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1.
J Virol ; 98(3): e0194423, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38421166

RESUMO

Since the first human infection reported in 2013, H7N9 avian influenza virus (AIV) has been regarded as a serious threat to human health. In this study, we sought to identify the virulence determinant of the H7N9 virus in mammalian hosts. By comparing the virulence of the SH/4664 H7N9 virus, a non-virulent H9N2 virus, and various H7N9-H9N2 hybrid viruses in infected mice, we first pinpointed PB2 as the primary viral factor accounting for the difference between H7N9 and H9N2 in mammalian virulence. We further analyzed the in vivo effects of individually mutating H7N9 PB2 residues different from the closely related H9N2 virus and consequently found residue 473, alongside the well-known residue 627, to be critical for the virulence of the H7N9 virus in mice and the activity of its reconstituted viral polymerase in mammalian cells. The importance of PB2-473 was further strengthened by studying reverse H7N9 substitutions in the H9N2 background. Finally, we surprisingly found that species-specific usage of ANP32A, a family member of host factors connecting with the PB2-627 polymorphism, mediates the contribution of PB2 473 residue to the mammalian adaption of AIV polymerase, as the attenuating effect of PB2 M473T on the viral polymerase activity and viral growth of the H7N9 virus could be efficiently complemented by co-expression of chicken ANP32A but not mouse ANP32A and ANP32B. Together, our studies uncovered the PB2 473 residue as a novel viral host range determinant of AIVs via species-specific co-opting of the ANP32 host factor to support viral polymerase activity.IMPORTANCEThe H7N9 avian influenza virus has been considered to have the potential to cause the next pandemic since the first case of human infection reported in 2013. In this study, we identified PB2 residue 473 as a new determinant of mouse virulence and mammalian adaptation of the viral polymerase of the H7N9 virus and its non-pathogenic H9N2 counterparts. We further demonstrated that the variation in PB2-473 is functionally linked to differential co-opting of the host ANP32A protein in supporting viral polymerase activity, which is analogous to the well-known PB2-627 polymorphism, albeit the two PB2 positions are spatially distant. By providing new mechanistic insight into the PB2-mediated host range determination of influenza A viruses, our study implicated the potential existence of multiple PB2-ANP32 interfaces that could be targets for developing new antivirals against the H7N9 virus as well as other mammalian-adapted influenza viruses.


Assuntos
Subtipo H7N9 do Vírus da Influenza A , Influenza Humana , Proteínas Nucleares , Proteínas de Ligação a RNA , Animais , Humanos , Camundongos , Subtipo H7N9 do Vírus da Influenza A/metabolismo , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Vírus da Influenza A Subtipo H9N2 , Influenza Humana/virologia , Mamíferos , Proteínas Nucleares/metabolismo , Nucleotidiltransferases/metabolismo , Proteínas de Ligação a RNA/metabolismo , RNA Polimerase Dependente de RNA/genética , RNA Polimerase Dependente de RNA/metabolismo , Virulência , Replicação Viral
2.
EMBO Rep ; 24(9): e55494, 2023 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-37493024

RESUMO

Human CST (CTC1-STN1-TEN1) is a ssDNA-binding complex that interacts with the replisome to aid in stalled fork rescue. We previously found that CST promotes telomere replication to maintain genomic integrity via G-quadruplex (G4) resolution. However, the detailed mechanism by which CST resolves G4s in vivo and whether additional factors are involved remains unclear. Here, we identify RECQ4 as a novel CST-interacting partner and show that RECQ4 can unwind G4 structures in vitro using a FRET assay. Moreover, G4s accumulate at the telomere after RECQ4 depletion, resulting in telomere dysfunction, including the formation of MTSs, SFEs, and TIFs, suggesting that RECQ4 is crucial for telomere integrity. Furthermore, CST is also required for RECQ4 telomere or chromatin localization in response to G4 stabilizers. RECQ4 is involved in preserving genomic stability by CST and RECQ4 disruption impairs restart of replication forks stalled by G4s. Overall, our findings highlight the essential roles of CST and RECQ4 in resolving G-rich regions, where they collaborate to resolve G4-induced replication deficiencies and maintain genomic homeostasis.


Assuntos
Replicação do DNA , Quadruplex G , Humanos , Proteínas de Ligação a Telômeros/genética , Homeostase do Telômero , Telômero/metabolismo
3.
Ecol Lett ; 27(7): e14469, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38990962

RESUMO

The decline in global plant diversity has raised concerns about its implications for carbon fixation and global greenhouse gas emissions (GGE), including carbon dioxide (CO2), nitrous oxide (N2O) and methane (CH4). Therefore, we conducted a comprehensive meta-analysis of 2103 paired observations, examining GGE, soil organic carbon (SOC) and plant carbon in plant mixtures and monocultures. Our findings indicate that plant mixtures decrease soil N2O emissions by 21.4% compared to monocultures. No significant differences occurred between mixtures and monocultures for soil CO2 emissions, CH4 emissions or CH4 uptake. Plant mixtures exhibit higher SOC and plant carbon storage than monocultures. After 10 years of vegetation development, a 40% reduction in species richness decreases SOC content and plant carbon storage by 12.3% and 58.7% respectively. These findings offer insights into the intricate connections between plant diversity, soil and plant carbon storage and GGE-a critical but previously unexamined aspect of biodiversity-ecosystem functioning.


Assuntos
Biodiversidade , Carbono , Gases de Efeito Estufa , Plantas , Solo , Solo/química , Gases de Efeito Estufa/análise , Carbono/metabolismo , Carbono/análise , Plantas/metabolismo , Óxido Nitroso/análise , Óxido Nitroso/metabolismo , Ecossistema , Dióxido de Carbono/metabolismo , Dióxido de Carbono/análise , Metano/metabolismo , Efeito Estufa
4.
BMC Plant Biol ; 24(1): 414, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760680

RESUMO

BACKGROUND: Variations in hydraulic conductivity may arise from species-specific differences in the anatomical structure and function of the xylem, reflecting a spectrum of plant strategies along a slow-fast resource economy continuum. Spruce (Picea spp.), a widely distributed and highly adaptable tree species, is crucial in preventing soil erosion and enabling climate regulation. However, a comprehensive understanding of the variability in anatomical traits of stems and their underlying drivers in the Picea genus is currently lacking especially in a common garden. RESULTS: We assessed 19 stem economic properties and hydraulic characteristics of 17 Picea species grown in a common garden in Tianshui, Gansu Province, China. Significant interspecific differences in growth and anatomical characteristics were observed among the species. Specifically, xylem hydraulic conductivity (Ks) and hydraulic diameter exhibited a significant negative correlation with the thickness to span ratio (TSR), cell wall ratio, and tracheid density and a significant positive correlation with fiber length, and size of the radial tracheid. PCA revealed that the first two axes accounted for 64.40% of the variance, with PC1 reflecting the trade-off between hydraulic efficiency and mechanical support and PC2 representing the trade-off between high embolism resistance and strong pit flexibility. Regression analysis and structural equation modelling further confirmed that tracheid size positively influenced Ks, whereas the traits DWT, D_r, and TSR have influenced Ks indirectly. All traits failed to show significant phylogenetic associations. Pearson's correlation analysis demonstrated strong correlations between most traits and longitude, with the notable influence of the mean temperature during the driest quarter, annual precipitation, precipitation during the wettest quarter, and aridity index. CONCLUSIONS: Our results showed that xylem anatomical traits demonstrated considerable variability across phylogenies, consistent with the pattern of parallel sympatric radiation evolution and global diversity in spruce. By integrating the anatomical structure of the stem xylem as well as environmental factors of origin and evolutionary relationships, our findings provide novel insights into the ecological adaptations of the Picea genus.


Assuntos
Clima , Picea , Madeira , Xilema , Picea/anatomia & histologia , Picea/fisiologia , Picea/crescimento & desenvolvimento , Madeira/anatomia & histologia , Xilema/anatomia & histologia , Xilema/fisiologia , China , Especificidade da Espécie , Caules de Planta/anatomia & histologia , Caules de Planta/fisiologia , Caules de Planta/crescimento & desenvolvimento
5.
J Transl Med ; 22(1): 598, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937806

RESUMO

BACKGROUND: Monocyte-derived alveolar macrophages (Mo_AMs) are increasingly recognised as potential pathogenic factors for idiopathic pulmonary fibrosis (IPF). While scRNAseq analysis has proven valuable in the transcriptome profiling of Mo_AMs, the integration analysis of multi-omics may provide additional dimensions of understanding of these cellular populations. METHODS: We performed multi-omics analysis on 116 scRNAseq, 119 bulkseq and five scATACseq lung tissue samples from IPF. We built a large-scale IPF scRNAseq atlas and conducted the Monocle 2/3 as well as the Cellchat to explore the developmental path and intercellular communication on Mo_AMs. We also reported the difference in metabolisms, tissue repair and phagocytosis between Mo_AMs and tissue-resident alveolar macrophages (TRMs). To determine whether Mo_AMs affected pulmonary function, we projected clinical phenotypes (FVC%pred) from the bulkseq dataset onto the scRNAseq atlas. Finally, we used scATATCseq to uncover the upstream regulatory mechanisms and determine key drivers in Mo_AMs. RESULTS: We identified three Mo_AMs clusters and the trajectory analysis further validated the origin of these clusters. Moreover, via the Cellchat analysis, the CXCL12/CXCR4 axis was found to be involved in the molecular basis of reciprocal interactions between Mo_AMs and fibroblasts through the activation of the ERK pathway in Mo_AMs. SPP1_RecMacs (RecMacs, recruited macrophages) were higher in the low-FVC group than in the high-FVC group. Specifically, compared with TRMs, the functions of lipid and energetic metabolism as well as tissue repair were higher in Mo_AMs than TRMs. But, TRMs may have higher level of phagocytosis than TRMs. SPIB (PU.1), JUNB, JUND, BACH2, FOSL2, and SMARCC1 showed stronger association with open chromatin of Mo_AMs than TRMs. Significant upregulated expression and deep chromatin accessibility of APOE were observed in both SPP1_RecMacs and TRMs. CONCLUSION: Through trajectory analysis, it was confirmed that SPP1_RecMacs derived from Monocytes. Besides, Mo_AMs may influence FVC% pred and aggravate pulmonary fibrosis through the communication with fibroblasts. Furthermore, distinctive transcriptional regulators between Mo_AMs and TRMs implied that they may depend on different upstream regulatory mechanisms. Overall, this work provides a global overview of how Mo_AMs govern IPF and also helps determine better approaches and intervention therapies.


Assuntos
Fibrose Pulmonar Idiopática , Macrófagos Alveolares , Monócitos , Humanos , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/genética , Macrófagos Alveolares/metabolismo , Macrófagos Alveolares/patologia , Monócitos/metabolismo , Masculino , Perfilação da Expressão Gênica , Feminino , Receptores CXCR4/metabolismo , Receptores CXCR4/genética , Pessoa de Meia-Idade , Fenótipo , Pulmão/patologia , Pulmão/metabolismo , Regulação da Expressão Gênica
6.
Appl Environ Microbiol ; 90(10): e0111324, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39365040

RESUMO

Heavy ion beam (HIB) irradiation is widely utilized in studies of cosmic rays-induced cellular effects and microbial breeding. Establishing an accurate dose-survival relationship is crucial for selecting the optimal irradiation dose. Typically, after irradiating logarithmic-phase cell suspensions with HIB, the survival fraction (SF) is determined by the ratio of clonal-forming units in irradiated versus control groups. However, our findings indicated that SF measurements were time sensitive. For the Saccharomyces cerevisiae model, the observed SF initially declined and subsequently increased in a eutrophic state; conversely, in an oligotrophic state, it remained relatively stable within 120 minutes. This time effect of SF observations in the eutrophic state can be ascribed to HIB-exposed cells experiencing cell cycle arrest, whereas the control proliferated rapidly, resulting in an over-time disproportionate change in viable cell count. Therefore, an alternative involves irradiating oligotrophic cells, determining SF thereafter, and transferring cells to the eutrophic state to facilitate DNA repair-mutation. Transcriptomic comparisons under these two trophic states yield valuable insights into the DNA damage response. Although DNA repair was postponed in an oligotrophic state, cells proactively mobilized specific repair pathways to advance this process. Effective nutritional supplementation should occur within 120 minutes, beyond this window, a decline in SF indicates an irreversible loss of repair capability. Upon transition to the eutrophic state, S. cerevisiae swiftly adapted and completed the repair. This study helps to minimize time-dependent variability in SF observations and to ensure effective damage repair and mutation in microbial breeding using HIB or other mutagens. It also promotes the understanding of microbial responses to complex environments.IMPORTANCEMutation breeding is a vital means of developing excellent microbial resources. Consequently, understanding the mechanisms through which microorganisms respond to complex environments characterized by mutagens and specific physiological-biochemical states holds significant theoretical and practical values. This study utilized Saccharomyces cerevisiae as a microbial model and highly efficient heavy ion beam (HIB) radiation as a mutagen, it revealed the time dependence of observations of survival fractions (SF) in response to HIB radiation and proposed an alternative to avoid the indeterminacy that this variable brings. Meanwhile, by incorporating an oligotrophic state into the alternative, this study constructed a dynamic map of gene expression during the fast-repair and slow-repair stages. It also highlighted the influence of trophic states on DNA repair. The findings apply to the survival-damage repair-mutation effects of single-celled microorganisms in response to various mutagens and contribute to elucidating the biological mechanisms underlying microbial survival in complex environments.


Assuntos
Reparo do DNA , Íons Pesados , Saccharomyces cerevisiae , Saccharomyces cerevisiae/efeitos da radiação , Saccharomyces cerevisiae/genética , Viabilidade Microbiana/efeitos da radiação
7.
J Vasc Surg ; 80(5): 1475-1486.e1, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38925348

RESUMO

OBJECTIVE: Carotid plaque vulnerability is a significant factor in the risk of cardiocerebrovascular events, with intraplaque neovascularization (IPN) being a crucial characteristic of plaque vulnerability. This study investigates the value of ultrasound vector flow imaging (V-flow) for measuring carotid plaque wall shear stress (WSS) in predicting the extent of IPN. METHODS: We enrolled 140 patients into three groups: 53 in the plaque group (72 plaques), 23 in the stenosis group (27 plaques), and 64 in the control group. V-flow was used to measure WSS parameters, including the average WSS (WSS mean) and the maximum WSS (WSS max), across three plaque locations: mid-upstream, maximum thickness, and mid-downstream. Contrast-enhanced ultrasound examination was used in 76 patients to analyze IPN and its correlation with WSS parameters. RESULTS: WSS max in the stenosis group was significantly higher than that in the control and plaque groups at the maximum thickness part (P < .05) and WSS mean in the stenosis group was significantly lower than that in the control group at the mid-upstream and mid-downstream segments (P < .05). WSS mean in the plaque group was significantly lower than that of the control group at all three locations (P < .05). Contrast-enhanced ultrasound examination revealed that plaques with neovascularization enhancement exhibited significantly higher WSS values (P < .05), with a positive correlation between WSS parameters and IPN enhancement grades, particularly WSS max at the thickest part (r = 0.508). Receiver operating characteristic curve analysis of WSS parameters for evaluating IPN showed that the efficacy of WSS max in evaluating IPN was better than that of WSS mean (P < .05), with an area under the curve of 0.7762 and 0.6973 (95% confidence intervals, 0.725-0.822 and 0.642-0.749, respectively). The cut-offs were 4.57 Pa and 1.12 Pa, sensitivities were 74.03% and 63.64%, and specificities were 75.00% and 68.18%. CONCLUSIONS: V-flow effectively measures WSS in carotid plaques. WSS max provides a promising metric for assessing IPN, offering potential insights into plaque characteristics and showing some potential in predicting plaque vulnerability.


Assuntos
Artérias Carótidas , Estenose das Carótidas , Placa Aterosclerótica , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Estresse Mecânico , Humanos , Masculino , Feminino , Idoso , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Estenose das Carótidas/complicações , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiopatologia , Pessoa de Meia-Idade , Neovascularização Patológica , Ruptura Espontânea , Meios de Contraste , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Índice de Gravidade de Doença , Curva ROC , Idoso de 80 Anos ou mais , Ultrassonografia Doppler em Cores
8.
Microb Pathog ; 195: 106882, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39197692

RESUMO

Cyclic di-GMP (c-di-GMP), a ubiquitous secondary messenger in bacteria, affects multiple bacterial behaviors including motility and biofilm formation. c-di-GMP is synthesized by diguanylate cyclase harboring a GGDEF domain and degraded by phosphodiesterase harboring an either EAL or HD-GYP domain. Vibrio parahaemolyticus, the leading cause of seafood-associated gastroenteritis, harbors more than 60 genes involved in c-di-GMP metabolism. However, roles of most of these genes including vpa0198, which encodes a GGDEF-domain containing protein, are still completely unknown. AphA and OpaR are the master quorum sensing (QS) regulators operating at low (LCD) and high cell density (HCD), respectively. QsvR integrates into QS to control gene expression via direct regulation of AphA and OpaR. In this study, we showed that deletion of vpa0198 remarkably reduced c-di-GMP production and biofilm formation, whereas promoted the swimming motility of V. parahaemolyticus. Overexpression of VPA0198 in the vpa0198 mutant strain significantly reduced the swimming and swarming motility and enhanced the biofilm formation ability of V. parahaemolyticus. In addition, transcription of vpa0198 was under the collective regulation of AphA, OpaR and QsvR. AphA activated the transcription of vpa0198 at LCD, whereas QsvR and OpaR coordinately and directly repressed vpa0198 transcription at HCD, thereby leading to a cell density-dependent expression of vpa0198. Therefore, this work expanded the knowledge of synthetic regulatory mechanism of c-di-GMP in V. parahaemolyticus.


Assuntos
Proteínas de Bactérias , Biofilmes , GMP Cíclico , Regulação Bacteriana da Expressão Gênica , Percepção de Quorum , Vibrio parahaemolyticus , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/metabolismo , Vibrio parahaemolyticus/fisiologia , Biofilmes/crescimento & desenvolvimento , Percepção de Quorum/genética , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fatores de Transcrição
9.
BMC Cancer ; 24(1): 654, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38811891

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated superior clinical efficacy in prolonging overall survival (OS) as the second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC), and were recommended by the guidelines. However, it remains uncertain which ICI is the most cost-effective. This study assessed the cost-effectiveness of ICIs as the second-line treatment for ESCC based on the perspective of the Chinese healthcare system. METHODS: A network meta-analysis (NMA) was performed to obtain the Hazard ratios (HRs) for indirect comparisons. A three-state Markov model with a 10-year time horizon was conducted to assess the cost-effectiveness. The state transition probabilities were calculated with Kaplan-Meier (KM) curves data from clinical trial and HRs from the NMA. Utilities and costs were derived from local charges or previously published studies. Univariate and probabilistic sensitivity analyses (PSA) were performed to examine model robustness. The results were assessed based on the total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Five clinical trials (ATTRACTION-3, ESCORT, KEYNOTE-181, ORIENT-2, RATIONALE-302) with a total of 1797 patients were included in the NMA. The NMA showed that both camrelizumab and tislelizumab received relatively high rankings for progression-free survival (PFS) and OS. Compared with sintilimab, treatment with tislelizumab and camrelizumab gained 0.018 and 0.034 additional QALYs, resulting in incremental ICERs of $75,472.65/QALY and $175,681.9/QALY, respectively. Nivolumab and pembrolizumab produced lower QALYs and greater costs, suggesting that both were dominated in comparison to sintilimab. HRs and health state utilities were the most influential parameters in most univariate sensitivity analyses of paired comparisons. PSA results suggested that sintilimab had an 84.4% chance of being the most cost-effective treatment regimen at the WTP threshold of $38,223.34/QALY. In the scenario analysis, sintilimab would no longer be cost-effective, if the price of camrelizumab was assumed to decrease by 64.6% or the price of tislelizumab was assumed to decrease by 16.9%. CONCLUSIONS AND RELEVANCE: Among the five potential competing ICIs, sintilimab was likely to be the most cost-effective regimen as the second-line treatment for locally advanced or metastatic ESCC in China.


Assuntos
Análise Custo-Benefício , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Inibidores de Checkpoint Imunológico , Metanálise em Rede , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/economia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Carcinoma de Células Escamosas do Esôfago/mortalidade , Carcinoma de Células Escamosas do Esôfago/economia , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Cadeias de Markov , Nivolumabe/uso terapêutico , Nivolumabe/economia , Análise de Custo-Efetividade
10.
Arch Microbiol ; 206(7): 321, 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907796

RESUMO

Vibrio parahaemolyticus possesses two distinct type VI secretion systems (T6SS), namely T6SS1 and T6SS2. T6SS1 is predominantly responsible for adhesion to Caco-2 and HeLa cells and for the antibacterial activity of V. parahaemolyticus, while T6SS2 mainly contributes to HeLa cell adhesion. However, it remains unclear whether the T6SS systems have other physiological roles in V. parahaemolyticus. In this study, we demonstrated that the deletion of icmF2, a structural gene of T6SS2, reduced the biofilm formation capacity of V. parahaemolyticus under low salt conditions, which was also influenced by the incubation time. Nonetheless, the deletion of icmF2 did not affect the biofilm formation capacity in marine-like growth conditions, nor did it impact the flagella-driven swimming and swarming motility of V. parahaemolyticus. IcmF2 was found to promote the production of the main components of the biofilm matrix, including extracellular DNA (eDNA) and extracellular proteins, and cyclic di-GMP (c-di-GMP) in V. parahaemolyticus. Additionally, IcmF2 positively influenced the transcription of cpsA, mfpA, and several genes involved in c-di-GMP metabolism, including scrJ, scrL, vopY, tpdA, gefA, and scrG. Conversely, the transcription of scrA was negatively impacted by IcmF2. Therefore, IcmF2-dependent biofilm formation was mediated through its effects on the production of eDNA, extracellular proteins, and c-di-GMP, as well as its impact on the transcription of cpsA, mfpA, and genes associated with c-di-GMP metabolism. This study confirmed new physiological roles for IcmF2 in promoting biofilm formation and c-di-GMP production in V. parahaemolyticus.


Assuntos
Proteínas de Bactérias , Biofilmes , GMP Cíclico , Sistemas de Secreção Tipo VI , Vibrio parahaemolyticus , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/fisiologia , Vibrio parahaemolyticus/metabolismo , Biofilmes/crescimento & desenvolvimento , Sistemas de Secreção Tipo VI/genética , Sistemas de Secreção Tipo VI/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Humanos , Regulação Bacteriana da Expressão Gênica , Células HeLa
11.
J Org Chem ; 89(1): 804-809, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38146924

RESUMO

A highly stereoselective strategy for 1,2-cis-xylopyranoside bond formation was established via a preactivation-based, additive-modulated trichloroacetimidate glycosidation strategy. The current protocol is mild, practical, and successful with various xylopyranosyl donors and glycosyl acceptors, including acceptors that are reported to be less reactive due to steric hindrance. The utility of this method was demonstrated with the facile assembly of matriglycan constituent tetra- and hexasaccharides.

12.
J Org Chem ; 89(11): 7865-7876, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38805026

RESUMO

Activation of O-glycosyl trihaloacetimidate glycosyl donors with AuCl3 as a catalyst and pivalonitrile (tBuCN) as a ligand led to excellent glycosidation results in terms of yield and anomeric selectivity. In this way, various ß-d-gluco- and ß-d-galactopyranosides were obtained conveniently and efficiently. Experimental studies and density functional theory (DFT) calculations, in order to elucidate the reaction course, support formation of the tBuCN-AuCl2-OR(H)+ AuCl4- complex as a decisive intermediate in the glycosidation event. Proton transfer from this acceptor complex to the imidate nitrogen leads to donor activation. In this way, guided by the C-2 configuration of the glycosyl donor, the alignment of the acceptor complex enforces the stereoselective ß-glycoside formation in an intramolecular fashion, thus promoting also a fast reaction course. The high stereocontrol of this novel 'Lewis acid-nitrile cooperative effect' is independent of the glycosyl donor anomeric configuration and without the support of neighboring group or remote group participation. The power of the methodology is shown by a successful glycoalkaloid solamargine synthesis.

13.
BMC Gastroenterol ; 24(1): 20, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38182996

RESUMO

BACKGROUND: To investigate the feasibility of a deformable self-assembled magnetic anastomosis ring (DSAMAR), designed and developed by us, for endoscopic gastrointestinal bypass anastomosis. METHODS: Ten experimental pigs were used as model animals. The DSAMAR comprises 10 trapezoidal magnetic units, arranged in a straight line under the constraint of a guide wire. When the desired anastomosis site is reached under the guidance of an endoscope, the catheter pushes the magnetic unit along the guide wire. The linear DSAMAR can be assembled into a circular DSAMAR. Two DSAMARs were inserted, one at the end of the duodenum and the other into the stomach successively. They attracted each other and compressed the wall of the stomach and duodenum to establish gastrointestinal bypass anastomosis. The experimental pigs were euthanized 4 weeks after the operation, and the gastrointestinal bypass anastomosis specimens were obtained. The anastomosis formation was evaluated by the naked eye and histology. RESULTS: Gastrointestinal bypass anastomosis with DSAMARs was successfully performed. The average operation time under an endoscope was 70.30 ± 19.05 min (range: 43-95 min). The DSAMARs were discharged through the anus 10-17 days after surgery. There were no complications such as gastrointestinal bleeding, perforation, anastomotic fistula, and gastrointestinal obstruction during and after the operation. Gastroscopy and gross specimen of the anastomosis showed a well-formed magnetic anastomosis. Histological observation showed good continuity of the serous membrane and the mucosa of magnetic anastomosis. CONCLUSION: The DSAMAR is a safe and feasible device for fashioning gastrointestinal bypass anastomosis in this animal model.


Assuntos
Gastroscopia , Estômago , Suínos , Animais , Anastomose Cirúrgica , Estômago/cirurgia , Duodeno , Fenômenos Magnéticos
14.
Environ Sci Technol ; 58(16): 7099-7112, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38536960

RESUMO

Reduced nitrogen-containing organic compounds (NOCs) in aerosols play a crucial role in altering their light-absorption properties, thereby impacting regional haze and climate. Due to the low concentration levels of individual NOCs in the air, the utilization of accurate detection and quantification technologies becomes essential. For the first time, this study investigated the diurnal variation, chemical characteristics, and potential formation pathways of NOCs in urban ambient aerosols in Shanghai using a versatile aerosol concentration enrichment system (VACES) coupled with HPLC-Q-TOF-MS. The results showed that NOCs accounted over 60% of identified components of urban organic aerosols, with O/N < 3 compounds being the major contributors (>70%). The predominance of the positive ionization mode suggested the prevalence of reduced NOCs. Higher relative intensities and number fractions of NOCs were observed during nighttime, while CHO compounds showed an opposite trend. Notably, a positive correlation between the intensity of NOCs and ammonium during the nighttime was observed, suggesting that the reaction of ammonium to form imines may be a potential pathway for the formation of reduced NOCs during the nighttime. Seven prevalent types of reduced NOCs in autumn and winter were identified and characterized by an enrichment of CH2 long-chain homologues. These NOCs included alkyl, cyclic, and aromatic amides in CHON compounds, as well as heterocyclic or cyclic amines and aniline homologue series in CHN compounds, which were associated with anthropogenic activities and may be capable of forming light-absorbing chromophores or posing harm to human health. The findings highlight the significant contributions of both primary emissions and ammonium chemistry, particularly amination processes, to the pollution of reduced NOCs in Shanghai's atmosphere.


Assuntos
Aerossóis , Poluentes Atmosféricos , Atmosfera , China , Atmosfera/química , Poluentes Atmosféricos/análise , Compostos Orgânicos/análise , Monitoramento Ambiental , Nitrogênio/análise
15.
Phys Chem Chem Phys ; 26(2): 1148-1155, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38099451

RESUMO

The rational design of a solid electrolyte interphase (SEI) with high ionic conductivity and high electrochemical stability is significantly important in improving the electrochemical performance of anode materials. Herein, lithium difluoro(oxalate)borate (LiDFOB) is used as an electrolyte additive to generate protective SEI films on Li3VO4 (LVO) anodes. The addition of LiDFOB is beneficial to form a dense, uniform, stable and LiF-richer SEI, which is helpful to boost the Li-ion storage kinetics. In addition, the generated SEI can inhibit the further decomposition of electrolytes and maintain the morphology of LVO anodes during charge/discharge processes. As a result, LVO-based anodes exhibit a much higher capacity (769.5 mA h g-1 at 0.5 A g-1), enhanced rate performance (243.3 mA h g-1 at 5.0 A g-1) and excellent long-term cycling stability (209.9 mA h g-1 after 5000 cycles) when cycled in 1 wt% LiDFOB addition electrolyte. This work confirms that LiDFOB is a promising multi-functional additive for LiPF6 electrolytes and provides new insights into SEI construction towards high-performance LVO anodes.

16.
Environ Res ; 252(Pt 1): 118425, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38325789

RESUMO

This study employed hydrothermal carbonization (HTC) in conjunction with ZnCl2 activation and pyrolysis to produce biochar from one traditional Chinese medicine astragali radix (AR) residue. The resultant biochar was evaluated as a sustainable adsorbent for tetracycline (TC) elimination from water. The adsorption performance of TC on two micropore-rich AR biochars, AR@ZnCl2 (1370 m2 g-1) and HAR@ZnCl2 (1896 m2 g-1), was comprehensively evaluated using adsorption isotherms, kinetics, and thermodynamics. By virtue of pore diffusion, π-π interaction, electrostatic attraction, and hydrogen bonding, the prepared AR biochar showed exceptional adsorption properties for TC. Notably, the maximum adsorption capacity (930.3 mg g-1) of TC on HAR@ZnCl2 can be achieved when the adsorbent dosage is 0.5 g L-1 and C0 is 500 mg L-1 at 323 K. The TC adsorption on HAR@ZnCl2 took place spontaneously. Furthermore, the impact of competitive ions behavior is insignificant when coexisting ion concentrations fall within the 10-100 mg L-1 range. Additionally, the produced biochar illustrated good economic benefits, with a payback of 701 $ t-1. More importantly, even after ten cycles, HAR@ZnCl2 still presented great TC removal efficiency (above 77%), suggesting a good application prosperity. In summary, the effectiveness and sustainability of AR biochar, a biowaste-derived product, were demonstrated in its ability to remove antibiotics from water, showing great potential in wastewater treatment application.


Assuntos
Carvão Vegetal , Medicamentos de Ervas Chinesas , Tetraciclina , Poluentes Químicos da Água , Adsorção , Carvão Vegetal/química , Tetraciclina/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/análise , Medicamentos de Ervas Chinesas/química , Antibacterianos/química , Purificação da Água/métodos , Cinética , Cloretos , Compostos de Zinco
17.
Cell Biochem Funct ; 42(2): e3977, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38494660

RESUMO

Langerhans cells (LCs) play a critical role in skin immune responses and the development of psoriasis. Yinxieling (YXL) is a representative Chinese herbal medicine for the treatment of psoriasis in South China. It was found to improve psoriasis without obvious side effects in the clinic. Here we attempted to clarify whether and how YXL regulates the differentiation and functions of LCs in Imiquimod (IMQ)-induced psoriasis in vivo and induced LCs in vitro. The Psoriasis Area Severity Index (PASI) score was used to evaluate the efficacy of YXL for IMQ-induced psoriasis-like mice. Flow cytometry was utilized to analyze the effects of YXL, to regulate the differentiation, migration, maturation, and antigen presentation of LCs. The results show that YXL significantly alleviated skin inflammation, as reduced in PASI score and classic psoriasis characteristics in pathological sections. Although there was no effect on the proportion of total DCs in the skin-draining lymph nodes, the expression of epidermal LCs and its transcription factor PU.1 were both markedly inhibited. LCs were also prevented from migrating from epidermal to skin-draining lymph nodes and mature. In addition, the number of LCs carrying antigens in the epidermis increased, which suggested that YXL could effectively prevent LCs from presenting antigens. In vitro, YXL had a significant impact on inhibiting the differentiation of LCs. Further data showed that YXL decreased the relative expression of transforming growth factor-ß (TGFß) messenger RNA (mRNA) and interleukin-23 (IL-23) mRNAs. Thus, YXL alleviates psoriasis by regulating differentiation, migration, maturation, and antigen presentation via the TGFß/PU.1/IL-23 signal axis.


Assuntos
Células de Langerhans , Psoríase , Animais , Camundongos , Interleucina-23 , Fator de Crescimento Transformador beta1 , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Fator de Crescimento Transformador beta , RNA Mensageiro
18.
Can J Microbiol ; 70(4): 128-134, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38415613

RESUMO

Vibrio parahaemolyticus, the leading cause of seafood-associated gastroenteritis, has a strong capacity to form biofilms on surfaces, which is strictly regulated by the CpsS-CpsR-CpsQ regulatory cascade. OpaR, a master regulator of quorum sensing, is a global regulator that controls multiple cellular pathways including biofilm formation and virulence. QsvR is an AraC-type regulator that works coordinately with OpaR to control biofilm formation and virulence gene expression of V. parahaemolyticus. QsvR and OpaR activate cpsQ transcription. OpaR also activates cpsR transcription, but lacks the detailed regulatory mechanisms. Furthermore, it is still unknown whether QsvR regulates cpsR transcription, as well as whether QsvR and OpaR regulate cpsS transcription. In this study, the results of quantitative real-time PCR and LacZ fusion assays demonstrated that deletion of qsvR and/or opaR significantly decreased the expression levels of cpsS and cpsR compared to the wild-type strain. However, the results of two-plasmid lacZ reporter and electrophoretic mobility-shift assays showed that both QsvR and OpaR were unable to bind the regulatory DNA regions of cpsS and cpsR. Therefore, transcription of cpsS and cpsR was coordinately and indirectly activated by QsvR and OpaR. This work enriched our knowledge on the regulatory network of biofilm formation in V. parahaemolyticus.


Assuntos
Fatores de Transcrição , Vibrio parahaemolyticus , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Vibrio parahaemolyticus/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Virulência/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Biofilmes
19.
Appl Opt ; 63(7): B59-B69, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437256

RESUMO

Retrieving a phase map from a single closed fringe pattern is a challenging task in optical interferometry. In this paper, a convolutional neural network (CNN), HRUnet, is proposed to demodulate phase from a closed fringe pattern. The HRUnet, derived from the Unet model, adopts a high resolution network (HRnet) module to extract high resolution feature maps of the data and employs residual blocks to erase the gradient vanishing in the network. With the trained network, the unwrapped phase map can be directly obtained by feeding a scaled fringe pattern. The high accuracy of the phase map obtained from HRUnet is demonstrated by demodulation of both simulated data and actual fringe patterns. Compared results between HRUnet and two other CNNS are also provided, and the results proved that the performance of HRUnet in accuracy is superior to the two other counterparts.

20.
Curr Microbiol ; 81(10): 330, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39196442

RESUMO

The type VI secretion system 2 (T6SS2) gene cluster of Vibrio parahaemolyticus comprises three operons: VPA1027-1024, VPA1043-1028, and VPA1044-1046. AcsS is a LysR-like transcriptional regulator that play a role in activating flagella-driven motility in V. parahaemolyticus. However, its potential roles in other cellular pathways remain poorly understood. In this study, we conducted a series of experiments to investigate the regulatory effects of AcsS on the transcription of VPA1027 (hcp2), VPA1043, and VPA1044. The findings revealed that AcsS indirectly inhibits the transcription of these genes. Additionally, deletion of acsS resulted in enhanced adhesion of V. parahaemolyticus to HeLa cells. However, disruption of T6SS2 alone or in conjunction with AcsS significantly diminished the adhesion capacity of V. parahaemolyticus to HeLa cells. Therefore, it is suggested that AcsS suppresses cell adhesion in V. parahaemolyticus by downregulating the transcription of T6SS2 genes.


Assuntos
Aderência Bacteriana , Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Transcrição Gênica , Sistemas de Secreção Tipo VI , Vibrio parahaemolyticus , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/metabolismo , Células HeLa , Humanos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sistemas de Secreção Tipo VI/genética , Sistemas de Secreção Tipo VI/metabolismo , Aderência Bacteriana/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Família Multigênica
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