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Topological superfluidity is an important concept in electronic materials as well as ultracold atomic gases1. However, although progress has been made by hybridizing superconductors with topological substrates, the search for a material-natural or artificial-that intrinsically exhibits topological superfluidity has been ongoing since the discovery of the superfluid 3He-A phase2. Here we report evidence for a globally chiral atomic superfluid, induced by interaction-driven time-reversal symmetry breaking in the second Bloch band of an optical lattice with hexagonal boron nitride geometry. This realizes a long-lived Bose-Einstein condensate of 87Rb atoms beyond present limits to orbitally featureless scenarios in the lowest Bloch band. Time-of-flight and band mapping measurements reveal that the local phases and orbital rotations of atoms are spontaneously ordered into a vortex array, showing evidence of the emergence of global angular momentum across the entire lattice. A phenomenological effective model is used to capture the dynamics of Bogoliubov quasi-particle excitations above the ground state, which are shown to exhibit a topological band structure. The observed bosonic phase is expected to exhibit phenomena that are conceptually distinct from, but related to, the quantum anomalous Hall effect3-7 in electronic condensed matter.
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The Hippo signaling is instrumental in regulating organ size, regeneration, and carcinogenesis. The cytoskeleton emerges as a primary Hippo signaling modulator. Its structural alterations in response to environmental and intrinsic stimuli control Hippo signaling pathway activity. However, the precise mechanisms underlying the cytoskeleton regulation of Hippo signaling are not fully understood. RAP2 GTPase is known to mediate the mechanoresponses of Hippo signaling via activating the core Hippo kinases LATS1/2 through MAP4Ks and MST1/2. Here we show the pivotal role of the reciprocal regulation between RAP2 GTPase and the cytoskeleton in Hippo signaling. RAP2 deletion undermines the responses of the Hippo pathway to external cues tied to RhoA GTPase inhibition and actin cytoskeleton remodeling, such as energy stress and serum deprivation. Notably, RhoA inhibitors and actin disruptors fail to activate LATS1/2 effectively in RAP2-deficient cells. RNA sequencing highlighted differential regulation of both actin and microtubule networks by RAP2 gene deletion. Consistently, Taxol, a microtubule-stabilizing agent, was less effective in activating LATS1/2 and inhibiting cell growth in RAP2 and MAP4K4/6/7 knockout cells. In summary, our findings position RAP2 as a central integrator of cytoskeletal signals for Hippo signaling, which offers new avenues for understanding Hippo regulation and therapeutic interventions in Hippo-impaired cancers.
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Vía de Señalización Hippo , Proteínas Serina-Treonina Quinasas , Transducción de Señal , Animales , Humanos , Ratones , Citoesqueleto/metabolismo , Microtúbulos/metabolismo , Paclitaxel/farmacología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas de Unión al GTP rap/metabolismo , Proteínas de Unión al GTP rap/genética , Proteína de Unión al GTP rhoA/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , FosforilaciónRESUMEN
BACKGROUND: Malignant pleural effusion is mostly a complication of advanced malignant tumors. However, the cancer markers such as carbohydrate antigen 125 (CA 125), carbohydrate antigen 15-3 (CA 15-3), carbohydrate antigen 19-9 (CA 19-9), and cytokeratin fragment 21-1 (CYFRA 21-1) have low sensitivity and organ specificity for detecting malignant pleural effusion. RESEARCH QUESTION: Is IR808@MnO nano-near infrared fluorescent dye worthy for the diagnosis in differentiating benign and malignant pleural effusions. STUDY DESIGN AND METHODS: This experiment was carried out to design and characterize the materials for in vitro validation of the new dye in malignant tumor cells in the A549 cell line and in patients with adenocarcinoma pleural effusion. The dye was verified to possess tumor- specific targeting capabilities. Subsequently, a prospective hospital-based observational study was conducted, enrolling 106 patients and excluding 28 patients with unknown diagnoses. All patients underwent histopathological analysis of thoracoscopic biopsies, exfoliative cytological analysis of pleural fluid, and analysis involving the new dye. Statistical analyses were performed using Microsoft Excel, GraphPad Prism, and the R language. RESULTS: The size of IR808@MnO was 136.8 ± 2.9 nm, with peak emission at 808 nm, and it has near-infrared fluorescence properties. Notably, there was a significant difference in fluorescence values between benign and malignant cell lines (p < 0.0001). The malignant cell lines tested comprised CL1-5, A549, MDA-MB-468, U-87MG, MKN-7, and Hela, while benign cell lines were BEAS-2B, HUVEC, HSF, and VE. The most effective duration of action was identified as 30 min at a concentration of 5 µl. This optimal duration of action and concentration were consistent in patients with lung adenocarcinoma accompanied by pleural effusion and 5 µl. Of the 106 patients examined, 28 remained undiagnosed, 39 were diagnosed with malignant pleural effusions, and the remaining 39 with benign pleural effusions. Employing the new IR808@MnO staining method, the sensitivity stood at 74.4%, specificity at 79.5%, a positive predictive value of 69.2%, and a negative predictive value of 82.1%. The area under the ROC curve was recorded as 0.762 (95% CI: 0.652-0.872). The confusion matrix revealed a positive predictive value of 75.7%, a negative predictive value of 75.6%, a false positive rate of 22.5%, and a false negative rate of 26.3%. INTERPRETATION: The IR808@MnO fluorescent probe represents an efficient, sensitive, and user-friendly diagnostic tool for detecting malignant pleural fluid, underscoring its significant potential for clinical adoption.
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Neoplasias Pulmonares , Derrame Pleural Maligno , Derrame Pleural , Humanos , Derrame Pleural Maligno/diagnóstico , Colorantes Fluorescentes , Estudios Prospectivos , Derrame Pleural/diagnóstico por imagen , CarbohidratosRESUMEN
Mammalian cells are surrounded by neighbouring cells and extracellular matrix (ECM), which provide cells with structural support and mechanical cues that influence diverse biological processes1. The Hippo pathway effectors YAP (also known as YAP1) and TAZ (also known as WWTR1) are regulated by mechanical cues and mediate cellular responses to ECM stiffness2,3. Here we identified the Ras-related GTPase RAP2 as a key intracellular signal transducer that relays ECM rigidity signals to control mechanosensitive cellular activities through YAP and TAZ. RAP2 is activated by low ECM stiffness, and deletion of RAP2 blocks the regulation of YAP and TAZ by stiffness signals and promotes aberrant cell growth. Mechanistically, matrix stiffness acts through phospholipase Cγ1 (PLCγ1) to influence levels of phosphatidylinositol 4,5-bisphosphate and phosphatidic acid, which activates RAP2 through PDZGEF1 and PDZGEF2 (also known as RAPGEF2 and RAPGEF6). At low stiffness, active RAP2 binds to and stimulates MAP4K4, MAP4K6, MAP4K7 and ARHGAP29, resulting in activation of LATS1 and LATS2 and inhibition of YAP and TAZ. RAP2, YAP and TAZ have pivotal roles in mechanoregulated transcription, as deletion of YAP and TAZ abolishes the ECM stiffness-responsive transcriptome. Our findings show that RAP2 is a molecular switch in mechanotransduction, thereby defining a mechanosignalling pathway from ECM stiffness to the nucleus.
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Proteínas Serina-Treonina Quinasas/metabolismo , Transducción de Señal , Proteínas de Unión al GTP rap/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Transformación Celular Neoplásica , Matriz Extracelular/química , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Femenino , Proteínas Activadoras de GTPasa/metabolismo , Quinasas del Centro Germinal , Factores de Intercambio de Guanina Nucleótido/metabolismo , Células HEK293 , Vía de Señalización Hippo , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones , Ratones Endogámicos NOD , Ratones Desnudos , Ratones SCID , Proteínas del Tejido Nervioso/metabolismo , Fosfolipasa C gamma/metabolismo , Fosfoproteínas/metabolismo , Transactivadores , Factores de Transcripción , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Transcriptoma , Proteínas Señalizadoras YAP , Proteínas de Unión al GTP rap/genéticaRESUMEN
Understanding strongly correlated quantum materials, such as high-T_{c} superconductors, iron-based superconductors, and twisted bilayer graphene systems, remains as one of the outstanding challenges in condensed matter physics. Quantum simulation with ultracold atoms in particular optical lattices, which provide orbital degrees of freedom, is a powerful tool to contribute new insights to this endeavor. Here, we report the experimental realization of an unconventional Bose-Einstein condensate of ^{87}Rb atoms populating degenerate p orbitals in a triangular optical lattice, exhibiting remarkably long coherence times. Using time-of-flight spectroscopy, we observe that this state spontaneously breaks the rotational symmetry and its momentum spectrum agrees with the theoretically predicted coexistence of exotic stripe and loop-current orders. Like certain strongly correlated electronic systems with intertwined orders, such as high-T_{c} cuprate superconductors, twisted bilayer graphene, and the recently discovered chiral density-wave state in kagome superconductors AV_{3}Sb_{5} (A=K, Rb, Cs), the newly demonstrated quantum state, in spite of its markedly different energy scale and the bosonic quantum statistics, exhibits multiple symmetry breakings at ultralow temperatures. These findings hold the potential to enhance our comprehension of the fundamental physics governing these intricate quantum materials.
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BACKGROUND: Aspiration pneumonia in patients in immunocompetent populations is rare, and secondary pyothorax due to puncture operations during treatment has been reported rarely. METHODS: We report a confirmed case of aspiration pneumonia caused by Prevotella. The pathogen was detected and confirmed using percutaneous lung puncture and high-throughput next-generation sequencing (NGS). RESULTS: The patient developed secondary pyothorax, severe rash, and exacerbation of symptoms following the lung puncture. Finally, after adjusting the antibiotic regimen and performing chest drainage and washout, the patient's lesions were absorbed, symptoms improved, and the rash disappeared. CONCLUSIONS: Prevotella aspiration pneumonia can occur in immunocompetent individuals, and invasive bronchoscopic alveolar lavage may be considered as an option to reduce the risk of infectious organism translocation.
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Empiema Pleural , Exantema , Neumonía por Aspiración , Humanos , Pulmón/patología , Neumonía por Aspiración/etiología , Neumonía por Aspiración/patología , Punciones , Empiema Pleural/diagnóstico , Empiema Pleural/etiología , Exantema/patologíaRESUMEN
T- lymphoblastic leukemia/lymphoma (T-LL) is an aggressive malignancy of immature T-cells with poor overall survival (OS) and in need of new therapies. LIM-domain only 2 (LMO2) is a critical regulator of hematopoietic cell development that can be overexpressed in T-LL due to chromosomal abnormalities. Deregulated LMO2 expression contributes to T-LL development by inducing block of T-cell differentiation and continuous thymocyte self-renewal. However, LMO2 expression and its biologic significance in T-LL remain largely unknown. We analyzed LMO2 expression in 100 initial and follow-up biopsies of T-LL from 67 patients, including 31 (46%) early precursor T-cell (ETP)-ALL, 26 (39%) cortical and 10 (15%) medullary type. LMO2 expression was present in 50 (74.6%) initial biopsies with an average of 87% positive tumor cells (range 30-100%). LMO2 expression in ETP, medullary and cortical T-LLs was not statistically different. In patients with biopsies after initial therapy, LMO2 expression was stable. LMO2 expression was associated with longer OS (p = 0.048) regardless of T-lymphoblast stage or other clinicopathologic features. These findings indicate that LMO2 is a promising new prognostic marker that could predict patients' outcomes and potentially be targeted for novel chemotherapy, i.e. PARP1/2 inhibitors, which have been shown to enhance chemotherapy sensitivity in LMO2 expressing diffuse large B cell lymphoma (DLBCL) tumors by decreasing DNA repair efficiency.
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Proteínas con Dominio LIM , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Proteínas Adaptadoras Transductoras de Señales/genética , Humanos , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , Linfocitos T/patologíaRESUMEN
Hexagonal optical lattices offer a tunable platform to study exotic orbital physics in solid state materials. Here, we present a versatile high-precision scheme to implement a hexagonal optical lattice potential, which is engineered by overlapping two independent triangular optical sublattices generated by laser beams with slightly different wavelengths around 1064 nm. This enables us to precisely control the detailed structure of the hexagonal lattice by adjusting the relative position and the relative lattice depth of the two triangular optical sublattices. Taking advantage of the sensitive dependence of the second Bloch band on small lattice deformations, we propose a strategy to optimize the optical lattice geometry with an extremely high precision. This method can also be extended to other lattice configurations involving more than two sublattices. Our work provides the experimental requirements in the search for novel orbital physics of ultracold atoms, for example, in the flat p-band of the hexagonal optical lattice.
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Traditionally cultured monolayers of primary human hepatocytes (PHHs) deteriorate within days and thereby become unsuitable for drug-related studies. PHH spheroids (3D PHHs) maintain liver functions for weeks, but are considerably more demanding. Recently, a chemical-based approach (5C PHHs) succeeded in long-term culture of hepatocyte monolayers, but it remains unclear whether the drug-related functions are preserved. To clarify this, we compared the 5C and 3D PHHs in terms of gene expression analysis, proteomic analysis, functionality (basal and induced activities of representative CYP450 enzymes and urea and albumin secretions), survival in culture, and sensitivity to representative drugs. In all comparisons, which spanned culture durations of up to 4 weeks, the 5C PHHs performed at least as well as the 3D PHHs. Hence, the novel 5C PHH monolayer format combines the convenience of the traditional monolayer format with the functionality and maintainability of the spheroid format. Our results suggest that 5C PHH monolayers can be used more conveniently and efficiently for high-throughput drug screening, preclinical drug safety evaluations, and mechanistic studies.
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Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Hepatocitos/metabolismo , Preparaciones Farmacéuticas/metabolismo , Esferoides Celulares/metabolismo , Células Cultivadas , Hepatocitos/efectos de los fármacos , HumanosRESUMEN
BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with myelofibrosis (MF). Bone marrow (BM) morphologic evaluation of myelofibrosis following allo-HSCT is known to be challenging in this context because resolution of morphologic changes is a gradual process. PATIENTS AND METHODS: We compared BM samples of patients with myelofibrosis who underwent first allo-HSCT and achieved molecular remission by day 100 with BM samples of patients who continued to have persistent molecular evidence of disease following allo-HSCT. RESULTS: The study group included 29 patients: 17 primary MF, 7 post-polycythemia vera (PV) MF, and 5 post-essential thrombocythemia (ET) MF. In this cohort there were 18 JAK2 p.V617F, 8 CALR; 1 MPL, and 2 patients had concurrent JAK2 p.V617F and MPL mutations. The control group included 5 patients with primary MF, one with post-PV MF, one with post-ET MF (5 JAK2 p.V617F; 2 CALR). Following allo-HSCT, both groups showed reduction in BM cellularity and number of megakaryocytes. The study cohort also less commonly had dense megakaryocyte clusters and endosteal located megakaryocytes and showed less fibrosis. There was no statistical difference in BM cellularity, presence of erythroid islands, degree of osteosclerosis, or megakaryocyte number, size, nuclear lobation, presence of clusters or intrasinusoidal location. CONCLUSIONS: Following allo-HSCT at 100 days, morphologic evaluation of BM in patients with MF cannot reliably predict persistence versus clearance of molecular evidence of MF. Disappearance of BM MF, dense megakaryocyte clusters, and endosteal localization of megakaryocytes are suggestive of disease response.
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Médula Ósea/patología , Trasplante de Células Madre Hematopoyéticas , Mielofibrosis Primaria/patología , Adulto , Anciano , Femenino , Humanos , Janus Quinasa 2/genética , Masculino , Persona de Mediana Edad , Mielofibrosis Primaria/genética , Mielofibrosis Primaria/terapia , Resultado del TratamientoRESUMEN
The deafness-associated m.12201T>C mutation affects the A5-U68 base-pairing within the acceptor stem of mitochondrial tRNAHis The primary defect in this mutation is an alteration in tRNAHis aminoacylation. Here, we further investigate the molecular mechanism of the deafness-associated tRNAHis 12201T>C mutation and test whether the overexpression of the human mitochondrial histidyl-tRNA synthetase gene (HARS2) in cytoplasmic hybrid (cybrid) cells carrying the m.12201T>C mutation reverses mitochondrial dysfunctions. Using molecular dynamics simulations, we demonstrate that the m.12201T>C mutation perturbs the tRNAHis structure and function, supported by decreased melting temperature, conformational changes, and instability of mutated tRNA. We show that the m.12201T>C mutation-induced alteration of aminoacylation tRNAHis causes mitochondrial translational defects and respiratory deficiency. We found that the transfer of HARS2 into the cybrids carrying the m.12201T>C mutation raises the levels of aminoacylated tRNAHis from 56.3 to 75.0% but does not change the aminoacylation of other tRNAs. Strikingly, HARS2 overexpression increased the steady-state levels of tRNAHis and of noncognate tRNAs, including tRNAAla, tRNAGln, tRNAGlu, tRNALeu(UUR), tRNALys, and tRNAMet, in cells bearing the m.12201T>C mutation. This improved tRNA metabolism elevated the efficiency of mitochondrial translation, activities of oxidative phosphorylation complexes, and respiration capacity. Furthermore, HARS2 overexpression markedly increased mitochondrial ATP levels and membrane potential and reduced production of reactive oxygen species in cells carrying the m.12201T>C mutation. These results indicate that HARS2 overexpression corrects the mitochondrial dysfunction caused by the tRNAHis mutation. These findings provide critical insights into the pathophysiology of mitochondrial disease and represent a step toward improved therapeutic interventions for mitochondrial disorders.
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Aminoacil-ARNt Sintetasas/genética , Sordera/enzimología , Sordera/genética , Mitocondrias/enzimología , Mitocondrias/patología , Mutación/genética , ARN de Transferencia de Histidina/genética , Adenosina Trifosfato/metabolismo , Aminoacil-ARNt Sintetasas/química , Aminoacil-ARNt Sintetasas/metabolismo , Aminoacilación , Línea Celular , Respiración de la Célula , ADN Mitocondrial/metabolismo , Transporte de Electrón , Humanos , Potencial de la Membrana Mitocondrial , Proteínas Mitocondriales/metabolismo , Simulación de Dinámica Molecular , Conformación de Ácido Nucleico , Desnaturalización de Ácido Nucleico , Estabilidad del ARN/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , ARN de Transferencia de Histidina/química , ARN de Transferencia de Histidina/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Fracciones Subcelulares/metabolismoRESUMEN
Vortices play a leading role in many fascinating quantum phenomena. Here we generate a large number of vortices by thermally quenching a fermionic superfluid of ^{6}Li atoms in an oblate optical trap and study their annihilation dynamics and spatial distribution. Over a wide interaction range from the attractive to the repulsive side across the Feshbach resonance, these quasi-two-dimensional vortices are observed to follow algebraic scaling laws both in time and space, having exponents consistent with the two-dimensional universality. We further simulate the classical XY model on the square lattice by a Glauber dynamics and find good agreement between the numerical and experimental behaviors. Our work provides a direct demonstration of the universal 2D vortex dynamics.
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The mediastinum contains essentially all major intrathoracic organs except for the lungs. A variety of both benign and malignant tumors can involve the mediastinum, of which lymphoma is the most common malignancy. Compared to secondary mediastinal involvement by systemic lymphomas, primary mediastinal lymphomas are less common with several specific entities that are mainly confined to mediastinal lymph nodes, and/or thymus. This review will summarize the clinical, histologic, immunophenotypic and molecular genetic features of the most common and most aggressive primary mediastinal lymphomas as well as provide suggested immunohistochemistry panels and differential diagnoses.
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BACKGROUND: The study aimed to investigate the independent and combined effects of midpoint of sleep and night sleep duration on type 2 diabetes mellitus (T2DM) in areas with limited resources. METHODS: A total of 37,276 participants (14,456 men and 22,820 women) were derived from the Henan Rural Cohort Study. Sleep information was assessed based on the Pittsburgh Sleep Quality Index. Logistic regression models and restricted cubic splines were used to estimate the relationship of the midpoint of sleep and night sleep duration with T2DM. RESULTS: Of the 37,276 included participants, 3580 subjects suffered from T2DM. The mean midpoint of sleep among the Early, Intermediate and Late groups were 1:05 AM ±23 min, 1:56 AM ±14 min, and 2:57 AM ±34 min, respectively. Compared to the Intermediate group, adjusted odds ratios (ORs) and 95% confidence interval (CI) of T2DM were 1.13 (1.04-1.22) and 1.14 (1.03-1.26) in the Early group and the Late group. Adjusted OR (95% CI) for T2DM compared with the reference (7- h) was 1.28 (1.08-1.51) for longer (≥ 10 h) night sleep duration. The combination of late midpoint of sleep and night sleep duration (≥ 9 h) increased 38% (95% CI 10-74%) prevalence of T2DM. These associations were more obvious in women than men. CONCLUSIONS: Late and early midpoint of sleep and long night sleep duration were all associated with higher prevalence of T2DM. Meanwhile, midpoint of sleep and night sleep duration might have combined effects on the prevalence of T2DM, which provided potential health implications for T2DM prevention, especially in rural women. TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699 ). Date of registration: 2015-07-06.
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Diabetes Mellitus Tipo 2 , China/epidemiología , Estudios de Cohortes , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Masculino , Factores de Riesgo , Población Rural , SueñoRESUMEN
BACKGROUND: The study aimed to characterize the prevalence of alcohol consumption and further investigate the relationship between alcohol consumption and type 2 diabetes mellitus (T2DM). METHODS: We studied 39,259 participants aged 18 to 79 years of the Henan Rural Cohort study. The associations between alcohol consumption and T2DM were examined using the logistic regression models and restricted cubic spline. RESULTS: For men, alcohol abstinence was associated with an increased risk of T2DM (1.491(1.265, 1.758)), whereas current drinkers were not associated with T2DM (1.03(0.91, 1.15)). Further analysis of alcohol drinkers revealed that only high-risk drinkers of WHO drinking risk levels increased the risk of T2DM (1.289(1.061,1.566)) compared to never drinkers. The risk of T2DM increased as the age of starting to consume alcohol decreased and as the number of years of consuming alcohol and the alcohol intake increased only in men. We further found that the risk of T2DM decreased as the number of years of abstinence increases and no association between alcohol abstinence and T2DM was found after more than 10 years of abstinence among men. CONCLUSIONS: Our results suggested that reducing the amount of alcohol consumed and adhering to abstinence from alcohol consumption are beneficial in reducing the risk of T2DM. TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 2015-07-06. http://www.chictr.org.cn/showproj.aspx?proj=11375.
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Diabetes Mellitus Tipo 2 , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/epidemiología , China/epidemiología , Estudios de Cohortes , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Humanos , Masculino , Prevalencia , Factores de Riesgo , Población RuralRESUMEN
BACKGROUND: Previous reports about health-related quality of life (HRQoL) of type 2 diabetes mellitus (T2DM) concentrated on general patients rather than patients in rural areas with poor infrastructure and limited resources. Thus, the aims of this study were to evaluate the HRQoL of diabetics in the countryside and explore its influencing factors. METHODS: A total of 23 053 participants aged from 18 to 79 years were drawn from the Henan Rural Cohort Study for this cross-sectional study. The HRQoL of participants were assessed by utility index and VAS-score of European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L) instrument. Binary logistic regression, generalized linear and tobit regression models were used to estimate the potential influencing factors on HRQoL. RESULTS: This study (23 053 participants) included 2231 T2DM patients with a crude prevalence of 9.68%. The utility index and VAS-score in health group were 0.96 ± 0.10 and 78.85 ± 14.53, while in T2DM group were 0.93 ± 0.15 and 74.09 ± 16.09, respectively. In total, most diabetics reported problem about pain/discomfort dimension. Being old, poverty, low physical activity, and with comorbidities was negatively related to HRQoL of diabetics, while high educational level was positively related to HRQoL. CONCLUSION: HRQoL of rural T2DM patients depended on several sociodemographic factors. More attention should be paid to diabetics with poor socioeconomic status in rural areas. CLINICAL TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699) http://www.chictr.org.cn/showproj.aspx?proj=11375.
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Diabetes Mellitus Tipo 2 , Calidad de Vida , Adulto , China/epidemiología , Estudios de Cohortes , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Humanos , Población Rural , Encuestas y CuestionariosRESUMEN
BACKGROUND: Circular RNAs (circRNAs) have been shown to play a crucial role in tumorigenesis. In this study, we investigated the function of hsa_circ_0137008 and its underlying molecular mechanism in colorectal cancer (CRC). METHODS: Gene expression was conducted by quantitative real-time PCR or western blot. Functional experiments were performed by cell count kit-8, colony formation assay, wound healing, and transwell assays. Luciferase reporter assay and RNA pull-down assay were performed to investigate the molecular mechanism of hsa_circ_0137008 in CRC. In addition, the xenograft tumor model was applied to determine the role of hsa_circ_0137008 in vivo. RESULTS: Downregulation of hsa_circ_0137008 was observed in CRC tissues and cell lines. Functionally, overexpression of hsa_circ_0137008 inhibited the proliferation of CRC cells, as indicated by the inhibition of proliferative protein expression (Ki67 and PCNA), reduced cell viability and colony formation ability. Upregulation of hsa_circ_0137008 suppressed the migration, invasion, and epithelial to mesenchymal transition (EMT) of CRC cells. Mechanically, hsa_circ_0137008 negatively regulated the expression of microRNA-338-5p (miR-338-5p). Furthermore, hsa_circ_0137008 abated the miR-338-5p mediated promotion on CRC cell progression. Tumor suppressive function of hsa_circ_0137008 was validated in vivo. CONCLUSION: These findings highlighted the fact that overexpression of hsa_circ_0137008 inhibited the progression of CRC via sponging miR-338-5p, suggesting that hsa_circ_0137008/miR-338-5p axis is a principal regulator of CRC tumorigenesis.
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This multi-institutional study retrospectively evaluated clinicopathologic and genetic characteristics in 351 patients with core-binding-factor acute myeloid leukemia (CBF-AML), comprising 69 therapy-related (t-CBF-AML) and 282 de novo cases. The T-CBF-AML patients were older, had lower WBC counts, and slightly higher hemoglobin than patients with de novo disease. Secondary cytogenetic abnormalities were more frequent in patients with de novo disease than t-CBF-AML (57.1% vs 41.1%, P = .026). Patients with secondary cytogenetic abnormalities had longer overall survival (OS) than those without abnormalities (median 190 vs 87 months, P = .021); trisomy 8, trisomy 22, and loss of the X or Y chromosome were associated with longer OS. In the 165 cases performed of targeted gene sequencing, pathogenic mutations were detected in 75.7% of cases, and were more frequent in de novo than in therapy-related disease (P = .013). Mutations were found in N/KRAS (37.0%), FLT3 (27.8%), KIT (17.2%), TET2 (4.9%), and ASXL1 (3.9%). The TET2 mutations were associated with shorter OS (P = .012) while N/KRAS mutation was associated with longer OS in t(8;21) AML patients (P = .001). The KIT mutation did not show prognostic significance in this cohort. Although they received similar therapy, t-CBF-AML patients had shorter OS than de novo patients (median 69 vs 190 months, P = .038). In multivariate analysis of all patients, older age and absence of any secondary cytogenetic abnormalities were significant predictors of shorter OS. Among the t-CBF-AML subset, age and hemoglobin were significant on multivariate analysis. This study demonstrated that although de novo and t-CBF-AML patients share many features, t-CBF-AML patients have worse clinical outcome than de novo patients.
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Aberraciones Cromosómicas , Factores de Unión al Sitio Principal , Leucemia Mieloide Aguda , Proteínas de Neoplasias , Adulto , Factores de Unión al Sitio Principal/genética , Factores de Unión al Sitio Principal/metabolismo , Supervivencia sin Enfermedad , Femenino , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: To explore potential value of guard-wire technology during percutaneous coronary intervention (PCI) in patients with ostial coronary lesions. METHODS: Patients, who underwent PCI, were collected between October 2011 and March 2017. Of the 141 patients, 63 (44.7%) have ostial lesions, and 78 (55.3%) have distal bifurcation sites. They were divided into group A (n = 71) and group B (n = 70). Group A received PCI after guard-wire technology. Group B were given balloon dilation and stent after placing guide wire through target lesion vessel. X-ray exposure time, contrast agent dosage, total PCI duration, pressure incarceration times, cases of malignant arrhythmia and cases of failed PCI of all patients were analyzed, respectively. RESULTS: The general clinical characteristics includes patients age, sex ratio, the proportion of complications, smoking ratio and left ventricular ejection fraction of both groups was not significantly different. X-ray exposure time, contrast agent dosage, PCI total time, stent positioning time, pressure infestation frequency, arrhythmia frequency and complication number of group B were higher than those of group A. There is no case of malignant arrhythmia and case of failed PCI in group A, while there were five malignant arrhythmia and four failed PCI in group B. Contrast agent dosage and cases of failed PCI increased in group B compared with group A. CONCLUSION: The guard wire technology is safer and more feasible to patients with ostial coronary lesions who underwent PCI.
Asunto(s)
Angioplastia Coronaria con Balón/instrumentación , Cateterismo Cardíaco/instrumentación , Catéteres Cardíacos , Enfermedad de la Arteria Coronaria/terapia , Estenosis Coronaria/terapia , Anciano , Cateterismo Cardíaco/efectos adversos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents , Factores de Tiempo , Resultado del TratamientoRESUMEN
An Eu(III)-functionalized strontium-organic framework (Eu3+@Sr-MOF) was synthesized by encapsulating Eu3+ ions into the pores of Sr-MOF via postsynthetic modification (PSM) and fully characterized by XRD, SEM, EDS, FTIR, and TGA. The luminescent properties of Eu3+@Sr-MOF were measured and investigated in detail, which demonstrated that Eu3+@Sr-MOF not only possessed excellent water and chemical stabilities in a wide pH range (5-10) but also displayed red luminescence with excitation/emission maxima at 332/617 nm. The Eu3+@Sr-MOF can be considered as a highly selective and sensitive recyclable luminescence probe for sensing Cr(III) and Cr(VI) based on strong luminescence quenching effects; it can be recycled at least five times. The luminescence probe for Cr3+, CrO42-, and Cr2O72- shows low detection limits (0.15 µM, 0.17 µM, and 0.13 µM, respectively), relatively broad linear ranges (0.6-150 µM, 0.1-200 µM and 0.4-180 µM, respectively), and high quenching constants KSV. The signals can be observed by the naked eye under UV light of 365 nm. The method was applied to the determination of total Cr in environmental water samples. Graphical abstract.