RESUMEN
Chronic stress-induced epinephrine (EPI) accelerates breast cancer progression and metastasis, but the molecular mechanisms remain unclear. Herein, we found a strong positive correlation between circulating EPI levels and the tumoral expression of ubiquitin-specific peptidase 22 (USP22) in patients with breast cancer. USP22 facilitated EPI-induced breast cancer progression and metastasis by enhancing adipose triglyceride lipase (ATGL)-mediated lipolysis. Targeted USP22 deletion decreased ATGL expression and lipolysis, subsequently inhibiting EPI-mediated breast cancer lung metastasis. USP22 acts as a bona fide deubiquitinase for the Atgl gene transcription factor FOXO1, and EPI architects a lipolysis signaling pathway to stabilize USP22 through AKT-mediated phosphorylation. Notably, USP22 phosphorylation levels are positively associated with EPI and with downstream pathways involving both FOXO1 and ATGL in breast cancers. Pharmacological USP22 inhibition synergized with ß-blockers in treating preclinical xenograft breast cancer models. This study reveals a molecular pathway behind EPI's tumor-promoting effects and provides a strong rationale for combining USP22 inhibition with ß-blockers to treat aggressive breast cancer.
Asunto(s)
Neoplasias de la Mama , Epinefrina , Lipólisis , Ubiquitina Tiolesterasa , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/tratamiento farmacológico , Lipólisis/efectos de los fármacos , Femenino , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Epinefrina/metabolismo , Humanos , Animales , Ratones , Línea Celular Tumoral , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Lipasa/metabolismo , Lipasa/genética , Transducción de Señal/efectos de los fármacos , Metástasis de la Neoplasia , Fosforilación , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , AciltransferasasRESUMEN
The live attenuated hepatitis A virus vaccine H2 strain was developed by passaging a wild- type H2w isolate in cell cultures. Currently, the mechanism underlying its attenuation phenotype remain largely unknown. In this study, we generated a full-length infectious cDNA clone of the H2 strain using in-fusion techniques. The recovered H2 strain (H2ic) from the cDNA clone exhibited an efficient replication in both the hepatoma cell line Huh7.5.1 and the 2BS cell line used for vaccine production, similar to the parental H2 strain. Additionally, H2ic did not cause disease in Ifnar1-/- C57 mice, consistent with the H2 strain. To explore the cell-adaptive mutations of the H2 strain, chimeric viruses were generated by replacing its non-structural proteins with corresponding regions from H2w using the infectious cDNA clone as a genetic backbone. The chimeric viruses carrying the 3C or 3D proteins from H2w showed decreased replication in Huh7.5.1 and 2BS cell lines compared to H2ic. Other chimeric viruses containing the 2B, 2C, or 3A proteins from H2w failed to be recovered. Furthermore, there were no significant differences in disease manifestation in mice between H2ic and the recovered chimeric viruses. These results demonstrate that adaptive mutations in the 2B, 2C, and 3A proteins are essential for efficient replication of the H2 strain in cell cultures. Mutations in the 3C and 3D proteins contribute to enhanced replication in cell cultures but did not influence the attenuated phenotypes in mice. Together, this study presents the first reverse genetic system of the H2 strain and identifies viral proteins essential for adaptation to cell cultures.
RESUMEN
OBJECTIVE: Chronic low back pain (cLBP) affects nociceptive responses in the cerebellum, which leads to increased pain perception and sensorimotor control dysfunction. This study aimed to investigate altered functional connectivity in the anterior and posterior lobes of the cerebellum during cLBP. DESIGN: Twenty patients with cLBP and 18 healthy participants underwent 3.0 T resting-state functional magnetic resonance imaging. The bilateral lobule V of the anterior cerebellum and Crus I of the posterior cerebellum were selected as the region of interest for identifying the corresponding networks. RESULTS: The left lobule V had a greater intrinsic connectivity with the left insular cortex, left orbitofrontal cortex, and bilateral medial prefrontal cortex in patients with cLBP. In contrast, the right lobule V and bilateral Crus I had a significantly decreased connectivity with the contralateral multimodal cerebral networks, including the default mode network, salience network, and emotional network. CONCLUSION: The cerebellum had mechanistic implications in pain-related changes, which are involved in motor control, cognition, and emotion processing. These findings provide a novel perspective on the role of functional subregions in cLBP, which add to the growing body of evidence that the cerebellum can be a potential target for noninvasive brain stimulation for chronic pain treatment.
RESUMEN
Frequent blasting disruptions can lead to cumulative damage within the cemented tailing backfill (CTB), increasing the risks associated with mining operations and reducing the recovery rate of the pillar. To address this issue, the Split Hopkinson Pressure Bar (SHPB) was utilized to conduct cyclic impact tests on CTB containing various cement tailing ratios (CTR) at different curing ages. The tests analyzed the stress-strain curve law, dynamic compressive strength (DCS), dynamic strength increase factor (DIF), absorption energy, and deformation failure characteristics of CTB under different impact velocities. Additionally, nuclear magnetic resonance (NMR) and scanning electron microscopy (SEM) were employed to investigate the internal pore structural properties of CTB. The research findings indicate that (1) Average strain rate exhibits a linear relationship with the DCS and impact velocity. A lower number of impacts occurred at higher impact velocities and shorter curing age. The number of impacts was drastically reduced when the impact velocity surpassed 3 m/s. As the CTR increased, the number of impacts also increased. When the number of impacts increased, the elastic modulus, dynamic impact strength, and peak strain initially increased before ultimately decreasing. (2) Under the cyclic impact load, the shear failure and axial splitting failure were the main failure modes of CTB. Increasing the CTR may be a more effective strategy for reducing the degree of CTB fragmentation compared to prolonging the curing age. When the impact velocity is lower than 3 m/s, CTB can withstand multiple impacts and maintain high levels of integrity. When the DIF of the first shock is below 1.5, the CTB demonstrates a capability to withstand more than four shocks. If the DIF exceeds 2, the CTB can only endure a single shock. (3) NMR and SEM observations revealed that CTB itself contains more pores. A dense network structure will grow inside CTB as the curing age and CTR are increased, reducing the porosity. The pore size observed in the samples also support that increasing CTR may be a more effective strategy. Our findings contribute to a better understanding of the kinetic response of CTB in deep mines under frequent blasting disruption and offer a valuable reference point for future research in this area.
Asunto(s)
Fuerza Compresiva , Microscopía Electrónica de Rastreo , Ensayo de MaterialesRESUMEN
PURPOSE: To investigate the prognostic significance of lymphovascular invasion in invasive breast cancer and the value of using specific vascular endothelial markers to further classify lymphovascular invasion. METHODS: We collected 2124 patients with invasive breast cancer who were hospitalized at the First Hospital of Dalian Medical University from 2012 to 2020. Statistical methods were used to investigate the relationship between lymphovascular invasion and clinicopathological characteristics of breast cancer, and the correlation between lymphovascular invasion on overall survival (OS) and disease-free survival (DFS) of various categories of breast cancers. Immunohistochemical staining of breast cancer samples containing lymphovascular invasion using specific vascular endothelial markers D2-40 and CD34 was used to classify lymphovascular invasion and to investigate the relationship between lymphovascular invasion and breast cancer progression. RESULTS: There was a high correlation between lymphovascular invasion and T stage, N stage and nerve invasion. Survival analyses showed that patients with lymphovascular invasion, especially luminal B, triple-negative, and Her-2 overexpression breast cancer patients, had poorer OS and DFS prognosis, and that lymphovascular invasion was an independent prognostic factor affecting OS and DFS in breast cancer. The immunohistochemical staining results showed that positive D2-40 staining of lymphovascular invasion was linked to the N stage and localized recurrence of breast cancer. CONCLUSION: Lymphovascular invasion is associated with aggressive clinicopathological features and is an independent poor prognostic factor in invasive breast cancer. Breast cancer localized recurrence rate and lymph node metastases are influenced by lymphatic vessel invasion. Immunohistochemical techniques should be added to the routine diagnosis of lymphovascular invasion.
Asunto(s)
Neoplasias de la Mama , Metástasis Linfática , Invasividad Neoplásica , Humanos , Femenino , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/clasificación , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Metástasis Linfática/patología , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Estadificación de Neoplasias , Recurrencia Local de Neoplasia/patología , Supervivencia sin Enfermedad , Receptor ErbB-2/metabolismo , Vasos Linfáticos/patologíaRESUMEN
Self-fermented oyster homogenates were prepared to investigate core microbes and their correlations with flavor formation mechanisms. Five bacterial and four fungal genera were identified. Correlation analysis showed that Saccharomyces cerevisiae, Kazachstania, and L. pentosus were core species for the flavor of fermented products. Four core microbes were selected for inoculation into homogenates. Twelve key aroma compounds with odor activity values >1 were identified by gas chromatography-mass spectrometry. L. plantarum and S. cerevisiae were beneficial for producing key aroma compounds such as 1-octen-3-ol, (E,Z)-2,6-nonadienal, and heptanal. Fermentation with four microbes resulted in significant increases in contents of Asp, Glu, Lys, inosine monophosphate, and guanosine monophosphate, which provided freshness and sweetness. Fermentation with four microbes resulted in high digestibility, antioxidant abilities, and zinc contents. This study has elucidated the mechanism of flavor formation by microbial action and provides a reference for targeted flavor control in fermented oyster products.
Asunto(s)
Bacterias , Crassostrea , Fermentación , Aromatizantes , Gusto , Animales , Crassostrea/microbiología , Crassostrea/metabolismo , Crassostrea/química , Aromatizantes/metabolismo , Aromatizantes/química , Bacterias/metabolismo , Bacterias/clasificación , Bacterias/aislamiento & purificación , Cromatografía de Gases y Espectrometría de Masas , Odorantes/análisis , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/química , Hongos/metabolismo , Hongos/clasificación , Compuestos Orgánicos Volátiles/metabolismo , Compuestos Orgánicos Volátiles/química , Compuestos Orgánicos Volátiles/análisis , Mariscos/análisis , Mariscos/microbiologíaRESUMEN
Objective:To evaluate the outcomes following the use of folded supraclavicular flap repaired hypopharyngeal combined neck skin defects. Methods:Folded supraclavicular flap were designed to repaired four cases of hypopharyngeal combined neck skin defects patients. Evaluate their repair effect ï¼3 men,1 woman; mean age:66 yearsï¼. Hypopharyngeal fistula from 3.2 cm×1.8 cm to 4.5 cm×3.8 cm,skin defects in the neck from 3.8 cm×2.2 cm to 5.1 cm×4.5 cm. The folded supraclavicular flap from 8 cm×5 cm to 13 cm×9 cm. Results:All flaps survived, head and neck appearance was satisfactory, and no patient experienced a major complication. All patients resumed an oral diet function. No fistula recurrence or stricture developed after 6-19 months of follow-up. Conclusion:The folded supraclavicular flap is a safe and effective flap Repaired for hypopharyngeal combined neck skin defects.
Asunto(s)
Fístula , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos , Masculino , Femenino , Humanos , Anciano , Colgajos Quirúrgicos , Cuello/cirugía , Trasplante de Piel , Cabeza/cirugía , Fístula/cirugía , Traumatismos de los Tejidos Blandos/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Motor control exercise (MCE) effectively alleviates nonspecific chronic low back pain (CLBP), but the neural mechanisms underlying this phenomenon are poorly understood. OBJECTIVE: To study MCE's neural mechanisms in patients with CLBP by resting-state functional magnetic resonance imaging (rs-fMRI). STUDY DESIGN: A prospective, single-blind, randomized, controlled trial. SETTING: Department of Rehabilitation Medicine, The First Affiliated Hospital, Sun Yat-sen University. METHODS: 58 patients were randomly assigned to either the MCE or the Manual Therapy (MT) group. Before and after treatment, all the patients underwent ultrasound imaging to measure transversus abdominis (TrA) activation, rs-fMRI scans and questionnaire assessments. We analyzed the activation and connectivity of the bilateral precuneus based on the fractional amplitude of low-frequency fluctuation (fALFF) and effective connectivity (EC) analyses. Further, we determined the association between imaging and clinical measures. RESULTS: Pain intensity, pain catastrophizing, and pain-related disability were alleviated significantly in both groups post-treatment. However, the MCE group showed a greater reduction in pain-related disability and a better improvement in activation of the right TrA than the MT group. After MCE, patients showed an increase in regional fALFF values in the key node of the default mode network (bilateral precuneus) and decreased EC from the bilateral precuneus to the key node of the frontoparietal network (the left dorsolateral prefrontal cortex (DLPFC)). The pre-to-post-treatment change in the EC from bilateral precuneus into the left DLPFC was significantly correlated with the pre-to-post-treatment change in visual analog scale scores and activation of the right TrA in the MCE group (r = 0.765, P < 0.001 and r = 0.481 and P = 0.043 respectively). LIMITATIONS: The present study showes the correlation between the alteration of brain functions and CLBP-related symptoms, which does not reveal the causal effect between them. Further, this study does not estimate the long-term efficacy of MCE on brain function, and the sample size was not calculated based on fMRI data. CONCLUSION: These findings demonstrate that MCE may alleviate CLBP symptoms in patients by modifying information transmission from the default mode network to the left frontoparietal network.
Asunto(s)
Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/terapia , Red en Modo Predeterminado , Estudios Prospectivos , Método Simple Ciego , Plasticidad NeuronalRESUMEN
BACKGROUND: Treatment for cancer patients presenting with acute myocardial infarction (AMI) remains challenging. The objective of the study was to investigate the safety and efficiency of drug eluting balloon (DEB) versus drug eluting stent (DES) in this high-risk group. METHODS: Between 1st January 2017 and 1st January 2022, cancer patients admitted to Beijing Chaoyang Hospital with AMI were retrospectively enrolled. The primary endpoint was major adverse cardiovascular event (MACE). The secondary endpoints included major bleeding events, heart failure and cardiac complications. RESULTS: A total of 164 cancer patients presenting with AMI were included in the final analysis. Patients treated with DEB had a numerically lower rate of MACE than those treated with DES during a median follow-up of 21.8 months (22.9% vs. 37.1%, p = 0.23). Patients treated with DEB had a trend towards lower rate of major bleeding events than patients treated with DES (6.3% vs. 18.1%, HR 2.96, 95% CI [0.88, 9.92], p = 0.08). There were no significant differences between the two groups with regards to the rate of heart failure (4.2% vs. 9.5%, p = 0.32) and cardiac complications (0.0% vs. 2.6%, p = 0.56). CONCLUSIONS: The present study demonstrated that in cancer patients with AMI, DEB had a trend towards lower rate of major bleeding events and a numerically lower rate of MACE compared with DES.
Asunto(s)
Stents Liberadores de Fármacos , Insuficiencia Cardíaca , Infarto del Miocardio , Neoplasias , Humanos , Stents Liberadores de Fármacos/efectos adversos , Estudios Retrospectivos , Infarto del Miocardio/cirugía , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Hospitalización , Neoplasias/complicacionesRESUMEN
Flocculation is important in the thickening process to improve the underflow concentration in thickeners for tailing suspensions. Traditional zone settling velocity (ZSV) functions ignore the effect of flocculant dosage on the ZSV and the thickening behavior of thickeners. To investigate the effect of flocculant dosage on the settling flux function, a series of batch settling tests were conducted at various flocculant dosages for unclassified and fine tailings. The correlation among flocculant dosage, solid fraction, and parameters in the ZSV function was revealed. Moreover, a simulation of continuous thickening based on the ZSV function was performed. Results indicated that flocculation influenced settling velocity and floc density. With an increased flocculant dosage, the settling velocity of floc increased, resulting in increased underflow concentration. Conversely, floc density decreased due to a stronger particle-particle interaction, leading to a decreased underflow concentration.
Asunto(s)
Bioensayo , Suspensiones , Tamaño de la Partícula , FloculaciónRESUMEN
BACKGROUND: Whether there are differences among the new-generation transcatheter aortic valve implantation (TAVI) devices for patients with aortic stenosis remains unclear. The aim of the study was to compare the efficiency and safety of different new-generation TAVI devices for patients with aortic stenosis. MATERIALS AND METHODS: A comprehensive search of PubMed, Embase and Web of Science from their inception to 1 February 2022. Randomized clinical trials and observational studies that compared two or more different TAVI devices were enroled. Pairwise meta-analysis and frequentist network meta-analysis were conducted to pool the outcome estimates of interest. RESULTS: A total of 79 studies were finally included. According to the surface under the cumulative ranking, the top two ranked valves for lower rates of events were as follows: direct flow medical (DFM) (4.6%) and Lotus (48.8%) for lower rate of device success; Sapien 3 (16.8%) and DFM (19.7%) for lower mortality; DFM (8.6%) and Sapien 3 (25.5%) for lower rates of stroke; Evolut (27.6%) and DFM (35.8%) for lower rates of major and life-threatening bleeding; Portico (22.6%) and Sapien 3 (41.9%) for lower rates of acute kidney injury; Acurate (8.6%) and DFM (13.2%) for lower rates of permanent pacemaker implantation; Lotus (0.3%) and Sapien 3 (22.7%) for lower rates of paravalvular leak; Evolut (1.4%) and Portico (29.1%) for lower rates of mean aortic valve gradients. CONCLUSIONS: The findings of the present study suggested that the device success rates were comparable among these new-generation valves except for DFM. After excluding DFM, Sapien 3 might be the best effective for decreased mortality and stroke; Lotus might be the best effective for decreased paravalvular leak; Evolut might be the best effective for decreased major and life-threatening bleeding and mean aortic valve gradients; Acurate and Portico might be the best effective for decreased permanent pacemaker implantation and acute kidney injury, respectively.
Asunto(s)
Lesión Renal Aguda , Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Accidente Cerebrovascular , Reemplazo de la Válvula Aórtica Transcatéter , Humanos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Válvula Aórtica/cirugía , Metaanálisis en Red , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Diseño de Prótesis , Índice de Severidad de la Enfermedad , Estenosis de la Válvula Aórtica/cirugíaRESUMEN
This study aimed to investigate the role of the gut microbiota (GM)-bile acid (BA)-fibroblast growth factor (FGF) 19 axis in patients with atrial fibrillation (AF). Gut bacterial metabolisms of BAs were determined in an AF metagenomic dataset. The composition of faecal BAs pools was characterized by targeted metabolomics in an independent AF cross-sectional cohort. Circulating levels of FGF19 were measured by ELISA. In vitro cell experiments were conducted to validate the regulatory role of FGF19 in atrial cardiomyocytes stimulated with palmitic acid. First, metagenomic profiling revealed that gut microbial biotransformation from primary to secondary BAs was dysregulated in AF patients. Second, the proportion of secondary BAs decreased in the faeces of patients with AF. Also, eight BAs were identified as AF-associated BAs, including seven AF-enriched BAs (ursodeoxycholic acid, chenodeoxycholic acid, etc.), and AF-decreased dehydrolithocholic acid. Third, reduced levels of circulating FGF19 were observed in patients with AF. Subsequently, FGF19 was found to protect against palmitic acid-induced lipid accumulation and dysregulated signalling in atrial cardiomyocytes, including attenuated phosphorylation of YAP and Ca2+ /calmodulin-dependent protein kinases II and secretion of interleukin-1ß, mediated via peroxisome proliferator-activated receptor α. Our data found decreased levels of secondary BAs and circulating FGF19, resulting in the impaired protective function of FGF19 against lipid accumulation in atrial cardiomyocytes.
Asunto(s)
Fibrilación Atrial , Microbioma Gastrointestinal , Humanos , Ácidos y Sales Biliares , Estudios Transversales , Ácido Palmítico , Factores de Crecimiento de Fibroblastos/metabolismoRESUMEN
Genome cyclization is essential for viral RNA (vRNA) replication of the vertebrate-infecting flaviviruses, and yet its regulatory mechanisms are not fully understood. Yellow fever virus (YFV) is a notorious pathogenic flavivirus. Here, we demonstrated that a group of cis-acting RNA elements in YFV balance genome cyclization to govern efficient vRNA replication. It was shown that the downstream of the 5'-cyclization sequence hairpin (DCS-HP) is conserved in the YFV clade and is important for efficient YFV propagation. By using two different replicon systems, we found that the function of the DCS-HP is determined primarily by its secondary structure and, to a lesser extent, by its base-pair composition. By combining in vitro RNA binding and chemical probing assays, we found that the DCS-HP orchestrates the balance of genome cyclization through two different mechanisms, as follows: the DCS-HP assists the correct folding of the 5' end in a linear vRNA to promote genome cyclization, and it also limits the overstabilization of the circular form through a potential crowding effect, which is influenced by the size and shape of the DCS-HP structure. We also provided evidence that an A-rich sequence downstream of the DCS-HP enhances vRNA replication and contributes to the regulation of genome cyclization. Interestingly, diversified regulatory mechanisms of genome cyclization, involving both the downstream of the 5'-cyclization sequence (CS) and the upstream of the 3'-CS elements, were identified among different subgroups of the mosquito-borne flaviviruses. In summary, our work highlighted how YFV precisely controls the balance of genome cyclization to ensure viral replication. IMPORTANCE Yellow fever virus (YFV), the prototype of the Flavivirus genus, can cause devastating yellow fever disease. Although it is preventable by vaccination, there are still tens of thousands of yellow fever cases per year, and no approved antiviral medicine is available. However, the understandings about the regulatory mechanisms of YFV replication are obscure. In this study, by a combination of bioinformatics, reverse genetics, and biochemical approaches, it was shown that the downstream of the 5'-cyclization sequence hairpin (DCS-HP) promotes efficient YFV replication by modulating the conformational balance of viral RNA. Interestingly, we found specialized combinations for the downstream of the 5'-cyclization sequence (CS) and upstream of the 3'-CS elements in different groups of the mosquito-borne flaviviruses. Moreover, possible evolutionary relationships among the various downstream of the 5'-CS elements were implied. This work highlighted the complexity of RNA-based regulatory mechanisms in the flaviviruses and will facilitate the design of RNA structure-targeted antiviral therapies.
Asunto(s)
Replicación Viral , Virus de la Fiebre Amarilla , Animales , Humanos , Ciclización , ARN Viral/metabolismo , Replicación Viral/genética , Fiebre Amarilla/virología , Virus de la Fiebre Amarilla/metabolismo , Genoma Viral/genética , Línea Celular , Cricetinae , Mesocricetus , Células A549RESUMEN
The Zika virus (ZIKV) represents an important global health threat due to its unusual association with congenital Zika syndrome. ZIKV strains are phylogenetically grouped into the African and Asian lineages. However, the viral determinants underlying the phenotypic differences between the lineages remain unknown. Here, multiple sequence alignment revealed a highly conserved residue at position 21 of the premembrane (prM) protein, which is glutamic acid and lysine in the Asian and African lineages, respectively. Using reverse genetics, we generated a recombinant virus carrying an E21K mutation based on the genomic backbone of the Asian lineage strain FSS13025 (termed E21K). The E21K mutation significantly increased viral replication in multiple neural cell lines with a higher ratio of M to prM production. Animal studies showed E21K exhibited increased neurovirulence in suckling mice, leading to more severe defects in mouse brains by causing more neural cell death and destruction of hippocampus integrity. Moreover, the E21K substitution enhanced neuroinvasiveness in interferon alpha/beta (IFN-α/ß) receptor knockout mice, as indicated by the increased mortality, and enhanced replication in mouse brains. The global transcriptional analysis showed E21K infection profoundly altered neuron development networks and induced stronger antiviral immune response than wild type (WT) in both neural cells and mouse brains. More importantly, the reverse K21E mutation based on the genomic backbone of the African strain MR766 caused less mouse neurovirulence. Overall, our findings support the 21st residue of prM functions as a determinant for neurovirulence and neuroinvasiveness of the African lineage of ZIKV. IMPORTANCE The suspected link of Zika virus (ZIKV) to birth defects led the World Health Organization to declare ZIKV a Public Health Emergency of International Concern. ZIKV has been identified to have two dominant phylogenetic lineages, African and Asian. Significant differences exist between the two lineages in terms of neurovirulence and neuroinvasiveness in mice. However, the viral determinants underlying the phenotypic differences are still unknown. Here, combining reverse genetics, animal studies, and global transcriptional analysis, we provide evidence that a single E21K mutation of prM confers to the Asian lineage strain FSS130125 significantly enhanced replication in neural cell lines and more neurovirulent and neuroinvasiveness phenotypes in mice. Our findings support that the highly conserved residue at position 21 of prM functions as a determinant of neurovirulence and neuroinvasiveness of the African lineage of ZIKV in mice.
Asunto(s)
Infección por el Virus Zika , Virus Zika , Animales , Ratones , Filogenia , Replicación Viral , Línea CelularRESUMEN
BACKGROUND: The purpose of this study was to determine the value of ultrasound elastic imaging (UE) in the differential diagnosis of the 3 negative breast cancer (TNBC) and non-TNBC. METHODS: We searched the PubMed, Cochrane Library, and CBM databases from inception to July 20, 2022 and used STATA version 14.0 and Meta-Disc version 1.4 software. We computed summary statistics for sensitivity (Sen), specificity, positive and negative likelihood ratio (LR+/LR-), diagnostic odds ratio, and summary receiver operating characteristic curves. Cochran Q-statistic and I2 test were used to assess potential heterogeneity between studies. Sen analysis was carried out to evaluate the effect of a single study on overall estimation. We also conducted a meta regression analysis to investigate potential sources of heterogeneity. RESULTS: Nine studies that fulfilled all the criteria for acceptance were incorporated into the meta-analysis. TNBC 317 and non-TNBC 1055 cases were evaluated. All breast tumors were histologically confirmed. The pooled Sen was 0.78 (95% confidence interval [CI] = 0.58-0.90); the pooled specificity was 0.86 (95%CI = 0.78-0.91). The pooled LR+ was 5.46 (95%CI = 3.07-9.73); the pooled negative LR- was 0.26 (95%CI = 0.12-0.55). The pooled diagnostic odds ratio of UE was 21.00 (95% CI = 6.14-71.78). The area under the summary receiver operating characteristic curve was 0.89 (SE = 0.0378). No evidence was found to reveal bias (t = 0.10, P = .92). CONCLUSION: Our meta-analysis showed that UE could have high diagnostic accuracy in distinguishing TNBC and non-TNBC.
Asunto(s)
Diagnóstico por Imagen de Elasticidad , Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/diagnóstico por imagen , Curva ROC , Ultrasonografía , Diagnóstico Diferencial , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The incidence of acute myocardial infarction (AMI) in the younger population has been increasing gradually in recent years. The objective of the present study is to investigate the safety and effectiveness of drug-eluting balloons (DEBs) in young patients with AMI. METHODS: All consecutive patients with AMI aged ≤ 45 years were retrospectively enrolled. The primary endpoint was a device-oriented composite endpoint (DOCE) of cardiac death, target vessel myocardial infarction (MI), or target lesion revascularization (TLR). The secondary study endpoints included heart failure and major bleeding events. RESULTS: A total of 276 young patients presenting with AMI were finally included. The median follow-up period was 1155 days. Patients treated with DEBs had a trend toward a lower incidence of DOCEs (3.0% vs. 11.0%, p = 0.12) mainly driven by the need for TLR (3.0% vs. 9.1%, p = 0.19) than those treated with DESs. No significant differences between the two groups were detected in the occurrence of cardiac death (0.0% vs. 0.5%, p = 0.69), MI (0.0% vs. 1.4%, p = 0.40), heart failure (0.0% vs. 1.9%, p = 0.39), or major bleeding events (1.5% vs 4.8%, p = 0.30). Multivariate regression analysis showed that DEBs were associated with a trend toward a lower risk of DOCEs (HR 0.13, 95% CI [0.02, 1.05], p = 0.06). CONCLUSIONS: The findings of the present study suggested that DEBs might be a potential treatment option in young patients with AMI. A larger scale, randomized, multicenter study is required to investigate the safety and effectiveness of DEBs in this setting.
RESUMEN
Low back pain is a major global public health problem, but the current intervention effect is not ideal. A large body of previous literature suggests that patients with chronic low back pain may have abnormal postural control, which is more evident in the dual task situation. In recent years, research on postural control in patients with low back pain under dual-task conditions has gradually become a hot topic. However, the results obtained from these studies were not entirely consistent. In this review, we summarized relevant studies on the performance of postural control in patients with low back pain under dual-task conditions, analyze it from the perspective of the theoretical model of dual-task interaction, the specific research paradigm of dual task, the performance of postural control, and the related factors affecting postural control performance, etc. It was reasonable to assume that patients with low back pain might have a certain degree of abnormal postural control, and this abnormality was affected by comprehensive factors such as age, cognitive resource capacity, attention needs, complex sensorimotor integration, external environment, etc. Furthermore, postural control performance in low back pain patients under dual-task conditions was further influenced by the nature and complexity of the different tasks. In general, the more attention resources were needed, the external environmental conditions were worse, and the age-related functions were degenerate, etc., the weaker posture control ability was. In short, a deeper understanding of postural control in patients with low back pain under dual-task conditions may shed light on more references for the rehabilitation and management of low back pain, as well as some new ideas for scientific research on cognition and postural control.