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Background: Staphylococcus aureus (S. aureus), a prevalent human pathogen known for its propensity to cause severe infections, has exhibited a growing resistance to antibiotics. Lysine acetylation (Kac) is a dynamic and reversible protein post-translational modification (PTM), played important roles in various physiological functions. Recent studies have shed light on the involvement of Kac modification in bacterial antibiotic resistance. However, the precise relationship between Kac modification and antibiotic resistance in S. aureus remains inadequately comprehended. Methods: We compared the differential expression of acetylated proteins between erythromycin-resistant (Ery-R) and erythromycin-susceptible (Ery-S) strains of S. aureus by 4D label-free quantitative proteomics technology. Additionally, we employed motif analysis, functional annotation and PPI network to investigate the acetylome landscape and heterogeneity of S. aureus. Furthermore, polysome profiling experiments were performed to assess the translational status of ribosome. Results: 6791 Kac sites were identified on 1808 proteins in S. aureus, among which 1907 sites in 483 proteins were quantified. A total of 548 Kac sites on 316 acetylated proteins were differentially expressed by erythromycin pressure. The differentially acetylated proteins were primarily enriched in ribosome assembly, glycolysis and lysine biosynthesis. Bioinformatic analyses implied that Kac modification of ribosomal proteins may play an important role in erythromycin resistance of S. aureus. Western bolt and polysome profiling experiments indicated that the increased Kac levels of ribosomal proteins in the resistant strain may partially offset the inhibitory effect of erythromycin on ribosome function. Conclusions: Our findings confirm that Kac modification is related to erythromycin resistance in S. aureus and emphasize the potential roles of ribosomal proteins. These results expand our current knowledge of antibiotic resistance mechanisms, potentially guiding future research on PTM-mediated antibiotic resistance.
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OBJECTIVES: The rising threat of antibiotic resistance poses a significant challenge to public health. The research on the new direction of resistance mechanisms is crucial for overcoming this hurdle. This study examines metabolic changes by comparing sensitive and experimentally induced ofloxacin-resistant Escherichia coli (E. coli) strains using multi-omics analyses, aiming to provide novel insights into bacterial resistance. METHODS: An ofloxacin-resistant E. coli strain was selected by being exposed to high concentration of ofloxacin. Comparative analyses involving transcriptomics, proteomics, and acetylomics were conducted between the wild-type (WT) and the ofloxacin-resistant (Re-OFL) strains. Enrichment pathways of differentially expressed genes, proteins and acetylated proteins between the two strains were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) method. In addition, the metabolic network of E. coli was mapped using integrated multi-omics analysis strategies. RESULTS: We identified significant differences in 2775 mRNAs, 1062 proteins, and 1015 acetylated proteins between WT and Re-OFL strains. Integrated omics analyses revealed that the common alterations enriched in metabolic processes, particularly the glycolytic pathway. Further analyses demonstrated that 14 metabolic enzymes exhibited upregulated acetylation levels and downregulated transcription and protein levels. Moreover, seven of these metabolic enzymes (fba, tpi, gapA, pykA, sdhA, fumA, and mdh) were components related to the glycolytic pathway. CONCLUSION: The changes of metabolic enzymes induced by antibiotics seem to be a key factor for E. coli to adapt to the pressure of antibiotics, which shed new light on understanding the adaptation mechanism when responding to ofloxacin pressure.
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The 31st FISU Summer World University Games (SWUG) was held in Chengdu, southwestern China, from July 22 to August 8, 2023. A series of control measures were carried out to ensure good air quality during the SWUG, providing an opportunity to investigate the atmospheric behaviors of light-absorbing aerosols under such a substantial disturbance caused by the control measures. To assess the impacts of emission controls on primary pollutants, a field campaign was conducted at a rural site in Chengdu to investigate the characterization of equivalent black carbon (eBC). The changes of eBC concentrations before, during, and after the SWUG were characterized. The sources of eBC were resolved, and the impacts of atmospheric processes on the absorption capacity were also investigated. During the SWUG, the eBC concentration decreased by 12.1 % and 25.3 % compared with those before and after the SWUG. A fossil fuel combustion (eBCff) and a biomass burning (eBCbb) originated eBC were resolved using the aethalometer model. Both eBCff and eBCbb decreased during the SWUG, indicating the effectiveness of control measures. After the SWUG, the influence of biomass burning emissions became more and more significant, and the contribution of brown carbon (BrC) to light absorption at 370-660 nm increased by 52, 19, 7, 6, and 17 % compared to those during the SWUG. As the biomass burning emitted aerosols aged, the absorption Ångström exponent and babs(BrC370nm) decreased gradually, which was mainly due to the photobleaching of the chromophores during the daytime. eBCff was mainly affected by strong wind, while high eBCbb concentration was mainly attributed to the gradual accumulation of biomass-burning emissions near the observation site. The results show the significant reduction of eBC with the implementation of the air pollution mitigation campaign, and provide insights on the impacts of atmospheric processes on BC optical properties during summertime.
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Poluentes Atmosféricos , Monitoramento Ambiental , Estações do Ano , Fuligem , China , Poluentes Atmosféricos/análise , Fuligem/análise , Monitoramento Ambiental/métodos , Aerossóis/análise , Carbono/análise , Universidades , Poluição do Ar/estatística & dados numéricos , Material Particulado/análiseRESUMO
The rapid development of B2B has brought about fierce competition among suppliers, and how to gain customer attention and improve performance has become a common concern in academia and industry. This study examined the drivers and mechanisms of B2B performance from an enterprise capability perspective. We collected transaction and enterprise data from 325 suppliers on Alibaba 1688 platform and constructed a structural equation model (SEM). Results showed that supplier service capability, logistics capability, and production capacity all positively impacted B2B performance through the mediating role of customer attention. In addition, we found that service and logistics capabilities are more critical for attracting customer attention for Original Equipment Manufacturer (OEM) suppliers than for non-OEM suppliers. The findings contribute to understanding B2B commerce and provide constructive directions for B2B suppliers to improve their performance.
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Comércio , Humanos , Comportamento do ConsumidorRESUMO
The sensitivity of tropospheric ozone (O3) to its precursors volatile organic compounds (VOCs) and nitrogen oxides (NOX) determines the emission reduction strategy for O3 mitigation. Due to the lack of comprehensive vertical measurements of VOCs, the vertical distribution of O3 sensitivity regimes has not been well understood. O3 precursor sensitivity determined by ground-level measurements has been generally used to guide O3 control strategy. Here, to precisely diagnose O3 sensitivity regimes at different heights in the planetary boundary layer (PBL), we developed a vertical measurement system based on an unmanned aerial vehicle platform to conduct comprehensive vertical measurements of VOCs, NOX and other relevant parameters. Our results suggest that the O3 precursor sensitivity shifts from a VOC-limited regime at the ground to a NOX-limited regime at upper layers, indicating that the ground-level O3 sensitivity cannot represent the situation of the whole PBL. We also found that the state-of-the-art photochemical model tends to underestimate oxygenated VOCs at upper layers, resulting in overestimation of the degree of VOCs-limited regime. Therefore, thorough vertical measurements of VOCs to accurately diagnose O3 precursor sensitivity is in urgent need for the development of effective O3 control strategies.
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Although both protein arginine methylation (PRMT) and jasmonate (JA) signaling are crucial for regulating plant development, the relationship between these processes in the control of spikelet development remains unclear. In this study, we used the CRISPR/Cas9 technology to generate two OsPRMT6a loss-of-function mutants that exhibit various abnormal spikelet structures. Interestingly, we found that OsPRMT6a can methylate arginine residues in JA signal repressors OsJAZ1 and OsJAZ7. We showed that arginine methylation of OsJAZ1 enhances the binding affinity of OsJAZ1 with the JA receptors OsCOI1a and OsCOI1b in the presence of JAs, thereby promoting the ubiquitination of OsJAZ1 by the SCFOsCOI1a/OsCOI1b complex and degradation via the 26S proteasome. This process ultimately releases OsMYC2, a core transcriptional regulator in the JA signaling pathway, to activate or repress JA-responsive genes, thereby maintaining normal plant (spikelet) development. However, in the osprmt6a-1 mutant, reduced arginine methylation of OsJAZ1 impaires the interaction between OsJAZ1 and OsCOI1a/OsCOI1b in the presence of JAs. As a result, OsJAZ1 proteins become more stable, repressing JA responses, thus causing the formation of abnormal spikelet structures. Moreover, we discovered that JA signaling reduces the OsPRMT6a mRNA level in an OsMYC2-dependent manner, thereby establishing a negative feedback loop to balance JA signaling. We further found that OsPRMT6a-mediated arginine methylation of OsJAZ1 likely serves as a switch to tune JA signaling to maintain normal spikelet development under harsh environmental conditions such as high temperatures. Collectively, our study establishes a direct molecular link between arginine methylation and JA signaling in rice.
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Arginina , Ciclopentanos , Oryza , Oxilipinas , Proteínas de Plantas , Proteína-Arginina N-Metiltransferases , Transdução de Sinais , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Oryza/crescimento & desenvolvimento , Oryza/genética , Oryza/metabolismo , Arginina/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Metilação , Proteína-Arginina N-Metiltransferases/metabolismo , Proteína-Arginina N-Metiltransferases/genética , Regulação da Expressão Gênica de PlantasRESUMO
This study presents the measurement of photochemical precursors during the lockdown period from January 23, 2020, to March 14, 2020, in Chengdu in response to the coronavirus (COVID-19) pandemic. To derive the lockdown impact on air quality, the observations are compared to the equivalent periods in the last 2 years. An observation-based model is used to investigate the atmospheric oxidation capacity change during lockdown. OH, HO2, and RO2 concentrations are simulated, which are elevated by 42, 220, and 277%, respectively, during the lockdown period, mainly due to the reduction in nitrogen oxides (NOx). However, the radical turnover rates, i.e., OH oxidation rate L(OH) and local ozone production rate P(O3), which determine the secondary intermediates formation and O3 formation, only increase by 24 and 48%, respectively. Therefore, the oxidation capacity increases slightly during lockdown, which is partly attributed to unchanged alkene concentrations. During the lockdown, alkene ozonolysis seems to be a significant radical primary source due to the elevated O3 concentrations. This unique data set during the lockdown period highlights the importance of controlling alkene emission to mitigate secondary pollution formation in Chengdu and may also be applicable in other regions of China given an expected NOx reduction due to the rapid transformation to electrified fleets in the future.
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Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Oxirredução , Ozônio , China , Atmosfera/química , Óxidos de Nitrogênio/análise , Monitoramento Ambiental , SARS-CoV-2 , HumanosRESUMO
The cloning of resistance-related genes CsROP5/CsROP10 and the analysis of their mechanism of action provide a theoretical basis for the development of molecular breeding of disease-resistant cucumbers. The structure domains of two Rho-related guanosine triphosphatases from plant (ROP) genes were systematically analyzed using the bioinformatics method in cucumber plants, and the genes CsROP5 (Cucsa.322750) and CsROP10 (Cucsa.197080) were cloned. The functions of the two genes were analyzed using reverse-transcription quantitative PCR (RT-qPCR), virus-induced gene silencing (VIGS), transient overexpression, cucumber genetic transformation, and histochemical staining technology. The conserved elements of the CsROP5/CsROP10 proteins include five sequence motifs (G1-G5), a recognition site for serine/threonine kinases, and a hypervariable region (HVR). The knockdown of CsROP10 through VIGS affected the transcript levels of ABA-signaling-pathway-related genes (CsPYL, CsPP2Cs, CsSnRK2s, and CsABI5), ROS-signaling-pathway-related genes (CsRBOHD and CsRBOHF), and defense-related genes (CsPR2 and CsPR3), thereby improving cucumber resistance to Corynespora cassiicola. Meanwhile, inhibiting the expression of CsROP5 regulated the expression levels of ROS-signaling-pathway-related genes (CsRBOHD and CsRBOHF) and defense-related genes (CsPR2 and CsPR3), thereby enhancing the resistance of cucumber to C. cassiicola. Overall, CsROP5 and CsROP10 may participate in cucumber resistance to C. cassiicola through the ROS and ABA signaling pathways.
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Generating genetic diversity lies at the heart of directed evolution which has been widely used to engineer genetic parts and gene circuits in synthetic biology. With the ever-expanding application of directed evolution, different approaches of generating genetic diversity are required to enrich the traditional toolbox. Here we show in vitro generation of genetic diversity for directed evolution by error-prone artificial DNA synthesis (epADS). This approach comprises a three-step process which incorporates base errors randomly generated during chemical synthesis of oligonucleotides under specific conditions into the target DNA. Through this method, 200 ~ 4000 folds of diversification in fluorescent strength have been achieved in genes encoding fluorescent proteins. EpADS has also been successfully used to diversify regulatory genetic parts, synthetic gene circuits and even increase microbial tolerance to carbenicillin in a short time period. EpADS would be an alternative tool for directed evolution which may have useful applications in synthetic biology.
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DNA , Evolução Molecular Direcionada , Variação Genética , Evolução Molecular Direcionada/métodos , DNA/genética , Biologia Sintética/métodos , Oligonucleotídeos/genética , Escherichia coli/genética , Escherichia coli/metabolismoRESUMO
BACKGROUND: The effectiveness of anti-programmed cell death protein 1(PD-1)/programmed cell death 1 ligand 1(PD-L1) therapy in treating certain types of cancer is associated with the level of PD-L1. However, this relationship has not been observed in colorectal cancer (CRC), and the underlying regulatory mechanism of PD-L1 in CRC remains unclear. METHODS: Binding of TMEM160 to PD-L1 was determined by co-immunoprecipitation (Co-IP) and GST pull-down assay.The ubiquitination levels of PD-L1 were verified using the ubiquitination assay. Phenotypic experiments were conducted to assess the role of TMEM160 in CRC cells. Animal models were employed to investigate how TMEM160 contributes to tumor growth.The expression and clinical significance of TMEM160 and PD-L1 in CRC tissues were evaluated by immunohistochemistry(IHC). RESULTS: In our study, we made a discovery that TMEM160 interacts with PD-L1 and plays a role in stabilizing its expression within a CRC model. Furthermore, we demonstrated that TMEM160 hinders the ubiquitination-dependent degradation of PD-L1 by competing with SPOP for binding to PD-L1 in CRC cells. Regarding functionality, the absence of TMEM160 significantly inhibited the proliferation, invasion, metastasis, clonogenicity, and radioresistance of CRC cells, while simultaneously enhancing the cytotoxic effect of CD8 + T cells on tumor cells. Conversely, the upregulation of TMEM160 substantially increased these capabilities. In severely immunodeficient mice, tumor growth derived from lentiviral vector shTMEM160 cells was lower compared with that derived from shNC control cells. Furthermore, the downregulation of TMEM160 significantly restricted tumor growth in immune-competent BALB/c mice. In clinical samples from patients with CRC, we observed a strong positive correlation between TMEM160 expression and PD-L1 expression, as well as a negative correlation with CD8A expression. Importantly, patients with high TMEM160 expression exhibited a worse prognosis compared with those with low or no TMEM160 expression. CONCLUSIONS: Our study reveals that TMEM160 inhibits the ubiquitination-dependent degradation of PD-L1 that is mediated by SPOP, thereby stabilizing PD-L1 expression to foster the malignant progress, radioresistance, and immune evasion of CRC cells. These findings suggest that TMEM160 holds potential as a target for the treatment of patients with CRC.
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Neoplasias Colorretais , Animais , Humanos , Camundongos , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos , Neoplasias Colorretais/patologia , Linfócitos do Interstício Tumoral , Proteínas Nucleares , Proteínas Repressoras , Evasão TumoralRESUMO
INTRODUCTION: In April 2021, the U.S. Food and Drug Administration (FDA) announced its intention to ban the sale of menthol cigarettes and cigars. Decades of research support the premise that a menthol ban will reduce initiation and disparities in tobacco-related disease among menthol smokers. The tobacco industry opposed such a policy and worked for decades to shape public opposition. Social media discourse can inform our understanding of public opinion about the proposed ban and guide communication strategies and policy implementation. AIMS AND METHODS: This research employed a mixed-methods design to explore TikTok posts discussing the announced menthol ban. Using a TikTok web scraper to extract all content in the #mentholban hashtag (nâ =â 171), we coded for 11 themes, characterized content with descriptive statistics, and created a semantic network of co-occurring hashtags. RESULTS: We found primarily negative attitudes towards the U.S. ban announcement and a large volume of menthol "hacks" to circumvent the bans. Our semantic network analysis revealed strong co-occurrences between #mentholban and popularity-seeking hashtags. The metadata associated with each TikTok demonstrated that most posters in #mentholban are not "influencers" in the sense of having many followers, aside from a few niche organizations with multiple posts. We found that perceived political and racial motivations shaped posters' assessments of the menthol ban. Furthermore, we uncovered how individuals and organizational actors shaped menthol ban content on TikTok. CONCLUSIONS: Our study indicates targeted marketing from alternative menthol product companies and advocacy organizations. The latter of these organizations is more likely to saturate the TikTok landscape with multiple posts and strategic hashtags. IMPLICATIONS: This study pursued an exploration of tobacco policy discussion on TikTok, specifically related to the FDA-proposed menthol ban. TikTok is a newer platform and our study provides early evidence of policy discussion emerging there, including the types of accounts creating the content and their valence toward the policy.
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Mentol , Produtos do Tabaco , Humanos , Estados Unidos , Produtos do Tabaco/legislação & jurisprudência , Mídias Sociais , United States Food and Drug Administration , Indústria do Tabaco/legislação & jurisprudência , Opinião PúblicaRESUMO
BACKGROUND AND OBJECTIVES: Proteinuria is a common complication after the application of bevacizumab therapy in patients with metastatic colorectal cancer, and severe proteinuria can lead to discontinuation of the drug. There is a lack of sophisticated means to predict bevacizumab-induced proteinuria, so the present study aims to predict bevacizumab-induced proteinuria using peripheral venous blood samples. METHODS: A total of 122 subjects were enrolled and underwent pre-treatment plasma markers, and we followed them for six months with proteinuria as the endpoint event. We then analyzed the clinical features and plasma markers for grade ≥ 2 proteinuria occurrence using machine learning to construct a model with predictive utility. RESULTS: One hundred sixteen subjects were included in the statistical analysis. We found that high baseline systolic blood pressure, low baseline HGF, high baseline ET1, high baseline MMP2, and high baseline ACE1 were risk factors for the development of grade ≥ 2 proteinuria in patients with metastatic colorectal cancer who received bevacizumab. Then, we constructed a support vector machine model with a sensitivity of 0.889, a specificity of 0.918, a precision of 0.615, and an F1 score of 0.727. CONCLUSION: We constructed a machine learning model for predicting grade ≥ 2 bevacizumab-induced proteinuria, which may provide proteinuria risk assessment for applying bevacizumab in patients with metastatic colorectal cancer.
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Bevacizumab , Neoplasias Colorretais , Aprendizado de Máquina , Proteinúria , Humanos , Bevacizumab/efeitos adversos , Bevacizumab/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Proteinúria/induzido quimicamente , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Metástase Neoplásica , Biomarcadores/sangue , Fatores de RiscoRESUMO
BACKGROUND: Chlorogenic acid (CA, United States Patent No. 10772340), a natural biologically active food ingredient, displays potent antitumor activity against a variety of cancer cells. However, the mechanism underlying its anticancer effect is not well elucidated. OBJECTIVE: In the present study, we hope to dissect the mechanism underlying the anticancer effects of CA in pancreatic cancer cells. METHODS: The cytotoxicity of CA in pancreatic cancer cells was determined by MTT assay. Flow cytometry was performed to evaluate the cells apoptosis, while a clonogenic assay was carried out to check the colony formation of cancer cells. Transwell assay was performed to assess the cells migration and invasion. The protein expression of AKT/GSK-3ß/ß-catenin signaling pathway was detected by Western Blot. RESULTS: Our data indicated that CA inhibited the proliferation of PANC-28 and PANC-1 cells in a dose and time-dependent manner. CA was able to inhibit colony formation, migration, and invasion ability and trigger apoptosis in PANC-28 and PANC-1 cells. Further study showed that CA down-regulated the expression of AKT, p-AKT(Thr308), p-GSK-3ß(Ser9), ß-catenin, N-cadherin, and vimentin while enhancing the expression of cleaved-caspase 3 and cleaved-caspase 7 in PANC-28 and PANC-1 cells. CONCLUSION: Our study provides significant evidence that CA is able to inhibit the growth of pancreatic cancer via the AKT/GSK-3ß/ß-catenin signaling pathway.
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Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas c-akt , Humanos , Apoptose , beta Catenina/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Ácido Clorogênico/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Patentes como Assunto , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
Artificial muscles, providing safe and close interaction between humans and machines, are essential in soft robotics. However, their insufficient deformation, output force, or configurability usually limits their applications. Herein, this work presents a class of lightweight fabric-lattice artificial muscles (FAMs) that are pneumatically actuated with large contraction ratios (up to 87.5%) and considerable output forces (up to a load of 20 kg, force-to-weight ratio of over 250). The developed FAMs consist of a group of active air chambers that are zigzag connected into a lattice through passive connecting layers. The geometry of these fabric components is programmable to convert the in-plane lattice of FAMs into out-of-plane configurations (e.g., arched and cylindrical) capable of linear/radial contraction. This work further demonstrates that FAMs can be configured for various soft robotic applications, including the powerful robotic elbow with large motion range and high load capability, the well-fitting assistive shoulder exosuit that can reduce muscle activity during abduction, and the adaptive soft gripper that can grasp irregular objects. These results show the unique features and broad potential of FAMs for high-performance soft robots.
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Robótica , Humanos , Robótica/métodos , Músculos/fisiologia , Movimento , Movimento (Física) , Fenômenos MecânicosRESUMO
Trichinellosis is a zoonotic parasitic disease that poses threats to human health, the meat industry, food safety, and huge financial losses. The critical stage of Trichinella spiralis (T. spiralis) infection is the invasion of intestinal larvae into the host's intestinal epithelial cells (IECs). T. spiralis Cathepsin B (TsCB) specifically interacts with IECs to facilitate the invasion of larvae. This study aims to look at how TsCB affects mouse IECs. TsCB was successfully cloned, expressed, and characterized, demonstrating its natural cysteine protease hydrolysis activity. A total of 140 proteins that interact with rTsCB were identified by GST pull-down combined with LC-MS/MS, including type I collagen, an essential component of the host's intestinal epithelial barrier system and intimately related to intestinal epithelial damage. TsCB transcription and expression levels rise, whereas type I collagen in the host's intestinal mucosa declines when the T. spiralis larvae invaded. Besides, it was discovered that TsCB bound to and degraded type I collagen of the host's intestine. This research can serve as a foundation for clarifying how T. spiralis invades the host's intestinal barrier and might provide information on potential targets for the creation of novel treatments to treat parasite illnesses.
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Trichinella spiralis , Triquinelose , Animais , Camundongos , Humanos , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Catepsina B/genética , Cromatografia Líquida , Espectrometria de Massas em Tandem , Intestinos , Triquinelose/metabolismo , Triquinelose/parasitologia , Larva/metabolismo , Camundongos Endogâmicos BALB C , Proteínas de Helminto/metabolismoRESUMO
Ca2+ signaling is essential for cardiac contractility and excitability in heart function and remodeling. Intriguingly, little is known about the role of a new family of ion channels, the endo-lysosomal non-selective cation "two-pore channel" (TPCs) in heart function. Here we have used double TPC knock-out mice for the 1 and 2 isoforms of TPCs (Tpcn1/2-/-) and evaluated their cardiac function. Doppler-echocardiography unveils altered left ventricular (LV) systolic function associated with a LV relaxation impairment. In cardiomyocytes isolated from Tpcn1/2-/- mice, we observed a reduction in the contractile function with a decrease in the sarcoplasmic reticulum Ca2+ content and a reduced expression of various key proteins regulating Ca2+ stores, such as calsequestrin. We also found that two main regulators of the energy metabolism, AMP-activated protein kinase and mTOR, were down regulated. We found an increase in the expression of TPC1 and TPC2 in a model of transverse aortic constriction (TAC) mice and in chronically isoproterenol infused WT mice. In this last model, adaptive cardiac hypertrophy was reduced by Tpcn1/2 deletion. Here, we propose a central role for TPCs and lysosomes that could act as a hub integrating information from the excitation-contraction coupling mechanisms, cellular energy metabolism and hypertrophy signaling.
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Canais de Cálcio , Canais de Dois Poros , Camundongos , Animais , Canais de Cálcio/metabolismo , Lisossomos/metabolismo , Transdução de Sinais , Camundongos Knockout , Cardiomegalia/metabolismo , NADP/metabolismo , Cálcio/metabolismo , Sinalização do CálcioRESUMO
Evidence is emerging on the roles of long noncoding RNAs (lncRNAs) as regulatory factors in a variety of viral infection processes, but the mechanisms underlying their functions in coxsackievirus group B type3 (CVB3)-induced acute viral myocarditis have not been explicitly delineated. We previously demonstrated that CVB3 infection decreases miRNA-21 expression; however, lncRNAs that regulate the miRNA-21-dependent CVB3 disease process have yet to be identified. To evaluate lncRNAs upstream of miRNA-21, differentially expressed lncRNAs in CVB3-infected mouse hearts were identified by microarray analysis and lncRNA/miRNA-21 interactions were predicted bioinformatically. MEG3 was identified as a candidate miRNA-21-interacting lncRNA upregulated in CVB3-infected mouse hearts. MEG3 expression was verified to be upregulated in HeLa cells 48 h post CVB3 infection and to act as a competitive endogenous RNA of miRNA-21. MEG3 knockdown resulted in the upregulation of miRNA-21, which inhibited CVB3 replication by attenuating P38-MAPK signaling in vitro and in vivo. Knockdown of MEG3 expression before CVB3 infection inhibited viral replication in mouse hearts and alleviated cardiac injury, which improved survival. Furthermore, the knockdown of CREB5, which was predicted bioinformatically to function upstream of MEG3, was demonstrated to decrease MEG3 expression and CVB3 viral replication. This study identifies the function of the lncRNA MEG3/miRNA-21/P38 MAPK axis in the process of CVB3 replication, for which CREB5 could serve as an upstream modulator.
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Infecções por Coxsackievirus , Enterovirus , MicroRNAs , Miocardite , RNA Longo não Codificante , Viroses , Animais , Humanos , Camundongos , Infecções por Coxsackievirus/complicações , Infecções por Coxsackievirus/genética , Enterovirus/genética , Enterovirus Humano B/genética , Enterovirus Humano B/metabolismo , Células HeLa/virologia , MicroRNAs/genética , MicroRNAs/metabolismo , Miocardite/genética , Miocardite/metabolismo , Miocardite/virologia , RNA Longo não Codificante/genética , Replicação ViralRESUMO
Online reviews and customer Q&As have emerged as two vital forms of electronic word-of-mouth (eWOM) that significantly influence consumer decisions in e-commerce. Yet, a comprehensive understanding of the individual and combined roles of these eWOM types in shaping market dynamics remains elusive. This study addresses this research gap by tracking and analyzing three months of eWOM and sales data for 120 laptops on Amazon, comprising 7,205 online reviews, 6,365 customer Q&A questions, and 7,419 answers. Leveraging the Panel Vector Autoregression (PVAR) model and STATA16.0 software, we unravel the intricate dynamics between online reviews, customer Q&As, and laptop sales. The empirical results reveal distinctive influence mechanisms of online reviews and customer Q&As on product sales, with review volume and answer valence positively affecting sales. Importantly, answer volume was found to stimulate online reviews and enhance their valence. Our study elucidates the interplay among online reviews, customer Q&As, and product sales, underscoring the need for future research on multi-type eWOM. Further, the insights gleaned offer valuable guidance for online platforms and retailers to strategize their eWOM management.
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Comércio , SoftwareRESUMO
CYP78A, a cytochrome P450 subfamily that includes rice (Oryza sativa L.) BIG GRAIN2 (BG2, CYP78A13) and Arabidopsis thaliana KLUH (KLU, CYP78A5), generate an unknown mobile growth signal (referred to as a CYP78A-derived signal) that increases grain (seed) size. However, the mechanism by which the CYP78A pathway increases grain size remains elusive. Here, we characterized a rice small grain mutant, small grain4 (smg4), with smaller grains than its wild type due to restricted cell expansion and cell proliferation in spikelet hulls. SMG4 encodes a multidrug and toxic compound extrusion (MATE) transporter. Loss of function of SMG4 causes smaller grains while overexpressing SMG4 results in larger grains. SMG4 is mainly localized to endoplasmic reticulum (ER) exit sites (ERESs) and partially localized to the ER and Golgi. Biochemically, SMG4 interacts with coat protein complex â ¡ (COPâ ¡) components (Sar1, Sec23, and Sec24) and CYP78As (BG2, GRAIN LENGTH 3.2 [GL3.2], and BG2-LIKE 1 [BG2L1]). Genetically, SMG4 acts, at least in part, in a common pathway with Sar1 and CYP78As to regulate grain size. In summary, our findings reveal a CYP78As-SMG4-COPâ ¡ regulatory pathway for grain size in rice, thus providing new insights into the molecular and genetic regulatory mechanism of grain size.
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Arabidopsis , Oryza , Oryza/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Grão Comestível/genética , Sementes/genética , Arabidopsis/genéticaRESUMO
Artificial muscles are promising in soft exoskeletons, locomotion robots, and operation machines. However, their performance in contraction ratio, output force, and dynamic response is often imbalanced and limited by materials, structures, or actuation principles. We present lightweight, high-contraction ratio, high-output force, and positive pressure-driven X-crossing pneumatic artificial muscles (X-PAMs). Unlike PAMs, our X-PAMs harness the X-crossing mechanism to directly convert linear motion along the actuator axis, achieving an unprecedented 92.9% contraction ratio and an output force of 207.9 Newtons per kilogram per kilopascal with excellent dynamic properties, such as strain rate (1603.0% per second), specific power (5.7 kilowatts per kilogram), and work density (842.9 kilojoules per meter cubed). These properties can overcome the slow actuation of conventional PAMs, providing robotic elbow, jumping robot, and lightweight gripper with fast, powerful performance. The robust design of X-PAMs withstands extreme environments, including high-temperature, underwater, and long-duration actuation, while being scalable to parallel, asymmetric, and ring-shaped configurations for potential applications.