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1.
Plant Cell ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38943676

RESUMO

The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene remains largely elusive. Here, by analyzing cell wall patterns, cell wall composition and gene expression in rice (Oryza sativa, L.) roots, we found that ethylene induces cell wall thickening and the expression of cell wall synthesis-related genes, including CELLULOSE SYNTHASE-LIKE C1, 2, 7, 9, 10 (OsCSLC1, 2, 7, 9, 10) and CELLULOSE SYNTHASE A3, 4, 7, 9 (OsCESA3, 4, 7, 9). Overexpression and mutant analyses revealed that OsCSLC2 and its homologs function in ethylene-mediated induction of xyloglucan biosynthesis mainly in the cell wall of root epidermal cells. Moreover, OsCESA-catalyzed cellulose deposition in the cell wall was enhanced by ethylene. OsCSLC-mediated xyloglucan biosynthesis likely plays an important role in restricting cell wall extension and cell elongation during the ethylene response in rice roots. Genetically, OsCSLC2 acts downstream of ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1)-mediated ethylene signaling, and OsCSLC1, 2, 7, 9 are directly activated by OsEIL1. Furthermore, the auxin signaling pathway is synergistically involved in these regulatory processes. These findings link plant hormone signaling with cell wall establishment, broadening our understanding of root growth plasticity in rice and other crops.

2.
Plant Cell ; 34(11): 4366-4387, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-35972379

RESUMO

Ethylene plays essential roles in adaptive growth of rice (Oryza sativa). Understanding of the crosstalk between ethylene and auxin (Aux) is limited in rice. Here, from an analysis of the root-specific ethylene-insensitive rice mutant mao hu zi 10 (mhz10), we identified the tryptophan aminotransferase (TAR) MHZ10/OsTAR2, which catalyzes the key step in indole-3-pyruvic acid-dependent Aux biosynthesis. Genetically, OsTAR2 acts downstream of ethylene signaling in root ethylene responses. ETHYLENE INSENSITIVE3 like1 (OsEIL1) directly activated OsTAR2 expression. Surprisingly, ethylene induction of OsTAR2 expression still required the Aux pathway. We also show that Os indole-3-acetic acid (IAA)1/9 and OsIAA21/31 physically interact with OsEIL1 and show promotive and repressive effects on OsEIL1-activated OsTAR2 promoter activity, respectively. These effects likely depend on their EAR motif-mediated histone acetylation/deacetylation modification. The special promoting activity of OsIAA1/9 on OsEIL1 may require both the EAR motifs and the flanking sequences for recruitment of histone acetyltransferase. The repressors OsIAA21/31 exhibit earlier degradation upon ethylene treatment than the activators OsIAA1/9 in a TIR1/AFB-dependent manner, allowing OsEIL1 activation by activators OsIAA1/9 for OsTAR2 expression and signal amplification. This study reveals a positive feedback regulation of ethylene signaling by Aux biosynthesis and highlights the crosstalk between ethylene and Aux pathways at a previously underappreciated level for root growth regulation in rice.


Assuntos
Etilenos , Ácidos Indolacéticos , Oryza , Raízes de Plantas , Triptofano Transaminase , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Triptofano Transaminase/genética , Triptofano Transaminase/metabolismo
3.
PLoS Genet ; 18(1): e1009981, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34982771

RESUMO

Chromatin remodelers such as the SWI/SNF complex coordinate metazoan development through broad regulation of chromatin accessibility and transcription, ensuring normal cell cycle control and cellular differentiation in a lineage-specific and temporally restricted manner. Mutations in genes encoding the structural subunits of chromatin, such as histone subunits, and chromatin regulating factors are associated with a variety of disease mechanisms including cancer metastasis, in which cancer co-opts cellular invasion programs functioning in healthy cells during development. Here we utilize Caenorhabditis elegans anchor cell (AC) invasion as an in vivo model to identify the suite of chromatin agents and chromatin regulating factors that promote cellular invasiveness. We demonstrate that the SWI/SNF ATP-dependent chromatin remodeling complex is a critical regulator of AC invasion, with pleiotropic effects on both G0 cell cycle arrest and activation of invasive machinery. Using targeted protein degradation and enhanced RNA interference (RNAi) vectors, we show that SWI/SNF contributes to AC invasion in a dose-dependent fashion, with lower levels of activity in the AC corresponding to aberrant cell cycle entry and increased loss of invasion. Our data specifically implicate the SWI/SNF BAF assembly in the regulation of the G0 cell cycle arrest in the AC, whereas the SWI/SNF PBAF assembly promotes AC invasion via cell cycle-independent mechanisms, including attachment to the basement membrane (BM) and activation of the pro-invasive fos-1/FOS gene. Together these findings demonstrate that the SWI/SNF complex is necessary for two essential components of AC invasion: arresting cell cycle progression and remodeling the BM. The work here provides valuable single-cell mechanistic insight into how the SWI/SNF assemblies differentially contribute to cellular invasion and how SWI/SNF subunit-specific disruptions may contribute to tumorigeneses and cancer metastasis.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiologia , Proteínas Cromossômicas não Histona/genética , Mutação , Proteínas Proto-Oncogênicas c-fos/metabolismo , Animais , Membrana Basal/metabolismo , Sistemas CRISPR-Cas , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Ciclo Celular , Movimento Celular , Proteínas Cromossômicas não Histona/metabolismo , Regulação da Expressão Gênica , Modelos Animais , Fenótipo , Análise de Célula Única
4.
Differentiation ; 137: 100765, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38522217

RESUMO

The acquisition of the post-mitotic state is crucial for the execution of many terminally differentiated cell behaviors during organismal development. However, the mechanisms that maintain the post-mitotic state in this context remain poorly understood. To gain insight into these mechanisms, we used the genetically and visually accessible model of C. elegans anchor cell (AC) invasion into the vulval epithelium. The AC is a terminally differentiated uterine cell that normally exits the cell cycle and enters a post-mitotic state before initiating contact between the uterus and vulva through a cell invasion event. Here, we set out to identify the set of negative cell cycle regulators that maintain the AC in this post-mitotic, invasive state. Our findings revealed a critical role for CKI-1 (p21CIP1/p27KIP1) in redundantly maintaining the post-mitotic state of the AC, as loss of CKI-1 in combination with other negative cell cycle regulators-including CKI-2 (p21CIP1/p27KIP1), LIN-35 (pRb/p107/p130), FZR-1 (Cdh1/Hct1), and LIN-23 (ß-TrCP)-resulted in proliferating ACs. Remarkably, time-lapse imaging revealed that these ACs retain their ability to invade. Upon examination of a node in the gene regulatory network controlling AC invasion, we determined that proliferating, invasive ACs do so by maintaining aspects of pro-invasive gene expression. We therefore report that the requirement for a post-mitotic state for invasive cell behavior can be bypassed following direct cell cycle perturbation.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Mitose , Animais , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Mitose/genética , Feminino , Ciclo Celular/genética , Vulva/citologia , Vulva/crescimento & desenvolvimento , Vulva/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Diferenciação Celular/genética , Movimento Celular/genética , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo
5.
Small ; : e2401134, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816761

RESUMO

Strain engineering has been widely used to optimize platinum-based oxygen reduction reaction (ORR) catalysts for proton exchange membrane fuel cells (PEMFCs). PtM3 (M is base metals), a well-known high-compressive-strain intermetallic alloy, shows promise as a low platinum ORR catalyst due to high intrinsic activity. However, during the alloying of Pt with a threefold amount of M, a notable phase separation between Pt and M may occur, with M particles rapidly sintering while Pt particles grow slowly, posing a challenge in achieving a well-defined PtM3 intermetallic alloy. Here, an entropy-driven Ostwald ripening reversal phenomenon is discovered that enables the synthesis of small-sized Pt(FeCoNiCu)3 intermetallic ORR catalysts. High entropy promotes the thermodynamic driving force for the alloying Pt with M, which triggers the Ostwald ripening reversal of sintered FeCoNiCu particles and facilitates the formation of uniform Pt(FeCoNiCu)3 intermetallic catalysts. The prepared Pt(FeCoNiCu)3 catalysts exhibit a high specific activity of 3.82 mA cm-2, along with a power density of ≈1.3 W cm-2 at 0.67 V and 94 °C with a cathode Pt loading of 0.1 mg cm-2 in H2-air fuel cell.

6.
Small ; : e2401439, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38845528

RESUMO

Solid-state sodium metal batteries have been extensively investigated because of their potential to improve safety, cost-effectiveness, and energy density. The development of such batteries urgently required a solid-state electrolyte with fast Na-ion conduction and favorable interfacial compatibility. Herein, the progress on developing the NaB3H8 solid-state electrolytes is reported, which show a liquid-like ionic conductivity of 0.05 S cm-1 at 56 °C with an activation energy of 0.35 eV after an order-disorder phase transformation, matching or surpassing the best single-anion hydridoborate conductors investigated up to now. The steady polarization voltage and significantly decreased resistance are achieved in the symmetric Na/NaB3H8/Na cell, indicating the great electrochemical stability and favorable interfacial contact with the Na metal of NaB3H8. Furthermore, a Na/NaB3H8/TiS2 battery, the first high-rate (up to 1 C) solid-state sodium metal battery using the single-anion hydridoborate electrolyte, is demonstrated, which exhibits superior rate capability (168.2 mAh g-1 at 0.1 C and 141.2 mAh g-1 at 1 C) and long-term cycling stability (70.9% capacity retention at 1 C after 300 cycles) at 30 °C. This work may present a new possibility to solve the interfacial limitations and find a new group of solid-state electrolytes for high-performance sodium metal batteries.

7.
J Antimicrob Chemother ; 79(5): 1069-1080, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38526879

RESUMO

OBJECTIVES: The emergence and expansion of carbapenem-resistant Klebsiella pneumoniae infections is a concern due to the lack of 'first-line' antibiotic treatment options. The ceftazidime/avibactam is an important clinical treatment for carbapenem-resistant K. pneumoniae infections but there is an increasing number of cases of treatment failure and drug resistance. Therefore, a potential solution is combination therapies that result in synergistic activity against K. pneumoniae carbapenemase: producing K. pneumoniae (KPC-Kp) isolates and preventing the emergence of KPC mutants resistant to ceftazidime/avibactam are needed in lieu of novel antibiotics. METHODS: To evaluate their synergistic activity, antibiotic combinations were tested against 26 KPC-Kp strains. Antibiotic resistance profiles, molecular characteristics and virulence genes were investigated by susceptibility testing and whole-genome sequencing. Antibiotic synergy was evaluated by in vitro chequerboard experiments, time-killing curves and dose-response assays. The mouse thigh model was used to confirm antibiotic combination activities in vivo. Additionally, antibiotic combinations were evaluated for their ability to prevent the emergence of ceftazidime/avibactam resistant mutations of blaKPC. RESULTS: The combination of ceftazidime/avibactam plus meropenem showed remarkable synergistic activity against 26 strains and restored susceptibility to both the partnering antibiotics. The significant therapeutic effect of ceftazidime/avibactam combined with meropenem was also confirmed in the mouse model and bacterial loads in the thigh muscle of the combination groups were significantly reduced. Furthermore, ceftazidime/avibactam plus meropenem showed significant activity in preventing the occurrence of resistance mutations. CONCLUSIONS: Our results indicated that the combination of ceftazidime/avibactam plus meropenem offers viable therapeutic alternatives in treating serious infections due to KPC-Kp.


Assuntos
Antibacterianos , Compostos Azabicíclicos , Proteínas de Bactérias , Ceftazidima , Modelos Animais de Doenças , Combinação de Medicamentos , Sinergismo Farmacológico , Infecções por Klebsiella , Klebsiella pneumoniae , Meropeném , Testes de Sensibilidade Microbiana , beta-Lactamases , Animais , Ceftazidima/farmacologia , Ceftazidima/uso terapêutico , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/genética , Compostos Azabicíclicos/farmacologia , Compostos Azabicíclicos/uso terapêutico , Meropeném/farmacologia , Meropeném/administração & dosagem , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Camundongos , beta-Lactamases/genética , Proteínas de Bactérias/genética , Feminino , Sequenciamento Completo do Genoma , Quimioterapia Combinada , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/genética
8.
New Phytol ; 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509454

RESUMO

Gene expression is regulated at multiple levels, including RNA processing and DNA methylation/demethylation. How these regulations are controlled remains unclear. Here, through analysis of a suppressor for the OsEIN2 over-expressor, we identified an RNA recognition motif protein SUPPRESSOR OF EIN2 (SOE). SOE is localized in nuclear speckles and interacts with several components of the spliceosome. We find SOE associates with hundreds of targets and directly binds to a DNA glycosylase gene DNG701 pre-mRNA for efficient splicing and stabilization, allowing for subsequent DNG701-mediated DNA demethylation of the transgene promoter for proper gene expression. The V81M substitution in the suppressor mutant protein mSOE impaired its protein stability and binding activity to DNG701 pre-mRNA, leading to transgene silencing. SOE mutation enhances grain size and yield. Haplotype analysis in c. 3000 rice accessions reveals that the haplotype 1 (Hap 1) promoter is associated with high 1000-grain weight, and most of the japonica accessions, but not indica ones, have the Hap 1 elite allele. Our study discovers a novel mechanism for the regulation of gene expression and provides an elite allele for the promotion of yield potentials in rice.

9.
J Med Virol ; 96(1): e29396, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38235848

RESUMO

The RNA-dependent RNA polymerase (RdRp) is a crucial element in the replication and transcription of RNA viruses. Although the RdRps of lethal human coronaviruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) have been extensively studied, the molecular mechanism of the catalytic subunit NSP12, which is involved in pathogenesis, remains unclear. In this study, the biochemical and cell biological results demonstrate the interactions between SARS-CoV-2 NSP12 and seven host proteins, including three splicing factors (SLU7, PPIL3, and AKAP8). The entry efficacy of SARS-CoV-2 considerably decreased when SLU7 or PPIL3 was knocked out, indicating that abnormal splicing of the host genome was responsible for this occurrence. Furthermore, the polymerase activity and stability of SARS-CoV-2 RdRp were affected by the three splicing factors to varying degrees. In addition, NSP12 and its homologues from SARS-CoV and MERS-CoV suppressed the alternative splicing of cellular genes, which were influenced by the three splicing factors. Overall, our research illustrates that SARS-CoV-2 NSP12 can engage with various splicing factors, thereby impacting virus entry, replication, and gene splicing. This not only improves our understanding of how viruses cause diseases but also lays the foundation for the development of antiviral therapies.


Assuntos
COVID-19 , Coronavírus da Síndrome Respiratória do Oriente Médio , Humanos , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , COVID-19/genética , RNA Polimerase Dependente de RNA/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Fatores de Processamento de RNA
10.
Neuropathol Appl Neurobiol ; 50(3): e12992, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38831600

RESUMO

PURPOSE: Radiation-induced brain injury, one of the side effects of cranial radiotherapy in tumour patients, usually results in durable and serious cognitive disorders. Microglia are important innate immune-effector cells in the central nervous system. However, the interaction between microglia and neurons in radiation-induced brain injury remains uncharacterised. METHODS AND MATERIALS: We established a microglia-neuron indirect co-culture model to assess the interaction between them. Microglia exposed to radiation were examined for pyroptosis using lactate dehydrogenase (LDH) release, Annexin V/PI staining, SYTOX staining and western blot. The role of nucleotide-binding oligomerisation domain-like receptor family pyrin domain containing 3 (NLRP3) was investigated in microglia exposed to radiation and in mouse radiation brain injury model through siRNA or inhibitor. Mini-mental state examination and cytokines in blood were performed in 23 patients who had experienced cranial irradiation. RESULTS: Microglia exerted neurotoxic features after radiation in the co-culture model. NLRP3 was up-regulated in microglia exposed to radiation, and then caspase-1 was activated. Thus, the gasdermin D protein was cleaved, and it triggered pyroptosis in microglia, which released inflammatory cytokines. Meanwhile, treatment with siRNA NLRP3 in vitro and NLRP3 inhibitor in vivo attenuated the damaged neuron cell and cognitive impairment, respectively. What is more, we found that the patients after radiation with higher IL-6 were observed to have a decreased MMSE score. CONCLUSIONS: These findings indicate that radiation-induced pyroptosis in microglia may promote radiation-induced brain injury via the secretion of neurotoxic cytokines. NLRP3 was evaluated as an important mediator in radiation-induced pyroptosis and a promising therapeutic target for radiation-induced brain injury.


Assuntos
Lesões Encefálicas , Microglia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Piroptose/efeitos da radiação , Piroptose/fisiologia , Microglia/metabolismo , Microglia/efeitos da radiação , Microglia/patologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Animais , Camundongos , Humanos , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Lesões Encefálicas/etiologia , Masculino , Neurônios/metabolismo , Neurônios/patologia , Neurônios/efeitos da radiação , Técnicas de Cocultura , Lesões por Radiação/patologia , Lesões por Radiação/metabolismo , Feminino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade
11.
Virol J ; 21(1): 11, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191404

RESUMO

BACKGROUND: The pathogenesis of severe fever with thrombocytopenia syndrome (SFTS) remained unclear. We aimed to profile the metabolic alterations in urine of SFTS patients and provide new evidence for its pathogenesis. METHODS: A case-control study was conducted in the 154th hospital in China. Totally 88 cases and 22 controls aged ≥ 18 years were enrolled. The cases were selected from laboratory-confirmed SFTS patients. The controls were selected among SFTSV-negative population. Those with diabetes, cancer, hepatitis and other sexually transmitted diseases were excluded in both groups. Fatal cases and survival cases were 1:1 matched. Inter-group differential metabolites and pathways were obtained, and the inter-group discrimination ability was evaluated. RESULTS: Tryptophan metabolism and phenylalanine metabolism were the top one important metabolism pathway in differentiating the control and case groups, and the survival and fatal groups, respectively. The significant increase of differential metabolites in tryptophan metabolism, including 5-hydroxyindoleacetate (5-HIAA), L-kynurenine (KYN), 5-hydroxy-L-tryptophan (5-HTP), 3-hydroxyanthranilic acid (3-HAA), and the increase of phenylpyruvic acid and decrease of hippuric acid in phenylalanine metabolism indicated the potential metabolic alterations in SFTSV infection. The increase of 5-HIAA, KYN, 5-HTP, phenylpyruvic acid and hippuric acid were involved in the fatal progress of SFTS patients. CONCLUSIONS: Tryptophan metabolism and phenylalanine metabolism might be involved in the pathogenesis of SFTSV infection. These findings provided new evidence for the pathogenesis and treatment of SFTS.


Assuntos
Febre Grave com Síndrome de Trombocitopenia , Humanos , 5-Hidroxitriptofano , Estudos de Casos e Controles , Ácido Hidroxi-Indolacético , Triptofano , Fenilalanina
12.
Langmuir ; 40(11): 5878-5889, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38452050

RESUMO

Shotcrete is widely used in tunnels, bridges, culverts, and other large-scale projects. The accelerator is an additive employed to expedite the setting time of shotcrete. Previous research primarily concentrated on enhancing the early strength of accelerators, whereas their long-term stability has been inadequately investigated. In this study, pseudoboehmite (PB) and amorphous aluminum hydroxide (AAH) were incorporated into the accelerator to enhance its stability over a period of 90 days without any signs of crystallization or delamination. Furthermore, the accelerator exhibited an initial setting time of 170 s, a final setting time of 550 s, and a compressive strength of 11.58 MPa after 1 day. The mechanism of effects was studied by isothermal calorimetry, FTIR, XRD, TG-DTG, and SEM analysis. The enhancement in stability is attributed to the distinctive adsorption and thixotropic properties of PB, which facilitate the formation of an electrical double-layer structure in acidic solutions. The expedited setting and hardening are primarily due to the equilibrium between Al3+, SO42-, and Ca2+ ions, which accelerates the hydration process of cement. This research offers a methodology for developing a high-performance, alkali-free liquid accelerator.

13.
J Nanobiotechnology ; 22(1): 66, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38368393

RESUMO

BACKGROUND: The transplantation of exosomes derived from human adipose-derived mesenchymal stem cells (hADSCs) has emerged as a prospective cellular-free therapeutic intervention for the treatment of neurodevelopmental disorders (NDDs), as well as autism spectrum disorder (ASD). Nevertheless, the efficacy of hADSC exosome transplantation for ASD treatment remains to be verified, and the underlying mechanism of action remains unclear. RESULTS: The exosomal long non-coding RNAs (lncRNAs) from hADSC and human umbilical cord mesenchymal stem cells (hUCMSC) were sequenced and 13,915 and 729 lncRNAs were obtained, respectively. The lncRNAs present in hADSC-Exos encompass those found in hUCMSC-Exos and are associated with neurogenesis. The biodistribution of hADSC-Exos in mouse brain ventricles and organoids was tracked, and the cellular uptake of hADSC-Exos was evaluated both in vivo and in vitro. hADSC-Exos promote neurogenesis in brain organoid and ameliorate social deficits in ASD mouse model BTBR T + tf/J (BTBR). Fluorescence in situ hybridization (FISH) confirmed lncRNA Ifngas1 significantly increased in the prefrontal cortex (PFC) of adult mice after hADSC-Exos intraventricular injection. The lncRNA Ifngas1 can act as a molecular sponge for miR-21a-3p to play a regulatory role and promote neurogenesis through the miR-21a-3p/PI3K/AKT axis. CONCLUSION: We demonstrated hADSC-Exos have the ability to confer neuroprotection through functional restoration, attenuation of neuroinflammation, inhibition of neuronal apoptosis, and promotion of neurogenesis both in vitro and in vivo. The hADSC-Exos-derived lncRNA IFNG-AS1 acts as a molecular sponge and facilitates neurogenesis via the miR-21a-3p/PI3K/AKT signaling pathway, thereby exerting a regulatory effect. Our findings suggest a potential therapeutic avenue for individuals with ASD.


Assuntos
Transtorno do Espectro Autista , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , RNA Longo não Codificante , Humanos , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Exossomos/metabolismo , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/terapia , Transtorno do Espectro Autista/metabolismo , Hibridização in Situ Fluorescente , Fosfatidilinositol 3-Quinases/metabolismo , Estudos Prospectivos , Distribuição Tecidual , Neurogênese , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Mesenquimais/metabolismo , Interferon gama/metabolismo
14.
BMC Health Serv Res ; 24(1): 387, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539184

RESUMO

PURPOSE: To gain an in-depth and comprehensive understanding of Chinese organ transplant recipients' perceptions, expectations, and suggestions of pharmacy services to hospital pharmacists. METHODS: This qualitative study was conducted in central China, from February to December 2020. Participants were collected with a purposive and snowball sampling method. Focus group discussions were conducted with organ transplant recipients and content analysis was applied to identify themes and subthemes. RESULTS: 21 recipients participated in the qualitative study. Four themes and thirteen subthemes were identified: (1) perceptions of clinical pharmacists and pharmacy services; (2) expectations for pharmacy service content; (3) expectations for pharmacy service form; and (4) difficulties as a special group. CONCLUSION: The pharmacy services provided by Chinese healthcare institutions are inadequate to meet the needs of organ transplant recipients. However, the acceptance and expectation of pharmacy services by transplant recipients are high. Therefore, China should learn from the experience of developed countries and focus on the actual needs of patients to establish a better pharmacy service system for organ transplantation.


Assuntos
Serviços Comunitários de Farmácia , Motivação , Humanos , Transplantados , Pesquisa Qualitativa , Grupos Focais , Farmacêuticos
15.
Pestic Biochem Physiol ; 201: 105879, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685245

RESUMO

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera, Noctuidae), is a highly polyphagous invasive pest that damages various crops. Pesticide control is the most common and effective strategy to control FAW. In this study, we evaluated the toxicity of metaflumizone and indoxacarb against third-instar FAW larvae using the insecticide-incorporated artificial diet method under laboratory conditions. Both metaflumizone and indoxacarb exhibited substantial toxicity against FAW, with LC50 values of 2.43 and 14.66 mg/L at 72 h, respectively. The sublethal effects of metaflumizone and indoxacarb on parental and F1 generation FAW were investigated by exposing third-instar larvae to LC10 and LC30 concentrations of these insecticides. Sublethal exposure to these two insecticides significantly shortened adult longevity, extended pupal developmental times and led to reduced pupal weight, pupation rates, and adult fecundity in the treated parental generation and F1 generation at LC10 or LC30 concentrations, in comparison to the control group. The larval developmental times were shortened in the parental generation but prolonged in the F1 generation, after being treated with sublethal concentrations of metaflumizone. Furthermore, larvae exposed to LC10 or LC30 concentrations of indoxacarb exhibited elevated activity levels of cytochrome P450 monooxygenase and glutathione S-transferase, which coincides with the observed synergistic effect of piperonyl butoxide and diethyl maleate. In conclusion, the high toxicity and negative impact of metaflumizone and indoxacarb on FAW provided significant implications for the rational utilization of insecticides against this pest.


Assuntos
Inseticidas , Larva , Oxazinas , Semicarbazonas , Spodoptera , Animais , Spodoptera/efeitos dos fármacos , Spodoptera/crescimento & desenvolvimento , Inseticidas/toxicidade , Inseticidas/farmacologia , Semicarbazonas/farmacologia , Larva/efeitos dos fármacos , Oxazinas/toxicidade , Longevidade/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Inativação Metabólica
16.
BMC Med Educ ; 24(1): 69, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233919

RESUMO

OBJECTIVE: The role of the Hospital Pharmacy Preceptor (HPP) is pivotal in upholding the excellence of experiential training and fostering the professional growth of pharmacy interns. However, there is a lack of studies that provide an overview of pharmacy internships from the perspective of HPP. This study explores the experience and expectations of HPPs regarding existing problems and possible coping strategies in intern teaching. METHODS: This is a qualitative study that was conducted through individual interviews and focus group discussions. HPPs were invited as participants from large-scale tertiary hospitals in representative provinces of mainland China. Interview and focus group discussion data were analyzed using thematic analysis to see emerging themes from the data. Nvivo 12 was utilized for data management and processing. RESULTS: Eight individual interviews and two focus group discussions were conducted, involving 14 HPPs as participants. Upon the examination of the interviews and focus group data, four themes were summarized regarding HPPs' perceptions: 1) current presenting problems; 2) possible coping strategies; 3) something HPPs should do; 4) something interns should do. CONCLUSION: This study found that from the HPPs' perspective, the hospital-based pharmacy internship still has some problems from policy to practice, which need to be addressed by the joint efforts of the state, schools, internship bases, pharmacy preceptors, and students.


Assuntos
Educação em Farmácia , Assistência Farmacêutica , Residências em Farmácia , Estudantes de Farmácia , Succinimidas , Humanos , Capacidades de Enfrentamento , Hospitais Gerais , Preceptoria , Pesquisa Qualitativa
17.
J Asian Nat Prod Res ; 26(7): 780-787, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38560992

RESUMO

Two new iridoid glycosides, piasezkiiosides A (1) and B (2), were isolated from aqueous extract of the whole plant of Rehmannia piasezkii. Their structures were established from the spectroscopic data, chemical transformation, and X-ray diffraction analysis. Compound 1 exhibited weak hepatoprotective activity against APAP-induced HepG2 cell damage.


Assuntos
Glicosídeos Iridoides , Rehmannia , Glicosídeos Iridoides/farmacologia , Glicosídeos Iridoides/química , Glicosídeos Iridoides/isolamento & purificação , Humanos , Células Hep G2 , Estrutura Molecular , Rehmannia/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação
18.
J Asian Nat Prod Res ; 26(3): 293-301, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37162445

RESUMO

Four new iridoid glycosides (1-4), rehmaglutosides L-O, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known mellittoside (5) and ajugol (6) were also obtained in the current investigation, and the structure of mellittoside was unequivocally defined using X-ray diffraction data. Compounds 1-6 were tested for their cytotoxicity against five human tumor cell lines and proliferation effects on Lactobacillus Reuteri.


Assuntos
Glicosídeos , Rehmannia , Humanos , Glicosídeos/farmacologia , Glicosídeos/química , Rehmannia/química , Glicosídeos Iridoides/farmacologia
19.
J Asian Nat Prod Res ; 26(2): 248-258, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37905564

RESUMO

Four new alkaloids (1 - 4), together with five known ones (5 - 9), were isolated from the bulbs of Dactylicapnos scandens. The structures were determined by analysis of their spectroscopic data and quantum-chemical calculations. All the isolates were tested for their ability to modulate neuronal Ca2+ mobilization in primary cultured neocortical neurons. Compound 8 inhibited spontaneous Ca2+ oscillations at low micromolar concentrations.


Assuntos
Alcaloides , Alcaloides/química , Raízes de Plantas/química , Neurônios
20.
J Asian Nat Prod Res ; 26(2): 280-292, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36877100

RESUMO

Seven new pentasaccharides (1-7), rehmaglupentasaccharides A-G, were isolated from the air-dried roots of Rehmannia glutinosa. Their structures were established from the spectroscopic data obtained and by chemical evidence. The known verbascose (8) and stachyose (9) were also obtained in the current investigation, and the structure of stachyose was unequivocally defined using X-ray diffraction data. Compounds 1-9 were tested for their cytotoxicity against five human tumor cell lines, influence on dopamine receptor activation, and proliferation effects against Lactobacillus reuteri.


Assuntos
Rehmannia , Humanos , Rehmannia/química , Linhagem Celular , Raízes de Plantas/química
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