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BACKGROUND: Von Hippel-Lindau (VHL) syndrome is an autosomal dominant hereditary disease affecting multiple organs, with pheochromocytoma in 26% of cases. However, VHL syndrome with congestive heart failure and dilated cardiomyopathy as the primary clinical manifestations has been rarely reported. CASE PRESENTATION: A 35-year-old male patient was admitted to the hospital with dyspnea. The patient had a history of cerebellar hemangioblastoma that had been resected, and a one-year history of hypertension. Echocardiography and cardiac magnetic resonance imaging demonstrated a dilated left ventricle, decreased systolic function, and nonischemic myocardial changes. Contrast-enhanced abdominal computed tomography showed pheochromocytoma, neoplastic lesions, and multiple cysts in the kidneys and pancreas. Genetic analysis revealed a missense mutation of the VHL gene, c.269 A > T (p.Asn90Ile), which was identified as the cause of the disease. Dilated cardiomyopathy and VHL syndrome type 2 were diagnosed. The patient was administered a diuretic, α-blocker, ß-blocker, and an angiotensin receptor neprilysin inhibitor (ARNI), but refused pheochromocytoma resection. At the six-month follow-up, the patient was asymptomatic with improved cardiac function. CONCLUSION: Cardiac involvement is an atypical manifestation in VHL syndrome. Early diagnosis with genetic screening is essential for avoiding life-threatening complications associated with VHL. The management of this rare manifestation of VHL syndrome requires further investigation.
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Neoplasias de las Glándulas Suprarrenales , Cardiomiopatía Dilatada , Feocromocitoma , Enfermedad de von Hippel-Lindau , Humanos , Masculino , Adulto , Enfermedad de von Hippel-Lindau/complicaciones , Enfermedad de von Hippel-Lindau/diagnóstico , Enfermedad de von Hippel-Lindau/genética , Feocromocitoma/diagnóstico , Feocromocitoma/diagnóstico por imagen , Cardiomiopatía Dilatada/etiología , Cardiomiopatía Dilatada/genética , Neoplasias de las Glándulas Suprarrenales/complicaciones , Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/genética , Pruebas GenéticasRESUMEN
BACKGROUND: Myocardial Ischemia with No Obstructive Coronary Artery Disease (MINOCA) is a common cause of type 2 acute myocardial infarction (AMI) which requires careful differential diagnosis. Coronary artery spasm (CAS) syndrome is one etiology that can lead to MINOCA. Nilotinib, a targeted treatment for chronic myeloid leukemia (CML), has been reported to be related with increased risk of adverse vascular events. CASE PRESENTATION: A 67-year-old male patient was admitted to hospital with acute chest pain. He had a past medical history of CML and a history of treatment with nilotinib for 12 months. Coronary angiography (CAG) showed no significant stenosis. Since the onset of angina was generally in the early morning, and ECG and echocardiography suggested right coronary artery (RCA) disease, an ergonovine provocation test was performed to confirm the diagnosis of CAS. After intracoronary administration of ergonovine, middle and distal RCA showed over 90% vasoconstriction. Nilotinib related MINOCA, CAS and CML were diagnosed. Lifestyle changes (cessation of smoking), anti-spasmodics, statin treatment and adjustment of the nilotinib dose (from 200 mg bid, to 150 mg bid) were recommended for this patient. Six-month's follow-up showed good recovery with no onsets of angina. CONCLUSIONS: Physicians should be vigilant to adverse vascular events when treating patients who have been prescribed nilotinib. It is suggested that in patients with MINOCA who have a history of treatment with nilotinib, CAS-induced MINOCA should be included in the differential diagnosis. Further studies are needed to clarify the mechanism and to find better management.
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Antineoplásicos/efectos adversos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , MINOCA/inducido químicamente , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Anciano , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , MINOCA/diagnóstico por imagen , MINOCA/terapia , Masculino , Cese del Hábito de Fumar , Resultado del Tratamiento , Vasodilatadores/uso terapéuticoRESUMEN
Temperature is an important environmental factor affecting the growth and development of silkworm (Bombyx mori). To analyze the effect of intestinal microbes on silkworm in response to a high-temperature environment, this study used a combination of high throughput sequencing and biochemical assays to detect silkworm intestinal microbes treated with high temperature for 72 h. The results show that high temperature affects the intestinal microbes of silkworm and that there are sex differences, specifically, females were more sensitive. The changes in the metabolism and transport ability of silkworm intestinal tissues under high temperature are related to the intestinal microbes. High temperatures may affect the intestinal microbes of silkworms, regulating the activity of related digestive enzymes and substance transport in the intestine, thereby affecting the silkworm's digestion and absorption of nutrients, and ultimately affecting growth and development.
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Bombyx , Animales , Bombyx/química , Femenino , Crecimiento y Desarrollo , Intestinos , Larva , Masculino , TemperaturaRESUMEN
BACKGROUND: Due to its low incidence and diverse manifestations, paradoxical embolism (PDE) is still under-reported and is not routinely considered in differential diagnoses. Concomitant acute myocardial infarction (AMI) and acute pulmonary embolism (PE) caused by PDE has rarely been reported. CASE PRESENTATION: A 45-year-old woman presented with acute chest pain and difficulty with breathing. Multiple imaging modules including ECG, echocardiography, emergency cardioangiogram (CAG), and CT angiography of the pulmonary arteries showed acute occlusion of the posterolateral artery and acute PE. After coronary aspiration, no residual stenosis was observed. One month later, a bubble study showed inter-atrial communication via a patent foramen ovale (PFO). The AMI in this patient was finally attributed to PDE via the PFO. PFO closure was performed, and long-term anticoagulation was prescribed to prevent recurrent thromboembolic events. CONCLUSIONS: PDE via PFO is a rare etiology of AMI, especially in patients with concomitant AMI and PE. Clinicians should be vigilant of this possibility and close the inter-atrial channel for secondary prevention.
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Embolia Paradójica/etiología , Foramen Oval Permeable/complicaciones , Infarto de la Pared Inferior del Miocardio/etiología , Embolia Pulmonar/etiología , Infarto del Miocardio con Elevación del ST/etiología , Anticoagulantes/uso terapéutico , Embolia Paradójica/diagnóstico por imagen , Embolia Paradójica/prevención & control , Femenino , Foramen Oval Permeable/diagnóstico por imagen , Foramen Oval Permeable/terapia , Humanos , Infarto de la Pared Inferior del Miocardio/diagnóstico por imagen , Infarto de la Pared Inferior del Miocardio/prevención & control , Persona de Mediana Edad , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/prevención & control , Recurrencia , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/prevención & control , Prevención Secundaria , Resultado del TratamientoRESUMEN
BACKGROUND: Cardiac injury is common in severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. We aimed to study predictors of in-hospital death, characteristics of arrhythmias and the effects of QT-prolonging therapy in patients with cardiac injury. METHODS: We conducted a retrospective cohort study involving patients with severe COVID-19 who were admitted to Tongji Hospital in Wuhan, China, between Jan. 29 and Mar. 8, 2020. Among patients who had cardiac injury, which we defined as an elevated level of cardiac troponin I (cTnI), we identified demographic and clinical characteristics associated with mortality and need for invasive ventilation. RESULTS: Among 1284 patients with severe COVID-19, 1159 had a cTnI level measured on admission to hospital, of whom 170 (14.7%) had results that showed cardiac injury. We found that mortality was markedly higher in patients with cardiac injury (71.2% v. 6.6%, p < 0.001). We determined that initial cTnI (per 10-fold increase, hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.06-1.66) and peak cTnI level during illness (per 10-fold increase, HR 1.70, 95% CI 1.38-2.10) were associated with poor survival. Peak cTnI was also associated with the need for invasive ventilation (odds ratio 3.02, 95% CI 1.92-4.98). We found arrhythmias in 44 of the 170 patients with cardiac injury (25.9%), including 6 patients with ventricular tachycardia or fibrillation, all of whom died. We determined that patients who received QT-prolonging drugs had longer QTc intervals than those who did not receive them (difference in medians, 45 ms, p = 0.01), but such treatment was not independently associated with mortality (HR 1.04, 95% CI 0.69-1.57). INTERPRETATION: We found that in patients with COVID-19 and cardiac injury, initial and peak cTnI levels were associated with poor survival, and peak cTnI was a predictor of need for invasive ventilation. Patients with COVID-19 warrant assessment for cardiac injury and monitoring, especially if therapy that can prolong repolarization is started. TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR2000031301.
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Arritmias Cardíacas/mortalidad , Arritmias Cardíacas/virología , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/fisiopatología , Lesiones Cardíacas/mortalidad , Lesiones Cardíacas/virología , Alta del Paciente/estadística & datos numéricos , Neumonía Viral/mortalidad , Neumonía Viral/fisiopatología , Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/sangre , Betacoronavirus/patogenicidad , Biomarcadores/sangre , COVID-19 , China/epidemiología , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/virología , Enfermedad Crítica , Lesiones Cardíacas/sangre , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Modelos Logísticos , Pandemias , Neumonía Viral/sangre , Neumonía Viral/virología , Pronóstico , Respiración Artificial/estadística & datos numéricos , Estudios Retrospectivos , SARS-CoV-2 , Troponina I/sangreRESUMEN
To compare the safetyand efficacy of warfarin treatment continuation and heparin-bridging therapy during cardiac rhythm device (CRD) implantation in patients chronically treated with anticoagulants.We performed a search and analysis of peer-reviewed studies Four randomized controlled trials (RCTs)were included in our analysis with 941 patients. The bleeding risk in patients continuing warfarin perioperatively was lower than those interrupting warfarin and using a heparin-bridge (RD -0.08, 95% CI -0.17 to 0.02, p< 0.05). There was no significant difference in ischaemic risk between two methods (RD 0, 95% CI -0.01 to 0.02, p=1.00). Hence, in patients undergoing long-term warfarin therapy, continuation of warfarin treatment is a safe and efficacious perioperative strategy for during CRD implantations, while interruption of warfarin with a heparin bridge may increase the bleeding risk in these patients.
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Anticoagulantes/uso terapéutico , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Hematoma/epidemiología , Heparina/uso terapéutico , Marcapaso Artificial , Atención Perioperativa/métodos , Hemorragia Posoperatoria/epidemiología , Implantación de Prótesis/métodos , Warfarina/uso terapéutico , Humanos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
CONTEXTE: Les atteintes cardiaques sont fréquentes dans les cas graves de maladie à coronavirus 2019 (COVID-19) et sont associées à un mauvais pronostic. Notre étude portait sur les facteurs prédictifs de mortalité intrahospitalière, les caractéristiques de l'arythmie et les effets des traitements qui allongent l'intervalle QT chez les patients ayant une atteinte cardiaque. MÉTHODES: Nous avons fait une étude de cohorte rétrospective des cas graves de COVID-19 admis à l'hôpital Tongji, à Wuhan, en Chine, entre le 29 janvier et le 8 mars 2020. En examinant ceux qui avaient une atteinte cardiaque, définie ici comme un taux élevé de troponine I cardiaque (TnIc), nous avons déterminé les caractéristiques biologiques et cliniques associées à la mortalité et au besoin de ventilation invasive. RÉSULTATS: Parmi les 1284 cas graves de COVID-19, 1159 avaient au dossier un taux de TnIc mesuré à l'admission, qui pour 170 (14,7 %) participants indiquait une atteinte cardiaque. Les patients ayant une atteinte cardiaque avaient un taux de mortalité nettement plus élevé que les autres patients (71,2 % c. 6,6 %; p < 0,001). Nous avons constaté que le taux de TnIc initial (pour chaque augmentation d'un facteur 10, rapport de risque [HR] 1,32, intervalle de confiance [IC] à 95 % 1,061,66) et le taux de TnIc maximal atteint au cours de la maladie (pour chaque augmentation d'un facteur 10, HR 1,70, IC à 95 % 1,382,10) étaient associés à de minces chances de survie. Le taux de TnIc maximal était aussi associé au besoin de ventilation invasive (rapport de cotes 3,02, IC à 95 % 1,924,98). Sur les 170 patients ayant une atteinte cardiaque, 44 (25,9 %) présentaient une arythmie. Les 6 qui souffraient de tachycardie ou de fibrillation ventriculaires sont morts. Nous avons remarqué que les patients qui recevaient des médicaments allongeant l'intervalle QT avaient un intervalle QTc plus long que ceux qui n'en recevaient pas (différence entre les médianes 45 ms; p = 0,01), mais que ce traitement n'était pas directement lié à la mortalité (HR 1,04, IC à 95 % 0,691,57). INTERPRÉTATION: Chez les patients ayant la COVID-19 et une atteinte cardiaque, les taux initial et maximal de TnIc sont associés à de minces chances de survie, et le taux maximal est un facteur prédictif du besoin de ventilation invasive. Les malades de la COVID-19 doivent subir un dépistage des atteintes cardiaques et être surveillés, surtout si on leur fait suivre un traitement qui peut prolonger la repolarisation. Enregistrement de l'essai : Registre des essais cliniques chinois, n° ChiCTR2000031301.
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MicroRNAs (miRNAs) are small non-coding RNAs, which silence target mRNA via cleavage or translational inhibition to function in regulating gene expression. MiRNAs act as important regulators of plant development and stress response. For understanding the role of miRNAs responsive to apple ring rot stress, we identified disease-responsive miRNAs using high-throughput sequencing in Malus × domestica Borkh.. Four small RNA libraries were constructed from two control strains in M. domestica, crabapple (CKHu) and Fuji Naga-fu No. 6 (CKFu), and two disease stress strains, crabapple (DSHu) and Fuji Naga-fu No. 6 (DSFu). A total of 59 miRNA families were identified and five miRNAs might be responsive to apple ring rot infection and validated via qRT-PCR. Furthermore, we predicted 76 target genes which were regulated by conserved miRNAs potentially. Our study demonstrated that miRNAs was responsive to apple ring rot infection and may have important implications on apple disease resistance.
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Regulación de la Expresión Génica de las Plantas , Malus/genética , MicroARNs/genética , Enfermedades de las Plantas/genética , Secuencia de Bases , Resistencia a la Enfermedad , Biblioteca de Genes , Silenciador del Gen , Secuenciación de Nucleótidos de Alto Rendimiento , Secuencias Invertidas Repetidas , MicroARNs/metabolismo , Datos de Secuencia Molecular , ARN de Planta/genética , Análisis de Secuencia de ARNRESUMEN
BACKGROUND: The high mobilization failure rate with the mobilization strategy of combining chemotherapy and filgrastim (rhG-CSF) in autologous hematopoietic stem cell transplantation (auto-HSCT) in lymphomas is one of the unresolved issues. Whether the combination of polyethylene glycol filgrastim [pegfilgrastim (PEG-FIL), PEG-rhG-CSF] and filgrastim (FIL) improves the mobilization success rate and the timing of combination therapy has not been studied. METHODS: 107 lymphoma patients who received auto-HSCT were retrospectively enrolled and divided into groups of PEG+FIL and FIL. The group of PEG+FIL received pegfilgrastim (9 mg) on the third day of the chemotherapy, followed by filgrastim (10 µg/kg/day) based on the counts of peripheral blood stem cells (PBSC). The group of FIL received filgrastim 10 µg /kg/day depending on the number of PBSCs. RESULTS: The incidence of neutropenic fever in the group of PEG+FIL was significantly lower than in the group of FIL. The mean recovery time of leukocytes at autologous stem cell transplantation was significantly shorter in the group of PEG+FIL than in the group of FIL. Compared to the groups of FIL, the group of PEG+FIL had lower hospitalization costs. We found that the combination therapy is more recommended for patients with a bone marrow hematopoietic area of less than 30%. Filgrastim is best administered 5-6 days after pegfilgrastim administration. CONCLUSIONS: Compared to conventional filgrastim mobilization, the combination of pegfilgrastim and filgrastim schedule has high efficacy, non-inferior safety, and superior health economic benefits during auto-HSCT.
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BACKGROUND: We recently demonstrated that acute administration of ibrutinib, a Bruton's tyrosine kinase inhibitor used in chemotherapy for blood malignancies, increases ventricular arrhythmia (VA) vulnerability. A pathway of ibrutinib-induced vulnerability to VA that can be modulated for cardioprotection remains unclear. METHODS AND RESULTS: The effects of ibrutinib on cardiac electrical activity and Ca2+ dynamics were investigated in Langendorff-perfused hearts using optical mapping. We also conducted Western blotting analysis to evaluate the impact of ibrutinib on various regulatory and Ca2+-handling proteins in rat cardiac tissues. Treatment with ibrutinib (10 mg/kg per day) for 4 weeks was associated with an increased VA inducibility (72.2%±6.3% versus 38.9±7.0% in controls, P<0.002) and shorter action potential durations during pacing at various frequencies (P<0.05). Ibrutinib also decreased heart rate thresholds for beat-to-beat duration alternans of the cardiac action potential (P<0.05). Significant changes in myocardial Ca2+ transients included lower amplitude alternans ratios (P<0.05), longer times-to-peak (P<0.05), and greater spontaneous intracellular Ca2+ elevations (P<0.01). We also found lower abundance and phosphorylation of myocardial AMPK (5'-adenosine monophosphate-activated protein kinase), indicating reduced AMPK activity in hearts after ibrutinib treatment. An acute treatment with the AMPK activator 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside ameliorated abnormalities in action potential and Ca2+ dynamics, and significantly reduced VA inducibility (37.1%±13.4% versus 72.2%±6.3% in the absence of 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside, P<0.05) in hearts from ibrutinib-treated rats. CONCLUSIONS: VA vulnerability inflicted by ibrutinib may be mediated in part by an impairment of myocardial AMPK activity. Pharmacological activation of AMPK may be a protective strategy against ibrutinib-induced cardiotoxicity.
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Proteínas Quinasas Activadas por AMP , Potenciales de Acción , Adenina , Arritmias Cardíacas , Piperidinas , Pirazoles , Pirimidinas , Animales , Adenina/análogos & derivados , Adenina/farmacología , Piperidinas/farmacología , Potenciales de Acción/efectos de los fármacos , Pirimidinas/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , Pirazoles/farmacología , Masculino , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/prevención & control , Inhibidores de Proteínas Quinasas/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Preparación de Corazón Aislado , Calcio/metabolismo , Ratas , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , Señalización del Calcio/efectos de los fármacos , Factores de TiempoRESUMEN
PURPOSE: This study aimed to assess the value of an HPV E6/E7 mRNA assay and HPV 16 18/45 genotype assay combined with age stratification for triaging women negative for intraepithelial lesions or malignancy (NILM) cytology. METHODS: From January 2017 to December 2021, a total of 162,309 eligible women underwent cervical cancer screening at the Affiliated Hospital of Jining Medical University, China. Excluding those with negative HPV E6/E7 mRNA, abnormal and unsatisfactory cytology, and those who failed to undergo colposcopy, 6,845 women were ultimately included in our study. We analysed the triage guidance for different subtypes of HPV in the presence of NILM cytology. RESULTS: Among 162,309 women, 19,834 (12.2%) were positive for HPV E6/E7 mRNA. Of the 6,845 women included in the study, 1,941 (28.4%), 561 (8.2%), 55 (0.8%) and 4,288 (62.6%) tested positive for HPV 16, HPV 18/45, HPV16/18/45 or other HR-HPV genotypes, respectively. The proportions of LSIL+ (including LSIL, HSIL and ICC) and HSIL+ (including HSIL and ICC) pathological results in the HPV 16/18/45 + group were 57% and 34.1%, respectively, higher than 36.3% and 11% in the other HR-HPV + group (χ2 = 653.214, P < 0.001). The percentages of LSIL + and HSIL + in the HPV16 + group (61.3% and 42.8%, respectively) and HPV16+/18/45 + group (76.3% and 41.9%, respectively) were much higher than those in the HPV18 + group (40.6% and 13.1%, respectively) (P < 0.001). However, there was no significant difference in the percentage of histopathological results between the HPV16 + group and HPV16+/18/45 + groups (P > 0.05). The above results were consistent after stratification according to age. CONCLUSION: The rate of histopathological abnormalities was still high for the other HR-HPV subtypes with NILM cytology, although the rate of histopathological abnormalities was much higher for the HPV 16/18/45 positive subtypes. Therefore, colposcopy should be performed in women with HPV E6/E7 mRNA positivity and NILM cytology, regardless of age and HPV genotype.
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BACKGROUND: Excess body weight has been found to associate with an increased risk of lymphomas and some metabolic pathways are currently recognized in lymphomagenesis. Bioactive lipid metabolites such as sphingosine-1-phosphate (S1P) have been proposed to play an important role linking obesity and lymphomas. However, the underlying mechanism(s) of S1P signaling in obesity-lymphomagenesis have not been well addressed. METHODS: The gene expression of sphingosine kinase (SPHK), lymphoma prognosis, and S1P production were analyzed using Gene Expression Omnibus (GEO) and human lymphoma tissue array. Obesity-lymphoma mouse models and lymphoma cell lines were used to investigate the S1P/SPHK-YAP axis contributing to obesity-lymphomagenesis. By using the mouse models and a monocyte cell line, S1P-mediated polarization of macrophages in the tumor microenvironment were investigated. RESULTS: In human study, up-regulated S1P/SPHK1 was found in human lymphomas, while obesity negatively impacted progression-free survival and overall survival in lymphoma patients. In animal study, obesity-lymphoma mice showed an aggressive tumor growth pattern. Both in vivo and in vitro data suggested the existence of S1P-YAP axis in lymphoma cells, while the S1P-ALOX15 signaling mediated macrophage polarization towards TAMs exacerbated the lymphomagenesis. In addition, treatment with resveratrol in obesity-lymphoma mice showed profound effects of anti-lymphomagenesis, via down-regulating S1P-YAP axis and modulating polarization of macrophages. CONCLUSION: S1P/S1PR initiated the feedback loops, whereby S1P-S1PR1/S1PR3-YAP signaling mediated lymphomagenesis contributing to tumor aggressive growth, while S1P-ALOX15 signaling mediated TAMs contributing to immunosuppressive microenvironment in obesity-lymphoma. S1P-targeted therapy could be potentially effective and immune-enhancive against obesity-lymphomagenesis.
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Neoplasias , Transducción de Señal , Animales , Ratones , Humanos , Receptores de Esfingosina-1-Fosfato/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Modelos Animales de Enfermedad , Obesidad/complicaciones , Obesidad/genética , Microambiente Tumoral , Araquidonato 15-Lipooxigenasa , Araquidonato 12-Lipooxigenasa/metabolismoRESUMEN
BACKGROUND: Exposure to environmental pollutants, including benzo[a]pyrene (BaP), has been implicated in allergic diseases and intestinal microbiota homeostasis, but the environment-microbiota-immunity triangular relationship and to what extent BaP-induced remodeling of the gut microbiota contributes to intestinal allergic inflammation remain to be established. OBJECTIVES: We investigated the impact of BaP on intestinal allergic inflammation and examined the relationship between this effect and gut microbiota dysbiosis. We explored the potential ability of intestinal bacteria to degrade BaP and alleviate cytotoxicity as a detoxification strategy to counteract the effects of BaP exposure. METHODS: We combined microbiome shotgun metagenomics with animal histological and intestinal allergic inflammatory responses to assess the effects of BaP (50µg/mouse per day) in a 23-d toxicity test in antigen-induced allergic female mice. In addition, genome annotation, quantitative analysis of BaP, and in vitro cytotoxicity-tests using CaCo-2 cells were conducted to infer the role of intestinal bacteria in BaP detoxification. RESULTS: BaP exposure impacted the taxonomic composition and the functional potential of the gut microbiota and aggravated antigen-induced intestinal allergic inflammatory responses. The level of inflammatory cytokines correlated with the abundance of specific bacterial taxa, including Lachnospiraceae bacterium 28-4 and Alistipes inops. We identified 614 bacteria harboring genes implicated in the degradation of BaP, and 4 of these bacterial strains were shown to significantly reduce the cytotoxicity of BaP to CaCo-2 cells in vitro. DISCUSSION: Using allergic female mice as a model, we investigated the relationship between BaP, microbiota, and host immune reactions, highlighting the role of gut bacteria in BaP-aggravated allergic reactions. Our findings offer novel insight toward establishing the causal relationship between BaP exposure and the occurrence of allergic disorders. Identifying gut bacteria that degrade BaP may provide new strategies for ameliorating BaP cytotoxicity. https://doi.org/10.1289/EHP11874.
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Microbioma Gastrointestinal , Hipersensibilidad , Humanos , Femenino , Animales , Ratones , Ovalbúmina/farmacología , Células CACO-2 , Inflamación , BacteriasRESUMEN
Fuji is susceptible to fungal diseases like apple powdery mildew. Non-expressor of pathogenesis-related gene 1 (NPR1) plays a key role in regulating salicylic acid (SA)-mediated systemic acquired resistance (SAR). Previous studies show that overexpressing the Malus hupehensis-derived NPR1 (MhNPR1) gene in tobacco induces the transcript expression of pathogenesis-related genes (PRs) and resistance to the fungus Botrytis cinerea. In this study we introduced the MhNPR1 gene into the 'Fuji' apple via Agrobacterium-mediated transformation. Four transgenic apple lines were verified by PCR and RT-PCR. The semi-quantitative RT-PCR results showed that transcript overexpression of the MhNPR1 gene induced the expression of MdPRs and MdMLO genes known to interact with powdery mildew. Furthermore, the transgenic apple plants resisted infection by apple powdery mildew better than the wild-type plants. As a result, transcript overexpression of the MhNPR1 gene induced SAR and enhanced the Fuji apple's resistance to fungal disease.
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Malus/genética , Malus/inmunología , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/inmunología , Proteínas de Plantas/genética , Expresión Génica , Regulación de la Expresión Génica de las Plantas , Malus/microbiología , Fenotipo , Plantas Modificadas GenéticamenteRESUMEN
QT interval prolongation and ventricular arrhythmias (VAs) induced by osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, are life-threatening complications. However, no consensus has been achieved regarding their management. Overdrive pacing has been shown to be effective in shortening the QT interval and terminating torsade de pointes (TdP). Here, we report a case of osimertinib-induced QT prolongation accompanied by frequent VAs and TdP. Osimertinib was immediately discontinued after it was identified as the etiology for QT prolongation and VAs. A temporary pacemaker and overdrive pacing were used after other anti-arrhythmia treatments had failed and successfully shortened the QTc interval and terminated VAs. Repeated Holter monitoring at 1 week showed no remaining VAs or TdP, and the pacemaker was removed. Routine electrocardiography (ECG) surveillance was conducted afterward, and three- and 6-month follow-ups showed good recovery and normal ECG results. Vigilance is required for rare vital arrhythmias in patients taking osimertinib, and ECG surveillance should be conducted.
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Clarifying the distribution pattern and overlapping relationship of sympatric relative species in the spatio-temporal niche is of great significance to the basic theory of community ecology and integrated management of multi-species habitats in the same landscape. In this study, based on a 9-year dataset (2012-2021) from 493 camera-trap sites in the Gongga Mountain National Nature Reserve, we analyzed the habitat distributions and activity patterns of tufted deer (Elaphodus cephalophus) and sambar (Rusa unicolor). (1) Combined with 235 and 153 valid presence sites of tufted deer and sambar, the MaxEnt model was used to analyze the distribution of the two species based on 11 ecological factors. The distribution areas of the two species were 1038.40 km2 and 692.67 km2, respectively, with an overlapping area of 656.67 km2. Additionally, the overlap indexes Schoener's D (D) and Hellinger's-based I (I) were 0.703 and 0.930, respectively. (2) Based on 10,437 and 5203 independent captures of tufted deer and sambar, their daily activity rhythms were calculated by using the kernel density estimation. The results showed that the daily activity peak in the two species appeared at dawn and dusk; however, the activity peak in tufted deer at dawn and dusk was later and earlier than sambar, respectively. Our findings revealed the spatio-temporal niche relationship between tufted deer and sambar, contributing to a further understanding of the coexistence mechanism and providing scientific information for effective wild animal conservation in the reserve and other areas in the southeastern edge of the Qinghai-Tibetan Plateau.
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Photoresponsive materials have been widely used in sensing, bioimaging, molecular switches, information storage, and encryption nowadays. Although a large amount of photoresponsive materials have been reported, the construction of these smart materials into precisely prescribed complex 3D geometries is rarely studied. Here we designed a novel photoresponsive material methyl methacrylate containing triphenylethylene (TrPEF2-MA) that can be directly used for digital light processing (DLP) 3D printing. Based on TrPEF2-MA, a series of photoresponsive 3D structures with reversible color switching under ultraviolet/visible light irradiations were fabricated. These complex photoresponsive 3D structures show high resolutions (50 µm), excellent repeatability (25 cycles without fatigue), and tunable saturate color degrees. Multicomponent DLP 3D printing processes were also carried out to demonstrate their great properties in information hiding and information-carrying properties. This design strategy for constructing photoresponsive 3D structures is attractive in the area of adaptive camouflage, information hiding, information storage, and flexible electronics.
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Rhythm control is the core part of the integrated management of atrial fibrillation (AF), especially in the early stages. Despite advances in catheter ablation (CA), the recurrence rate of AF after CA remains high. As a result, stratification and early management of AF recurrence after CA are critical. Currently, predictors of recurrence of AF after CA are mostly based on dysfunction caused by structural remodeling, apart from traditional risk factors. Atrial strain is a recently developed important parameter for detecting the deformability of atrial myocardium during the cardiac cycle prior to atrial remodeling. Although there is only preliminary evidence, atrial strain is still a promising parameter in predicting the recurrence of AF after CA at an early stage. This review focuses on the evaluation of atrial strain, the current applications of atrial strain in assessing atrial function, and predicting the recurrence of AF after CA. We summarize the contents related as follows: (1) CA for rhythm control in AF; (2) Evaluation methods of atrial strain; (3) Atrial strain in the remodeling and reverse remodeling of AF; and (4) Clinical applications of atrial strain in predicting the recurrence of AF after CA. Although there is accumulating evidence on the role of decreased atrial strain in the early prediction of AF recurrence, atrial strain is limited in clinical practice for lacking exact cut-off values and difficulty in distinguishing specific function phases of the atrium. More research is needed in the future to add strength to the early prediction value of atrial strain in AF recurrences.
RESUMEN
The intestine, a high-turnover tissue, plays a critical role in regulating aging and health in both vertebrates and invertebrates. Maintaining the epithelial barrier function of the intestine by preserving innate immune homeostasis significantly delays aging and prevents mortality. In an effort to explore effective chemicals and materials that can improve intestinal integrity, we performed a nonbiased screen utilizing Drosophila as an animal model. We showed that long-term uptake of aspirin markedly prevented age-onset gut leakage, the over-proliferation of intestinal stem cells, and the dysbiosis of commensal microbiota in fruit flies. Mechanistically, aspirin efficiently downregulated chronic activation of intestinal immune deficiency signaling during aging. Furthermore, our in vivo and in vitro biochemical analyses indicated that aspirin is a negative modulator in control of the K63-linked ubiquitination of Imd. Our findings uncover a novel regulatory mechanism by which aspirin positively modulates intestinal homeostasis, thus delaying aging, in Drosophila.
RESUMEN
Photodeformable materials are a class of molecules that can convert photon energy into mechanical energy, which have attracted tremendous attention in the last few decades. Owing to their unique photoinduced deformable properties, including fast light-response and diverse mechanical behaviors, photodeformable materials have exhibited great potential in many practical applications such as actuators, photoswitches, artificial muscles, and bioimaging. In this review, we sort out the current state of photodeformable crystals and classify them into six categories by molecular structures: diarylethenes, azobenzenes, anthracenes, olefins, triarylethylenes, and other systems. Three distinct light-responsive mechanisms, photocyclization, trans-cis isomerization, and photodimerization, are revealed to play significant roles in the molecular photodeformation. Their corresponding photodeformable behaviors such as twisting, bending, hopping, bursting, and curling, as well as the potential applications, are also discussed. Furthermore, the challenges and prospective development directions of photodeformable crystals are highlighted.