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In vivo cell fate conversions have emerged as potential regeneration-based therapeutics for injury and disease. Recent studies reported that ectopic expression or knockdown of certain factors can convert resident astrocytes into functional neurons with high efficiency, region specificity, and precise connectivity. However, using stringent lineage tracing in the mouse brain, we show that the presumed astrocyte-converted neurons are actually endogenous neurons. AAV-mediated co-expression of NEUROD1 and a reporter specifically and efficiently induces reporter-labeled neurons. However, these neurons cannot be traced retrospectively to quiescent or reactive astrocytes using lineage-mapping strategies. Instead, through a retrograde labeling approach, our results reveal that endogenous neurons are the source for these viral-reporter-labeled neurons. Similarly, despite efficient knockdown of PTBP1 in vivo, genetically traced resident astrocytes were not converted into neurons. Together, our results highlight the requirement of lineage-tracing strategies, which should be broadly applied to studies of cell fate conversions in vivo.
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Astrócitos/citologia , Diferenciação Celular , Linhagem da Célula , Neurônios/citologia , Animais , Astrócitos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Encéfalo/patologia , Lesões Encefálicas/patologia , Linhagem Celular Tumoral , Reprogramação Celular , Dependovirus/metabolismo , Regulação para Baixo , Regulação da Expressão Gênica , Genes Reporter , Proteína Glial Fibrilar Ácida/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Integrases/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/metabolismoRESUMO
A holy grail of regenerative medicine is to replenish the cells that are lost due to disease. The adult mammalian central nervous system (CNS) has, however, largely lost such a regenerative ability. An emerging strategy for the generation of new neurons is through glia-to-neuron (GtN) conversion in vivo, mainly accomplished by the regulation of fate-determining factors. When inhibited, PTBP1, a factor involved in RNA biology, was reported to induce rapid and efficient GtN conversion in multiple regions of the adult CNS. Remarkably, PTBP1 inhibition was also claimed to greatly improve behaviors of mice with neurological diseases or aging. These phenomenal claims, if confirmed, would constitute a significant advancement in regenerative medicine. Unfortunately, neither GtN conversion nor therapeutic potential via PTBP1 inhibition was validated by the results of multiple subsequent replication studies with stringent methods. Here we review these controversial studies and conclude with recommendations for examining GtN conversion in vivo and future investigations of PTBP1.
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Neuroglia , Neurônios , Animais , Camundongos , Neurônios/fisiologia , Sistema Nervoso Central , Retina , MamíferosRESUMO
SignificanceOutside the neurogenic niches, the adult brain lacks multipotent progenitor cells. In this study, we performed a series of in vivo screens and reveal that a single factor can induce resident brain astrocytes to become induced neural progenitor cells (iNPCs), which then generate neurons, astrocytes, and oligodendrocytes. Such a conclusion is supported by single-cell RNA sequencing and multiple lineage-tracing experiments. Our discovery of iNPCs is fundamentally important for regenerative medicine since neural injuries or degeneration often lead to loss/dysfunction of all three neural lineages. Our findings also provide insights into cell plasticity in the adult mammalian brain, which has largely lost the regenerative capacity.
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Astrócitos/citologia , Astrócitos/metabolismo , Diferenciação Celular , Linhagem da Célula , Reprogramação Celular , Corpo Estriado/citologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Diferenciação Celular/genética , Linhagem da Célula/genética , Reprogramação Celular/genética , Corpo Estriado/metabolismo , Imunofluorescência , Neurônios GABAérgicos/citologia , Neurônios GABAérgicos/metabolismo , Expressão Gênica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Genes Reporter , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Camundongos , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Neurogênese , RNA-Seq , Receptores Notch/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismoRESUMO
Huanglian Jiedu decoction (HLJD) has been used to treat ischemic stroke in clinic. However, the detailed protective mechanisms of HLJD on ischemic stroke have yet to be elucidated. The aim of this study is to elucidate the underlying pharmacological mechanisms of HLJD based on the inhibition of neuroinflammation and the amelioration of nerve cell damage. A middle cerebral artery occlusion reperfusion (MCAO/R) model was established in rats and received HLJD treatment. Effects of HLJD on neurological function was assessed based on Bederson's score, postural reflex test and asymmetry score. 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining, Hematein and eosin (HE) and Nissl staining were used to observe the pathological changes in brain. Then, transcriptomics was used to screen the differential genes in brain tissue in MCAO/R model rats following HLJD intervention. Subsequently, the effects of HLJD on neutrophil extracellular trap (NET) formation-related neuroinflammation, gamma-aminobutyric acid (GABA)ergic synapse activation, nerve cell damage and proliferation were validated using immunofluorescence, western blot and enzyme-linked immunosorbent assay (ELISA). Our results showed that HLJD intervention reduced the Bederson's score, postural reflex test score and asymmetry score in MCAO/R model rats. Pathological staining indicated that HLJD treatment decreased the cerebral infarction area, mitigated neuronal damage and increased the numbers of Nissl bodies. Transcriptomics suggested that HLJD affected 435 genes in MCAO/R rats. Among them, several genes involving in NET formation and GABAergic synapses pathways were dysregulated. Subsequent experimental validation showed that HLJD reduced the MPO+CitH3+ positive expression area, reduced the protein expression of PAD4, p-P38/P38, p-ERK/ERK and decreased the levels of IL-1ß, IL-6 and TNF-α, reversed the increase of Iba1+TLR4+, Iba1+p65+ and Iba1+NLRP3+ positive expression area in brain. Moreover, HLJD increased GABA levels, elevated the protein expression of GABRG1 and GAT3, decreased the TUNEL positive expression area and increased the Ki67 positive expression area in brain. HLJD intervention exerts a multifaceted positive impact on ischemia-induced cerebral injury in MCAO/R rats. This intervention effectively inhibits neuroinflammation by mitigating NET formation, and concurrently improves nerve cell damage and fosters nerve cell proliferation through activating GABAergic synapses.
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Isquemia Encefálica , Medicamentos de Ervas Chinesas , Ratos Sprague-Dawley , Sinapses , Animais , Medicamentos de Ervas Chinesas/farmacologia , Ratos , Masculino , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamento farmacológico , Modelos Animais de Doenças , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo , Infarto da Artéria Cerebral Média/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/complicações , Fármacos Neuroprotetores/farmacologia , Encéfalo/patologia , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacosRESUMO
PURPOSE: To report a case of a five-month-old Chinese infant who died of interleukin-1 receptor-associated kinase-4 (IRAK-4) deficiency presenting with rapid and progressive Pseudomonas aeruginosa sepsis. METHODS: The genetic etiology of IRAK-4 deficiency was confirmed through trio-whole exome sequencing and Sanger sequencing. Functional consequences were invested using an in vitro minigene splicing assay. RESULTS: Trio-whole exome sequencing of genomic DNA identified two novel compound heterozygous mutations, IRAK-4 (NM_016123.3): c.942-1G > A and c.644_651+ 6delTTGCAGCAGTAAGT in the proband, which originated from his symptom-free parents. These mutations were predicted to cause frameshifts and generate three truncated proteins without enzyme activity. CONCLUSIONS: Our findings expand the range of IRAK-4 mutations and provide functional support for the pathogenic effects of splice-site mutations. Additionally, this case highlights the importance of considering the underlying genetic defects of immunity when dealing with unusually overwhelming infections in previously healthy children and emphasizes the necessity for timely treatment with wide-spectrum antimicrobials.
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Quinases Associadas a Receptores de Interleucina-1 , Infecções por Pseudomonas , Pseudomonas aeruginosa , Sepse , Humanos , Quinases Associadas a Receptores de Interleucina-1/genética , Quinases Associadas a Receptores de Interleucina-1/deficiência , Pseudomonas aeruginosa/genética , Infecções por Pseudomonas/genética , Masculino , Lactente , Sepse/genética , Sepse/microbiologia , Doenças da Imunodeficiência Primária/genética , Mutação com Perda de Função , Heterozigoto , Sequenciamento do Exoma , Síndromes de Imunodeficiência/genéticaRESUMO
OBJECTIVES: Klebsiella pneumoniae is a significant pathogen with increasing resistance and high mortality rates. Conventional antibiotic susceptibility testing methods are time-consuming. Next-generation sequencing has shown promise for predicting antimicrobial resistance (AMR). This study aims to develop prediction models using whole-genome sequencing data and assess their feasibility with metagenomic next-generation sequencing data from clinical samples. METHODS: On the basis of 4170 K. pneumoniae genomes, the main genetic characteristics associated with AMR were identified using a LASSO regression model. Consequently, the prediction model was established, validated and optimized using clinical isolate read simulation sequences. To evaluate the efficacy of the model, clinical specimens were collected. RESULTS: Four predictive models for amikacin, ciprofloxacin, levofloxacin and piperacillin/tazobactam, initially had positive predictive values (PPVs) of 90%, 85%, 84% and 94%, respectively, when they were originally constructed. When applied to clinical specimens, their PPVs increased to 96%, 96%, 95% and 100%, respectively. Meanwhile, there were negative predictive values (NPVs) of 100% for ciprofloxacin and levofloxacin, and 'not applicable' (NA) for amikacin and piperacillin/tazobactam. Our method achieved antibacterial phenotype classification accuracy rates of 96.08% for amikacin, 96.15% for ciprofloxacin, 95.31% for levofloxacin and 100% for piperacillin/tazobactam. The sequence-based prediction antibiotic susceptibility testing (AST) reported results in an average time of 19.5 h, compared with the 67.9 h needed for culture-based AST, resulting in a significant reduction of 48.4 h. CONCLUSIONS: These preliminary results demonstrated that the performance of prediction model for a clinically significant antimicrobial-species pair was comparable to that of phenotypic methods, thereby encouraging the expansion of sequence-based susceptibility prediction and its clinical validation and application.
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Chronic lead (Pb) exposure causes neurodysfunction and contributes to the development of neurodegenerative disease. However, the mechanism of Pb-induced neurological dysfunction have yet to be fully elucidated. This study determined the role pyroptosis plays in Pb-induced neurodysfunction in neurons. We used both in vitro and in vivo approaches to explore whether Pb exposure induces caspase-1-mediated pyroptosis in neurons and its relationship to Pb-induced neurological disorders. Our findings showed that caspase-1-mediated pyroptosis in Pb-exposed neurons activated glycogen synthase kinase 3 protease activity by disrupting Ca2+/calmodulin-dependent protein kinase II/cAMP-response element binding protein pathway, leading to neurological disorders. Moreover, the caspase-1 inhibition VX-765 or the non-steroidal anti-inflammatory drug sodium para-aminosalicylic acid (PAS-Na) attenuated the Pb-induced neurological disorders by alleviating caspase-1 mediated neuronal pyroptosis. Our novel studies suggest that caspase-1-mediated pyroptosis in neurons represents a potential mechanism for Pb-induced neurodysfunction, identifying a putative target for attenuating the neurodegenerative effects induced by this metal.
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Caspase 1 , Chumbo , Neurônios , Piroptose , Piroptose/efeitos dos fármacos , Animais , Caspase 1/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/patologia , Chumbo/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Masculino , Dipeptídeos , para-AminobenzoatosRESUMO
KEY MESSAGE: VyPUB21 plays a key role during the defense against powdery mildew in grapes. Ubiquitin-ligating enzyme (E3), a type of protein widely found in plants, plays a key role in their resistance to disease. Yet how E3 participates in the disease-resistant response of Chinese wild grapevine (Vitis yeshanensis) remains unclear. Here we isolated and identified a U-box type E3 ubiquitin ligase, VyPUB21, from V. yeshanensis. This gene's expression level rose rapidly after induction by exogenous salicylic acid (SA), jasmonic acid (JA), and ethylene (ETH) and powdery mildew. In vitro ubiquitination assay results revealed VyPUB21 could produce ubiquitination bands after co-incubation with ubiquitin, ubiquitin-activating enzyme (E1), and ubiquitin-conjugating enzyme (E2); further, mutation of the conserved amino acid site in the U-box can inhibit the ubiquitination. Transgenic VyPUB21 Arabidopsis had low susceptibility to powdery mildew, and significantly fewer conidiophores and spores on its leaves. Expression levels of disease resistance-related genes were also augmented in transgenic Arabidopsis, and its SA concentration also significantly increased. VyPUB21 interacts with VyNIMIN and targets VyNIMIN protein hydrolysis through the 26S proteasome system. Thus, the repressive effect of the NIMIN-NPR complex on the late systemic acquired resistance (SAR) gene was attenuated, resulting in enhanced resistance to powdery mildew. These results indicate that VyPUB21 encoding ubiquitin ligase U-box E3 activates the SA signaling pathway, and VyPUB21 promotes the expression of late SAR gene by degrading the important protein VyNIMIN of SA signaling pathway, thus enhancing grape resistance to powdery mildew.
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Arabidopsis , Ascomicetos , Vitis , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Vitis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Ascomicetos/fisiologia , Ubiquitinas/metabolismo , Resistência à Doença/genética , Doenças das Plantas/genéticaRESUMO
BACKGROUND: The administration of anesthesia during gastrointestinal endoscopy potentially contributes to post-anesthesia cognitive dysfunction (PACD), with detrimental impacts for cognitive function. This study aimed to assess the knowledge, attitudes, and practices (KAP) towards PACD among patients undergoing gastrointestinal endoscopy in Wenzhou region. METHODS: This cross-sectional study was conducted between June and August 2023, and recruited individuals undergoing gastrointestinal endoscopy. Demographic data and KAP scores were collected through questionnaires. Pearson correlation analysis was applied to evaluate correlations between KAP scores, and logistic regression was utilized to identify influential factors. RESULTS: We collected 405 valid questionnaires, with 54.57% being male and 29.88% aged 31-40 years. Mean KAP scores were 13.99 ± 4.80, 16.19 ± 2.35, and 15.61 ± 2.86, respectively (possible range: 0-16, 0-25, and 0-25). Pearson correlation analysis demonstrated significant positive correlations between knowledge and practice (r = 0.209, P < 0.001), attitude and practice (r = 0.233, P < 0.001), and knowledge and attitude (r = 0.328, P < 0.001). Multivariate logistic regression revealed negative associations of opting for standard gastrointestinal endoscopy (without anesthesia) with knowledge (OR = 0.227, 95%CI: 0.088-0.582, P = 0.002) and practice scores (OR = 0.336, 95%CI: 0.154-0.731, P = 0.006). Additionally, the presence of cognitive-related diseases or symptoms before undergoing gastrointestinal endoscopy was negatively associated with knowledge scores (OR = 0.429, 95%CI: 0.225-0.818, P = 0.010). CONCLUSION: Patients undergoing gastrointestinal endoscopy demonstrated good knowledge, neutral attitudes, and moderate practices regarding PACD. Educational interventions and behavior modification are recommended, particularly for individuals with lower monthly income, undergoing standard gastrointestinal endoscopy, or experiencing cognitive-related conditions.
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Endoscopia Gastrointestinal , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Feminino , Adulto , Estudos Transversais , Endoscopia Gastrointestinal/métodos , Pessoa de Meia-Idade , Inquéritos e Questionários , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Anestesia/métodos , Adulto JovemRESUMO
BACKGROUND: The mode of delivery for twins born before 32 weeks of gestation remains controversial. Our purpose is to conduct a meta-analysis of twin pregnancies less than 32 weeks or twin weight less than 1500 g, so as to find a suitable delivery mode. METHODS: We searched PubMed database, Cochrane Library database, and EMBASE database through December 2022. This protocol was registered with PROSPERO (CRD42023386946) prior to initiation. Studies that compared vaginal delivery to cesarean section for newborns less than 32 weeks of gestation or birthweight under 1500 g were included. The primary result was neonatal mortality rate. Secondary result was neonatal morbidity. The quality of literatures included in the research was evaluated in accordance with Newcastle-Ottawa Scale (NOS) literature quality evaluation scale. We use odds ratio (OR) as the effect index for binary variables. Point estimates and 95% confidence intervals (95% CI) were calculated. P < 0. 05 indicated statistically significant difference. RESULTS: Our search generated 5310 articles, and a total of 8 articles comprising a total of 14,703 newborns were included in the analysis. The odds ratios of neonatal mortality rate were for twins delivered by vaginal delivery compared to cesarean section were 0.84 (95% CI 0.57-1.24, P = 0.38). The 5-min Apgar score < 7 (95% CI 0.44-1.75, P = 0.72), necrotizing enterocolitis (95% CI 0.81-1.19, P = 0.82), intraventricular hemorrhage (95% CI 0.41-1.86, P = 0.71), periventricular leukomalacia (95% CI 0.16-4.52, P = 0.84), bronchopulmonary dysplasia (95% CI 0.88-1.36, P = 0.42), and respiratory distress syndrome (95% CI 0.23-2.01, P = 0.48) were not statistically significant between the two groups. CONCLUSION: We have observed that vaginal delivery does not confer an increased risk of neonatal morbidity and mortality in twins born before 32 weeks of gestation. However, the current results are affected by substantial heterogeneity and confounding factors. We still need high-quality randomized-controlled studies require to address this important question.
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Cesárea , Parto Obstétrico , Recém-Nascido , Gravidez , Humanos , Feminino , Peso ao Nascer , Parto Obstétrico/métodos , Gêmeos , Gravidez de GêmeosRESUMO
Facile and sensitive methods for detecting neonicotinoids (NEOs) in aquatic environments are crucial because they are found in extremely low concentrations in complex matrices. Herein, nitrogen-based magnetic conjugated microporous polymers (Fe3O4@N-CMP) with quaternary ammonium groups were synthesized for efficient magnetic solid-phase extraction (MSPE) of NEOs from tap water, rainwater, and lake water. Fe3O4@N-CMP possessed a suitable specific surface area, extended π-conjugated system, and numerous cationic groups. These properties endow Fe3O4@N-CMP with superior extraction efficiency toward NEOs. The excellent adsorption capacity of Fe3O4@N-CMP toward NEOs was attributed to its π-π stacking, Lewis acid-base, and electrostatic interactions. The proposed MSPE-HPLC-DAD approach based on Fe3O4@N-CMP exhibited a wide linear range (0.1-200 µg/L), low detection limits (0.3-0.5 µg/L), satisfactory precision, and acceptable reproducibility under optimal conditions. In addition, the established method was effectively utilized for the analysis of NEOs in tap water, rainwater, and lake water. Excellent recoveries of NEOs at three spiked levels were in the range of 70.4 to 122.7%, with RSDs less than 10%. This study provides a reliable pretreatment method for monitoring NEOs in environmental water samples.
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OBJECTIVE: To explore the correlation between structural chromosomal abnormality and clinical characteristics of a child featuring gonadal dysplasia. METHODS: A 13-year-old child who was admitted to Lianyungang Maternal and Child Health Care Hospital on February 7, 2023 for primary amenorrhoea and occasional abdominal pain was selected as the study subject. Clinical data of the child was collected, and peripheral blood samples of the child and her parents were collected. G-banding chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out. "Pseudodual centromere isochromosome X" and "psu idic(X)" were used as keywords to search the CNKI, Wanfang and PubMed databases, and the search period was set as from January 1, 2002 to June 1, 2023. Relevant literature on the structural abnormality of X chromosome was searched and analyzed retrospectively. RESULTS: The child has a height of 153 cm and weighed 45 kg. She has no obvious facial dysmorphism. Laboratory tests showed that she had higher FSH and luteinizing hormone, and lower E2. Ultrasonography showed that she had small ovaries and rudimentary uterus. She was found to have a karyotype of 46,X,psu idic(X)(q21.3)[40]/mos 45,X[3], whilst both of her parents had a normal karyotype. CNV-seq showed that she had a 63.27 Mb deletion in Xq21.32q28 and a 91.59 Mb duplication in Xp22.33q21.32 (mosaicism rate = 74%). A total of 11 relevant literature were retrieved. Clinical phenotypes of patients with similar structural chromosomal abnormalities were diverse, which was closely related to the mosaicism rate of the 45,X karyotype and the location of the breaking point. CONCLUSION: 46,X,psu idic(X)(q21.3)/45,X probably underlay the dysplasia of uterus and ovary and sex hormone abnormalities in this child, while her height was spared. Deletion of Xq21.32q28 is a key factor leading to Turner syndrome-like phenotype such as rudimentary uterus and ovarian dysplasia.
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Cariotipagem , Humanos , Feminino , Adolescente , Cromossomos Humanos X/genética , Aberrações dos Cromossomos Sexuais , Variações do Número de Cópias de DNA , Bandeamento Cromossômico , Testes GenéticosRESUMO
Single-atom catalysts (SACs) have recently become highly attractive for selective hydrogenation reactions owing to their remarkably high selectivity. However, compared to their nanoparticle counterparts, atomically dispersed metal atoms in SACs often show inferior activity and are prone to aggregate under reaction conditions. Here, by theoretical calculations, we show that tuning the local electronic structures of metal anchor sites on g-C3N4 by doping B atoms (BCN) with relatively lower electronegativity allows achieving zero-valence Pd SACs with reinforced metal-support orbital hybridizations for high stability and upshifted Pd 4d orbitals for high activity in H2 activation. The precise synthesis of Pd SACs on BCN supports with varied B contents substantiated the theoretical prediction. A zero-valence Pd1/BCN SAC was achieved on a BCN support with a relatively low B content. It exhibited much higher stability in a H2 reducing environment, and more strikingly, a hydrogenation activity, approximately 10 and 34â times greater than those high-valence Pd1/g-C3N4 and Pd1/BCN with a high B content, respectively.
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Reactive metal-support interactions (RMSIs) induce the formation of bimetallic alloys and offer an effective way to tune the electronic and geometric properties of metal sites for advanced catalysis. However, RMSIs often require high-temperature reductions (>500 °C), which significantly limits the tuning of bimetallic compositional varieties. Here, we report that an atomically thick Ga2O3 coating of Pd nanoparticles enables the initiation of RMSIs at a much lower temperature of â¼250 °C. State-of-the-art microscopic and in situ spectroscopic studies disclose that low-temperature RMSIs initiate the formation of rarely reported Ga-rich PdGa alloy phases, distinct from the Pd2Ga phase formed in traditional Pd/Ga2O3 catalysts after high-temperature reduction. In the CO2 hydrogenation reaction, the Ga-rich alloy phases impressively boost the formation of methanol and dimethyl ether â¼5 times higher than that of Pd/Ga2O3. In situ infrared spectroscopy reveals that the Ga-rich phases greatly favor formate formation as well as its subsequent hydrogenation, thus leading to high productivity.
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Eleven blaPER-1-positive Pseudomonas aeruginosa clinical isolates showed variable susceptibility to ceftazidime-avibactam (CZA). The genetic contexts of blaPER-1 were identical (ISCR1-blaPER-1-gst) except for the ST697 isolate HS204 (ISCR1-ISPa1635-blaPER-1-gst). The insertion of ISPa1635 in ISCR1 upstream of blaPER-1 created a hybrid promoter, which elevated the blaPER-1 transcription level and resulted in increased resistance to CZA, ceftolozane-tazobactam, cefepime-zidebactam, and cefiderocol. Diversity in the promoter activity of blaPER-1 partially explains the variable susceptibility to CZA in PER-producing isolates.
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Infecções por Pseudomonas , Inibidores de beta-Lactamases , Humanos , Inibidores de beta-Lactamases/farmacologia , Inibidores de beta-Lactamases/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Lactamas , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/genética , CefiderocolRESUMO
Photosynthetic tissues are dynamic structures whose homeostasis depends on the coordination of two antagonistic processes: self-maintenance and supporting sink tissues. The balance of these processes determines plant development, which might be mediated by cytokinin. However, little is known about the link between sucrose transport signaling and cytokinin. Rice (Oryza sativa) DNA BINDING WITH ONE FINGER11 (OsDOF11) is a transcription factor that mediates sucrose transport by inducing the expression of sucrose transporter genes. Here, we found that OsDOF11 loss-of-function mutants showed a semi-dwarf phenotype with a smaller cell length due to increased cytokinin content in source tissues. RNA sequencing and reverse transcription quantitative PCR analyses revealed that genes involved in cytokinin signaling and metabolism were affected in osdof11 mutants. Yeast one-hybrid, dual-luciferase reporter, and chromatin immunoprecipitation experiments showed that OsDOF11 directly binds to the promoter regions of O. sativa CYTOKININ OXIDASE/DEHYDROGENASE4 (OsCKX4). Moreover, mutation of osckx4 in the osdof11 osckx4 double mutant rescued the semi-dwarf phenotype of the osdof11 mutant. Interestingly, exogenous application of kinetin promoted OsDOF11 expression earlier than OsCKX4, and overexpression of O. sativa VIN3-LIKE 2 caused an increase in active cytokinin levels and induced OsDOF11 transcript levels. Taken together, our results suggest a model in which both a sucrose transport regulator (OsDOF11) and cytokinin via OsCKX4 establish a feedback loop to maintain dynamic tissue homeostasis.
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Oryza , Transporte Biológico , Citocininas/metabolismo , Regulação da Expressão Gênica de Plantas , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sacarose/metabolismoRESUMO
High-resolution jitter measurement is essential for the next generation of electronic communications and sensor systems. However, most electrical timing jitter measurement equipment has a low resolution because of the limitations of electronic processing accuracy. Meanwhile, photonics-based jitter measurement methods have a higher resolution but cannot measure the widely used electrical signals. This work proposes a potential high-resolution jitter measurement method for electrical signals based on the photonics time stretch technique. The jitter information can be magnified in the optical domain and then measured by electrical equipment. The experimental results demonstrate that the jitter of an electrical pulse is magnified from 59.02 ps to 663.29 ps when the magnification factor is 11.24.
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We propose and verify a direct detection (DD) system based on a single photodiode (PD) receiving the independent quadruple-single-sideband (quadruple-SSB) signal. At the transmitter side, an I/Q modulator is utilized to modulate the independent quadruple-SSB signal, the signal is received via one PD without optical bandpass filters (OBPFs). Then, the independent quadruple-SSB signal is separated into four sideband signals by subsequent digital signal processing (DSP). In the scheme of back-to-back (BTB), 1-km and 5-km standard single-mode fiber (SSMF) transmission, the four sideband signals are extensively studied and analyzed. The simulation results show that the bit error rate (BER) of 1Gbaud, 2Gbaud and 4Gbaud independent quadruple-SSB signal can reach the 7% hard-decision forward error correction (HD-FEC) threshold of 3.8 × 10-3 when the received optical power (ROP) is -21, -20 and -17.2 dBm in 5-km SSMF transmission. Meanwhile, as the frequency interval gets wider, the crosstalk in the sideband signal reception can be mitigated and the BER decreases. This scheme for the first time demonstrates that the independent quadruple-SSB signal can further expand the system transmission capacity and enhance the spectrum efficiency. Our simplified independent quadruple-SSB signal direct detection system has a simple structure and high spectral efficiency, which will have a promising future in high-speed optical communication.
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To meet the ultra-bandwidth high-capacity communication, improve spectral efficiency and reduce the complexity of system structure, we have proposed the independent triple-sideband signal transmission system based on photonics-aided terahertz-wave (THz-wave). In this paper, we demonstrate up to 16-Gbaud independent triple-sideband 16-ary quadrature amplitude modulation (16QAM) signal transmission over 20â km standard single mode fiber (SSMF) at 0.3 THz. At the transmitter, independent triple-sideband 16QAM signals are modulated by an in-phase/quadrature (I/Q) modulator. Carrying independent triple-sideband signals optical carrier coupled with another laser to generate independent triple-sideband terahertz optical signals with a carrier frequency interval of 0.3THz. While at the receiver side, enabled by a photodetector (PD) conversion, we successfully obtain independent triple-sideband terahertz signals with a frequency of 0.3THz. Then we employ a local oscillator (LO) to drive mixer to generate intermediate frequency (IF) signal, and only one ADC is used to sample independent triple-sideband signals, digital signal processing (DSP) is finally performed to obtain independent triple-sideband signals. In this scheme, independent triple-sideband 16QAM signals is delivered over 20â km SSMF under the bit error ratio (BER) of 7% hard-decision forward-error-correction (HD-FEC) threshold of 3.8 × 10-3. Our simulation results show that the independent triple-sideband signal can further improve THz system transmission capacity and spectral efficiency. Our simplified independent triple-sideband THz system has a simple structure, high spectral efficiency, and reduced bandwidth requirements for DAC and ADC, which is a promising solution for future high-speed optical communications.
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BACKGROUND: Cisplatin, carboplatin, and oxaliplatin are the only three platinum-based antineoplastic drugs that have been accepted worldwide for treating various cancers. Up to 83.6% of patients treated with platinum-based antineoplastic drugs will develop chemotherapy-induced peripheral neuropathy (CIPN), manifesting as sensory paresthesias, dysesthesias, and hypoesthesias that can cause significant adverse impact to daily activities. AIM: To investigate how these three platinum-based drugs affect mitochondrial function and myelination state of Schwann cells and the signalling pathway involved. METHOD: 2 µM Cisplatin, 20 µM carboplatin, and 1 µM oxaliplatin were used to inhibit the growth of CAL-27 by 20% respectively. These drugs were then used to induce chemotherapy-induced peripheral neuropathy in Rat Schwann Cells (RSC96). The changes in cell metabolism and myelin formation in RSC96 were investigated. RESULT: Cisplatin and carboplatin, but not oxaliplatin increased intracellular and mitochondrial reactive oxygen species in RSC96. Only Cisplatin and carboplatin decreased mitochondrial membrane potential (ΔΨm) and ATP production in RSC96. Both Cisplatin and carboplatin led to demyelination of RSC96, characterized by increased expression of p75NTR and decreased expression of myelin protein zero (MPZ). CONCLUSION: Cisplatin and carboplatin, but not oxaliplatin, caused mitochondrial dysfunction and induced demyelination in RSC96 while showing similar toxicity to head and neck cancer cells. Oxaliplatin may be a potential chemotherapy drug to prevent CIPN in patients with head and neck cancer.