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Elucidating the cellular organization of the cerebral cortex is critical for understanding brain structure and function. Using large-scale single-nucleus RNA sequencing and spatial transcriptomic analysis of 143 macaque cortical regions, we obtained a comprehensive atlas of 264 transcriptome-defined cortical cell types and mapped their spatial distribution across the entire cortex. We characterized the cortical layer and region preferences of glutamatergic, GABAergic, and non-neuronal cell types, as well as regional differences in cell-type composition and neighborhood complexity. Notably, we discovered a relationship between the regional distribution of various cell types and the region's hierarchical level in the visual and somatosensory systems. Cross-species comparison of transcriptomic data from human, macaque, and mouse cortices further revealed primate-specific cell types that are enriched in layer 4, with their marker genes expressed in a region-dependent manner. Our data provide a cellular and molecular basis for understanding the evolution, development, aging, and pathogenesis of the primate brain.
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Córtex Cerebral , Macaca , Análise de Célula Única , Transcriptoma , Animais , Humanos , Camundongos , Córtex Cerebral/citologia , Córtex Cerebral/metabolismo , Macaca/metabolismo , Transcriptoma/genéticaRESUMO
As an important posttranslational modification, SUMOylation plays critical roles in almost all biological processes. Although it has been well-documented that SUMOylated proteins are mainly localized in the nucleus and have roles in chromatin-related processes, we showed recently that the SUMOylation machinery is actually enriched in the nuclear matrix rather than chromatin. Here, we provide compelling biochemical, cellular imaging and proteomic evidence that SUMOylated proteins are highly enriched in the nuclear matrix. We demonstrated that inactivation of SUMOylation by inhibiting SUMO-activating E1 enzyme or KO of SUMO-conjugating E2 enzyme UBC9 have only mild effect on nuclear matrix composition, indicating that SUMOylation is neither required for nuclear matrix formation nor for targeting proteins to nuclear matrix. Further characterization of UBC9 KO cells revealed that loss of SUMOylation did not result in significant DNA damage, but led to mitotic arrest and chromosome missegregation. Altogether, our study demonstrates that SUMOylated proteins are selectively enriched in the nuclear matrix and suggests a role of nuclear matrix in mediating SUMOylation and its regulated biological processes.
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Segregação de Cromossomos , Matriz Nuclear , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina , Sumoilação , Cromatina/metabolismo , Matriz Nuclear/metabolismo , Proteômica , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/genética , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Humanos , Animais , Drosophila melanogasterRESUMO
Currently, cancer is the second leading cause of death worldwide, and potential targeted drugs and molecular pathways for cancer development and progression have been a hot research topic worldwide. In recent years, the importance of the kinase superfamily in diseases has been well demonstrated by studies on various molecular mechanisms of kinases and the successful application of their inhibitors in diseases. Pseudokinases are members of the kinase superfamily, which have been increasingly documented to play a crucial role in cancers year after year. As a member of pseudokinases, tribbles homolog 3 (TRIB3) also exerts diverse functions in different cancers through different interacting proteins and molecular pathways, especially in tumor immunity, stemness, drug resistance, metabolism, and autophagy. In addition, peptide drugs targeting TRIB3 have high specificity in preclinical studies, which shows great promise for TRIB3 application in diseases including cancers. In this review, we dissect diverse functions played by TRIB3 in different cancers, describing the underlying mechanisms in detail. Notably, inhibitors and agonists currently available for TRIB3 are discussed, indicating the potential for TRIB3 as a therapeutic target.
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Proteínas de Ciclo Celular , Neoplasias , Proteínas Serina-Treonina Quinases , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Animais , Proteínas Repressoras/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Terapia de Alvo Molecular/métodos , Autofagia , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Resistencia a Medicamentos AntineoplásicosRESUMO
Nuclear factor of activated T cells 5 (NFAT5) is an osmosensitive transcription factor that is well-studied in renal but rarely explored in cardiac diseases. Although the association of Coxsackievirus B3 (CVB3) with viral myocarditis is well-established, the role of NFAT5 in this disease remains largely unexplored. Previous research has demonstrated that NFAT5 restricts CVB3 replication yet is susceptible to cleavage by CVB3 proteases. Using an inducible cardiac-specific Nfat5-knockout mouse model, we uncovered that NFAT5-deficiency exacerbates cardiac pathology, worsens cardiac function, elevates viral load, and reduces survival rates. RNA-seq analysis of CVB3-infected mouse hearts revealed the significant impact of NFAT5-deficiency on gene pathways associated with cytokine signaling and inflammation. Subsequent in vitro and in vivo investigation validated the disruption of the cytokine signaling pathway in response to CVB3 infection, evidenced by reduced expression of key cytokines such as interferon ß1 (IFNß1), C-X-C motif chemokine ligand 10 (CXCL10), interleukin 6 (IL6), among others. Furthermore, NFAT5-deficiency hindered the formation of stress granules, leading to a reduction of important stress granule components, including plakophilin-2, a pivotal protein within the intercalated disc, thereby impacting cardiomyocyte structure and function. These findings unveil a novel mechanism by which NFAT5 inhibits CVB3 replication and pathogenesis through the promotion of antiviral type I interferon signaling and the formation of cytoplasmic stress granules, collectively identifying NFAT5 as a new cardio protective protein.
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INTRODUCTION: Incontinentia pigmenti (IP) is a rare neuroectodermal dysplasia caused by a defect in the IKBKG gene. The pathogenesis of central nervous system injury is believed to be related to microvascular ischemia. Currently, few treatment strategies are available for the inflammatory phase. MATERIALS AND METHODS: This retrospective descriptive analysis included the clinical data of 41 children with IP collected from 2007 to 2021 in Xi'an, China, comprising clinical characteristics, imaging findings, blood cell analysis, skin histopathology, and genetic data. RESULTS: Fourteen children (34%) aged 4 days to 5 months exhibited clinical signs and symptoms, including convulsions, delayed psychomotor development following neurological damage, and revealed significant MRI abnormalities, including ischemia, hypoxia, cerebral hypoperfusion, hemorrhage, encephalomalacia, and cerebral atrophy. Eight of the 24 patients (33%) presented with retinal vascular tortuosity and telangiectasis, accompanied by neovascularization and hemorrhage. Thirty-eight children (93%) had elevated eosinophils (mean: 3.63 ± 4.46 × 109), and 28 children (68%) had significantly elevated platelets (mean: 420.16 ± 179.43 × 109). Histopathology of skin revealed microvascular extravasation and vasodilation with perivascular and intravascular eosinophilic infiltration. CONCLUSION: Brain injury in IP occurs during infancy until 5 months of age, which is also the acute dermatitis phase accompanied by eosinophilia and an increased platelet count. This study provides evidence of microvascular damage to the skin and fundus during the inflammatory phase. The mechanism of microvascular damage may be similar to that in the brain.
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Incontinência Pigmentar , Humanos , Incontinência Pigmentar/patologia , Incontinência Pigmentar/genética , Lactente , Feminino , Estudos Retrospectivos , Masculino , China , Recém-Nascido , Imageamento por Ressonância Magnética , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Pré-Escolar , População do Leste AsiáticoRESUMO
DNA methylase 1 (Dnmt1) is an important regulatory factor associated with biochemical signals required for insect development. It responds to changes in the environment and triggers phenotypic plasticity. Meanwhile, Tuta absoluta Meyrick (Lepidoptera: Gelechiidae)-a destructive invasive pest-can rapidly invade and adapt to different habitats; however, the role of Dnmt1 in this organism has not been elucidated. Accordingly, this study investigates the mechanism(s) underlying the rapid adaptation of Tuta absoluta to temperature stress. Potential regulatory genes were screened via RNAi (RNA interference), and the DNA methylase in Tuta absoluta was cloned by RACE (Rapid amplification of cDNA ends). TaDnmt1 was identified as a potential regulatory gene via bioinformatics; its expression was evaluated in response to temperature stress and during different development stages using real-time polymerase chain reaction. Results revealed that TaDnmt1 participates in hot/cold tolerance, temperature preference and larval development. The full-length cDNA sequence of TaDnmt1 is 3765 bp and encodes a 1254 kDa protein with typical Dnmt1 node-conserved structural features and six conserved DNA-binding active motifs. Moreover, TaDnmt1 expression is significantly altered by temperature stress treatments and within different development stages. Hence, TaDnmt1 likely contributes to temperature responses and organismal development. Furthermore, after treating with double-stranded RNA and exposing Tuta absoluta to 35°C heat shock or -12°C cold shock for 1 h, the survival rate significantly decreases; the preferred temperature is 2°C lower than that of the control group. In addition, the epidermal segments become enlarged and irregularly folded while the surface dries up. This results in a significant increase in larval mortality (57%) and a decrease in pupation (49.3%) and eclosion (50.9%) rates. Hence, TaDnmt1 contributes to temperature stress responses and temperature perception, as well as organismal growth and development, via DNA methylation regulation. These findings suggest that the rapid geographic expansion of T absoluta has been closely associated with TaDnmt1-mediated temperature tolerance. This study advances the research on 'thermos Dnmt' and provides a potential target for RNAi-driven regulation of Tuta absoluta.
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Proteínas de Insetos , Larva , Mariposas , Animais , Mariposas/crescimento & desenvolvimento , Mariposas/genética , Mariposas/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Larva/crescimento & desenvolvimento , Larva/genética , Larva/metabolismo , Temperatura , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/genética , Sequência de Aminoácidos , Filogenia , Espécies IntroduzidasRESUMO
The serine/arginine-rich splicing factors (SRSFs) play an important role in regulating the alternative splicing of precursor RNA (pre-RNA). During this procedure, introns are removed from the pre-RNA, while the exons are accurately joined together to produce mature mRNA. In addition, SRSFs also involved in DNA replication and transcription, mRNA stability and nuclear export, and protein translation. It is reported that SRSFs participate in hematopoiesis, development, and other important biological process. They are also associated with the development of several diseases, particularly cancers. While the basic physiological functions and the important roles of SRSFs in solid cancer have been extensively reviewed, a comprehensive summary of their significant functions in normal hematopoiesis and hematopoietic malignancies is currently absent. Hence, this review presents a summary of their roles in normal hematopoiesis and hematopoietic malignancies.
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OBJECTIVE: To explore the role of HIF-1α in hypercoagulable state of COPD induced by lipopolysaccharide plus smoking in rats. It also has to explore the regulatory mechanism of HIF-1α-EPO/EDN-1/VEGF pathway by using its activator and inhibitor. METHODS: 60 Sprague-Dawley rats (SD rats) were randomly divided into healthy control group, COPD hypercoagulable control group, activator group, and inhibitor group with 15 rats in each group. The healthy control group was fed freely. The other groups were given smoke and lipopolysaccharide by tracheal instillation to establish the experimental animal model of COPD hypercoagulability. After successful modeling, each experimental group was given 0.9 % sodium chloride solution and corresponding drugs by intraperitoneal injection for 7 days. Lung function was detected after drug administration. Hematoxylin-eosin staining was used to observe the pathological changes of lung tissue. Enzyme-linked immunosorbent assay was used to detect serum D-D,F (1 + 2),IL-6,TNF-α. The mRNA expressions of HIF-1α, EPO, EDN-1, and VEGF were detected by RT-PCR. Western-Blot and IHC were used to detect the expression of HIF-1α, EPO, EDN-1, and VEGF in lung tissue of rats. RESULTS: Compared with the healthy control group, rats in COPD hypercoagulable control group had COPD symptoms/signs, decreased lung function, increased the expression of serum D-D and F (1 + 2), increased the expression of inflammatory factors IL-6,TNF-α, and increased the expression of proteins HIF-1α, EPO, EDN-1 and VEGF. Compared with COPD hypercoagulable control group, lung function in activator group and inhibitor group had no obvious changes. The expressions of serum D-D,F (1 + 2),IL-6,TNF-α in activator group have increased noticeably. The expressions of proteins HIF-1α, EPO, EDN-1, and VEGF have further increased. Compared with COPD hypercoagulable control group, the expression of serum D-D, F (1 + 2), HIF-1α, EPO, EDN-1, and VEGF in the inhibitor group decreased. CONCLUSION: HIF-1α-EPO/EDN-1/VEGF pathway plays an important role in the hypercoagulable state of COPD. HIF-1α inhibitor can improve airway inflammation and reduce hypercoagulability in COPD model rats.
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Doença Pulmonar Obstrutiva Crônica , Trombofilia , Animais , Ratos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Interleucina-6 , Lipopolissacarídeos , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/metabolismo , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Layered double hydroxides (LDHs) have garnered significant attention from researchers in the field of adsorption due to their unique laminated structures and ion exchange properties. LDHs with various anion intercalation showed different adsorption effects on adsorbing ions, but the corresponding adsorption mechanisms are ambiguous. In this study, three types of NiAl-LDHs were synthesized, utilizing NO3-, CO32-, or Cl- as the interlayer anions. Batch tests were conducted to study their adsorption performances for Br-. Among them, the LDH with a NO3- intercalation layer exhibited the highest adsorption capacity for Br-, reaching up to 1.40 mmol g-1. The adsorption kinetics, mechanism, and renewability of these NiAl-LDHs were systematically compared. As a result, the type of Br- adsorption by all three materials was single molecular layer chemisorption. Moreover, the thermodynamic results of adsorption suggested that the adsorption of Br- was a spontaneous exothermic process. X-ray photoelectron spectroscopy, X-ray diffraction, and point of zero charge analysis collectively indicated that the adsorption of Br- by LDHs primarily occurred through interlayer ion exchange and electrostatic interactions. Structural characterizations of the adsorbents revealed that Br- entered the interlayers of the three LDHs, causing varying degrees of reduction in the interlayer spacing. Density functional theory calculations indicated that the interlayer binding energy of LDH with NO3- intercalation was the lowest, thereby making it more susceptible NO3- to be exchanged with Br-. Finally, the stability of the NiAl-LDHs was studied. The NiAl-LDHs retains a high removal efficiency of Br- even after 5 cycles of adsorption and desorption.
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Rubidium (Rb) and cesium (Cs) have important applications in highly technical fields. Salt lakes contain huge reserves of Rb and Cs with industrial significance, which can be utilized after extraction. In this study, a composite magnetic adsorbent (Fe3O4@ZIF-8@AMP, AMP = ammonium phosphomolybdate) was prepared and its adsorption properties for Rb+ and Cs+ were studied in simulated and practical brine. The structure of the adsorbent was characterized by SEM, XRD, N2 adsorption-desorption, FT-IR, and vibrating sample magnetometer (VSM). The adsorbent had good adsorption affinity for Rb+ and Cs+. The Langmuir model and pseudo-second-order dynamics described the adsorbing isotherm and kinetic dates, respectively. The adsorption capacity and adsorption rate of Fe3O4@ZIF-8@AMP were increased by 1.86- and 2.5-fold compared with those of powdered crystal AMP, owing to the large specific surface area and high dispersibility of the adsorbent in the solution. The adsorbent was rapidly separated from the solution within 17 s using an applied magnetic field owing to the good magnetic properties. The composite adsorbent selectively adsorbed Rb+ and Cs+ from the practical brine even in the presence of a large number of coexisting ions. The promising adsorbent can be used to extract Rb+ and Cs+ from aqueous solutions.
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Picolyl group directed B(3,5)-dialkenylation and B(4)-monoalkenylation of o-carboranes has been developed with a very low palladium catalyst loading. The degree of substitution is determined by the cage C(2)-substituents due to steric reasons. On the basis of experimental results, a plausible mechanism is proposed including electrophilic palladation and alkyne insertion followed by protonation.
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Asthma is an inflammatory disease. Airway epithelial cell pyroptosis and cytokine secretion promote asthma progression. Tripartite motif 47 (TRIM47) belongs to the E3 ubiquitin ligase family and is associated with apoptosis and inflammation in a range of diseases. However, the role of TRIM47 in asthma has not been explored. In this study, the human bronchial epithelial cell line BEAS-2B was treated with house dust mite (HDM) and TRIM47 expression was detected by RT-qPCR and Western blot. After transfection with TRIM47 interfering and overexpressing plasmids, the synthesis and secretion of cytokines, as well as pyroptosis-related indicators, were examined. Nuclear factor kappa-B (NF-κB) pathway proteins and nod-like receptor protein 3 (NLRP3) inflammasome were measured to explore the mechanism of TRIM47 action. In addition, the effect of TRIM47 on the level of NF-κB essential modulator (NEMO) ubiquitination was detected by an immunoprecipitation assay. The results showed that TRIM47 was upregulated in HDM-induced BEAS-2B cells and that TRIM47 mediated HDM-induced BEAS-2B cell pyroptosis and cytokine secretion. Mechanistically, TRIM47 promoted the K63-linked ubiquitination of NEMO and facilitated NF-κB/NLRP3 pathway activation. In conclusion, TRIM47 may promote cytokine secretion mediating inflammation and pyroptosis in bronchial epithelial cells by activating the NF-κB/NLRP3 pathway. Therefore, TRIM47 may be a potential therapeutic target for HDM-induced asthma.
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Brônquios , Células Epiteliais , NF-kappa B , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Transdução de Sinais , Ubiquitinação , Humanos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Células Epiteliais/metabolismo , Brônquios/metabolismo , Brônquios/patologia , Animais , Linhagem Celular , Quinase I-kappa B/metabolismo , Pyroglyphidae , Asma/metabolismo , Asma/patologia , Inflamassomos/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Citocinas/metabolismo , Proteínas com Motivo Tripartido/metabolismo , Proteínas com Motivo Tripartido/genéticaRESUMO
Short tandem repeat (STR) genotyping provides parental origin information about aneuploidy pregnancy loss and has become the current gold standard for hydatidiform mole diagnosis. STR genotyping diagnostic support most commonly relies on formalin-fixed paraffin-embedded samples, but maternal contamination is one of the most common issues based on traditional unstained sections. To evaluate the influence of hematoxylin and eosin (H&E) staining on DNA quality and STR genotyping, DNA was isolated from unstained, deparaffinized hydrated, and H&E-stained tissue sections (i.e. 3 groups) from each of 6 formalin-fixed paraffin-embedded placentas. The macrodissected view field, DNA quality, and polymerase chain reaction amplification efficiency were compared among groups. STR genotyping analysis was performed in both the test cohort (n = 6) and the validation cohort (n = 149). H&E staining not only did not interfere with molecular DNA testing of formalin-fixed paraffin-embedded tissue but also had a clearer macrodissected field of vision. In the test cohort, H&E-stained sections were the only group that did not exhibit maternal miscellaneous peaks in STR genotyping results. In the validation cohort, 138 (92.62%) cases yielded satisfactory amplification results without maternal contamination. Thus, H&E staining helped to reduce maternal contamination in STR genotyping for hydatidiform mole diagnosis, suggesting that H&E-stained sections can be incorporated into the hydatidiform mole molecular diagnostic workflow.
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As a representative gas of food spoilage, the development of rapid hydrogen sulfide (H2S) analysis strategies for food safety control is in great demand. Despite traditional methods for H2S detection possessing great achievements, they are still incapable of meeting the requirement of portability and quantitative detection at the same time. Herein, a nanozyme catalysis pressure-powered sensing platform that enables visual quantification with the naked eye is proposed. In this methodology, Pt nanozyme inherits the catalase-like activity to facilitate the decomposition of H2O2 to O2, which can significantly improve the pressure in the closed container, further pushing the movement of indicator dye. Furthermore, H2S was found to effectively inhibit the catalytic activity of Pt nanozyme, indicating that the catalase-like activity of PtNPs may be regulated by varying concentrations of H2S. Therefore, by utilizing a self-designed pressure-powered microchannel device, the concentration of H2S was successfully converted into a distinct signal variation in distance. The effectiveness of the as-designed sensor in assessing the spoilage of red wine by H2S determination has been demonstrated. It exhibits a strong correlation between the change in dye distance and H2S concentration within the range of 1-250 µM, with a detection limit of 0.17 µM. This method is advantageous as it enhances the quantitative detection of H2S with the naked eye based on the portable pressure-powered sensing platform, as compared to traditional H2S biosensors. Such a pressure-powered distance variation platform would greatly broaden the application of H2S-based detection in food spoilage management.
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Primary mucinous tumors of the renal pelvis are extremely rare and pose challenges in terms of diagnosis and treatment. This study reviewed the clinical and pathological characteristics of mucinous tumors of the renal pelvis, including mucinous cystadenocarcinomas and mucinous cystadenomas. Immunohistochemical analysis was conducted in three cases, along with KRAS gene detection using the Amplification Refractory Mutation System (ARMS) method. The results revealed mucinous epithelium with acellular mucinous pools in all cases, and acellular mucinous pools were observed in the renal parenchyma and perirenal fat capsules. All tumors expressed CK20 and CDX2, and one case showed KRAS gene mutation. The study suggests that mucinous cystadenomas of the renal pelvis may exhibit borderline biological behaviors. This study is the first to report a KRAS gene mutation in a mucinous cystadenoma of the renal pelvis, offering valuable insights into the diagnosis and treatment of this rare condition.
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Neoplasias Renais , Pelve Renal , Proteínas Proto-Oncogênicas p21(ras) , Humanos , Pelve Renal/patologia , Neoplasias Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/diagnóstico , Feminino , Pessoa de Meia-Idade , Masculino , Proteínas Proto-Oncogênicas p21(ras)/genética , Cistadenoma Mucinoso/patologia , Cistadenoma Mucinoso/genética , Cistadenoma Mucinoso/diagnóstico , Mutação , Adulto , Queratina-20/metabolismo , Queratina-20/genética , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Imuno-Histoquímica/métodos , Cistadenocarcinoma Mucinoso/patologia , Cistadenocarcinoma Mucinoso/genética , Cistadenocarcinoma Mucinoso/diagnósticoRESUMO
OBJECTIVES: Deep brain stimulation (DBS) to treat chronic neuropathic pain has shown variable outcomes. Variations in pain etiologies and DBS targets are considered the main contributing factors, which are, however, underexplored owing to a paucity of patient data in individual studies. An updated meta-analysis to quantitatively assess the influence of these factors on the outcome of DBS for chronic neuropathic pain is warranted, especially considering that the anterior cingulate cortex (ACC) has emerged recently as a new DBS target. MATERIALS AND METHODS: A comprehensive literature review was performed in PubMed, Embase, and Cochrane data bases to identify studies reporting quantitative outcomes of DBS for chronic neuropathic pain. Pain and quality of life (QoL) outcomes, grouped by etiology and DBS target, were extracted and analyzed (α = 0.05). RESULTS: Twenty-five studies were included for analysis. Patients with peripheral neuropathic pain (PNP) had a significantly greater initial stimulation success rate than did patients with central neuropathic pain (CNP). Both patients with CNP and patients with PNP with definitive implant, regardless of targets, gained significant follow-up pain reduction. Patients with PNP had greater long-term pain relief than did patients with CNP. Patients with CNP with ACC DBS gained less long-term pain relief than did those with conventional targets. Significant short-term QoL improvement was reported in selected patients with CNP after ACC DBS. However, selective reporting bias was expected, and the improvement decreased in the long term. CONCLUSIONS: Although DBS to treat chronic neuropathic pain is generally effective, patients with PNP are the preferred population over patients with CNP. Current data suggest that ACC DBS deserves further investigation as a potential way to treat the affective component of chronic neuropathic pain.
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Estimulação Encefálica Profunda , Neuralgia , Humanos , Giro do Cíngulo/fisiologia , Neuralgia/etiologia , Neuralgia/terapia , Manejo da Dor , Qualidade de Vida , Resultado do TratamentoRESUMO
Teleost zebrafish and neonatal mammalian hearts exhibit the remarkable capacity to regenerate through dedifferentiation and proliferation of pre-existing cardiomyocytes (CMs). Although many mitogenic signals that stimulate zebrafish heart regeneration have been identified, transcriptional programs that restrain injury-induced CM renewal are incompletely understood. Here, we report that mutations in gridlock (grl; also known as hey2), encoding a Hairy-related basic helix-loop-helix transcriptional repressor, enhance CM proliferation and reduce fibrosis following damage. In contrast, myocardial grl induction blunts CM dedifferentiation and regenerative responses to heart injury. RNA sequencing analyses uncover Smyd2 lysine methyltransferase (KMT) as a key transcriptional target repressed by Grl. Reduction in Grl protein levels triggered by injury induces smyd2 expression at the wound myocardium, enhancing CM proliferation. We show that Smyd2 functions as a methyltransferase and modulates the Stat3 methylation and phosphorylation activity. Inhibition of the KMT activity of Smyd2 reduces phosphorylated Stat3 at cardiac wounds, suppressing the elevated CM proliferation in injured grl mutant hearts. Our findings establish an injury-specific transcriptional repression program in governing CM renewal during heart regeneration, providing a potential strategy whereby silencing Grl repression at local regions might empower regeneration capacity to the injured mammalian heart.
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Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Coração/fisiologia , Lisina/genética , Metiltransferases/genética , Regeneração/genética , Transcrição Gênica/genética , Vertebrados/genética , Proteínas de Peixe-Zebra/genética , Animais , Animais Recém-Nascidos , Diferenciação Celular/genética , Proliferação de Células/genética , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Fosforilação/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais/genética , Peixe-Zebra/genéticaRESUMO
BACKGROUND: Determining the grade and molecular marker status of intramedullary gliomas is important for assessing treatment outcomes and prognosis. Invasive biopsy for pathology usually carries a high risk of tissue damage, especially to the spinal cord, and there are currently no non-invasive strategies to identify the pathological type of intramedullary gliomas. Therefore, this study aimed to develop a non-invasive machine learning model to assist doctors in identifying the intramedullary glioma grade and mutation status of molecular markers. METHODS: A total of 461 patients from two institutions were included, and their sagittal (SAG) and transverse (TRA) T2-weighted magnetic resonance imaging scans and clinical data were acquired preoperatively. We employed a transformer-based deep learning model to automatically segment lesions in the SAG and TRA phases and extract their radiomics features. Different feature representations were fed into the proposed neural networks and compared with those of other mainstream models. RESULTS: The dice similarity coefficients of the Swin transformer in the SAG and TRA phases were 0.8697 and 0.8738, respectively. The results demonstrated that the best performance was obtained in our proposed neural networks based on multimodal fusion (SAG-TRA-clinical) features. In the external validation cohort, the areas under the receiver operating characteristic curve for graded (WHO I-II or WHO III-IV), alpha thalassemia/mental retardation syndrome X-linked (ATRX) status, and tumor protein p53 (P53) status prediction tasks were 0.8431, 0.7622, and 0.7954, respectively. CONCLUSIONS: This study reports a novel machine learning strategy that, for the first time, is based on multimodal features to predict the ATRX and P53 mutation status and grades of intramedullary gliomas. The generalized application of these models could non-invasively provide more tumor-specific pathological information for determining the treatment and prognosis of intramedullary gliomas.
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Neoplasias Encefálicas , Glioma , Humanos , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genética , Neoplasias Encefálicas/genética , Imageamento por Ressonância Magnética/métodos , Glioma/diagnóstico , Glioma/genética , Aprendizado de Máquina , Biomarcadores , MutaçãoRESUMO
The tropical forest carbon (C) balance threatened by extensive socio-economic development in the Greater Mekong Subregion (GMS) in Asia is a notable data gap and remains contentious. Here we generated a long-term spatially quantified assessment of changes in forests and C stocks from 1999 to 2019 at a spatial resolution of 30 m, based on multiple streams of state-of-the-art high-resolution satellite imagery and in situ observations. Our results show that (i) about 0.54 million square kilometers (21.0% of the region) experienced forest cover transitions with a net increase in forest cover by 4.3% (0.11 million square kilometers, equivalent to 0.31 petagram of C [Pg C] stocks); (ii) forest losses mainly in Cambodia, Thailand, and in the south of Vietnam, were also counteracted by forest gains in China due mainly to afforestation; and (iii) at the national level during the study period an increase in both C stocks and C sequestration (net C gain of 0.087 Pg C) in China from new plantation, offset anthropogenetic emissions (net C loss of 0.074 Pg C) mainly in Cambodia and Thailand from deforestation. Political, social, and economic factors significantly influenced forest cover change and C sequestration in the GMS, positively in China while negatively in other countries, especially in Cambodia and Thailand. These findings have implications on national strategies for climate change mitigation and adaptation in other hotspots of tropical forests.
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Efeitos Antropogênicos , Carbono , Carbono/análise , Florestas , Tailândia , Sequestro de Carbono , Conservação dos Recursos Naturais , ÁrvoresRESUMO
INTRODUCTION: Anaphylaxis is a serious systemic hypersensitivity reaction that usually has a rapid onset and may cause death. The aim of this study was to clarify the clinical characteristics of anaphylaxis in children of all ages in Xi'an, China. METHODS: A retrospective study was conducted on anaphylaxis cases in the emergency department of the Affiliated Children's Hospital of Xi'an Jiaotong University between January 1, 2016, and July 1, 2021. The statistical methods used were the χ2 test, Fisher's exact test, and Z-test. RESULTS: A total of 110 cases of anaphylaxis were collected: 70% were male, 13 were <1 year old, 17 were 1-2 years old, 42 were 3-6 years old, 38 were 7-16 years old, 10 (9.1%) had ≥2 anaphylaxis, and 75 (68.1%) had a previous history of allergy. The triggers of anaphylaxis were analyzed: 50 cases (45.5%) were induced by food, 37 cases (33.6%) by drugs, 6 cases (5.5%) by insect bites, 4 cases (3.6%) by exercise, and 12 cases (11.8%) by unknown causes. Common food allergens were milk (20%, 10/50), buckwheat (16%, 8/50), eggs (14%, 7/50), and fruits (14%, 7/50). The most common drug triggers were antibiotics (59.4%, 22/37), non-steroidal anti-inflammatory drugs (NSAIDs) (10.8%, 4/37), vaccines (10.8%, 4/37), and herbal medicines (10.8%, 4/37). Common food allergens vary by age: milk and eggs for infants, fruit for children aged 1-2 years, and buckwheat for children older than 3 years. Ninety-eight cases (89.1%) had skin mucosal involvement, 78 (70.9%) had respiratory compromise, 45 (40.9%) had cardiovascular compromise, and 31 (28.2%) had gastrointestinal symptoms. Cardiovascular compromise and reduced level of consciousness were statistically different between the age groups (p < 0.05). Twenty cases (18.2%) had resolved spontaneously when they reached the hospital, 53 cases (48.1%) received epinephrine, 18 (16.4%) were hospitalized, and 2 (1.8%) experienced a biphasic reaction. CONCLUSIONS: Males are overrepresented in children with anaphylaxis, and food and drugs are common triggers in children. However, the types of common food triggers differ across age groups, and infants are more likely to have cardiovascular compromise and a reduced level of consciousness. However, the use of epinephrine remains inadequate. The training of clinical staff in recognizing anaphylaxis needs to be strengthened.