence of single-cell sequencing enables a deeper understanding of the tumor microenvironment and provides a new strategy for discovering the potential mechanism of tumor metastasis. Herein, we integrated the single-cell expression profiling of primary and metastatic triple-negative breast cancer by Seurat package. Nine tumor cell subgroups were identified. Enrichment analysis suggested tumor subgroups (C0, C4) were associated with tumor metastasis with poor prognosis in TNBC. Weighted gene co-expression network was constructed and identified NENF was a metastasis-related gene. Subsequently, RT-qPCR, Immunohistochemistry, and western blot confirmed NENF is highly expressed in TNBC tissues. And cell function assays indicated NENF promote cell invasion and migration through regulating EMT in TNBC. Finally, TIDE and Connectivity Map database suggest the candidate drugs for targeting NENF. In conclusion, our findings provide a new insight into the progression and metastasis of TNBC and uncover NENF may be a prognostic biomarker and potential therapy targets.
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More than 80% of patients with myasthenia gravis (MG) are positive for anti-acetylcholine receptor (AChR) antibodies. Regulatory T cells (Tregs) suppress overproduction of these antibodies, and patients with AChR antibody-positive MG (AChR MG) exhibit impaired Treg function and reduced Treg numbers. The gut microbiota and their metabolites play a crucial role in maintaining Treg differentiation and function. However, whether impaired Tregs correlate with gut microbiota activity in patients with AChR MG remains unknown. Here, we demonstrate that butyric acid-producing gut bacteria and serum butyric acid level are reduced in patients with AChR MG. Butyrate supplementation effectively enhanced Treg differentiation and their suppressive function of AChR MG. Mechanistically, butyrate activates autophagy of Treg cells by inhibiting the mammalian target of rapamycin. Activation of autophagy increased oxidative phosphorylation and surface expression of cytotoxic T-lymphocyte-associated protein 4 on Treg cells, thereby promoting Treg differentiation and their suppressive function in AChR MG. This observed effect of butyrate was blocked using chloroquine, an autophagy inhibitor, suggesting the vital role of butyrate-activated autophagy in Tregs of patients with AChR MG. We propose that gut bacteria derived butyrate has potential therapeutic efficacy against AChR MG by restoring impaired Tregs.
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Microbioma Gastrointestinal , Miastenia Gravis , Humanos , Receptores Colinérgicos/metabolismo , Linfócitos T Reguladores , Ácido Butírico/farmacologia , Ácido Butírico/metabolismo , Miastenia Gravis/metabolismo , Autoanticorpos/metabolismoRESUMO
BACKGROUND : There are limited data on the feasibility of endoscopic submucosal dissection (ESD) for superficial esophageal neoplasia (SEN) located at or adjacent to esophageal varices. We aimed to evaluate the outcomes of ESD in these patients. METHODS: This multicenter retrospective study included cirrhotic patients with a history of esophageal varices with SEN located at or adjacent to the esophageal varices who underwent ESD. RESULTS: 23 patients with SEN (median lesion size 30 mm; 16 squamous cell neoplasia and seven Barrett's esophagus-related neoplasia) were included. The majority were Child-Pugh B (57â%) and had small esophageal varices (87â%). En bloc, R0, and curative resections were achieved in 22 (96â%), 21 (91â%), and 19 (83â%) of patients, respectively. Severe intraprocedural bleeding (nâ=â1) and delayed bleeding (nâ=â1) were successfully treated endoscopically. No delayed perforation, hepatic decompensation, or deaths were observed. During a median (interquartile range) follow-up of 36 (22-55) months, one case of local recurrence occurred after noncurative resection. CONCLUSION: ESD is feasible and effective for SEN located at or adjacent to esophageal varices in cirrhotic patients. Albeit, the majority of the esophageal varices in our study were small in size, when expertise is available, ESD should be considered as a viable option for such patients.
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Ressecção Endoscópica de Mucosa , Neoplasias Esofágicas , Varizes Esofágicas e Gástricas , Humanos , Estudos Retrospectivos , Ressecção Endoscópica de Mucosa/efeitos adversos , Varizes Esofágicas e Gástricas/complicações , Varizes Esofágicas e Gástricas/cirurgia , Esofagoscopia/efeitos adversos , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Cirrose Hepática/complicações , Resultado do TratamentoRESUMO
OBJECTIVE: Systematic literature reviews (SLRs) are critical for life-science research. However, the manual selection and retrieval of relevant publications can be a time-consuming process. This study aims to (1) develop two disease-specific annotated corpora, one for human papillomavirus (HPV) associated diseases and the other for pneumococcal-associated pediatric diseases (PAPD), and (2) optimize machine- and deep-learning models to facilitate automation of the SLR abstract screening. METHODS: This study constructed two disease-specific SLR screening corpora for HPV and PAPD, which contained citation metadata and corresponding abstracts. Performance was evaluated using precision, recall, accuracy, and F1-score of multiple combinations of machine- and deep-learning algorithms and features such as keywords and MeSH terms. RESULTS AND CONCLUSIONS: The HPV corpus contained 1697 entries, with 538 relevant and 1159 irrelevant articles. The PAPD corpus included 2865 entries, with 711 relevant and 2154 irrelevant articles. Adding additional features beyond title and abstract improved the performance (measured in Accuracy) of machine learning models by 3% for HPV corpus and 2% for PAPD corpus. Transformer-based deep learning models that consistently outperformed conventional machine learning algorithms, highlighting the strength of domain-specific pre-trained language models for SLR abstract screening. This study provides a foundation for the development of more intelligent SLR systems.
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Aprendizado de Máquina , Infecções por Papillomavirus , Humanos , Infecções por Papillomavirus/diagnóstico , Economia Médica , Algoritmos , Avaliação de Resultados em Cuidados de Saúde/métodos , Aprendizado Profundo , Indexação e Redação de Resumos/métodosRESUMO
BACKGROUND: Delayed bleeding (DB) is a serious complication after cold snare polypectomy (CSP) for polyps in the colon. The present study aimed to investigate the incidence and risk factors of DB after CSP and to develop a risk-scoring model for predicting DB. METHODS: A retrospective study was conducted in four Chinese medical institutions. 10650 patients underwent CSP from June 2019 to May 2023. The study analyzed the rate of DB and extracted the general clinical information and polyp-related information of patients with postoperative DB. As a control, non-DB patients who received CSP at the same 4 hospitals were analyzed. A multivariate Cox regression analysis was performed to develop the prediction model. The model was further validated using a Kaplan-Meier log-rank analysis, receiver operating characteristic curve (ROC) plot and risk plot. RESULTS: In our study, we found a 0.24% rate of DB and the risk factors were history of hypertension, hyperlipidemia, antithrombotics use, antiplatelet use, anticoagulant use, abdominal operation, sigmoid colon lesion, hematoma, cold snare defect protrusion, polyp size, wound size, the grade of wound bleeding, and morphology of Ip. These factors were incorporated into the prediction model for DB after CSP. For 1, 3, and 5 days of bleeding, the AUC of the ROC curve was 0.912, 0.939, and 0.923, respectively. The Kaplan-Meier analysis indicated that the high-risk group had a significantly higher risk of DB than the low-risk group. CONCLUSIONS: This study screened the risk factors and established a prediction model of DB after CSP. The results may help preventing and reducing the DB rate after CSP of colorectal polyps.
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Pólipos do Colo , Humanos , Fatores de Risco , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Pólipos do Colo/cirurgia , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/epidemiologia , Curva ROC , Idoso , Fatores de Tempo , Adulto , Colonoscopia/efeitos adversosRESUMO
BACKGROUND: The Chiari network, a remnant of fetal anatomy, consists of a mesh-like structure within the right atrium. With advancements in cardiac interventions, complications associated with the Chiari network have increasingly been reported. However, there are few reports about guidewire or catheter entrapment in the Chiari network during the insertion of a dialysis catheter. CASE PRESENTATION: A 46-year-old male with end-stage renal disease was hospitalized and underwent a digital subtraction angiography-assisted catheterization of the right internal jugular vein tunnel-cuffed dialysis catheter. When the guide wire entered a depth of about 20 cm, it was difficult to advance, manifested as resistance when twisting the guide wire and inability to enter the inferior vena cava. After the peelable sheath was inserted, it was difficult to pull out the guide wire. After repeated attempts to rotate the guide wire, the guide wire was finally pulled out. A fibrous tissue was wrapped around the tip of the guide wire. Its length was 6 cm, with a smooth surface and tough texture. We considered that the tissue we pulled out was most likely a part of a Chiari network. CONCLUSIONS: This case highlights the potential for the Chiari network to complicate surgical procedures, including difficulty with guidewire and catheter manipulation. Attention should be paid to Chiari networks. Echocardiography can be used to identify the Chiari network. During the surgery, forcefully pulling out a stuck guidewire is not suggested, to avoid the risk of tearing the atrial wall and causing pericardial tamponade. An urgent consultation with ultrasound doctors and cardiac surgeons might be helpful in such cases.
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Átrios do Coração , Diálise Renal , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/instrumentação , Átrios do Coração/diagnóstico por imagem , Falência Renal Crônica/terapia , Falência Renal Crônica/complicações , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Cateteres de Demora/efeitos adversosRESUMO
Objective: To provide genetic information about the fetuses from carriers of Robertsonian (Rob) translocation and to explore the application value of extravillous trophoblasts (EVTs) cells collected from the cervical canal for prenatal diagnosis. Method: Trophoblast retrieval and isolation from the cervix (TRIC) is an approach that non-invasively isolates homogeneous trophoblast cells. In this study, the EVT cells were collected from the cervix of 20 pregnant women between 5-7 weeks gestation. Thereafter, STR analysis and fluorescence in situ hybridization (FISH) were performed on these trophoblast cells. Results: In 1 case (P5), we failed to collect the trophoblast cells, STR analysis showed maternal cell contamination in 4 cases, 6 cases were normal/balanced chromosome, and 9 cases were associated with unbalanced chromosome. The results of these 15 cases were consistent with those of villi FISH examination or cytogenetic analysis of cultured amniocytes. Conclusion: The collection of fetal trophoblast cells from the cervix provides a feasible approach for prenatal diagnosis. Rob translocation homozygosity could be seen as a potential means of speciation in humans with 44 chromosomes.
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Objective: To analyze the clinical characteristics of multiple sclerosis (MS) patients complicated by disabilities in China, and to discuss the related factors of disease progression. Methods: Ninety-three MS patients presented to our hospital between March 2017 and December 2019 were selected as the research participants to conduct a retrospective analysis. Demographic information, onset time, onset age, clinical symptoms, MS types, and Expanded Disability Status Scale (EDSS) score were collected from all patients, and preliminary observation was made on MS cases in China. Subsequently, patients were grouped according to their sex, onset age and MS types to observe the differences in clinical characteristics of MS under different conditions. Finally, Logistic analysis was conducted to analyze the related factors affecting disease progression in MS patients. Results: MS was likely to occur in all age groups, among which the 30-40 age group had a slightly higher predilection. Women were more predisposed to MS, with motor symptoms as the major clinical presentations. The number of patients with sensory symptoms and the frequency of episodes in the past year were higher in female patients than in male patients (P < .05). Clinical isolated syndrome (CIS) patients had lower baseline ESDD than relapsing remitting MS (RRMS) patients (P < .05). According to Logistic regression analysis, baseline ESDD score and the frequency of episodes in the past year were independent risk factors affecting MS progression (P < .05). Conclusions: The clinical characteristics of MS in the Chinese population are basically similar to those in foreign countries, but RRMS accounts for a relatively low proportion. The ESDD score and the frequency of episodes in the past year are independent risk factors for MS progression.
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Pessoas com Deficiência , Progressão da Doença , Esclerose Múltipla , Humanos , Masculino , Feminino , Adulto , Fatores de Risco , Esclerose Múltipla/epidemiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , China/epidemiologia , Pessoas com Deficiência/estatística & dados numéricos , Adulto Jovem , Adolescente , Avaliação da DeficiênciaRESUMO
In order to better design handling-assisted exoskeletons, it is necessary to analyze the biomechanics of human hand movements. In this study, Anybody Modeling System (AMS) simulation was used to analyze the movement state of muscles during human handling. Combined with surface electromyography (sEMG) experiments, specific analysis and verification were carried out to obtain the position of muscles that the human body needs to assist during handling. In this study, the simulation and experiment were carried out for the manual handling process. A treatment group and an experimental group were set up. This study found that the vastus medialis muscle, vastus lateralis muscle, latissimus dorsi muscle, trapezius muscle, deltoid muscle and triceps brachii muscle require more energy in the process of handling, and it is reasonable and effective to combine sEMG signals with the simulation of the musculoskeletal model to analyze the muscle condition of human movement.
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Eletromiografia , Exoesqueleto Energizado , Músculo Esquelético , Humanos , Eletromiografia/métodos , Músculo Esquelético/fisiologia , Fenômenos Biomecânicos/fisiologia , Movimento/fisiologia , Masculino , Adulto , Mãos/fisiologiaRESUMO
In the present study, we used a transformer model and a fusion of biosignals to estimate rotational acceleration in elbow and shoulder joints. To achieve our study objectives, we proposed a mechanomyography (MMG) signal isolation technique based on a variational mode decomposition (VMD) algorithm. Our results show that the VMD algorithm delivered excellent performance in MMG signal extraction compared to the commonly used technique of empirical mode decomposition (EMD). In addition, we found that transformer models delivered estimates of joint acceleration that were more precise than those produced by mainstream time series forecasting models. The average R2 values of transformer are 0.967, 0.968, and 0.935, respectively. Finally, we found that using a fusion of signals resulted in more precise estimation performance compared to using MMG signals alone. The differences between the average R2 values are 0.041, 0.053, and 0.043, respectively. Taken together, the VMD isolation method, the transformer algorithm and the signal fusion technique described in this paper can be seen as supplying a robust framework for estimating rotational acceleration in upper-limb joints. Further study is warranted to examine the effectiveness of this framework in other musculoskeletal contexts.
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Articulação do Cotovelo , Ombro , Extremidade Superior , Aceleração , AlgoritmosRESUMO
Underwater mobile acoustic source target localization encounters several challenges, including the unknown propagation speed of the source signal, uncertainty in the observation platform's position and velocity (i.e., platform systematic errors), and economic costs. This paper proposes a new two-step closed-form localization algorithm that jointly estimates the angle of arrival (AOA), time difference of arrival (TDOA), and frequency difference of arrival (FDOA) to address these challenges. The algorithm initially introduces auxiliary variables to construct pseudo-linear equations to obtain the initial solution. It then exploits the relationship between the unknown and auxiliary variables to derive the exact solution comprising solely the unknown variables. Both theoretical analyses and simulation experiments demonstrate that the proposed method accurately estimates the position, velocity, and speed of the sound source even with an unknown sound speed and platform systematic errors. It achieves asymptotic optimality within a reasonable error range to approach the Cramér-Rao lower bound (CRLB). Furthermore, the algorithm exhibits low complexity, reduces the number of required localization platforms, and decreases the economic costs. Additionally, the simulation experiments validate the effectiveness of the proposed localization method across various scenarios, outperforming other comparative algorithms.
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The serine carboxypeptidase-like (SCPL) gene family plays a crucial role in the regulation of plant growth, development, and stress response through activities such as acyltransferases in plant secondary metabolism pathways. Although SCPL genes have been identified in various plant species, their specific functions and characteristics in soybean (Glycine max) have not yet been studied. We identified and characterized 73 SCPL genes, grouped into three subgroups based on gene structure and phylogenetic relationships. These genes are distributed unevenly across 20 soybean chromosomes and show varied codon usage patterns influenced by both mutation and selection pressures. Gene ontology (GO) enrichment suggests these genes are involved in plant cell wall regulation and stress responses. Expression analysis in various tissues and under stress conditions, including the presence of numerous stress-related cis-acting elements, indicated that these genes have varied expression patterns. This suggests that they play specialized roles such as modulating plant defense mechanisms against nematode infections, enhancing tolerance to drought and high salinity, and responding to cold stress, thereby helping soybean adapt to environmental stresses. Moreover, the expression of specific GmSCPLs was significantly affected following exposure to nematode infection, drought, high salt (NaCl), and cold stresses. Our findings underscore the potential of SCPL genes in enhancing stress resistance in soybean, providing a valuable resource for future genetic improvement and breeding strategies.