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Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized "pattern-block" correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning.
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Dermatoglifia , Dedos/crecimiento & desarrollo , Organogénesis/genética , Polimorfismo de Nucleótido Simple , Dedos del Pie/crecimiento & desarrollo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Pueblo Asiatico/genética , Tipificación del Cuerpo/genética , Niño , Estudios de Cohortes , Femenino , Miembro Anterior/crecimiento & desarrollo , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Humanos , Proteína del Locus del Complejo MDS1 y EV11/genética , Masculino , Ratones , Persona de Mediana Edad , Adulto JovenRESUMEN
Sirt2 is a nicotinamide adenine dinucleotide (NAD+)-dependent protein lysine deacylase that can remove both acetyl group and long-chain fatty acyl groups from lysine residues of many proteins. It was reported to affect inflammatory bowel disease (IBD) symptoms in a mouse model. However, conflicting roles were reported, with genetic knockout aggravating while pharmacological inhibition alleviating IBD symptoms. These seemingly conflicting reports cause confusion and deter further efforts in developing Sirt2 inhibitors as a potential treatment strategy for IBD. We investigated these conflicting reports and elucidated the role of Sirt2 in the mouse model of IBD. We essentially replicated these conflicting results and confirmed that Sirt2 inhibitors' protective effect is not through off-targets as two very different Sirt2 inhibitors (TM and AGK2) showed similar protection in the IBD mouse model. We believe that the differential effects of inhibitors and knockout are due to the fact that the Sirt2 inhibitors only inhibit some but not all the activities of Sirt2. This hypothesis is confirmed by the observation that a PROTAC degrader of Sirt2 did not protect mice in the IBD model, similar to Sirt2 knockout. Our study provides an interesting example where genetic knockout and pharmacological inhibition do not align and emphasizes the importance of developing substrate-dependent inhibitors. Importantly, we showed that the effect of Sirt2 inhibition in IBD is through regulating the gut epithelium barrier by inhibiting Arf6-mediated endocytosis of E-cadherin, a protein important for the intestinal epithelial integrity. This mechanistic understanding further supports Sirt2 as a promising therapeutic target for treating IBD.
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Colitis , Mucosa Intestinal , Sirtuina 2 , Animales , Humanos , Ratones , Cadherinas/metabolismo , Cadherinas/genética , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/prevención & control , Modelos Animales de Enfermedad , Furanos , Enfermedades Inflamatorias del Intestino/metabolismo , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/patología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Ratones Endogámicos C57BL , Ratones Noqueados , Quinolinas , Sirtuina 2/metabolismo , Sirtuina 2/antagonistas & inhibidores , Sirtuina 2/genéticaRESUMEN
Cysteine palmitoylation or S-palmitoylation catalyzed by the ZDHHC family of acyltransferases regulates the biological function of numerous mammalian proteins as well as viral proteins. However, understanding of the role of S-palmitoylation in antiviral immunity against RNA viruses remains very limited. The adaptor protein MAVS forms functionally essential prion-like aggregates upon activation by viral RNA-sensing RIG-I-like receptors. Here, we identify that MAVS, a C-terminal tail-anchored mitochondrial outer membrane protein, is S-palmitoylated by ZDHHC7 at Cys508, a residue adjacent to the tail-anchor transmembrane helix. Using superresolution microscopy and other biochemical techniques, we found that the mitochondrial localization of MAVS at resting state mainly depends on its transmembrane tail-anchor, without regulation by Cys508 S-palmitoylation. However, upon viral infection, MAVS S-palmitoylation stabilizes its aggregation on the mitochondrial outer membrane and thus promotes subsequent propagation of antiviral signaling. We further show that inhibition of MAVS S-palmitoylation increases the host susceptibility to RNA virus infection, highlighting the importance of S-palmitoylation in the antiviral innate immunity. Also, our results indicate ZDHHC7 as a potential therapeutic target for MAVS-related autoimmune diseases.
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Aciltransferasas , Proteínas Adaptadoras Transductoras de Señales , Inmunidad Innata , Lipoilación , Membranas Mitocondriales , Humanos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Membranas Mitocondriales/metabolismo , Aciltransferasas/metabolismo , Células HEK293 , Mitocondrias/metabolismo , Animales , Cisteína/metabolismo , Transducción de Señal/inmunología , Agregado de ProteínasRESUMEN
The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.
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Proteína 7 Similar a la Angiopoyetina , Proteína 1 Inhibidora de la Diferenciación , Leucemia Mieloide Aguda , Animales , Ratones , Proteína 7 Similar a la Angiopoyetina/genética , Proteína 7 Similar a la Angiopoyetina/metabolismo , Médula Ósea/metabolismo , Modelos Animales de Enfermedad , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Microambiente Tumoral , Humanos , Proteína 1 Inhibidora de la Diferenciación/metabolismoRESUMEN
Optofluidic time-stretch imaging flow cytometry (OTS-IFC) provides a suitable solution for high-precision cell analysis and high-sensitivity detection of rare cells due to its high-throughput and continuous image acquisition. However, transferring and storing continuous big data streams remains a challenge. In this study, we designed a high-speed streaming storage strategy to store OTS-IFC data in real-time, overcoming the imbalance between the fast generation speed in the data acquisition and processing subsystem and the comparatively slower storage speed in the transmission and storage subsystem. This strategy, utilizing an asynchronous buffer structure built on the producer-consumer model, optimizes memory usage for enhanced data throughput and stability. We evaluated the storage performance of the high-speed streaming storage strategy in ultra-large-scale blood cell imaging on a common commercial device. The experimental results show that it can provide a continuous data throughput of up to 5891 MB/s.
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Ultrashort optical pulse manipulation is one of the key techniques for applications such as high-speed imaging and high-precision laser processing. In this study, we demonstrate the multidimensional manipulation of ultrashort optical pulses by integrating spatial dispersion and spatial light modulation. Specifically, by modulating the phase of each wavelength, we achieve arbitrary adjustments in multiple dimensions, including number of sub pulses, time interval, intensity, and pulse width simultaneously and independently with a simple setup and few calculations. The performance of the optical pulse manipulation method is verified through both numerical simulations and experiments.
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The survival path mapping approach has been proposed for dynamic prognostication of cancer patients using time-series survival data. The SurvivalPath R package was developed to facilitate building personalized survival path models. The package contains functions to convert time-series data into time-slices data by fixed interval based on time information of input medical records. After the pre-processing of data, under a user-defined parameters on covariates, significance level, minimum bifurcation sample size and number of time slices for analysis, survival paths can be computed using the main function, which can be visualized as a tree diagram, with important parameters annotated. The package also includes function for analyzing the connections between exposure/treatment and node transitions, and function for screening patient subgroup with specific features, which can be used for further exploration analysis. In this study, we demonstrate the application of this package in a large dataset of patients with hepatocellular carcinoma, which is embedded in the package. The SurvivalPath R package is freely available from CRAN, with source code and documentation hosted at https://github.com/zhangt369/SurvivalPath.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Programas Informáticos , Factores de TiempoRESUMEN
BACKGROUND: Ptosis and upper eyelid depression were previously diagnosed as 2 separate diseases. The authors found that in patients with aponeurotic ptosis accompanied by upper eyelid depression, the main cause of upper eyelid depression was impaired dynamic transmission of the levator aponeurosis. OBJECTIVE: To analyze the causes of upper eyelid depression in patients with aponeurotic ptosis accompanied by upper eyelid depression and to introduce the best treatment methods. METHODS: The authors enrolled 15 eyes (11 patients) with aponeurotic ptosis accompanied by upper eyelid depression from October 2021 to August 2022. The authors analyzed the causes of upper eyelid depression in those patients and performed aponeurotic ptosis correction surgery and orbital septum fat release surgery. After 6 to 12 months of follow-up, the authors reviewed the patient's medical records and photographs to evaluate the treatment outcomes. RESULTS: After surgery, ptosis was corrected and upper eyelid depression significantly improved in all the patients. One patient had poor eyelid morphology and upper eyelid depression due to habitual brow lifting, which was relieved after an injection of botulinum toxin into the frontalis muscle. One patient had overcorrection of the upper eyelid depression on the affected side and no other complications. CONCLUSION: The main cause of upper eyelid depression in patients with aponeurotic ptosis is impaired dynamic transmission of the levator aponeurosis. Aponeurotic ptosis repair surgery and orbital septum fat release surgery are simple surgical procedures that restore the normal anatomy and physiology of the upper eyelid and maintain the normal structure of the eyelid, with good post-operative outcomes.
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Most soil ammonia (NH3) emissions originate from soil nitrogen (N) that has been in the form of exchangeable ammonium. Emitted NH3 not only induces nutrient loss but also has adverse effects on the cycling of N and accelerates global warming. There is evidence that arbuscular mycorrhizal (AM) fungi can alleviate N loss by reducing N2O emissions in N-limited ecosystems, however, some studies have also found that global changes, such as warming and N deposition, can affect the growth and development of AM fungi and alter their functionality. Up to now, the impact of AM fungi on NH3 emissions, and whether global changes reduce the AM fungi's contribution to NH3 emissions reduction, has remained unclear. In this study, we examined how warming, N addition, and AM fungi alter NH3 emissions from high pH saline soils typical of a temperate meadow through a controlled microscopic experiment. The results showed that warming significantly increased soil NH3 emissions, but N addition and combined warming plus N addition had no impact. Inoculations with AM fungi strongly reduced NH3 emissions both under warming and N addition, but AM fungi effects were more pronounced under warming than following N addition. Inoculation with AM fungi reduced soil NH4+-N content and soil pH, and increased plant N content and soil net N mineralization rate while increasing the abundance of ammonia-oxidizing bacterial (AOB) gene. Structural equation modeling (SEM) shows that the regulation of NH3 emissions by AM fungi may be related to soil NH4+-N content and soil pH. These findings highlight that AM fungi can reduce N loss in the form of NH3 by increasing N turnover and uptake under global changes; thus, AM fungi play a vital role in alleviating the aggravation of N loss caused by global changes and in mitigating environmental pollution in the future.
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Micorrizas , Micorrizas/fisiología , Nitrógeno , Suelo/química , Ecosistema , Amoníaco , Pradera , Hongos , Microbiología del SueloRESUMEN
The objective of this research was to investigate the role of lncRNA MALAT1 and HSP90 in the regulation of neuronal necroptosis in mice with cerebral ischemia-reperfusion (CIR). We used male C57BL/6J mice to establish a middle cerebral artery occlusion (MCAO) model and conducted in vitro experiments using the HT-22 mouse hippocampal neuron cell line. The cellular localization of NeuN and MLKL, as well as the expression levels of neuronal necroptosis factors, MALAT1, and HSP90 were analyzed. Cell viability and necroptosis were assessed, and we also investigated the relationship between MALAT1 and HSP90. The results showed that MALAT1 expression increased after MCAO and oxygen-glucose deprivation/re-oxygenation (OGD/R) treatment in both cerebral tissues and cells compared with the control group. The levels of neuronal necroptosis factors and the co-localization of NeuN and MLKL were also increased in MCAO mice compared with the Sham group. MALAT1 was found to interact with HSP90, and inhibition of HSP90 expression led to decreased phosphorylation levels of neuronal necroptosis factors. Inhibition of MALAT1 expression resulted in decreased co-localization levels of NeuN and MLKL, decreased phosphorylation levels of neuronal necroptosis factors, and reduced necroptosis rate in cerebral tissues. Furthermore, inhibiting MALAT1 expression also led to a shorter half-life of HSP90, increased ubiquitination level, and decreased phosphorylation levels of neuronal necroptosis factors in cells. In conclusion, this study demonstrated that lncRNA MALAT1 promotes neuronal necroptosis in CIR mice by stabilizing HSP90.
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Isquemia Encefálica , Proteínas HSP90 de Choque Térmico , ARN Largo no Codificante , Daño por Reperfusión , Animales , Masculino , Ratones , Apoptosis/genética , Isquemia Encefálica/metabolismo , Glucosa/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Necroptosis , Neuronas/metabolismo , Reperfusión , Daño por Reperfusión/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Proteínas HSP90 de Choque Térmico/metabolismoRESUMEN
A new five-dimensional potential energy surface (PES) for H2O-Kr which explicitly includes the intramolecular 2OH overtone state of the H2O monomer is presented. The intermolecular potential energies were evaluated using explicitly correlated coupled cluster theory [CCSD(T)-F12] with a large basis set. Four vibrationally averaged analytical intermolecular PESs for H2O-Kr with H2O molecules in its |00+ã, |02+ã, |02-ã, and |11+ã states are obtained by fitting to the multi-dimensional Morse/Long-Range potential function form. Each vibrationally averaged PES fitted to 578 points has root-mean-square (RMS) deviations smaller than 0.14 cm-1 and requires only 58 parameters. The combined radial discrete variable representation/angular finite basis representation method and the Lanczos algorithm were employed to calculate the rovibrational energy levels for |00+ã, |02+ã, |02-ã, and |11+ã states of the H2O-Kr complexes. The calculated |02-ãΠf/e(101) â |00+ãΣe(000) and |02+ãΠf/e(110) â |00+ãΣe(101) infrared transitions are in excellent agreement with the experimental values with RMS discrepancies being only 0.007 and 0.016 cm-1, respectively. These analytical PESs can be used to provide reliable theoretical guidance for future infrared overtone spectroscopy of H2O-Kr.
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This report aimed to explore whether miR-188-5p regulated the pathological regulatory network of cerebral ischemia/reperfusion (I/R) injury. We simulated the cerebral I/R injury model with MACO/R and OGD/R treatments. Neuronal viability and apoptosis were assessed. The contents of miR-188-5p and Lin 28a were evaluated. The abundances of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) were measured. The interaction of miR-188-5p and Lin28a was confirmed. Lin28a silencing was supplemented to determine the delicate regulation of miR-188-5p. We revealed that miR-188-5p was upregulated and Lin28a was downregulated in I/R rats and OGD/R-induced cells. miR-188-5p silencing remarkably reduced the cerebral infarction volume, neurobehavioral score, brain edema, and Evans blue leakage. miR-188-5p silencing enhanced neuronal viability and alleviated apoptosis. The abundance of Bax and cleaved caspase-3 was reduced by miR-188-5p silencing, while Bcl-2 was augmented. miR-188-5p silencing impeded the contents of TNF-α, IL-1ß, and IL-6. miR-188-5p interacted with Lin28a and negatively regulated its expression. Interestingly, extra Lin28a silencing reversed apoptosis and the content of inflammatory cytokines. Our studies confirmed that miR-188-5p silencing alleviated neuronal apoptosis and inflammation by mediating the expression of Lin28a. The crosstalk of miR-188-5p and Lin28a offered a different direction for ischemic stroke therapy.
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Isquemia Encefálica , MicroARNs , Daño por Reperfusión , Animales , Ratas , Apoptosis , Proteína X Asociada a bcl-2 , Isquemia Encefálica/metabolismo , Caspasa 3 , Citocinas/metabolismo , Glucosa , Infarto de la Arteria Cerebral Media/metabolismo , Interleucina-6 , MicroARNs/genética , MicroARNs/metabolismo , Daño por Reperfusión/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Bamboo is a nontimber woody plant featuring a long vegetative stage and uncertain flowering time. Therefore, the genes belonging to flowering repressors might be essential in regulating the transition from the vegetative to reproductive stage in bamboo. The Short Vegetative Phase ( SVP) gene plays a pivotal role in floral transition and development. However, little is known about the bamboo SVP homologues. In this study, Phyllostachys violascens PvSVP1 is isolated by analysis of the P. edulis transcriptome database. Phylogenetic analysis shows that PvSVP1 is closely related to OsMADS55 (rice SVP homolog). PvSVP1 is ubiquitously expressed in various tissues, predominantly in vegetative tissues. To investigate the function of PvSVP1, PvSVP1 is overexpressed in Arabidopsis and rice under the influence of the 35S promoter. Overexpression of PvSVP1 in Arabidopsis causes early flowering and produces abnormal petals and sepals. Quantitative real-time PCR reveals that overexpression in Arabidopsis produces an early flowering phenotype by downregulating FLC and upregulating FT and produces abnormal floral organs by upregulating AP1, AP3 and PI expressions. Simultaneously, overexpression of PvSVP1 in rice alters the expressions of flowering-related genes such as Hd3a, RFT1, OsMADS56 and Ghd7 and promotes flowering under field conditions. In addition, PvSVP1 may be a nuclear protein which interacts with PvVRN1 and PvMADS56 on the yeast two-hybrid and BiFC systems. Our study suggests that PvSVP1 may play a vital role in flowering time and development by interacting with PvVRN1 and PvMADS56 in the nucleus. Furthermore, this study paves the way toward understanding the complex flowering process of bamboo.
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Proteínas de Arabidopsis , Arabidopsis , Oryza , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Oryza/genética , Oryza/metabolismo , Filogenia , Factores de Transcripción/metabolismo , Flores/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
The existing optical strain sensors based on fiber Bragg grating (FBG) have limitations, such as a complex structure, a limited strain range (±200 µÎµ) and poor linearity performance (R-squared value < 0.9920); these limitations affect their potential practical applications. Here, four FBG strain sensors equipped with planar UV-curable resin are investigated. The proposed FBG strain sensors have a simple structure, a large strain range (±1800 µÎµ) and excellent linearity performance (R-squared value ≥ 0.9998); they further produce the following performances: (1) good optical properties, including an undistorted Bragg peak shape, narrow bandwidth (-3 dB bandwidth ≤ 0.65 nm) and a high side mode suppression ratio (SMSR, the absolute value of SMSR ≥ 15 dB); (2) good temperature sensing properties with high temperature sensitivities (≥47.7 pm/°C) and a good linearity performance (R-squared value ≥ 0.9990); and (3) excellent strain sensing properties with no hysteresis behavior (hysteresis error ≤ 0.058%) and excellent repeatability (repeatability error ≤ 0.045%). Based on their excellent properties, the proposed FBG strain sensors are expected to be applied as high-performance strain sensing devices.
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BACKGROUND: Molecular breeding accelerates the speed of animal breeding. Screening molecular markers that can affect economic traits through genome-wide association studies (GWAS) can provide a theoretical basis for molecular breeding. At present, a large number of molecular markers have been screened in poultry research, but few reports on how molecular markers affect economic traits exist. It is particularly important to reveal the action mechanisms of molecular markers, which can provide more accurate information for molecular breeding. RESULTS: The aim of this study was to investigate the relationships between two indels (NUDT15-indel-2777 and NUDT15-indel-1673) in the promoter region of NUDT15 and growth and carcass traits in chickens and to explore the regulatory mechanism of NUDT15. Significant differences were found in genotype and allele frequencies among commercial broilers, commercial laying hens and dual-purpose chickens. The results of association analyses showed that these two indel loci could significantly affect growth traits, such as body weight, and carcass traits. Tissue expression profiling at E12 showed that the expression of NUDT15 was significantly higher in skeletal muscle, and time-expression profiling of leg muscle showed that the expression of NUDT15 in myoblasts was significantly higher in the E10 and E12 proliferation stages than in other stages. Promoter activity analysis showed that pro-1673-I and pro-1673-D significantly inhibited promoter activity, and the promoter activity of pro-1673-D was significantly lower than that of pro-1673-I. In addition, when NUDT15 was overexpressed or underwent interference in chicken primary myoblasts (CPMs), NUDT15 could inhibit the proliferation of CPMs. CONCLUSION: The results suggest that the studied indels in the promoter region of NUDT15 may regulate the proliferation of CPMs by affecting NUDT15 expression, ultimately affecting the growth and carcass traits of chickens. These indel polymorphisms may be used together as molecular markers for improving economic traits in chickens.
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Pollos , Estudio de Asociación del Genoma Completo , Animales , Proliferación Celular , Pollos/genética , Femenino , Genotipo , Mutación INDEL , Mioblastos , Regiones Promotoras GenéticasRESUMEN
SETD2, the histone H3 lysine 36 methyltransferase, previously identified by us, plays an important role in the pathogenesis of hematologic malignancies, but its role in myelodysplastic syndromes (MDSs) has been unclear. In this study, low expression of SETD2 correlated with shortened survival in patients with MDS, and the SETD2 levels in CD34+ bone marrow cells of those patients were increased by decitabine. We knocked out Setd2 in NUP98-HOXD13 (NHD13) transgenic mice, which phenocopies human MDS, and found that loss of Setd2 accelerated the transformation of MDS into acute myeloid leukemia (AML). Loss of Setd2 enhanced the ability of NHD13+ hematopoietic stem and progenitor cells (HSPCs) to self-renew, with increased symmetric self-renewal division and decreased differentiation and cell death. The growth of MDS-associated leukemia cells was inhibited though increasing the H3K36me3 level by using epigenetic modifying drugs. Furthermore, Setd2 deficiency upregulated hematopoietic stem cell signaling and downregulated myeloid differentiation pathways in the NHD13+ HSPCs. Our RNA-seq and chromatin immunoprecipitation-seq analysis indicated that S100a9, the S100 calcium-binding protein, is a target gene of Setd2 and that the addition of recombinant S100a9 weakens the effect of Setd2 deficiency in the NHD13+ HSPCs. In contrast, downregulation of S100a9 leads to decreases of its downstream targets, including Ikba and Jnk, which influence the self-renewal and differentiation of HSPCs. Therefore, our results demonstrated that SETD2 deficiency predicts poor prognosis in MDS and promotes the transformation of MDS into AML, which provides a potential therapeutic target for MDS-associated acute leukemia.
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Anemia Refractaria con Exceso de Blastos/patología , Calgranulina B/fisiología , N-Metiltransferasa de Histona-Lisina/deficiencia , N-Metiltransferasa de Histona-Lisina/fisiología , Leucemia Mieloide Aguda/etiología , Anemia Refractaria con Exceso de Blastos/genética , Anemia Refractaria con Exceso de Blastos/metabolismo , Animales , Calgranulina B/biosíntesis , Calgranulina B/genética , Transformación Celular Neoplásica , Células Cultivadas , Decitabina/farmacología , Regulación hacia Abajo , Regulación Leucémica de la Expresión Génica , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/patología , Código de Histonas/efectos de los fármacos , N-Metiltransferasa de Histona-Lisina/biosíntesis , N-Metiltransferasa de Histona-Lisina/genética , Proteínas de Homeodominio/genética , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Síndromes Mielodisplásicos/patología , Proteínas de Complejo Poro Nuclear/genética , Proteínas de Fusión Oncogénica/genética , Pronóstico , Proteínas Recombinantes/uso terapéutico , Factores de Tiempo , Análisis de Matrices Tisulares , TranscriptomaRESUMEN
The ab initio intra- and inter-molecular potential energy surfaces (PESs) for the H2O-Ne system that explicitly incorporate the intramolecular overtone state (vOH = 2) of H2O are presented. The electronic structure computations have been carried out at the explicitly correlated coupled cluster theory [CCSD(T)-F12] level with an augmented correlation-consistent triple zeta basis set and an additional bond function. The vibrationally averaged three-dimensional intermolecular potentials for |00+ã, |02+ã, |02-ã and |11+ã are obtained analytically by fitting to the multi-dimensional Morse/Long-range potential function form. These fits to 46 980 points have a root-mean-square (RMS) discrepancy of 0.12 cm-1 for interaction energies less than 1000.0 cm-1. With the vibrationally averaged PESs for the H2O-Ne, we employed the combined radial discrete variable representation/angular finite basis representation method and Lanczos algorithm to calculate rovibrational energy levels (J = 0-10, ns ≤ 2). The predicted infrared transitions and intensities of the para- and ortho-H2O-Ne complex are in good agreement with the available experimental data for |02-ã â |00+ã, |02+ã â |00+ã transitions. In particular, the RMS discrepancy for |02-ã∑e(000,0) â |00+ã∑e(101,0), including P and R branch patterns, is only 0.045 cm-1, which is comparable with the experimental values. These results will provide reliable theoretical guidance for the future infrared overtone spectroscopy of clusters.
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Vestigial-like (Vgll) genes are widespread in vertebrates and play an important role in muscle development. In this study, we used bioinformatics methods to systematically identify the chicken VGLL family in the whole genome and investigated its evolutionary history and gene structure features. Tissue expression spectra combined with real-time PCR data were used to analyze the organizational expression pattern of the genes. Based on the maximum likelihood method, a phylogenetic tree of the VGLL family was constructed, and 94 VGLL genes were identified in 24 breeds, among which four VGLL family genes were identified in the chicken genome. Ten motifs were detected in the VGLL genes, and the analysis of introns combined with gene structure revealed that the family was conserved during evolution. Tissue expression analysis suggested that the expression profiles of the VGLL family genes in 16 tissues differed between LU Shi and AA broilers. In addition, a single gene (VGLL2) showed increased expression in chickens at embryonic days 10-16 and was involved in the growth and development of skeletal muscle in chickens in the embryonic stage. In summary, VGLL genes are involved in chicken muscle growth and development, which provides useful information for subsequent functional studies of VGLL genes.
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Pollos , Genoma , Animales , Filogenia , Genoma/genética , Factores de Transcripción/genética , Intrones , Perfilación de la Expresión Génica/veterinariaRESUMEN
Small extracellular vesicles (sEVs) secreted by mesenchymal stem cells (MSCs) have shown great therapeutic potential in cerebral ischemia-reperfusion injury (CIRI). In this study, we firstly performed a systematic review to evaluate the efficacy of MSCs-derived sEV for experimental cerebral ischemia/reperfusion injury. 24 studies were identified by searching 8 databases from January 2012 to August 2022. The methodological quality was assessed by using the SYRCLE 's risk of bias tool for animal studies. All the data were analyzed using RevMan 5.3 software. As a result, the score of study quality ranged from 3 to 9 in a total of ten points. Meta-analyses showed that MSCs-derived sEVs could effectively alleviate neurological impairment scores, reduced the volume of cerebral infarction and brain water content, and attenuated neuronal apoptosis. Additionally, the possible mechanisms of MSCs-derived sEVs for attenuating neuronal apoptosis were inhibiting microglia-mediated neuroinflammation. Thus, MSCs-derived sEVs might be regarded as a novel insight for cerebral ischemic stroke. However, further mechanistic studies, therapeutic safety, and clinical trials are required. Systematic review registration. PROSPERO CRD42022312227.
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Isquemia Encefálica , Vesículas Extracelulares , Células Madre Mesenquimatosas , Daño por Reperfusión , Accidente Cerebrovascular , Animales , Roedores , Isquemia Encefálica/terapia , Accidente Cerebrovascular/terapiaRESUMEN
Depression and chronic prostatitis (CP) are two common diseases that affect the human population worldwide. Clinically, it has been demonstrated that andrological patients often simultaneously suffer from depression and CP. Prior investigations have established that depression acts as an independent risk factor for CP. Herein, we explored the correlation between depression and CP using bioinformatics tools and through animal experiments. The potential targets and signalling pathways involved in depression and CP were predicted using bioinformatics tool, while depression in the rat model was established through chronic restraint stress. The expression of the related proteins and mRNA was assessed by Western blotting and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Relative to those in the control rats, the protein contents of PI3K, p-Akt, and p-mTOR were lower in the model rats (p < 0.05). Similarly, the transcript levels of PI3K, Akt, and mTOR was also relatively lower in the model rats (p < 0.05). And PI3K/Akt agonists reduced inflammation in rat prostate tissue, accompanied by significant increases in the transcript and protein expression levels of PI3K, Akt, and mTOR. Thus, we proposed that depression model rats may induce CP as a result of mediation by the negative regulation of the PI3K/Akt/mTOR signalling network.