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Birds are descended from non-avialan theropod dinosaurs of the Late Jurassic period, but the earliest phase of this evolutionary process remains unclear owing to the exceedingly sparse and spatio-temporally restricted fossil record1-5. Information about the early-diverging species along the avialan line is crucial to understand the evolution of the characteristic bird bauplan, and to reconcile phylogenetic controversies over the origin of birds3,4. Here we describe one of the stratigraphically youngest and geographically southernmost Jurassic avialans, Fujianvenator prodigiosus gen. et sp. nov., from the Tithonian age of China. This specimen exhibits an unusual set of morphological features that are shared with other stem avialans, troodontids and dromaeosaurids, showing the effects of evolutionary mosaicism in deep avialan phylogeny. F. prodigiosus is distinct from all other Mesozoic avialan and non-avialan theropods in having a particularly elongated hindlimb, suggestive of a terrestrial or wading lifestyle-in contrast with other early avialans, which exhibit morphological adaptations to arboreal or aerial environments. During our fieldwork in Zhenghe where F. prodigiosus was found, we discovered a diverse assemblage of vertebrates dominated by aquatic and semi-aquatic species, including teleosts, testudines and choristoderes. Using in situ radioisotopic dating and stratigraphic surveys, we were able to date the fossil-containing horizons in this locality-which we name the Zhenghe Fauna-to 148-150 million years ago. The diversity of the Zhenghe Fauna and its precise chronological framework will provide key insights into terrestrial ecosystems of the Late Jurassic.
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Aves , Dinosaurios , Fósiles , Animales , China , Dinosaurios/anatomía & histología , Dinosaurios/clasificación , Ecosistema , Mosaicismo , Filogenia , Aves/anatomía & histología , Aves/clasificación , Historia Antigua , Miembro PosteriorRESUMEN
The human FACT (facilitates chromatin transcription) complex, composed of two subunits SPT16 (Suppressor of Ty 16) and SSRP1 (Structure-specific recognition protein-1), plays essential roles in nucleosome remodeling. However, the molecular mechanism of FACT reorganizing the nucleosome still remains elusive. In this study, we demonstrate that FACT displays dual functions in destabilizing the nucleosome and maintaining the original histones and nucleosome integrity at the single-nucleosome level. We found that the subunit SSRP1 is responsible for maintenance of nucleosome integrity by holding the H3/H4 tetramer on DNA and promoting the deposition of the H2A/H2B dimer onto the nucleosome. In contrast, the large subunit SPT16 destabilizes the nucleosome structure by displacing the H2A/H2B dimers. Our findings provide mechanistic insights by which the two subunits of FACT coordinate with each other to fulfill its functions and suggest that FACT may play essential roles in preserving the original histones with epigenetic identity during transcription or DNA replication.
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Proteínas de Unión al ADN/metabolismo , Proteínas del Grupo de Alta Movilidad/metabolismo , Nucleosomas/metabolismo , Factores de Elongación Transcripcional/metabolismo , Animales , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cromatina/metabolismo , ADN/metabolismo , Replicación del ADN , Proteínas de Unión al ADN/genética , Proteínas del Grupo de Alta Movilidad/genética , Histonas/metabolismo , Humanos , Modelos Moleculares , Nucleosomas/genética , Unión Proteica , Multimerización de Proteína , Proteínas de Saccharomyces cerevisiae/metabolismo , Células Sf9 , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factores de Elongación Transcripcional/genéticaRESUMEN
Mesozoic fossils of frogs are rare in the palaeontological record, particularly those exhibiting soft tissues that offer limited insights into early life-history characteristics. Here we report on a skeletally immature frog from the Lower Cretaceous of northwest China, with egg masses in the body and eggs in the oviduct, indicative of a gravid female. CT reconstruction of the specimen allows referral to Gansubatrachus qilianensis and we assign it as a paratype complementing the diagnosis of the type species. The new fossil, which might represent a younger individual than the holotype of Gansubatrachus, shows that sexual maturation occurred before full adulthood in this frog and provides evidence of death linked to mating behaviour. We also discuss other potential sources of variation and life-history traits of Gansubatrachus. The new finding represents the oldest Early Cretaceous frog preserving in situ eggs and provides a glimpse into ancient anuran development during Mesozoic times.
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Fósiles , Rasgos de la Historia de Vida , Animales , Femenino , Anuros , Paleontología , China , FilogeniaRESUMEN
In eukaryotes, the packaging of genomic DNA into chromatin plays a critical role in gene regulation. However, the dynamic organization of chromatin fibers and its regulatory mechanisms remain poorly understood. Using single-molecule force spectroscopy, we reveal that the tetranucleosomes-on-a-string appears as a stable secondary structure during hierarchical organization of chromatin fibers. The stability of the tetranucleosomal unit is attenuated by histone chaperone FACT (facilitates chromatin transcription) in vitro. Consistent with in vitro observations, our genome-wide analysis further shows that FACT facilitates gene transcription by destabilizing the tetranucleosomal unit of chromatin fibers in yeast. Additionally, we found that the linker histone H1 not only enhances the stability but also facilitates the folding and unfolding kinetics of the outer nucleosomal wrap. Our study demonstrates that the tetranucleosome is a regulatory structural unit of chromatin fibers beyond the nucleosome and provides crucial mechanistic insights into the structure and dynamics of chromatin fibers during gene transcription.
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ADN de Hongos/química , Proteínas de Unión al ADN/química , Regulación Fúngica de la Expresión Génica , Proteínas del Grupo de Alta Movilidad/química , Histonas/química , Nucleosomas/genética , Proteínas de Saccharomyces cerevisiae/química , Transcripción Genética , Factores de Elongación Transcripcional/química , Secuencia de Aminoácidos , ADN de Hongos/genética , ADN de Hongos/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Proteínas del Grupo de Alta Movilidad/genética , Proteínas del Grupo de Alta Movilidad/metabolismo , Histonas/genética , Histonas/metabolismo , Modelos Moleculares , Nucleosomas/metabolismo , Nucleosomas/ultraestructura , Pliegue de Proteína , Multimerización de Proteína , Estabilidad Proteica , Estructura Secundaria de Proteína , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/ultraestructura , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Imagen Individual de Molécula , Factores de Elongación Transcripcional/genética , Factores de Elongación Transcripcional/metabolismoRESUMEN
Objective: The objective of this study was to investigate the transition readiness of juvenile epilepsy patients during the transition period from childhood to adulthood and analyze the impact of patients' basic characteristics and self-management on their transition readiness. Methods: A total of 376 adolescent epileptic patients were selected as research objects from 3A general hospitals located in Chongqing, Guizhou, and Yunnan respectively, and a 3A children's specialist hospital in Chongqing, Jiangxi from May 2021 to February 2022. The readiness for transition was assessed using a transition readiness questionnaire, and patients' self-management skills were evaluated using the Self-Management Scale for Epilepsy Patients. Data analysis was conducted to determine the readiness for transition and examine the factors influencing it. Results: The mean overall transition readiness score in adolescent epilepsy patients was (56.60±12.51). Among the six dimensions, drug management, disease understanding, doctor-patient interaction, health responsibility, medical involvement, and resource utilization were ranked highest to lowest. The examination identified age, epilepsy duration, medication types, and primary caregivers as the primary factors influencing transition readiness in adolescent epilepsy patients (P < .001). Additionally, there was a favorable correlation between the total disease self-management score and transition readiness (r=0.487, P < .01), signifying the positive predictive impact of self-management skills on transition readiness. Conclusion: Adolescent epilepsy patients exhibited moderate readiness for the transition from childhood to adulthood. Older patients with longer disease duration and stronger self-management skills displayed a higher level of readiness. Targeted clinical interventions that prioritize self-management skills are essential for facilitating a smoother transition into adulthood for patients.
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BACKGROUND: Malnutrition and cachexia are common syndromes in patients with gastric cancer (GC) and are associated with poor quality of life and poor disease prognosis. However, there is still a lack of molecular factors that can predict malnutrition or cachexia in cancer. Studies have shown that among the potential contributors to the development of cancer cachexia, the level of the inflammatory response to P-selectin is regulated by single nucleotide polymorphisms (SNPs) located in the promoter region of the SELP gene. The aim of this study was to evaluate the association between the single nucleotide polymorphism (SNP)-2028 A/G of the SELP gene and malnutrition in patients receiving chemotherapy for gastric cancer (GC). METHODS: The study group consisted of 220 GC patients treated with chemotherapy at Jinhua Municipal Central Hospital. DNA was extracted from peripheral leukocytes of whole blood samples using an animal DNA extraction kit. DNA was amplified using a 1.1 × T3 Super PCR mix, and loci corresponding to the peaks were genotyped using SNP1 software. RESULTS: Patients carrying the A allele had a reduced risk of developing malnutrition compared to patients with the GG genotype (P < 0.001; OR = 3.411; 95% CI = 1.785-6.516). In addition, multivariate analysis indicated that the AA genotype significantly (more than 16-fold) reduced the risk of developing malnutrition (P < 0.001; OR = 0.062; 95% CI = 0.015-0.255). CONCLUSION: SELP -2028A/G SNP may be a useful marker for assessing the risk of malnutrition in GC patients.
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Desnutrición , Neoplasias Gástricas , Animales , Humanos , Caquexia/genética , Estudios de Casos y Controles , ADN , Predisposición Genética a la Enfermedad , Genotipo , Desnutrición/genética , Polimorfismo de Nucleótido Simple , Calidad de Vida , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genéticaRESUMEN
INTRODUCTION: To investigate the correlation between home blood pressure variability and cognitive function in maintenance hemodialysis (MHD) patients. METHODS: Patients who received MHD were included. Their home blood pressure on nondialysis days within 1 week was collected. All patients were assessed with the Montreal Cognitive Assessment scale, according to which the patients were divided into cognitive impairment (CI) group and non-CI group, and the differences between two groups were compared. RESULTS: A total of 224 patients were included in the study, of which 168 had CI (75%). Compared with non-CI group, patients in CI group had larger variability of systolic blood pressure (SBPV) (8.4 [6.7, 10.6]% vs. 6.9 [4.9, 8.8]%, P < 0.001). The smooth fitting curve (OR = 1.2, 95% CI [1.1-1.4], P < 0.001) and trend test (P for trend = 0.004) showed that the risk of CI raised with the increase of SBPV. The patients were further divided into tertiles according to the SBPV. We also found a gradual increase in the proportion of incident CI in the three tertiles. Multiple logistic regression analysis showed that age, shorter years of education, less frequency of hemodialysis, and greater SBPV were the dependent risk of CI. CONCLUSION: In conclusion, greater SBPV indicates higher risk of cognitive impairment in MHD patients.
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Disfunción Cognitiva , Diálisis Renal , Presión Sanguínea , Disfunción Cognitiva/etiología , Humanos , Diálisis Renal/efectos adversosRESUMEN
Until recently, regional cerebral blood flow (rCBF) in major depressive disorder (MDD) patients treated with electroconvulsive therapy (ECT) using arterial spin labeling (ASL) magnetic resonance imaging (MRI) have seldom been studied. We report here 10 patients with MDD treated by bilateral frontotemporal ECT. rCBF was assessed with ASL MRI pre- and post-ECT, and compared with patients treated by antidepressants. Compared to pre-ECT, rCBF significantly decreased in the bilateral frontal gyrus. Compared to medication, in patients treated with ECT, rCBF showed a significant decrease in the left amygdala, parahippocampal and olfactory gyrus, and right occipital, lingual, calcarine gyrus, and significantly increased in the bilateral frontal gyrus and right frontal gyrus. Compared with antidepressants, ECT altered rCBF, and showed potential to be a superior treatment for major depressive disorder.
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Trastorno Depresivo Mayor , Terapia Electroconvulsiva , Encéfalo , Circulación Cerebrovascular/fisiología , Depresión , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/patología , Trastorno Depresivo Mayor/terapia , Humanos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Marcadores de SpinRESUMEN
The swan goose (Anser cygnoides) is the ancestor of the Chinese domestic goose. A previous study reported a scaffold-level genome version for a Chinese indigenous goose breed, and this assembly was used as the swan goose's reference genome. To date, there is still a lack of a chromosome-level genome for the swan goose. Here, we reported a de novo assembly of the genome of a wild swan goose using an integrated strategy that combines Illumina Hiseq, Oxford Nanopore and chromosome conformation capture (Hi-C) sequencing. A total of 134.6 Gb Nanopore data with sequencing coverage of 110.33 and 69.45 Gb Illumina data with coverage of 56.93 were obtained. The genome assembly size was 1153.41 Mb, with a contig N50 of 22.75 Mb. The total size and N50 length of our assembly were larger than the previously reported scaffold-level genome version. In addition, whole-genome sequencing data of 10 geese were mapped to the previous and the current assemblies. On average, 97.88 and 93.18% of the reads were properly mapped and paired into our and the previous assemblies. This high-quality chromosome-level swan goose genome could provide a valuable resource for the utilisation of goose studies and breeding.
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Gansos , Genoma , Animales , Gansos/genética , Secuenciación Completa del Genoma/veterinaria , Cromosomas/genética , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
BACKGROUND: Pyogenic granuloma (PG) is a common vascular neoplasm in children. Data on 595 nm pulsed dye lasers for the treatment of PG in children remain scarce. OBJECTIVE: To summarize the clinical characteristics and to evaluate the effectiveness and safety of the 595 nm pulsed dye laser for the treatment of PG in children. STUDY DESIGN: Retrospective case series. METHODS: A retrospective study was performed on 212 patients treated for PG with a 595 nm pulsed dye laser. SPSS version 19.0 was used for statistical analysis. RESULTS: Among all 212 patients treated, 208 showed complete resolution of the lesion, and 4 dropped out after one treatment due to bleeding. A single treatment was sufficient in 139 (66.8%) patients, while two or three treatments were sufficient in 69 (33.2%) patients. Male patients responded better than female patients (χ2 = 7.603, p =0.006). Lesions in the nonorbital region responded better than those in the orbital region (χ2 = 7.445, p =0.006). The size of the lesion affected the effectiveness, and lesions with smaller diameters (t = -5.776, p <0.01) and heights (t = -10.368, p <0.01) showed better results. COMPLICATIONS AND SIDE EFFECTS: Twelve patients (5.8%) were reported to have local complications and side effects, including edematous erythema, slight bleeding, hyperpigmentation, and hypopigmentation. The edematous erythema and slight bleeding disappeared gradually after several days. The localized pigment changes usually resolved spontaneously and disappeared completely after 6 months. CONCLUSIONS: Our experience confirmed the efficacy and safety of the 595 nm pulsed dye laser for the treatment of PG in children.
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Granuloma Piogénico , Láseres de Colorantes , Niño , Eritema , Femenino , Granuloma Piogénico/cirugía , Humanos , Láseres de Colorantes/uso terapéutico , Masculino , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Pedicle length deficiency in microsurgical procedure is a challenging issue. The aim of this report is to present a case series of a flap-splitting technique for pedicle lengthening of large multiple perforator-based (MPB) free flaps. METHODS: In this retrospective case series, we reviewed the medical records of patients who underwent free flap repair with "split flap" pedicle-lengthening technique between August 2017 and December 2021. Main outcome measures included patient demographics, indications, defect size, flap type, additional vascular pedicle length, and flap survival. RESULTS: Data from 16 patients (age 38-78 years) were reviewed. Indications included breast reconstruction, repair of scalp malignancy or titanium mesh implant exposure, and repair of burn scar contracture. Flaps included ALT flap, LD flap and DIEP flap. The mean added pedicle length was 3.8 cm. Fifteen flaps survived completely and one flap was necrotic distally. No major complications occurred. CONCLUSIONS: The 'split flap' technique could be an effective remedy for unexpected pedicle length deficiencies in large MPB free flaps.
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Contractura , Colgajos Tisulares Libres , Mamoplastia , Colgajo Perforante , Procedimientos de Cirugía Plástica , Adulto , Anciano , Contractura/etiología , Colgajos Tisulares Libres/cirugía , Humanos , Mamoplastia/métodos , Persona de Mediana Edad , Colgajo Perforante/irrigación sanguínea , Procedimientos de Cirugía Plástica/métodos , Estudios RetrospectivosRESUMEN
OBJECTIVE: To analyze the incidence, phenotype, genotype and prognosis of neonatal medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in Zibo city of Shandong province. METHODS: A total of 241 297 neonates were screened for MCADD in Zibo city of Shandong province from November 2013 to January 2022. Non-derivatized tandem mass spectrometry was used to detect blood free carnitine and acylcarnitine profiles in neonatal screening. Neonates with octanoylcarnitine (C8)≥0.25â µmol/L, or combined with C8/decanoylcarnitine (C10)≥1.5 were recalled, and second-generation high-throughput sequencing was performed for genetic diagnosis. RESULTS: Among 241â 297 neonates, 6 cases of MCADD were screened, including 2 boys and 4 girls, with an incidence of 1/40 216. Two mutation sites of ACADM gene were identified in all MCADD infants, and 12 mutation with 8 types were detected in total. The hot spot mutations were c.449_452del (p.T150Rfs*4) and c.387+1delGï¼ and exon 11 c.1076C>T (p.A359V) was a newly detected mutation. No phenotype-genotype correlation was found. One case died on day 4 after birth; 5 cases were followed up for 2 to 60â months, none of them received special diet treatment. The growth and intellectual development of the surviving cases were normal, and no abnormality was found in routine biochemical indicators. CONCLUSIONS: The incidence of MCADD in Zibo city seems to be higher than that in other areas in China. The ACADM gene mutations c.449_452del (p.T150Rfs*4) and c.387+1delG are common, and a new mutation c.1076C>T (p.A359V) has been detected. No phenotype-genotype correlation has been found. Early diagonsis and treatment are effective measures to reduce poor prognosis.
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Errores Innatos del Metabolismo Lipídico , Acil-CoA Deshidrogenasa/deficiencia , Acil-CoA Deshidrogenasa/genética , Carnitina , Estudios de Seguimiento , Humanos , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/genética , MutaciónRESUMEN
Colorectal cancer (CRC) is the third most common solid tumor worldwide and has shown resistance to several immunotherapies, particularly immune checkpoint blockade therapy, which is effective in many other types of cancer. Our previous studies indicated that the active fraction of Garcinia yunnanensis (YTE-17), had potent anticancer activities by regulating multiple signaling pathways. However, knowledge regarding the mechanism and effect of YTE-17 in the prevention of CRC is limited. This study tested the effects of YTE-17 on colon cancer development in vivo by using two murine models: the carcigenic azoxymethane/dextran sulfate sodium (AOM/DSS)-induced CRC model and a genetically induced model using ApcMin/+ mice. Here, the tumor load, tumor number, histology, and even some oncogenes were used to evaluate the effect of YTE-17. The intragastric administration of YTE-17 for 12 weeks significantly decreased CRC incidence, tumor number and size, immunity, and some tumor-associated macrophage (TAM) markers, including CD206, Arg-1, IL-10, and TGF-ß. Importantly, the macrophages depletion by clodronate (CEL) also played a role in reducing the tumor burden and inhibiting tumor development, which were not affected by YTE-17 in the ApcMin/+ mice. Moreover, the YTE-17 treatment attenuated CRC cell growth in a co-culture system in the presence of macrophages. Consistently, YTE-17 effectively reduced the tumor burden and macrophage infiltration and enhanced immunity in the AOM/DSS and ApcMin/+ colon tumor models. Altogether, we demonstrate that macrophages in the microenvironment may contribute to the development and progression of CRC cells and propose YTE-17 as a new potential drug option for the treatment of CRC.
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Polaridad Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Garcinia/química , Macrófagos/efectos de los fármacos , Preparaciones de Plantas/farmacología , Animales , Antineoplásicos/farmacología , Azoximetano/farmacología , Línea Celular , Línea Celular Tumoral , Transformación Celular Neoplásica/efectos de los fármacos , Transformación Celular Neoplásica/metabolismo , Transformación Celular Neoplásica/patología , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Sulfato de Dextran/farmacología , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Activación de Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Preparaciones de Plantas/química , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacosRESUMEN
BACKGROUND: Major depressive disorder (MDD) with comorbid borderline personality disorder (BPD) makes the clinical symptoms of patients more complex and more difficult to treat, so more attention should be paid to the recognition of their clinical features. This study investigated the differences between patients with MDD with and without BPD in clinical traits. METHODS: Propensity score matching was used to analyze the retrospective patients' data from August 2012 to September 2019. Altogether, 1381 patients with MDD were enrolled; 38 patients with MDD were matched to compare demographic data, and scores on the Hamilton Depression Scale, Hamilton Anxiety Scale (HAMA), Self-Rating Depression Scale (SDS), Modified Overt Aggression Scale (MOAS), and the frequency of nonsuicidal self-harm (NSSH). RESULTS: Compared to patients with MDD without BPD, the age of onset of patients with MDD with comorbid BPD was significantly earlier (t = 3.25, p = .00). The scores of HAMA (t = -2.28, p = .03), SDS (t = 9.31, p = .00), MOAS (t = -13.67, p = .00), verbal aggression (t = -3.79, p = .00), aggression against objects (t = -2.84, p = .00), aggression against others (t = -6.70, p = .00), and aggression against self (t = -9.22, p = .00) were significantly higher in patients with MDD with comorbid BPD. Moreover, the frequency of NHSS in these patients was significantly higher (χ2 = 20.13, p = .00). MOAS was an independent influencing factor in these (odds ratio = 7.38, p = .00). CONCLUSIONS: Patients with BPD showed early onset and increased complaints relative to symptoms, accompanied by obvious anxiety symptoms, impulsive behavior, and NSSH. Therefore, patients with MDD with impulsive behavior have comorbid BPD.
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Trastorno de Personalidad Limítrofe , Trastorno Depresivo Mayor , Trastorno de Personalidad Limítrofe/epidemiología , Comorbilidad , Trastorno Depresivo Mayor/epidemiología , Humanos , Conducta Impulsiva , Puntaje de Propensión , Estudios RetrospectivosRESUMEN
Hemodialysis patients are susceptible to coronavirus disease 2019 (COVID-19). The aim of this study was to describe the epidemiological, clinical characteristics, and mortality-related risk factors for those who undergoing hemodialysis with COVID-19. We conducted a retrospective study. A total of 49 hemodialysis patients with COVID-19 (Group 1) and 74 uninfected patients (Group 2) were included. For patients in Group 1, we found the median age was 62 years (36-89 years), 59.3% were male, and the median dialysis vintage was 26 months. Twenty-eight patients (57%) had three or more comorbidities and two patients (4%) died. The most common symptoms were fever (32.7%) and dry cough (46.9%), while nine patients (18.4%) were asymptomatic. Blood routine tests indicated lymphocytopenia, the proportion of lymphocyte subsets was generally reduced, and chest CT scans showed ground-glass opacity (45.8%) and patchy shadowing (35.4%). However, these findings were not specific to hemodialysis patients with COVID-19, and similar manifestations could be found in patients without SARS-CoV-2 infection. In conclusion, for hemodialysis patients with COVID-19, lymphocytopenia and ground-glass opacities or patchy opacities were common but not specific to them, early active treatment and interventions against nosocomial infection can significantly reduce the mortality and the risk of SARS-CoV-2 infection.
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COVID-19/complicaciones , Diálisis Renal , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , COVID-19/mortalidad , China/epidemiología , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía Viral/epidemiología , Neumonía Viral/mortalidad , Neumonía Viral/virología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , SARS-CoV-2RESUMEN
DNA methylation is an important epigenetic modification that is essential for various developmental processes through regulating gene expression, genomic imprinting, and epigenetic inheritance. Mammalian genomic DNA methylation is established during embryogenesis by de novo DNA methyltransferases, DNMT3A and DNMT3B, and the methylation patterns vary with developmental stages and cell types. DNA methyltransferase 3-like protein (DNMT3L) is a catalytically inactive paralogue of DNMT3 enzymes, which stimulates the enzymatic activity of Dnmt3a. Recent studies have established a connection between DNA methylation and histone modifications, and revealed a histone-guided mechanism for the establishment of DNA methylation. The ATRX-DNMT3-DNMT3L (ADD) domain of Dnmt3a recognizes unmethylated histone H3 (H3K4me0). The histone H3 tail stimulates the enzymatic activity of Dnmt3a in vitro, whereas the molecular mechanism remains elusive. Here we show that DNMT3A exists in an autoinhibitory form and that the histone H3 tail stimulates its activity in a DNMT3L-independent manner. We determine the crystal structures of DNMT3A-DNMT3L (autoinhibitory form) and DNMT3A-DNMT3L-H3 (active form) complexes at 3.82 and 2.90 Å resolution, respectively. Structural and biochemical analyses indicate that the ADD domain of DNMT3A interacts with and inhibits enzymatic activity of the catalytic domain (CD) through blocking its DNA-binding affinity. Histone H3 (but not H3K4me3) disrupts ADD-CD interaction, induces a large movement of the ADD domain, and thus releases the autoinhibition of DNMT3A. The finding adds another layer of regulation of DNA methylation to ensure that the enzyme is mainly activated at proper targeting loci when unmethylated H3K4 is present, and strongly supports a negative correlation between H3K4me3 and DNA methylation across the mammalian genome. Our study provides a new insight into an unexpected autoinhibition and histone H3-induced activation of the de novo DNA methyltransferase after its initial genomic positioning.
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ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , ADN (Citosina-5-)-Metiltransferasas/química , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Histonas/química , Histonas/metabolismo , Animales , Dominio Catalítico , Cristalografía por Rayos X , ADN/metabolismo , Metilación de ADN , ADN Metiltransferasa 3A , Activación Enzimática , Humanos , Ratones , Modelos Moleculares , Estructura Terciaria de Proteína , Xenopus laevisRESUMEN
Brain edema is a common and serious complication of ischemic stroke with limited effective treatment. We previously reported that methylene blue (MB) attenuated ischemic brain edema in rats, but the underlying mechanisms remained unknown. Aquaporin 4 (AQP4) in astrocytes plays a key role in brain edema. We also found that extracellular signal-regulated kinase 1/2 (ERK1/2) activation was involved in the regulation of AQP4 expression in astrocytes. In the present study, we investigated whether AQP4 and ERK1/2 were involved in the protective effect of MB against cerebral edema. Rats were subjected to transient middle cerebral artery occlusion (tMCAO), MB (3 mg/kg, for 30 min) was infused intravenously through the tail vein started immediately after reperfusion and again at 3 h after ischemia (1.5 mg/kg, for 15 min). Brain edema was determined by MRI at 0.5, 2.5, and 48 h after tMCAO. The decreases of apparent diffusion coefficient (ADC) values on diffusion-weighted MRI indicated cytotoxic brain edema, whereas the increase of T2 MRI values reflected vasogenic brain edema. We found that MB infusion significantly ameliorated cytotoxic brain edema at 2.5 and 48 h after tMCAO and decreased vasogenic brain edema at 48 h after tMCAO. In addition, MB infusion blocked the AQP4 increases and ERK1/2 activation in the cerebral cortex in ischemic penumbra at 48 h after tMCAO. In a cell swelling model established in cultured rat astrocyte exposed to glutamate (1 mM), we consistently found that MB (10 µM) attenuated cell swelling, AQP4 increases and ERK1/2 activation. Moreover, the ERK1/2 inhibitor U0126 (10 µM) had the similar effects as MB. These results demonstrate that MB improves brain edema and astrocyte swelling, which may be mediated by the inhibition of AQP4 expression via ERK1/2 pathway, suggesting that MB may be a potential choice for the treatment of brain edema.
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Acuaporina 4/antagonistas & inhibidores , Edema Encefálico/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Azul de Metileno/uso terapéutico , Animales , Animales Recién Nacidos , Astrocitos/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/patología , Edema Encefálico/etiología , Edema Encefálico/patología , Butadienos/farmacología , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/patología , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Nitrilos/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Ratas Sprague-DawleyRESUMEN
Thermal treatment and composting are effective methods of degrading antibiotics and organic matter in penicillin fermentation residues (PFR), respectively. However, the composting efficiency and environmental safety of thermally treated PFR (HT-PFR) remain unclear. In this study, HT-PFR was composted with cattle manure and maize straw at ratios of 0:1:1 (CK), 1.5:1:1 (T1), and 5:1:1 (T2). Changes in physicochemical properties, seed germination index (GI), and microbial antibiotic resistance genes (ARGs) were determined. Addition of HT-PFR significantly reduced the C:N ratio of each compost (P < 0.05) and prolonged the thermophilic stage. The GI of CK and T1 composts increased during processing, whereas that of T2 compost remained low. The PO43- concentrations of T1 and T2 composts were 6.3- and 11.1-fold higher than that of CK, respectively. HT-PFR contained relatively small amounts of mineral elements, and composting it with cattle manure and maize straw provided balanced nutrients for plant growth. After 52 days of composting, most ARGs of the microflora were reduced to low levels, but blaTEM increased significantly in T2 compost. Overall, composting HT-PFR at up to 42% of a mix containing equal parts of cattle manure and wheat straw is an environmentally safe and effective way of transforming it into organic fertilizer.
Asunto(s)
Compostaje , Animales , Bovinos , Fermentación , Estiércol , Penicilinas , SueloRESUMEN
OBJECTIVE: We retrospectively analyzed the data of 32 hemodialysis patients with COVID-19 to clarify the epidemiological characteristics of this special population. METHOD: The data of 32 hemodialysis patients with COVID-19, including epidemiological, demographic, clinical, laboratory, and radiological, were collected from the Blood Purification Department of Wuhan Fourth Hospital from February 3 to 16, 2020. RESULTS: Of the 32 patients, 23 were male, and the median age was 58 years; the median dialysis vintage was 33 months. Two groups were divided according to the patient's primary renal disease: group 1 (16 patients with diabetic nephropathy), group 2 (12 patients with primary glomerulonephritis, 2 with obstructive kidney disease, 1 with hypertensive renal damage, and 1 with polycystic kidney). No significant differences were observed between the two groups in epidemiological characteristics, blood cell counts, and radiological performance. Hemodialysis patients are susceptible to COVID-19 at all ages, and patients with diabetes may be a high-risk population (50%). Common symptoms included fever (15 cases), cough (21 cases), and fatigue (7 cases). The blood lymphocyte count decreased in 84.6% of the patients (median: 0.765 × 109/L). Chest CT revealed ground-glass-like lesions in 18 cases, unilateral lung patchiness in 7 cases, bilateral lung patchiness in 7 cases, and pleural effusion in 2 cases. CONCLUSION: Only 46.875% of the hemodialysis patients with COVID-19 had fever in the early stage; and diabetics may be the most susceptible population. A decrease in blood lymphocyte count and ground-glass opacity on chest CT scan is beneficial in identifying the high-risk population.
Asunto(s)
Infecciones por Coronavirus/epidemiología , Fallo Renal Crónico/complicaciones , Neumonía Viral/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Betacoronavirus , COVID-19 , China/epidemiología , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico por imagen , Femenino , Humanos , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/sangre , Neumonía Viral/complicaciones , Neumonía Viral/diagnóstico por imagen , Radiografía Torácica , Estudios Retrospectivos , SARS-CoV-2RESUMEN
Linker histone H1 has a key role in maintaining higher order chromatin structure and genome stability, but how H1 functions in these processes is elusive. Here, we report that acetylation of lysine 85 (K85) within the H1 globular domain is a critical post-translational modification that regulates chromatin organization. H1K85 is dynamically acetylated by the acetyltransferase PCAF in response to DNA damage, and this effect is counterbalanced by the histone deacetylase HDAC1. Notably, an acetylation-mimic mutation of H1K85 (H1K85Q) alters H1 binding to the nucleosome and leads to condensed chromatin as a result of increased H1 binding to core histones. In addition, H1K85 acetylation promotes heterochromatin protein 1 (HP1) recruitment to facilitate chromatin compaction. Consequently, H1K85 mutation leads to genomic instability and decreased cell survival upon DNA damage. Together, our data suggest a novel model whereby H1K85 acetylation regulates chromatin structure and preserves chromosome integrity upon DNA damage.