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1.
J Biol Chem ; 300(8): 107554, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39002667

RESUMO

Cyclic GMP-AMP synthase (cGAS), a cytosolic DNA sensor, also exhibits nuclear genomic localization and is involved in DNA damage signaling. In this study, we investigated the impact of cGAS crotonylation on the regulation of the DNA damage response, particularly homologous recombination repair, following exposure to ionizing radiation (IR). Lysine 254 of cGAS is constitutively crotonylated by the CREB-binding protein; however, IR-induced DNA damage triggers sirtuin 3 (SIRT3)-mediated decrotonylation. Lysine 254 decrotonylation decreased the DNA-binding affinity of cGAS and inhibited its interaction with PARP1, promoting homologous recombination repair. Moreover, SIRT3 suppression led to homologous recombination repair inhibition and markedly sensitized cancer cells to IR and DNA-damaging chemicals, highlighting SIRT3 as a potential target for cancer therapy. Overall, this study revealed the crucial role of cGAS crotonylation in the DNA damage response. Furthermore, we propose that modulating cGAS and SIRT3 activities could be potential strategies for cancer therapy.


Assuntos
Dano ao DNA , Nucleotidiltransferases , Poli(ADP-Ribose) Polimerase-1 , Reparo de DNA por Recombinação , Sirtuína 3 , Humanos , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli(ADP-Ribose) Polimerase-1/genética , Sirtuína 3/metabolismo , Sirtuína 3/genética , DNA/metabolismo , Lisina/metabolismo , Lisina/química , Radiação Ionizante , Células HEK293
2.
Nano Lett ; 24(27): 8445-8452, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38917425

RESUMO

The interfacial FeSe/TiO2-δ coupling induces high-temperature superconductivity in monolayer FeSe films. Using cryogenic atomically resolved scanning tunneling microscopy/spectroscopy, we obtained atomic-site dependent surface density of states, work function, and the pairing gap in the monolayer FeSe on the SrTiO3(001)-(√13 × âˆš13)-R33.7° surface. Our results disclosed the out-of-plane Se-Fe-Se triple layer gradient variation, switched DOS for Fe sites on and off TiO5□, and inequivalent Fe sublattices, which gives global spatial modulation of pairing gap contaminants with the (√13 × âˆš13) pattern. Moreover, the coherent lattice coupling induces strong inversion asymmetry and in-plane anisotropy in the monolayer FeSe, which is demonstrated to correlate with the particle-hole asymmetry in coherence peaks. These results disclose delicate atomic-scale correlations between pairing and lattice-electronic coupling in the Bardeen-Cooper-Schrieffer to Bose-Einstein condensation crossover regime, providing insights into understanding the pairing mechanism of multiorbital superconductivity.

3.
J Infect Dis ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39225478

RESUMO

Coronavirus disease 2019 (COVID-19) vaccines reduce severe disease and mortality and may lessen transmission, measured by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL). Evaluating vaccine associations in VL at COVID-19 diagnosis in 4 phase 3 randomized, placebo-controlled vaccine trials, July 2020 to July 2021, VL reductions were 2.78 log10 copies/mL (95% confidence interval [CI], 1.38-4.18; n = 60 placebo, 11 vaccine) and 2.12 log10 copies/mL (95% CI, 1.44-2.80; n = 594 placebo, 36 vaccine) for NVX-CoV2373 and mRNA-1273, respectively. Associations were not significant for AZD1222 (0.59 log10 copies/mL; 95% CI, -.19 to 1.36; n = 90 placebo, 78 vaccine) or Ad26.COV2.S (0.23 log10 copies/mL; 95% CI, -.01 to .47; n = 916 placebo, 424 vaccine). Thus, vaccines potentially decreased transmission when ancestral SARS-CoV-2 predominated. Clinical Trials Registration. NCT04470427, NCT04505722, NCT04516746, NCT04611802.

4.
J Bacteriol ; 206(4): e0009524, 2024 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-38564677

RESUMO

Bacterial communities exhibit complex self-organization that contributes to their survival. To better understand the molecules that contribute to transforming a small number of cells into a heterogeneous surface biofilm community, we studied acellular aggregates, structures seen by light microscopy in Pseudomonas aeruginosa colony biofilms using light microscopy and chemical imaging. These structures differ from cellular aggregates, cohesive clusters of cells important for biofilm formation, in that they are visually distinct from cells using light microscopy and are reliant on metabolites for assembly. To investigate how these structures benefit a biofilm community we characterized three recurrent types of acellular aggregates with distinct geometries that were each abundant in specific areas of these biofilms. Alkyl quinolones (AQs) were essential for the formation of all aggregate types with AQ signatures outside the aggregates below the limit of detection. These acellular aggregates spatially sequester AQs and differentiate the biofilm space. However, the three types of aggregates showed differing properties in their size, associated cell death, and lipid content. The largest aggregate type co-localized with spatially confined cell death that was not mediated by Pf4 bacteriophage. Biofilms lacking AQs were absent of localized cell death but exhibited increased, homogeneously distributed cell death. Thus, these AQ-rich aggregates regulate metabolite accessibility, differentiate regions of the biofilm, and promote survival in biofilms.IMPORTANCEPseudomonas aeruginosa is an opportunistic pathogen with the ability to cause infection in the immune-compromised. It is well established that P. aeruginosa biofilms exhibit resilience that includes decreased susceptibility to antimicrobial treatment. This work examines the self-assembled heterogeneity in biofilm communities studying acellular aggregates, regions of condensed matter requiring alkyl quinolones (AQs). AQs are important to both virulence and biofilm formation. Aggregate structures described here spatially regulate the accessibility of these AQs, differentiate regions of the biofilm community, and despite their association with autolysis, correlate with improved P. aeruginosa colony biofilm survival.


Assuntos
Infecções por Pseudomonas , Quinolonas , Humanos , Quinolonas/metabolismo , Biofilmes , Infecções por Pseudomonas/microbiologia , Virulência , Pseudomonas aeruginosa/metabolismo
5.
BMC Genomics ; 25(1): 842, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39251911

RESUMO

BACKGROUND: DNA metabarcoding applies high-throughput sequencing approaches to generate numerous DNA barcodes from mixed sample pools for mass species identification and community characterisation. To date, however, most metabarcoding studies employ second-generation sequencing platforms like Illumina, which are limited by short read lengths and longer turnaround times. While third-generation platforms such as the MinION (Oxford Nanopore Technologies) can sequence longer reads and even in real-time, application of these platforms for metabarcoding has remained limited possibly due to the relatively high read error rates as well as the paucity of specialised software for processing such reads. RESULTS: We show that this is no longer the case by performing nanopore-based, cytochrome c oxidase subunit I (COI) metabarcoding on 34 zooplankton bulk samples, and benchmarking the results against conventional Illumina MiSeq sequencing. Nanopore R10.3 sequencing chemistry and super accurate (SUP) basecalling model reduced raw read error rates to ~ 4%, and consensus calling with amplicon_sorter (without further error correction) generated metabarcodes that were ≤ 1% erroneous. Although Illumina recovered a higher number of molecular operational taxonomic units (MOTUs) than nanopore sequencing (589 vs. 471), we found no significant differences in the zooplankton communities inferred between the sequencing platforms. Importantly, 406 of 444 (91.4%) shared MOTUs between Illumina and nanopore were also found to be free of indel errors, and 85% of the zooplankton richness could be recovered after just 12-15 h of sequencing. CONCLUSION: Our results demonstrate that nanopore sequencing can generate metabarcodes with Illumina-like accuracy, and we are the first study to show that nanopore metabarcodes are almost always indel-free. We also show that nanopore metabarcoding is viable for characterising species-rich communities rapidly, and that the same ecological conclusions can be obtained regardless of the sequencing platform used. Collectively, our study inspires confidence in nanopore sequencing and paves the way for greater utilisation of nanopore technology in various metabarcoding applications.


Assuntos
Código de Barras de DNA Taxonômico , Sequenciamento de Nucleotídeos em Larga Escala , Nanoporos , Código de Barras de DNA Taxonômico/métodos , Animais , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação INDEL , Sequenciamento por Nanoporos/métodos , Complexo IV da Cadeia de Transporte de Elétrons/genética , Zooplâncton/genética , Zooplâncton/classificação , Análise de Sequência de DNA/métodos
6.
Kidney Int ; 105(3): 442-444, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38388145

RESUMO

This commentary provides an analysis of the study by Fu et al. in Kidney International, which employs 3 administrative databases to investigate the hyperkalemia protective effects of sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors. It emphasizes the methodological approach, notably the use of a fixed-effect model to aggregate pairwise comparisons from 3 data sets. In addition, we explored the broader cardiorenal and potential nonrenal benefits of these drug classes, underscoring the imperative for continued research in this domain.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Hipoglicemiantes/efeitos adversos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Receptor do Peptídeo Semelhante ao Glucagon 1
7.
Br J Cancer ; 130(10): 1621-1634, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38575732

RESUMO

BACKGROUND: DNA double-strand break (DSB) induction and repair are important events for determining cell survival and the outcome of cancer radiotherapy. The DNA-dependent protein kinase (DNA-PK) complex functions at the apex of DSBs repair, and its assembly and activity are strictly regulated by post-translation modifications (PTMs)-associated interactions. However, the PTMs of the catalytic subunit DNA-PKcs and how they affect DNA-PKcs's functions are not fully understood. METHODS: Mass spectrometry analyses were performed to identify the crotonylation sites of DNA-PKcs in response to γ-ray irradiation. Co-immunoprecipitation (Co-IP), western blotting, in vitro crotonylation assays, laser microirradiation assays, in vitro DNA binding assays, in vitro DNA-PK assembly assays and IF assays were employed to confirm the crotonylation, identify the crotonylase and decrotonylase, and elucidate how crotonylation regulates the activity and function of DNA-PKcs. Subcutaneous xenografts of human HeLa GCN5 WT or HeLa GCN5 siRNA cells in BALB/c nude mice were generated and utilized to assess tumor proliferation in vivo after radiotherapy. RESULTS: Here, we reveal that K525 is an important site of DNA-PKcs for crotonylation, and whose level is sharply increased by irradiation. The histone acetyltransferase GCN5 functions as the crotonylase for K525-Kcr, while HDAC3 serves as its dedicated decrotonylase. K525 crotonylation enhances DNA binding activity of DNA-PKcs, and facilitates assembly of the DNA-PK complex. Furthermore, GCN5-mediated K525 crotonylation is indispensable for DNA-PKcs autophosphorylation and the repair of double-strand breaks in the NHEJ pathway. GCN5 suppression significantly sensitizes xenograft tumors of mice to radiotherapy. CONCLUSIONS: Our study defines K525 crotonylation of DNA-PKcs is important for the DNA-PK complex assembly and DSBs repair activity via NHEJ pathway. Targeting GCN5-mediated K525 Kcr of DNA-PKcs may be a promising therapeutic strategy for improving the outcome of cancer radiotherapy.


Assuntos
Quebras de DNA de Cadeia Dupla , Reparo do DNA , Tolerância a Radiação , Fatores de Transcrição de p300-CBP , Animais , Feminino , Humanos , Camundongos , Proteína Quinase Ativada por DNA/metabolismo , Células HeLa , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/radioterapia , Neoplasias/metabolismo , Neoplasias/genética , Fatores de Transcrição de p300-CBP/metabolismo , Processamento de Proteína Pós-Traducional , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Eur J Neurosci ; 59(7): 1567-1584, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38314648

RESUMO

The spontaneously hypertensive rat (SHR) is a selectively bred animal strain that is frequently used to model attention-deficit hyperactivity disorder (ADHD) because of certain genetically determined behavioural characteristics. To test the hypothesis that the characteristically altered response to positive reinforcement in SHRs may be due to altered phasic dopamine response to reward, we measured phasic dopamine signals in the SHRs and Sprague Dawley (SD) rats using in vivo fast-scan cyclic voltammetry. The effects of the dopamine reuptake inhibitor, methylphenidate, on these signals were also studied. Phasic dopamine signals during the pairing of a sensory cue with electrical stimulation of midbrain dopamine neurons were significantly smaller in the SHRs than in the SD rats. Over repeated pairings, the dopamine response to the sensory cue increased, whereas the response to the electrical stimulation of dopamine neurons decreased, similarly in both strains. However, the final amplitude of the response to the sensory cue after pairing was significantly smaller in SHRs than in the SD rats. Methylphenidate increased responses to sensory cues to a significantly greater extent in the SHRs than in the SD rats, due largely to differences in the low dose effect. At a higher dose, methylphenidate increased responses to sensory cues and electrical stimulation similarly in SHRs and SD rats. The smaller dopamine responses may explain the reduced salience of reward-predicting cues previously reported in the SHR, whereas the action of methylphenidate on the cue response suggests a potential mechanism for the therapeutic effects of low-dose methylphenidate in ADHD.


Assuntos
Estimulantes do Sistema Nervoso Central , Metilfenidato , Ratos , Animais , Metilfenidato/farmacologia , Metilfenidato/uso terapêutico , Ratos Endogâmicos SHR , Dopamina , Ratos Endogâmicos WKY , Ratos Sprague-Dawley , Modelos Animais de Doenças , Estimulantes do Sistema Nervoso Central/farmacologia
9.
Br J Haematol ; 205(2): 510-516, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38671583

RESUMO

There is an urgent need for an oral, efficient and safe regimen for high-risk APL under the pandemic of COVID-19. We retrospectively analysed 60 high-risk APL patients. For induction therapy (IT), in addition to all-trans retinoic acid (ATRA) and oral arsenic (RIF), 22 patients received oral etoposide (VP16) as cytotoxic chemotherapy (CC), and 38 patients received intravenous CC as historical control group. The median dose of oral VP16 was 1000 mg [interquartile rage (IQR), 650-1250]. One patient died during IT in the control group, 59 evaluable patients (100%) achieved complete haematological remission (CHR) after IT and complete molecular remission (CMR) after consolidation therapy. The median time to CHR and CMR was 36 days (33.8-44) versus 35 days (32-42; p = 0.75) and 3 months (0.8-3.5) versus 3.3 months (2.4-3.7; p = 0.58) in the oral VP16 group and in the control group. Two (9.1%) and 3 (7.9%) patients experienced molecular relapse in different group respectively. The 2-year estimated overall survival and event-free survival were 100% versus 94.7% (p = 0.37) and 90.9% versus 89.5% (p = 0.97) respectively. A completely oral, efficient and safe induction regimen including oral VP16 as cytoreductive chemotherapy combined with ATRA and RIF is more convenient to administer for patients with high-risk APL.


Assuntos
Etoposídeo , Quimioterapia de Indução , Leucemia Promielocítica Aguda , Humanos , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Administração Oral , Estudos Retrospectivos , Quimioterapia de Indução/métodos , Infusões Intravenosas , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , COVID-19 , Tretinoína/administração & dosagem , Tretinoína/uso terapêutico , SARS-CoV-2 , Indução de Remissão , Arsênio/administração & dosagem , Idoso
10.
Environ Sci Technol ; 58(37): 16410-16420, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39236253

RESUMO

Environmental DNA (eDNA) analysis is a powerful tool for studying biodiversity in forests and tree canopies. However, collecting representative eDNA samples from these high and complex environments remains challenging. Traditional methods, such as surface swabbing or tree rolling, are labor-intensive and require significant effort to achieve adequate coverage. This study proposes a novel approach for unmanned aerial vehicles (UAVs) to collect eDNA within tree canopies by using a surface swabbing technique. The method involves lowering a probe from a hovering UAV into the canopy and collecting eDNA as it descends and ascends through branches and leaves. To achieve this, a custom-designed robotic system was developed featuring a winch and a probe for eDNA collection. The design of the probe was optimized, and a control logic for the winch was developed to reduce the risk of entanglement while ensuring sufficient interaction force to facilitate transfer of eDNA onto the probe. The effectiveness of this method was demonstrated during the XPRIZE Rainforest Semi-Finals as 10 eDNA samples were collected from the rainforest canopy, and a total of 152 molecular operational taxonomic units (MOTUs) were identified using eDNA metabarcoding. We further investigate how the number of probe interactions with vegetation, the penetration depth, and the sampling duration influence the DNA concentration and community composition of the samples.


Assuntos
DNA Ambiental , Árvores , Biodiversidade , Dispositivos Aéreos não Tripulados
11.
BMC Cardiovasc Disord ; 24(1): 358, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003493

RESUMO

BACKGROUND: The plasma uric acid to albumin ratio (UAR) is considered as a novel indicator for Inflammation. However, the association between UAR and coronary slow flow phenomenon (CSFP) remains unclear. METHODS: A total of 1328 individuals with chronic coronary syndrome (CCS) receiving coronary angiography (CAG) and found no obvious obstructive stenosis (< 40%) were included in this study. 79 individuals developed CSFP and were divided into CSFP group. The 1:2 age-matched patients with normal coronary blood flow were allocated to the control group (n = 158). The clinical characteristics, laboratory parameters including uric acid, albumin ratio, UAR and the angiographic characteristics were compared between the two groups. RESULTS: Patients with CSFP had a higher level of uric acid (392.3 ± 85.3 vs. 273.8 ± 71.5, P < 0.001), UAR (10.7 ± 2.2 vs. 7.2 ± 1.9, P < 0.001), but a lower level of plasma albumin (36.9 ± 4.2 vs. 38.5 ± 3.6, P = 0.003). Moreover, UAR increased as the numbers of vessels involved in CSFP increased. The logistic regression analysis demonstrated that UAR was independent predictors for CSFP. The Receiver operating characteristic (ROC) curve analysis showed that when UAR was more than 7.9, the AUC was 0.883 (95% CI: 0.840-0.927, p < 0.001), with the sensitivity and specificity were 78.2% and 88.2% respectively. CONCLUSION: Combined uric acid with plasma albumin, UAR could serve as an independent predictor for CSFP.


Assuntos
Biomarcadores , Angiografia Coronária , Circulação Coronária , Fenômeno de não Refluxo , Valor Preditivo dos Testes , Albumina Sérica Humana , Ácido Úrico , Humanos , Masculino , Ácido Úrico/sangue , Feminino , Pessoa de Meia-Idade , Biomarcadores/sangue , Idoso , Albumina Sérica Humana/análise , Fatores de Risco , Fenômeno de não Refluxo/sangue , Fenômeno de não Refluxo/fisiopatologia , Fenômeno de não Refluxo/diagnóstico por imagem , Fenômeno de não Refluxo/diagnóstico , Fenômeno de não Refluxo/etiologia , Doença Crônica , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico , Estudos de Casos e Controles , Estudos Retrospectivos , Vasos Coronários/fisiopatologia , Vasos Coronários/diagnóstico por imagem
12.
Mol Ther ; 31(9): 2633-2650, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37482682

RESUMO

Chromatin remodeling and N6-methyladenosine (m6A) modification are two critical layers in controlling gene expression and DNA damage signaling in most eukaryotic bioprocesses. Here, we report that poly(ADP-ribose) polymerase 1 (PARP1) controls the chromatin accessibility of METTL3 to regulate its transcription and subsequent m6A methylation of poly(A)+ RNA in response to DNA damage induced by radiation. The transcription factors nuclear factor I-C (NFIC) and TATA binding protein (TBP) are dependent on PARP1 to access the METTL3 promoter to activate METTL3 transcription. Upon irradiation or PARP1 inhibitor treatment, PARP1 disassociated from METTL3 promoter chromatin, which resulted in attenuated accessibility of NFIC and TBP and, consequently, suppressed METTL3 expression and RNA m6A methylation. Lysophosphatidic Acid Receptor 5 (LPAR5) mRNA was identified as a target of METTL3, and m6A methylation was located at A1881. The level of m6A methylation of LPAR5 significantly decreased, along with METTL3 depression, in cells after irradiation or PARP1 inhibition. Mutation of the LPAR5 A1881 locus in its 3' UTR results in loss of m6A methylation and, consequently, decreased stability of LPAR5 mRNA. METTL3-targeted small-molecule inhibitors depress murine xenograft tumor growth and exhibit a synergistic effect with radiotherapy in vivo. These findings advance our comprehensive understanding of PARP-related biological roles, which may have implications for developing valuable therapeutic strategies for PARP1 inhibitors in oncology.


Assuntos
Cromatina , Neoplasias , Humanos , Camundongos , Animais , Cromatina/genética , Metilação , RNA/metabolismo , Fatores de Transcrição/genética , RNA Mensageiro/genética , Neoplasias/genética , Neoplasias/radioterapia , Metiltransferases/genética , Metiltransferases/metabolismo , Poli(ADP-Ribose) Polimerase-1/genética , Poli(ADP-Ribose) Polimerase-1/metabolismo , Receptores de Ácidos Lisofosfatídicos/genética , Receptores de Ácidos Lisofosfatídicos/metabolismo
13.
Biochem Genet ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38502457

RESUMO

We aimed to investigate therapeutic effect of Bushenhuoxue recipe in intrauterine adhesions (IUA) and explore the underlying molecular mechanism via integrating network pharmacology and in vitro experimental verification. The active compounds and gene targets of Bushenhuoxue recipe were screened in the TCMSP database and the IUA-related genes were identified using GeneCards database by the keyword "Intrauterine adhesions". Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to reveal the underlying molecular mechanism of Bushenhuoxue recipe treating IUA. T-HESC cells were inducted to fibrotic state using TGF-ß1 of 10 ng/ml concentration treating for 24 h. RT-qPCR or western blot was used to demonstrate the expression levels of fibrosis markers (COL1A1 and α-SMA) and KEGG pathway markers. Cell counting kit-8 (CCK8) assay was performed to illustrate the cell viability of endometrial stromal cell. The treatment of Bushenhuoxue recipe could significantly inhibit the proliferation and fibrosis of endometrial stromal cells. We obtained a total of 169 no-repeat ingredients of Bushenhuoxue recipe and 3044 corresponding targets. After taking intersection with 4230 no-repeat IUA-related genes, a total of 83 target genes related to both Bushenhuoxue recipe and IUA were finally identified. KEGG analysis found that PI3K-AKT signaling pathway might be the key pathway. Further experiment revealed that PI3K-AKT signaling pathway was significantly activated in endometrial stromal cells of fibrotic state and the treatment of Bushenhuoxue recipe could inhibit the PI3K-AKT signaling pathway. Further rescue assay demonstrated that Bushenhuoxue recipe suppressed the proliferation and fibrosis of endometrial stromal cells via PI3K-AKT signaling pathway. Bushenhuoxue recipe suppresses the proliferation and fibrosis of endometrial stromal cells via PI3K-AKT signaling pathway, eventually inhibiting the progression of IUA.

14.
Chem Biodivers ; 21(2): e202301949, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38326086

RESUMO

Five new iridoids, valeralides A-E (1-5), two new acyclic monoterpenoids, valeralides F (6) and G (7), together with two known iridoids (8 and 9), were isolated from the roots and rhizomes of Valeriana officinalis var. latifolia. Their structures were elucidated based on 1D and 2D NMR, as well as HR-ESI-MS spectroscopic data. The absolute configuration of compounds 1-4 were elucidated based on electronic circular dichroism (ECD) calculation. In addition, all the isolates were evaluated for their inhibition on nitric oxide production, cytotoxicity and anti-influenza A virus activity.


Assuntos
Rizoma , Valeriana , Estrutura Molecular , Valeriana/química , Iridoides/química , Monoterpenos/análise , Raízes de Plantas/química
15.
BMC Med Educ ; 24(1): 1024, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294630

RESUMO

BACKGROUND: Junior OB/GYN residents lack opportunities for fundamental surgical skills training of cesarean section, and most OB/GYN residents lack the experience of cervical laceration suturing due to its low incidence. METHODS: A porcine stomach simulation model was designed for obstetrics surgical training. The surface of the stomach simulated the uterus, and the pylorus and cardia simulated the cervical canal. EXPERIENCE: Materials are available from the nearby market. The total cost of the model isï¿¥41. This model can be used in the training in uterus incision and repair of cesarean section and training in cervical laceration suturing. CONCLUSION: The porcine stomach simulation model is pragmatic and realistic. They can be applied in the OB/GYN skill courses to introduce the fundamental obstetrics process to medical students and residents.


Assuntos
Cesárea , Lacerações , Treinamento por Simulação , Estômago , Técnicas de Sutura , Animais , Suínos , Cesárea/educação , Técnicas de Sutura/educação , Feminino , Lacerações/cirurgia , Estômago/cirurgia , Estômago/lesões , Humanos , Gravidez , Obstetrícia/educação , Colo do Útero/cirurgia , Colo do Útero/lesões , Modelos Animais , Competência Clínica , Modelos Anatômicos
16.
Sensors (Basel) ; 24(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38339583

RESUMO

The confining pressure has a great effect on the internal force of the tunnel. During construction, the confining pressure which has a crucial impact on tunnel construction changes due to the variation of groundwater level and applied load. Therefore, the safety of tunnels must have the magnitude of confining pressure accurately estimated. In this study, a complete tunnel confining pressure time axis was obtained through high-frequency field monitoring, the data are segmented into a training set and a testing set. Using GRU and RNN models, a confining pressure prediction model was established, and the prediction results were analyzed. The results indicate that the GRU model has a fast-training speed and higher accuracy. On the other hand, the training speed of the RNN model is slow, with lower accuracy. The dynamic characteristics of soil pressure during tunnel construction require accurate prediction models to maintain the safety of the tunnel. The comparison between GRU and RNN models not only highlights the advantages of the GRU model but also emphasizes the necessity of balancing speed accuracy in tunnel construction confining pressure prediction modeling. This study is helpful in improving the understanding of soil pressure dynamics and developing effective prediction tools to promote safer and more reliable tunnel construction practices.

17.
Sensors (Basel) ; 24(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38475093

RESUMO

With the advancement of engineering techniques, underground shield tunneling projects have also started incorporating emerging technologies to monitor the forces and displacements during the construction and operation phases of shield tunnels. Monitoring devices installed on the tunnel segment components generate a large amount of data. However, due to various factors, data may be missing. Hence, the completion of the incomplete data is imperative to ensure the utmost safety of the engineering project. In this research, a missing data imputation technique utilizing Random Forest (RF) is introduced. The optimal combination of the number of decision trees, maximum depth, and number of features in the RF is determined by minimizing the Mean Squared Error (MSE). Subsequently, complete soil pressure data are artificially manipulated to create incomplete datasets with missing rates of 20%, 40%, and 60%. A comparative analysis of the imputation results using three methods-median, mean, and RF-reveals that this proposed method has the smallest imputation error. As the missing rate increases, the mean squared error of the Random Forest method and the other two methods also increases, with a maximum difference of about 70%. This indicates that the random forest method is suitable for imputing monitoring data.

18.
Nano Lett ; 23(23): 11260-11265, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38048438

RESUMO

This work reports a scaffold-templated, bottom-up synthesis of 3D anisotropic nanofeatures on periodic arrays of gold nanoparticles (AuNPs). Our method relies on substrate-bound AuNPs as large seeds with hemispherical shapes and smooth surfaces after the thermal annealing of as-fabricated particles. Spiky features were grown by immersing the patterned AuNPs into a growth solution consisting of a gold salt and Good's buffer; the number and length of spikes could be tuned by changing the solution pH and buffer concentration. Intermediate structures that informed the growth mechanism were characterized as a function of time by correlating the optical properties and spike features. Large-area (cm2) spiky AuNP arrays exhibited surface-enhanced Raman spectroscopy enhancement that was associated with increased numbers of high-aspect-ratio spikes formed on the AuNP seeds.

19.
J Fish Biol ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39228134

RESUMO

Identification of fish larvae based on morphology is typically limited to higher taxonomic ranks (e.g., family or order), as larvae possess few morphological diagnostic characters for precise discrimination to species. When many samples are presented at any one time, the use of morphology to identify such specimens can be laborious and time-consuming. Using a reverse workflow for specimen sorting and identification leveraging high-throughput DNA sequencing, thousands of fish larvae can be DNA barcoded and sorted into molecular operational taxonomic units (mOTUs) in a single sequencing run with the nanopore sequencing technology (e.g., MinION). This process reduces the time and financial costs of morphology-based sorting and instead deploys experienced taxonomists for species taxonomic work where they are needed most. In this study, a total of 3022 fish larval specimens from plankton tows across four sites in Singapore were collected and sorted based on this workflow. Eye tissue from individual samples was used for DNA extraction and sequencing of cytochrome c oxidase subunit I. We generated a total of 2746 barcodes after quality filtering (90.9% barcoding success), identified 2067 DNA barcodes (75.3% identification success), and delimited 256 mOTUs (146 genera, 52 families). Our analyses identified specific challenges to species assignment, such as the potential misidentification of publicly available sequences used as reference barcodes. We highlighted how the conservative application and comparison of a local sequence database can help resolve identification conflicts. Overall, this proposed approach enables and expedites taxonomic identification of fish larvae, contributing to the enhancement of reference barcode databases and potentially better understanding of fish connectivity.

20.
Molecules ; 29(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38543028

RESUMO

The burgeoning demand for miniaturized energy storage devices compatible with the miniaturization trend of electronic technologies necessitates advancements in micro-supercapacitors (MSCs) that promise safety, cost efficiency, and high-speed charging capabilities. However, conventional aqueous MSCs face a significant limitation due to their inherently narrow electrochemical potential window, which restricts their operational voltage and energy density compared to their organic and ionic liquid counterparts. In this study, we introduce an innovative aqueous NaCl/H2O/EG hybrid gel electrolyte (comprising common salt (NaCl), H2O, ethylene glycol (EG), and SiO2) for Ti3C2Tx MXene MSCs that substantially widens the voltage window to 1.6 V, a notable improvement over traditional aqueous system. By integrating the hybrid electrolyte with 3D-printed MXene electrodes, we realized MSCs with remarkable areal capacitance (1.51 F cm-2) and energy density (675 µWh cm-2), significantly surpassing existing benchmarks for aqueous MSCs. The strategic formulation of the hybrid electrolyte-a low-concentration NaCl solution with EG-ensures both economic and environmental viability while enabling enhanced electrochemical performance. Furthermore, the MSCs fabricated via 3D printing technology exhibit exceptional flexibility and are suitable for modular device integration, offering a promising avenue for the development of high-performance, sustainable energy storage devices. This advancement not only provides a tangible solution to the challenge of limited voltage windows in aqueous MXene MSCs but also sets a new precedent for the design of next-generation MSCs that align with the needs of an increasingly microdevice-centric world.

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