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Isoquinolinone is an important heterocyclic framework in natural products and biologically active molecules, and the efficient synthesis of this structural motif has received much attention in recent years. Herein, we report a (phenyliodonio)sulfamate (PISA)-mediated, solvent-dependent synthesis of different isoquinolinone derivatives. The method provides highly chemoselective access to 3- or 4-substituted isoquinolinone derivatives by reacting o-alkenylbenzamide derivatives with PISA in either acetonitrile or wet hexafluoro-2-isopropanol.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trombosis , Humanos , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Masculino , Trombosis/etiología , Trombosis/diagnóstico por imagen , Hepatectomía/métodos , Neoplasias de los Conductos Biliares , Persona de Mediana Edad , Anciano , Resultado del TratamientoRESUMEN
Understanding how distinct functional circuits are coordinated to fine-tune mood and behavior is of fundamental importance. Here, we observe that within the dense projections from basolateral amygdala (BLA) to bed nucleus of stria terminalis (BNST), there are two functionally opposing pathways orchestrated to enable contextually appropriate expression of anxiety-like behaviors in male mice. Specifically, the anterior BLA neurons predominantly innervate the anterodorsal BNST (adBNST), while their posterior counterparts send massive fibers to oval BNST (ovBNST) with moderate to adBNST. Optogenetic activation of the anterior and posterior BLA inputs oppositely regulated the activity of adBNST neurons and anxiety-like behaviors, via disengaging and engaging the inhibitory ovBNST-to-adBNST microcircuit, respectively. Importantly, the two pathways exhibited synchronized but opposite responses to both anxiolytic and anxiogenic stimuli, partially due to their mutual inhibition within BLA and the different inputs they receive. These findings reveal synergistic interactions between two BLA-to-BNST pathways for appropriate anxiety expression with ongoing environmental demands.
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Ansiedad , Complejo Nuclear Basolateral , Optogenética , Núcleos Septales , Animales , Masculino , Núcleos Septales/fisiología , Núcleos Septales/metabolismo , Complejo Nuclear Basolateral/metabolismo , Complejo Nuclear Basolateral/fisiología , Ratones , Conducta Animal/fisiología , Neuronas/metabolismo , Neuronas/fisiología , Ratones Endogámicos C57BL , Vías Nerviosas/fisiologíaRESUMEN
OBJECTIVES: Ovarian cancer (OC) can occur at different ages and is affected by a variety of factors. In order to evaluate the risk of cardiovascular mortality in patients with ovarian cancer, we included influencing factors including age, histological type, surgical method, chemotherapy, whether distant metastasis, race and developed a nomogram to evaluate the ability to predict occurrence. At present, we have not found any correlation studies on cardiovascular death events in patients with ovarian cancer. This study was designed to provide targeted measures for effective prevention of cardiovascular death in patients with ovarian cancer. METHODS: Kaplan-Meier analysis and multivariable Cox proportional model were performed to evaluate the effectiveness of cardiovascular diseases on overall survival (OS) and ovarian cancer-specific survival (OCSS). We compared multiple groups including clinical, demographic, therapeutic characteristics and histological types. Cox risk regression analysis, Kaplan-Meier survival curves, and propensity score matching were employed for analyzing the data. RESULTS: A total of 88,653 ovarian cancer patients were collected, of which 2,282 (2.57%) patients died due to cardiovascular-related diseases. Age, chemotherapy and whether satisfactory cytoreduction surgery is still the most important factors affecting the prognosis of ovarian cancer patients, while different histological types, diagnosis time, and race also have a certain impact on the prognosis. The newly developed nomogram model showed excellent predictive performance, with a C-index of 0.759 (95%CI: 0.757-0.761) for the group. Elderly patients with ovarian cancer are still a high-risk group for cardiovascular death [HR: 21.07 (95%CI: 5.21-85.30), p < 0.001]. The calibration curve showed good agreement from predicted survival probabilities to actual observations. CONCLUSION: This study found that age, histology, surgery, race, chemotherapy, and tumor metastasis are independent prognostic factors for cardiovascular death in patients with ovarian cancer. The nomogram-based model can accurately predict the OS of ovarian cancer patients. It is expected to inform clinical decision-making and help develop targeted treatment strategies for this population.
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Enfermedades Cardiovasculares , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/patología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/complicaciones , Persona de Mediana Edad , Anciano , Nomogramas , Adulto , Pronóstico , Factores de Riesgo , Estimación de Kaplan-Meier , Modelos de Riesgos Proporcionales , Anciano de 80 o más AñosRESUMEN
Objectives: This study aimed to estimate the life expectancy (LE) and health-adjusted life expectancy (HALE) of type 2 diabetes mellitus (T2DM) among the rural elderly population. Methods: A total of 10,318 participants aged 65 to 79 were derived from the Henan Rural Cohort. The LE and HALE were calculated via the Sullivan method and multistate life table. Results: Among 10,318 subjects, 1,325 suffered from T2DM at the baseline, and 394 participants had newly-developed T2DM. The results from the Sullivan method showed that the LE, HALE, and HALE/LE were 17.98, 16.18 years, and 89.95% for men aged 65 to 69, and the corresponding estimates for women were 21.81, 18.73 years, and 85.86%, respectively. The LE, HALE and HALE/LE calculated via multistate life table were 19.86, 17.53 years, and 88.29% for men at aged 65, and the corresponding values for women were 25.01, 20.87 years, and 83.44%, respectively. Conclusion: Rural elderly women have a longer LE and HALE of T2DM, but they have lower quality of life than men. More attention should be paid to T2DM among rural elderly people, especially in women. Clinical Trial Registration: The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 06 July 2015. http://www.chictr.org.cn/showproj.aspx?proj=11375.
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Diabetes Mellitus Tipo 2 , Masculino , Humanos , Anciano , Femenino , Diabetes Mellitus Tipo 2/epidemiología , Calidad de Vida , Estudios de Cohortes , Esperanza de Vida , Población Rural , China/epidemiologíaRESUMEN
The cultured meat technology has developed rapidly in recent years, but there are still many technical challenges that hinder the large-scale production and commercialization of cultured meat. Firstly, it is necessary to lay the foundation for cultured meat production by obtaining seed cells and maintaining stable cell functions. Next, technologies such as bioreactors are used to expand the scale of cell culture, and three-dimensional culture technologies such as scaffold culture or 3D printing are used to construct the three-dimensional structure of cultured meat. At the same time, it can reduce production costs by developing serum-free medium suitable for cultured meat. Finally, the edible quality of cultured meat is improved by evaluating food safety and sensory flavor, and combining ethical and consumer acceptability issues. Therefore, this review fully demonstrates the current development status and existing technical challenges of the cultured meat production technology with regard to the key points described above, in order to provide research ideas for the industrial production of cultured meat.
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The supercritical CO2 enhanced coalbed methane (ScCO2-ECBM) technology is still in the development stage, and many simulation experiments and theoretical studies related to ScCO2-ECBM are being improved. Previous research works have conducted many studies on the competitive adsorption of CO2 and CH4 in coal, but there is less research on the competitive adsorption of ScCO2 and CH4 and its impact on methane extraction characteristics. In this study, a permeability model considering the competitive effects of effective stress and adsorption swelling on permeability was established. Based on the assumed conditions and permeability evolution model, different injected pressure and initial methane pressure conditions were set to obtain quantitative results of the competitive adsorption of ScCO2 and CH4, permeability changes, and CH4 production. By obtaining the competitive adsorption relationship between ScCO2 and CH4, we analyzed the evolution law of permeability and its impact on CH4 production. It was found that ScCO2 has a stronger competitive adsorption capacity, and the competitive adsorption capacity of ScCO2 and CH4 is more sensitive to injected pressure. Under two different conditions, it was found that the higher the injected pressure or injected differential pressure, the higher the initial permeability. However, due to the greater sensitivity of the competitive adsorption capacity of ScCO2 and CH4 to injected pressure, the greater the injected pressure in the later stage, the greater the decrease in permeability, resulting in a situation where the permeability at an injected pressure of 10 MPa is lower than that at an injected pressure of 8 MPa. A simple comparison was made between gaseous CO2 and ScCO2, and it was found that although injecting ScCO2 has a stronger adsorption swelling capacity that affects permeability changes, its stronger adsorption capacity can effectively displace methane and higher injected pressure, injected temperature, and advantages such as fracturing and extraction that are not yet reflected in the model. This study provides some guidance for numerical simulation of the ScCO2-ECBM process and the enhancement of coalbed methane extraction.
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Adipocytes are the primary sites for fatty acid storage, but the synthesis rate of fatty acids is very low. The physiological significance of this phenomenon remains unclear. Here, we show that surplus fatty acid synthesis in adipocytes induces necroptosis and lipodystrophy. Transcriptional activation of FASN elevates fatty acid synthesis, but decreases NADPH level and increases ROS production, which ultimately leads to adipocyte necroptosis. We identify MED20, a subunit of the Mediator complex, as a negative regulator of FASN transcription. Adipocyte-specific male Med20 knockout mice progressively develop lipodystrophy, which is reversed by scavenging ROS. Further, in a murine model of HIV-associated lipodystrophy and a human patient with acquired lipodystrophy, ROS neutralization significantly improves metabolic disorders, indicating a causal role of ROS in disease onset. Our study well explains the low fatty acid synthesis rate in adipocytes, and sheds light on the management of acquired lipodystrophy.
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Adipocitos , Lipodistrofia , Masculino , Ratones , Humanos , Animales , Especies Reactivas de Oxígeno/metabolismo , Adipocitos/metabolismo , Lipodistrofia/genética , Lipodistrofia/metabolismo , Ácidos Grasos/metabolismo , Estrés Oxidativo , Ratones NoqueadosRESUMEN
Let α, ß be positive real numbers and let Xα,ß be a Gamma random variable with shape parameter α and scale parameter ß. We study infimum values of the function (α,ß)â¦P{Xα,ß≤κE[Xα,ß]} for any fixed κ>0 and the function (α,ß)â¦P{|Xα,ß-E[Xα,ß]|≤Var(Xα,ß)}. We show that infα,ßP{Xα,ß≤E[Xα,ß]}=12 and infα,ßP{|Xα,ß-E[Xα,ß]|≤Var(Xα,ß)}=P{|Z|≤1}≈0.6827, where Z is a standard normal random variable.
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Resistivity measurements are widely exploited to uncover electronic excitations and phase transitions in metallic solids. While single crystals are preferably studied to explore crystalline anisotropies, these usually cancel out in polycrystalline materials. Here we show that in polycrystalline Mn3Zn0.5Ge0.5N with non-collinear antiferromagnetic order, changes in the diagonal and, rather unexpected, off-diagonal components of the resistivity tensor occur at low temperatures indicating subtle transitions between magnetic phases of different symmetry. This is supported by neutron scattering and explained within a phenomenological model which suggests that the phase transitions in magnetic field are associated with field induced topological orbital momenta. The fact that we observe transitions between spin phases in a polycrystal, where effects of crystalline anisotropy are cancelled suggests that they are only controlled by exchange interactions. The observation of an off-diagonal resistivity extends the possibilities for realising antiferromagnetic spintronics with polycrystalline materials.
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OBJECTIVES: Evidence on the health-related quality of life (HRQoL) among Chinese rural populations and its influence factors were limited. This study aimed to describe the distribution of HRQoL assessed by EQ-5D-5L and its determinants among a Chinese rural population. METHODS: A total of 23,510 eligible participants (9542 men and 13,968 women) from the Henan rural cohort study were included. Tobit regression and generalized linear models were performed to investigate the associations between demographic characteristics, lifestyle factors, common chronic diseases, and HRQoL. RESULTS: Of all respondents, the most frequently reported problem was pain/discomfort dimension (23.05%), followed by mobility (12.72%), anxiety/depression (7.77%), and usual activities (6.45%), while the least reported was the self-care dimension (3.84%). The more problems reported in all dimensions with age increased except anxiety/depression. The mean (standard deviation) utility index and VAS score were 0.954 (0.111) and 78.34 (14.80), respectively. The regression analysis indicated that increasing age, former drinkers, poor sleep quality, and suffering from common chronic diseases were significantly associated with low HRQoL, while high education level, average monthly income, and physical activity were significantly associated with high HRQoL. CONCLUSION: This study described the distribution of HRQoL and its influence factors among the Chinese rural population, which was helpful for medical institutions and policymakers to allocate medical resources and better understand HRQoL among the Chinese rural population.
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Estado de Salud , Calidad de Vida , Adulto , Masculino , Humanos , Femenino , Población Rural , Estudios de Cohortes , Estudios Transversales , Enfermedad Crónica , Encuestas y CuestionariosRESUMEN
OBJECTIVES: To estimate the safety and effectiveness of emergent transjugular intrahepatic portosystemic shunt (TIPS) creation for acute variceal bleeding (AVB) in cirrhotic patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Data of thirty-three patients with AVB and HCC undergoing emergent TIPS creation from January 2016 to January 2022 were enrolled and were retrospectively analyzed. The primary outcomes were the safety of emergent TIPS creation, the bleeding control rate, and the rebleeding rate. The secondary outcomes included overall survival (OS), liver function, overt hepatic encephalopathy (HE), and shunt dysfunction. RESULTS: Emergent TIPS creation was technically successful in 33 patients (100%) and one (3.0%) patient suffered a major procedure-related adverse event. The control rate of bleeding (within 5 days) was 100%. During a median follow-up period of 26.3 months, rebleeding occurred in 6 (18.2%) patients. The median OS was 20.0 months. The 6-week and 1-year survival rates were 87% and 65%, respectively. Laboratory tests showed no significant impairment of liver function following TIPS creation. The incidences of overt HE and shunt dysfunction were 24.2% and 6.1%, respectively. CONCLUSION: Emergent TIPS creation is feasible and effective for treatment of AVB in cirrhotic patients with HCC.
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Carcinoma Hepatocelular , Várices Esofágicas y Gástricas , Neoplasias Hepáticas , Derivación Portosistémica Intrahepática Transyugular , Humanos , Carcinoma Hepatocelular/complicaciones , Carcinoma Hepatocelular/cirugía , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/cirugía , Hemorragia Gastrointestinal/cirugía , Hemorragia Gastrointestinal/complicaciones , Estudios Retrospectivos , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia , Cirrosis Hepática/complicaciones , Resultado del TratamientoRESUMEN
Stimulation of adult cardiomyocyte proliferation is a promising strategy for treating myocardial infarction (MI). Earlier studies have shown increased CCL2 levels in plasma and cardiac tissue both in MI patients and mouse models. In present study we investigated the role of CCL2 in cardiac regeneration and the underlying mechanisms. MI was induced in adult mice by permanent ligation of the left anterior descending artery, we showed that the serum and cardiac CCL2 levels were significantly increased in MI mice. Intramyocardial injection of recombinant CCL2 (rCCL2, 1 µg) immediately after the surgery significantly promoted cardiomyocyte proliferation, improved survival rate and cardiac function, and diminished scar sizes in post-MI mice. Alongside these beneficial effects, we observed an increased angiogenesis and decreased cardiomyocyte apoptosis in post-MI mice. Conversely, treatment with a selective CCL2 synthesis inhibitor Bindarit (30 µM) suppressed both CCL2 expression and cardiomyocyte proliferation in P1 neonatal rat ventricle myocytes (NRVMs). We demonstrated in NRVMs that the CCL2 stimulated cardiomyocyte proliferation through STAT3 signaling: treatment with rCCL2 (100 ng/mL) significantly increased the phosphorylation levels of STAT3, whereas a STAT3 phosphorylation inhibitor Stattic (30 µM) suppressed rCCL2-induced cardiomyocyte proliferation. In conclusion, this study suggests that CCL2 promotes cardiac regeneration via activation of STAT3 signaling, underscoring its potential as a therapeutic agent for managing MI and associated heart failure.
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Insuficiencia Cardíaca , Infarto del Miocardio , Humanos , Ratones , Animales , Ratas , Quimiocina CCL2/metabolismo , Infarto del Miocardio/metabolismo , Miocitos Cardíacos , Insuficiencia Cardíaca/metabolismo , Regeneración , Ratones Endogámicos C57BL , Apoptosis , Factor de Transcripción STAT3/metabolismoRESUMEN
Background: The CRAFITY (C-reactive protein and alpha-fetoprotein in immunotherapy) score has demonstrated prognostic significance in hepatocellular carcinoma (HCC) patients undergoing immunotherapy. The study aimed to validate accuracy of CRAFITY score on predicting prognosis for patients with HCC treated with transarterial chemoembolization (TACE) combined with PD-(L)1 inhibitors and molecular targeted therapy. Methods: Eighty-five HCC patients who underwent TACE in combination with molecular targeted therapy (MTT) and PD-(L)1 Inhibitors were consecutively enrolled from November 2019 to November 2022. Patients were divided into CRAFITY 0 score (n=32), CRAFITY 1 score (n=31), and CRAFITY 2 score (n=22), respectively. The primary outcomes were overall survival (OS) and progression-free survival (PFS), and the secondary outcomes included tumor response rate and treatment-related adverse events (TRAEs). Factors affecting survival were identified via Cox regression analysis. Results: The median overall survival (OS) for HCC patients with CRAFITY scores of 0, 1, and 2 was 33.4 months (95% confidence interval [CI]: 27.1-39.7), 34.5 months (95% CI: 23.1-45.9), and 24.2 months (95% CI: 13.9-39.3), respectively, there were statistical differences among the three groups (p<0.05). The progression-free survival (PFS) was 14.1 months (95% CI: 10.0-18.2), 14.1 months (95% CI: 9.0-19.2), and 9.3 months (95% CI: 7.2-11.4) for patients with CRAFITY scores of 1, 2, and 3, respectively, with a significant difference between the three groups (p<0.05). In patients with CRAFITY scores of 1, 2, and 3, the disease control rates (DCR) were 94%, 84%, and 73%, respectively (p < 0.05), while the overall response rates (ORR) were 78.1%, 67.7%, and 59.1%, respectively (p = 0.318). A higher CRAFITY score showed a correlation with an increased frequency of fatigue and grade 3 fever (p<0.05). Moreover, CRAFITY 2 score was an independent risk factor for both OS (HR = 2.610(1.281-4.564), p = 0.014) and PFS (HR = 2.419(1.281-4.564), p = 0.006). Conclusion: The CRAFITY score may provide an efficient predictive capacity for prognosis in HCC patients undergoing TACE combined with PD-(L)1 inhibitors and molecular targeted therapy.
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BACKGROUND: Gait impairment is common in Parkinson's disease (PD) patients, which greatly reduces their quality of life. Executive dysfunction is associated with gait impairment. Compensatory strategies, including visual cues, have been shown to be effective in improving PD gait. In this study, we aimed to understand whether carpets with visual cues could improve PD gait, and how the improvement varies across patients with different executive function state. METHODS: We designed carpets with chessboard and stripe cues. A total of 65 Chinese PD patients were recruited. Movement Disorder Society Unified Parkinson's Disease Rating Scale, L-dopa equivalent daily dosage, Hoehn & Yahr stage, Frontal Assessment Battery, Mini Mental State Examination Scale, Hamilton Anxiety Scale, and Hamilton Depression Scale were evaluated. Gait parameters including stride length, gait speed and fall risk were recorded by a wearable electronic device. RESULTS: The stride length and gait speed were significantly improved and the fall risk was significantly mitigated when PD patients walked on carpets with chessboard and stripe patterns. Further analysis showed the amelioration of gait parameters was independent of executive dysfunction. CONCLUSIONS: Our study demonstrates that carpets with visual cues can improve the gait of PD patients even in those with mild executive dysfunction.
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Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Función Ejecutiva , Señales (Psicología) , Pisos y Cubiertas de Piso , Calidad de Vida , MarchaRESUMEN
Artificial solid-state nanochannels have aroused intense interests in biosensors and bioelectronics because of their special architectures. Herein, we pioneered an ingenious approach of target-triggered cascade signal amplification in porous anodic aluminum oxide (AAO) nanochannels for ultrasensitive photoelectrochemical (PEC) DNA bioanalysis. In the design, AAO nanochannels were modified initially with capture DNA (cDNA) and then incorporated with a photoelectrode, yielding the desired architecture of highly ordered nanoarrays on top of the signal transducer. For target DNA (tDNA) probing, exonuclease III (Exo-III) mediated target recycling (ETR) was first activated to generate plenty of output DNA (oDNA) fragments. After oDNA and the conjugate of Au-labeled probe DNA (Au-pDNA) were anchored within the nanochannels via DNA hybridization, in-situ synthesis of Ag shells on tethered Au nanoparticles was conducted. The resulting large-sized Au@Ag core-shell nanostructure within the nanochannels would cause conspicuous blocking effect to hinder the transportation of electrons accessing the photoelectrode. Since the signal inhibition was directly related to tDNA concentration, an innovative nanochannels PEC DNA assay was exploited and qualified for ultrasensitive detection. The anti-interference ability of this platform was also emphasized by the split AAO membrane for biological incubation without participation of the photoelectrode. This featured nanochannels PEC strategy with cascade amplification launched a novel detecting platform for trace levels of DNA, and it could spark more inspiration for a follow-up exploration of other smart nanochannels PEC bioassays.
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Técnicas Biosensibles , Nanopartículas del Metal , Oro/química , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Nanopartículas del Metal/química , ADN/análisis , Óxido de Aluminio , Límite de DetecciónRESUMEN
BACKGROUNDS AND AIMS: Evidence on the association between habitual snoring, excessive daytime sleepiness (EDS), and cardiovascular diseases (CVDs) remains uncertain and limited. The study aimed to explore the independent and joint association between habitual snoring, EDS, and CVDs in rural Chinese adults. METHODS AND RESULTS: A total of 28,140 participants from the Henan rural cohort study were included. Sleep status information was obtained by self-reported. Based on their sleep status, the participants were classified into four groups: "no snoring and no EDS (NSNS) (reference group)", "snoring and no EDS (SNS)", "no snoring and EDS (NSS)", "snoring and EDS (SS)." The logistic regression models were used to calculate independent and joint odds ratios (OR) and 95% confidence intervals (CI) between the snoring, EDS status and stroke, CHD, and CVD. Of the 28,140 participants, 740 subjects reported snoring and sleepiness. The ORs and (95% CIs) for CVDs in the adjusted model were 1.31 (1.20-1.43) for participants who snored frequently and 2.44 (1.76-3.39) for frequent sleepiness compared with no snoring and no sleepiness. Individuals with both snoring and sleepiness had higher odds of CVDs compared with no snoring and no sleepiness (OR: 2.18, 95%CI: 1.80-2.62). CONCLUSION: Habitual snoring and excessive daytime sleepiness were independently and jointly associated with CVDs in the Chinese rural population. More studies are needed to explore the mechanisms of the relationship. CLINICAL TRIAL REGISTRATION: The Henan Rural Cohort Study has been registered at the Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699). Date of registration: 2015-52 07-06. http://www.chictr.org.cn/showproj.aspx?proj=11375.
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Enfermedades Cardiovasculares , Trastornos de Somnolencia Excesiva , Humanos , Adulto , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Ronquido/diagnóstico , Ronquido/epidemiología , Estudios de Cohortes , Población Rural , Somnolencia , Pueblos del Este de Asia , Trastornos de Somnolencia Excesiva/diagnóstico , Trastornos de Somnolencia Excesiva/epidemiologíaRESUMEN
Nasopharyngeal carcinoma (NPC) is a common malignant epithelial tumor of the head and neck that often exhibits local recurrence and distant metastasis. The molecular mechanisms are understudied, and effective therapeutic targets are still lacking. In our study, we found that the transcription factor ZIC2 was highly expressed in NPC. Although ZIC family members play important roles in neural development and carcinogenesis, the specific mechanism and clinical significance of ZIC2 in the tumorigenesis and immune regulation of NPC remain elusive. Here, we first reported that high expression of ZIC2 triggered the secretion of MCSF in NPC cells, induced M2 polarization of tumor-associated macrophages (TAMs), and affected the secretion of TAM-related cytokines. Mechanistically, ChIP-seq and RNA-seq analyses identified JUNB as a downstream target of ZIC2. Furthermore, ZIC2 was significantly enriched in the promoter site of JUNB and activated JUNB promoter activity, as shown by ChIP-qPCR and luciferase assays. In addition, JUNB and MCSF participated in ZIC2-induced M2 TAMs polarization. Thus, blocking JUNB and MCSF could reverse ZIC2-mediated M2 TAMs polarization. Moreover, Kaplan-Meier survival analyses indicated that high expression of ZIC2, JUNB, and CD163 was positively associated with a poor prognosis in NPC. Overexpression of ZIC2 induced tumor growth in vivo, with the increase of JUNB, MCSF secretion, and CD163. In summary, our study implies that ZIC2 induces M2 TAM polarization, at least in part through regulation of JUNB/MCSF and that ZIC2, JUNB, and CD163 can be utilized as prognostic markers for NPC and as therapeutic targets for cancer immunotherapy.
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Carcinoma , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Carcinogénesis , Neoplasias Nasofaríngeas/genética , Macrófagos , Proteínas Nucleares , Factores de Transcripción/genéticaRESUMEN
Cultured meat is one of the meat substitutes produced through tissue engineering and other technologies. Large-scale cell culture is the key for cultured meat products to enter the market. Therefore, this study is aimed to explore the effect of long-term passage in vitro on smooth muscle cells (SMCs) and the effect of transforming growth factor-ß1 (TGF-ß1) on SMCs in the late passage. Multiple passages lead to the decline of the proliferation rate of SMCs in the proliferation stage and the differentiation ability in the differentiation stage. Transcriptome results showed that the ECM pathway and aging-related signaling pathways were significantly up-regulated in the late passage period. TGF-ß1 did not promote SMCs of late passage proliferation at the proliferation stage but promoted the gene and protein expression of collagen as the main protein of the extracellular matrix proteins at the differentiation stage. In addition, proteomic analysis revealed that TGF-ß1 promoted the expression of cell adhesion molecules which activate the Hippo signaling pathway and the HIF-1 signaling pathway and further promoted the production of collagen-containing extracellular matrix proteins. This could provide ideas for large-scale production of cultured meat products using SMCs.
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Alzheimer's disease (AD) is a degenerative disease of the central nervous system. Numerous studies have shown that imbalances in cholesterol homeostasis in the brains of AD patients precede the onset of clinical symptoms. In addition, cholesterol deposition has been observed in the brains of AD patients even though peripheral cholesterol does not enter the brain through the bloodâbrain barrier (BBB). Studies have demonstrated that cholesterol metabolism in the brain is associated with many pathological conditions, such as amyloid beta (Aß) production, Tau protein phosphorylation, oxidative stress, and inflammation. In 2022, some scholars put forward a new hypothesis of AD: the disease involves lipid invasion and its exacerbation of the abnormal metabolism of cholesterol in the brain. In this review, by discussing the latest research progress, the causes and effects of cholesterol retention in the brains of AD patients are analyzed and discussed. Additionally, the possible mechanism through which AD may be improved by targeting cholesterol is described. Finally, we propose that improving the impairments in cholesterol removal observed in the brains of AD patients, instead of further reducing the already impaired cholesterol synthesis in the brain, may be the key to preventing cholesterol deposition and improving the corresponding pathological symptoms.