RESUMO
Importance: Acupuncture has been used to treat neurological and neuropsychiatric symptoms in China and other parts of the world. These symptoms, such as fatigue, headache, cognitive impairment, anxiety, depression, and insomnia, are common in people experiencing long COVID. Objective: This study aims to explore the feasibility of acupuncture in the treatment of neurological and neuropsychiatric symptoms in long COVID patients. Data Sources: A systematic search was conducted in four English and four Chinese databases from inception to 23 June 2023. Literature selection and data extraction were conducted by two pairs of independent reviewers. Study Selection: Randomized controlled trials (RCTs) that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included. Data Extraction and Synthesis: RCTs that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included. A meta-analysis was performed using R software. Heterogeneity was measured using I2. Subgroup analyses were performed focusing on the duration of treatment and acupuncture modalities. The systematic review protocol was registered on PROSPERO (registration number: CRD42022354940). Main outcomes and measures: Widely adopted clinical outcome scales included the Fatigue Scale for assessing fatigue, the Hamilton Depression Rating Scale for evaluating depression, the Mini-Mental State Examination for assessing cognitive impairment, the Visual Analog Scale for headache severity, and the Pittsburgh Sleep Quality Index for measuring insomnia. Results: A total of 110 RCTs were included in the systematic review and meta-analysis. Overall, acupuncture was found to improve the scores of the Fatigue Scale (vs. medication: mean differences (MD): -2.27, P < 0.01; vs. sham acupuncture: MD: -3.36, P < 0.01), the Hamilton Depression Rating Scale (vs. medication: MD: -1.62, 95%, P < 0.01; vs. sham acupuncture: MD: -9.47, P < 0.01), the Mini-Mental State Examination (vs. medication: MD: 1.15, P < 0.01; vs. sham acupuncture: MD: 1.20, P < 0.01), the Visual Analog Scale (vs. medication: MD: -1.05, P < 0.01; vs. waitlist: MD: -0.48, P=0.04), and the Pittsburgh Sleep Quality Index (vs. medication: MD: -2.33, P < 0.01; vs. sham acupuncture: MD: -4.19, P < 0.01). Conclusion and relevance: This systematic review suggested acupuncture as a potentially beneficial approach for the treatment of neurological and neuropsychiatric symptoms, as assessed using clinical scales, and it may have applicability in long COVID patients. Further well-designed clinical studies specifically targeting long COVID patients are needed to validate the role of acupuncture in alleviating long COVID symptoms. Systematic Review Registration: PROSPERO, identifier [CRD42022354940].
RESUMO
[This corrects the article DOI: 10.7150/jca.60066.].
RESUMO
OBJECTIVES: To investigate the knowledge, attitude and practice (KAP) towards insomnia and sleep hygiene among patients with chronic insomnia. DESIGN: Web-based cross-sectional survey. SETTING: Shaanxi Provincial People's Hospital (northwest China) between January 2023 and May 2023. PARTICIPANTS: Patients with chronic insomnia. PRIMARY AND SECONDARY OUTCOME MEASURES: Demographic characteristics and KAP towards insomnia and sleep hygiene were collected by distributing a questionnaire developed by the authors. RESULTS: A total of 613 people participated in this study, with a Mean Knowledge Score of 7.63±2.56 (total score of 12), a Mean Attitude Score of 48.39±6.643 (total score of 70) and a Mean Practice Score of 42.37±8.592 (total score of 70). Knowledge was significantly correlated with attitude (r=0.447, p<0.001) and practice (r=0.327, p<0.001), and attitude was significantly correlated with practice (r=0.486, p<0.001). Multivariable logistic regression showed that higher knowledge (OR=1.181 (1.062-1.314), p=0.002) and better attitude (OR=1.171 (1.124-1.221), p<0.001) were independently associated with good practice. According to the structural equation modelling analysis, knowledge directly influenced practice (ß=0.457, p=<0.001) and attitude (ß=1.160, p=<0.001), while attitude influenced practice (ß=0.550, p=<0.001). CONCLUSION: The KAP towards insomnia and sleep hygiene among patients with chronic insomnia in Northwest China in 2023 was moderate, with better practice showing signs of being influenced by better knowledge and more positive attitudes.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Higiene do Sono , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Estudos Transversais , Feminino , Masculino , China/epidemiologia , Pessoa de Meia-Idade , Adulto , Inquéritos e Questionários , Doença Crônica , Modelos Logísticos , Idoso , Adulto JovemRESUMO
Acoustic agglomeration is employed as a precursor technique that modifies the sound field of fine particles to increase their size, thereby facilitating more efficient emission control. This paper reviews progress in the field of acoustic agglomeration technology, clarifies the mechanisms at play within the acoustic agglomeration process, and outlines its applicability in both gas-liquid and gas-solid phases. Furthermore, it analyzes the factors impacting the efficacy of acoustic agglomeration, summarizes the numerical simulation research of acoustic agglomeration, and proposes directions for technological enhancement.
RESUMO
Electrochemical energy storage stations serve as an important means of load regulation, and their proportion has been increasing year by year. The temperature monitoring of lithium batteries necessitates heightened criteria. Ultrasonic thermometry, based on its noncontact measurement characteristics, is an ideal method for monitoring the internal temperature of lithium batteries. In this study, temperature and ultrasonic time delay measurement experiments were conducted on 18650 lithium batteries and laminated and wound lithium batteries to obtain the corresponding relationship between temperature and time delay and validate the temperature measurement for the same type of battery. The experimental results show that (1) the ultrasonic temperature measurement technique exhibits a relatively large error when used for 18650 Li-ion batteries under experimental conditions; (2) in the experiments on laminated and wound soft-pack lithium batteries, the relationship between temperature and time delay exhibits a nonlinear characteristic; and (3) under the experimental conditions, the ultrasonic temperature measurement errors were ±1.1 °C for stacked Li-ion batteries and ±1.4 °C for wound Li-ion batteries.
RESUMO
Polyurethane (PU) catheters are commonly used in clinical treatment. However, the hydrophobic nature of the PU catheter surface leads to adhesion or adsorption to platelets, proteins, bacteria, and other molecules when used in human treatment. To achieve a surface with strong hydrophilicity, high stability and excellent biocompatibility, it is necessary to functionalize the PU catheters. In this paper, a coating with antifouling function was constructed on the surface of PU catheters using plasma technology and an amide coupling reaction. A series of characterization methods, including X-ray photoelectron spectroscopy (XPS), water contact angles (WCA), and atomic force microscopy (AFM), were used to prove the successful modification of the polymer coatings. The coatings showed good stability under conditions such as PBS (pH 7.4, 720 h), 75% ethanol (6 h) and 1 wt% SDS (10 min). Additionally, the coatings exhibit excellent hemocompatibility and antibacterial properties. The PU/PEI/PCSB coating has the best anti-fouling performance among them, which means that using the PCSB copolymer has the potential to modify different clinical catheters into highly effective antifouling coatings.
Assuntos
Betaína , Propriedades de Superfície , Humanos , Betaína/química , Betaína/análogos & derivados , Betaína/farmacologia , Poliuretanos/química , Poliuretanos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Incrustação Biológica/prevenção & controle , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Animais , Teste de Materiais , Polímeros/química , Polímeros/farmacologiaRESUMO
Toward the realization of efficient, durable, and sustainable fiber-based perovskite solar cells (fb-PSCs), a comprehensive optimization strategy focused on enhancing electron transport layer (ETL), perovskite (PVK) photovoltaic layer, and hole transport layer (HTL) is presented. A champion PCE of 10.66 % with 37.9 % relative enhancement over control has been achieved in the optimized fb-PSC. A significantly improved mechanical resilience and storage durability are also recorded. Decorating the SnO2 ETL with methylammonium lead triiodide (MAPbI3) strengthened the ETL/PVK interfacial integrity, and doping the MAPbI3 layer with the multi-functional polymer of PJ71 remarkably enhanced the PVK layer's crystallization quality, and effectively passivated the grain boundary defects. A CO2 pre-treatment of the spiro-OMeTAD HTL enhanced its hole conductivity. It is the synergetic combination of these methodologies that mutually contributed to the performance boost of the fb-PSC. The phenomenological model based on layer conductance shows that the PVK layer chiefly influences the device's anti-bending ability, followed by the ETL, and HTL the least impact. To further enhance the PCE of fb-PSCs, optimizing the interface and minimizing the stress-induced defects are essential. These measures, coupled with increasing carrier diffusion length and reducing surface recombination, are key to advancing the fb-PSC performance. An encapsulation with polyolefin elastomer substantially reduced the potential lead leakage of the device, and facilitated its eco-friendly application.
RESUMO
Adsorption heat conversion systems can provide heating and cooling across time and space in a more environmentally friendly way. Porous materials are potential candidates for water-based adsorption thermal conversion, in which a metal-organic framework (MOF) has a larger specific surface area and porosity than other porous matrices. However, many MOFs with high saturated adsorption capacity have great deficiencies in performance at low water vapor partial pressure, which hinder their application in adsorption thermal conversion. To improve the water vapor adsorption performance of MIL-101 (Cr), different contents of magnesium chloride, lithium chloride, and lanthanum chloride are mixed into MIL-101 (Cr) by an impregnation method. The properties and structures of the materials are characterized by XRD, SEM, nitrogen adsorption tests, water vapor adsorption tests, TG, FTIR, and so on. The results show that the saturated water vapor adsorption capacity of the sample impregnated with salt increases by 1.5-2.3 times, up to 2.24 g/g, compared with that of the unimpregnated sample. When the partial pressure of water vapor is 0.3, the adsorption capacity increases by 5.3-7.5 times and reaches 0.68 g/g at most. The maximum heat storage density of impregnated samples can be increased by 866 J/g. Impregnated MgCl2 can greatly improve the adsorption and thermal conversion performance of MOF, and impregnated MgCl2 and the proper amount of LiCl can further improve the performance of the material system. Our experiments show that the composite impregnation of magnesium chloride and the proper amount of lithium chloride can improve the application performance of the MOF materials in the adsorption thermal conversion process.
RESUMO
BACKGROUND: Central obesity is considered as a significant health threat to individuals. Scientific research has demonstrated that intra-abdominal fat accumulation is associated with higher metabolic and cardiovascular disease risks independent of Body Mass Index (BMI). This study aimed to evaluate the efficacy and safety of electro-acupuncture in treating central obesity compared with sham acupuncture. METHOD: This was a patient-assessor blinded, randomized, sham-controlled clinical trial. One hundred sixty eight participants aged between 18 and 65 years old with BMI ≥ 25 kg/m2 and waist circumference (WC) of men ≥ 90 cm / women ≥ 80 cm were enrolled and allocated to the acupuncture or sham acupuncture group equally. For the acupuncture group, disposable acupuncture needles were inserted into eight body acupoints, including Tianshu (ST-25), Daheng (SP-15), Daimai (GB-26), Qihai (CV-6), Zhongwan (CV-12), Zusanli (ST-36), Fenglong (ST-40), and Sanyinjiao (SP-6) with electrical stimulation. For the control group, Streitberger's non-invasive acupuncture needles were utilized at the same acupoints with identical stimulation modalities. The treatment duration was 8 weeks with 2 sessions per week and the follow-up period was 8 weeks. The primary outcome was the change in WC before and after the treatment. The secondary outcomes were the changes in hip circumference, waist-to-hip circumference ratio, BMI, and body fat percentage during the treatment and follow-up period. RESULTS: The acupuncture group displayed a significant change in WC compared to the sham group both treatment and follow-up period (MD = -1.1 cm, 95% CI = -2.8 to 4.1). Significant change in body fat percentage was recorded for both groups after treatment but no significance was observed during the follow-up period (MD = -0.1%, 95% CI = -1.9 to 2.2). The changes in hip circumference were also significant both treatment and follow-up period for the acupuncture group (MD = -2.0 cm, 95% CI = -3.7 to -1.7). Compared with sham acupuncture, the body weight (MD = -1 kg, 95% CI = -3.3 to 5.3), BMI (MD = -0.5, 95% CI = -0.7 to 1.9) also decreased significantly within and between groups. The incidence of adverse events was similar in the two groups. CONCLUSION: This study provided evidence that electro-acupuncture could be effective in treating central obesity by reducing WC, hip circumference, body weight, BMI, and waist-to-hip circumference ratio. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03815253, Registered 24 Jan 2019.
Assuntos
Terapia por Acupuntura , Obesidade Abdominal , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Obesidade Abdominal/terapia , Obesidade/terapia , Peso Corporal , Índice de Massa CorporalRESUMO
BACKGROUND: Previous studies show that spinal cord ischemia and hypoxia is an important cause of spinal cord necrosis and neurological loss. Therefore, the study aimed to identify genes related to ischemia and hypoxia after spinal cord injury (SCI) and analyze their functions, regulatory mechanism, and potential in regulating immune infiltration. METHODS: The expression profiles of GSE5296, GSE47681, and GSE217797 were downloaded from the Gene Expression Omnibus database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to determine the function and pathway enrichment of ischemia- and hypoxia-related differentially expressed genes (IAHRDEGs) in SCI. LASSO model was constructed, and support vector machine analysis was used to identify key genes. The diagnostic values of key genes were evaluated using decision curve analysis and receiver operating characteristic curve analysis. The interaction networks of miRNAs-IAHRDEGs and IAHRDEGs-transcription factors were predicted and constructed with the ENCORI database and Cytoscape software. CIBERSORT algorithm was utilized to analyze the correlation between key gene expression and immune cell infiltration. RESULTS: There were 27 IAHRDEGs identified to be significantly expressed in SCI at first. These genes were mostly significantly enriched in wound healing function and the pathway associated with lipid and atherosclerosis. Next, five key IAHRDEGs (Abca1, Casp1, Lpl, Procr, Tnfrsf1a) were identified and predicted to have diagnostic value. Moreover, the five key genes are closely related to immune cell infiltration. CONCLUSION: Abca1, Casp1, Lpl, Procr, and Tnfrsf1a may promote the pathogenesis of ischemic or hypoxic SCI by regulating vascular damage, inflammation, and immune infiltration.
Assuntos
Traumatismos da Medula Espinal , Fatores de Transcrição , Humanos , Receptor de Proteína C Endotelial , Traumatismos da Medula Espinal/genética , Isquemia , Biologia ComputacionalRESUMO
Macroautophagy/autophagy is the major degradation pathway in neurons for eliminating damaged proteins and organelles in Parkinson disease (PD). Like neurons, glial cells are important contributors to PD, yet how autophagy is executed in glia and whether it is using similar interplay as in neurons or other tissues, remain largely elusive. Recently, we reported that the PD risk factor, GAK/aux (cyclin-G-associated kinase/auxilin), regulates the onset of glial autophagy. In the absence of GAK/aux, the number and size of the autophagosomes and autophagosomal precursors increase in adult fly glia and mouse microglia. The protein levels of components in the initiation and class III phosphatidylinositol 3-kinase (PtdIns3K) complexes are generally upregulated. GAK/aux interacts with the master initiation regulator ULK1/Atg1 (unc-51 like autophagy activating kinase 1) via its uncoating domain, hinders autophagy activation by competing with ATG13 (autophagy related 13) for binding to the ULK1 C terminus, and regulates ULK1 trafficking to phagophores. Nonetheless, lack of GAK/aux impairs the autophagic flux and blocks substrate degradation, suggesting that GAK/aux might play additional roles. Overall, our findings reveal a new regulator of autophagy initiation in glia, advancing our understanding on how glia contribute to PD in terms of eliminating pathological protein aggregates.Abbreviations: ATG13: autophagy related 13; GAK/aux: cyclin G associated kinase/auxilin; PtdIns3K: phosphatidylinositol 3-kinase; PD: Parkinson disease; ULK1/Atg1: unc-51 like autophagy activating kinase 1.
Assuntos
Autofagia , Doença de Parkinson , Animais , Camundongos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Autofagia/fisiologia , Proteínas Relacionadas à Autofagia/metabolismo , Doença de Parkinson/metabolismo , Auxilinas , Neuroglia/metabolismoRESUMO
Parkinson's disease is a progressive neurodegenerative disease characterized by motor deficits, dopaminergic neuron loss, and brain accumulation of α-synuclein aggregates called Lewy bodies. Dysfunction in protein degradation pathways, such as autophagy, has been demonstrated in neurons as a critical mechanism for eliminating protein aggregates in Parkinson's disease. However, it is less well understood how protein aggregates are eliminated in glia, the other cell type in the brain. In the present study, we show that autophagy-related gene 9 (Atg9), the only transmembrane protein in the autophagy machinery, is highly expressed in Drosophila glia from adult brain. Results from immunostaining and live cell imaging analysis reveal that a portion of Atg9 localizes to the trans-Golgi network, autophagosomes, and lysosomes in glia. Atg9 is persistently in contact with these organelles. Lacking glial atg9 reduces the number of omegasomes and autophagosomes, and impairs autophagic substrate degradation. This suggests that glial Atg9 participates in the early steps of autophagy, and hence the control of autophagic degradation. Importantly, loss of glial atg9 induces parkinsonian symptoms in Drosophila including progressive loss of dopaminergic neurons, locomotion deficits, and glial activation. Our findings identify a functional role of Atg9 in glial autophagy and establish a potential link between glial autophagy and Parkinson's disease. These results may provide new insights on the underlying mechanism of Parkinson's disease.
RESUMO
Abundant biomass resources provide us with sufficient material basis, while a large amount of bio-waste is also produced and the high-value utilization of bio-waste is still highly desirable. Herein, we reported a facile one-pot fabrication approach towards efficient utilization of sugarcane bagasse via carboxymethylation to adsorb and recycle Cu2+ ions. The modified sugarcane bagasse possessed outstanding adsorption efficiency, with a maximum capacity of 263.7 mg g-1, owing to the functional groups such as carboxyl and hydroxyl groups, as well as aromatic structure. It was noted that the carboxymethylated sugarcane bagasse (MSB40) swelled rapidly when suffering Cu2+ ions solution, and more adsorption sites were available since the physical diffusion barrier was removed, thereby enhancing the absorption capacity. Interestingly, Cu2+ ions could induce the aggregation of MSB40 due to the Cu2+ ions compress colloid double layer, neutralizes surface charges, which benefited the following separation process. Ultimately, copper oxide was recovered and the purity reached 97.9%. Additionally, in the presence of both Ca2+ and Mg2+ ions, MSB40 exhibited excellent selectivity for the adsorption of Cu2+ ions. This strategy offers a facile and novel clue for the high-value utilization of bio-waste and the recovery of copper for biomaterial and environmental applications.
RESUMO
To improve the accuracy of short-term multi-energy load prediction models for integrated energy systems, the historical development law of the multi-energy loads must be considered. Moreover, understanding the complex coupling correlation of the different loads in the multi-energy systems, and accounting for other load-influencing factors such as weather, may further improve the forecasting performance of such models. In this study, a two-stage fuzzy optimization method is proposed for the feature selection and identification of the multi-energy loads. To enrich the information content of the prediction input feature, we introduced a copula correlation feature analysis in the proposed framework, which extracts the complex dynamic coupling correlation of multi-energy loads and applies Akaike information criterion (AIC) to evaluate the adaptability of the different copula models presented. Furthermore, we combined a NARX neural network with Bayesian optimization and an extreme learning machine model optimized using a genetic algorithm (GA) to effectively improve the feature fusion performances of the proposed multi-energy load prediction model. The effectiveness of the proposed short-term prediction model was confirmed by the experimental results obtained using the multi-energy load time-series data of an actual integrated energy system.
RESUMO
Post-synthetic modification can be used for structural replacement or functional modification of materials after they have been formed or assembled. It can effectively combine various modification methods for metal-organic frameworks (MOFs) such as defect control, replacement of metal sites, or functionalization of ligands. In this work, organic ligands that incorporate N-functionalities or amino groups were introduced into defective UiO-66 through post-synthetic ligand exchange (PSE) to improve its water adsorption performance. Parameters such as water adsorption capacity, half adsorption value (α), and Henry constant KH were used to characterize the water adsorption performance. After PSE, new ligands in different molar ratios entered the skeleton of UiO-66. The N sites or amino groups on the ligands provided new sites for the adsorption of water molecules. The water adsorption capacity and hydrophilicity of all samples were significantly superior to those of LD-UiO-66, which had almost no defects. H-UiO-66-PyDC samples exhibited the highest ligand replacement ratio and a significant enhancement of water adsorption performance. Compared to the unchanged H-UiO-66, the water uptake of H-UiO-66-PyDC increased from 0.08 g g-1 to 0.23 g g-1 at P/P0 = 0.30 and α decreased from 0.36 to 0.28. After 20 water adsorption/desorption tests, the water uptake of all samples did not decrease, showing excellent cycling stability. These results suggest that the combination of defect modulation and PSE is a potential tool to make UiO-66 more appropriate for applications based on reversible adsorption.
RESUMO
Mitochondrial dysfunction has pleiotropic effects and is frequently caused by mitochondrial DNA mutations. However, factors such as significant variability in clinical manifestations make interpreting the pathogenicity of variants in the mitochondrial genome challenging. Here, we present APOGEE 2, a mitochondrially-centered ensemble method designed to improve the accuracy of pathogenicity predictions for interpreting missense mitochondrial variants. Built on the joint consensus recommendations by the American College of Medical Genetics and Genomics/Association for Molecular Pathology, APOGEE 2 features an improved machine learning method and a curated training set for enhanced performance metrics. It offers region-wise assessments of genome fragility and mechanistic analyses of specific amino acids that cause perceptible long-range effects on protein structure. With clinical and research use in mind, APOGEE 2 scores and pathogenicity probabilities are precompiled and available in MitImpact. APOGEE 2's ability to address challenges in interpreting mitochondrial missense variants makes it an essential tool in the field of mitochondrial genetics.
Assuntos
Aminoácidos , Mutação de Sentido Incorreto , Humanos , Mutação , Aprendizado de Máquina , Mitocôndrias/genéticaRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed mitochondrial gene expression in nasopharyngeal and autopsy tissues from patients with coronavirus disease 2019 (COVID-19). In nasopharyngeal samples with declining viral titers, the virus blocked the transcription of a subset of nuclear DNA (nDNA)-encoded mitochondrial OXPHOS genes, induced the expression of microRNA 2392, activated HIF-1α to induce glycolysis, and activated host immune defenses including the integrated stress response. In autopsy tissues from patients with COVID-19, SARS-CoV-2 was no longer present, and mitochondrial gene transcription had recovered in the lungs. However, nDNA mitochondrial gene expression remained suppressed in autopsy tissue from the heart and, to a lesser extent, kidney, and liver, whereas mitochondrial DNA transcription was induced and host-immune defense pathways were activated. During early SARS-CoV-2 infection of hamsters with peak lung viral load, mitochondrial gene expression in the lung was minimally perturbed but was down-regulated in the cerebellum and up-regulated in the striatum even though no SARS-CoV-2 was detected in the brain. During the mid-phase SARS-CoV-2 infection of mice, mitochondrial gene expression was starting to recover in mouse lungs. These data suggest that when the viral titer first peaks, there is a systemic host response followed by viral suppression of mitochondrial gene transcription and induction of glycolysis leading to the deployment of antiviral immune defenses. Even when the virus was cleared and lung mitochondrial function had recovered, mitochondrial function in the heart, kidney, liver, and lymph nodes remained impaired, potentially leading to severe COVID-19 pathology.
Assuntos
COVID-19 , Cricetinae , Humanos , Animais , Camundongos , COVID-19/patologia , SARS-CoV-2 , Roedores , Genes Mitocondriais , Pulmão/patologiaRESUMO
Autophagy is a major means for the elimination of protein inclusions in neurons in neurodegenerative diseases such as Parkinson's disease (PD). Yet, the mechanism of autophagy in the other brain cell type, glia, is less well characterized and remains largely unknown. Here, we present evidence that the PD risk factor, Cyclin-G-associated kinase (GAK)/Drosophila homolog Auxilin (dAux), is a component in glial autophagy. The lack of GAK/dAux increases the autophagosome number and size in adult fly glia and mouse microglia, and generally up-regulates levels of components in the initiation and PI3K class III complexes. GAK/dAux interacts with the master initiation regulator UNC-51like autophagy activating kinase 1/Atg1 via its uncoating domain and regulates the trafficking of Atg1 and Atg9 to autophagosomes, hence controlling the onset of glial autophagy. On the other hand, lack of GAK/dAux impairs the autophagic flux and blocks substrate degradation, suggesting that GAK/dAux might play additional roles. Importantly, dAux contributes to PD-like symptoms including dopaminergic neurodegeneration and locomotor function in flies. Our findings identify an autophagy factor in glia; considering the pivotal role of glia under pathological conditions, targeting glial autophagy is potentially a therapeutic strategy for PD.
Assuntos
Proteínas de Drosophila , Doença de Parkinson , Animais , Camundongos , Drosophila/metabolismo , Auxilinas/metabolismo , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Autofagia , Ciclinas/metabolismo , Neuroglia/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas de Membrana/metabolismoRESUMO
PURPOSE: The optimal method for achieving proper graft tension during patellofemoral ligament reconstruction is a topic of debate. In the past, a digital tensiometer was used to simulate the knee structure, and a tension of approximately 2N was identified as suitable for restoring the patellofemoral track. However, it is unclear whether this tension level is sufficient during the actual surgery. The objective of this study was to verify the efficacy of graft tension using a digital tensiometer for medial patellofemoral ligament (MPFL) reconstruction and to conduct a mid-term follow-up. METHODS: The study enrolled 39 patients who had experienced recurrent patellar dislocation. Preoperative computed tomography scans and X-rays confirmed patellar instability, patellar tilt angle patellar congruence angle and the history of dislocation and patellar apprehension test. Knee function was evaluated using preoperative and postoperative Lysholm and Kujala scores. RESULTS: The study included 39 knees, comprising 22 females and 17 males, with an average age of 21.10 ± 7.26. The patients were followed up for at least 24 months through telephone or face-to-face questionnaires. All patients had a preoperative history of ≥2 patellar dislocations, none of which were surgically treated. During surgery, all patients underwent isolated MPFL reconstruction and lateral retinacula release. The mean Kujala and Lysholm scores were 91.28 ± 4.90 and 90.67 ± 5.15, respectively. The mean PTA and PCA were 11.5 ± 2.63 and 2.38 ± 3.58, respectively. The study found that a tension of approximately 27.39 ± 5.57N (14.3-33.5N) was required to restore the patellofemoral track in patients with recurrent patellar dislocation. No patients required reoperation during the follow-up period. Overall, 36 out of 39 patients (92.31%) reported no pain when completing daily activities at the last follow-up. CONCLUSION: In conclusion, a tension level of approximately 27.39 ± 5.57N is necessary to restore normal patellofemoral relationships during clinical practice, which indicates that using a tension of 2N is too low. The use of a tensiometer during patellofemoral ligament reconstruction is a more accurate and reliable surgical procedure for treating recurrent patellar dislocation.
Assuntos
Instabilidade Articular , Luxação Patelar , Articulação Patelofemoral , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Luxação Patelar/diagnóstico por imagem , Luxação Patelar/cirurgia , Articulação Patelofemoral/diagnóstico por imagem , Articulação Patelofemoral/cirurgia , Seguimentos , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/cirurgia , Ligamentos Articulares/cirurgiaRESUMO
Transcriptional enhancers have been extensively characterized, but cis-regulatory elements involved in acute gene repression have received less attention. Transcription factor GATA1 promotes erythroid differentiation by activating and repressing distinct gene sets. Here, we study the mechanism by which GATA1 silences the proliferative gene Kit during murine erythroid cell maturation and define stages from initial loss of activation to heterochromatinization. We find that GATA1 inactivates a potent upstream enhancer but concomitantly creates a discrete intronic regulatory region marked by H3K27ac, short noncoding RNAs, and de novo chromatin looping. This enhancer-like element forms transiently and serves to delay Kit silencing. The element is ultimately erased via the FOG1/NuRD deacetylase complex, as revealed by the study of a disease-associated GATA1 variant. Hence, regulatory sites can be self-limiting by dynamic co-factor usage. Genome-wide analyses across cell types and species uncover transiently active elements at numerous genes during repression, suggesting that modulation of silencing kinetics is widespread.