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Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease distinguished by airway remodelling and progressive inflammation. PAI-1 is an important regulator of fibrosis. Recent studies have shown that PAI-1 seems to be involved in COPD progression. Elevated levels of PAI-1 have been found in the lungs of patients with acute inflammation. PAI-1 has been shown to regulate the levels of proinflammatory cytokines in the lungs, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, indicating that PAI-1 may play a fundamental role during inflammation. In the present study, we investigated the anti-inflammatory role of baicalin, the main active component of Scutellaria baicalensis, against cigarette smoke (extract) (CS/CSE)-induced airway inflammation in vivo and in vitro. For the in vivo study, SD rats were exposed to CS for 1 h/day, 6 days/week, for 24 weeks and treated with baicalin (40, 80 and 160 mg/kg) or budesonide (0.2 mg/kg). For this study, HBE cells were pretreated with baicalin (10, 20, 40 µM) or dexamethasone (10-7 M) and then exposed to CSE. We found that baicalin treatment could ameliorate CS-induced airway inflammatory infiltration in rats and decrease PAI-1 expression. The ELISA results showed that baicalin significantly inhibited the levels of TNF-α and IL-1ß in CS/CSE-exposed rats and cells. Mechanistic studies showed that baicalin enhanced histone deacetylase 2 (HDAC2) protein expression and inhibited the expression of NF-κB and its downstream target PAI-1, and these effects were reversed by the HDAC2 inhibitor CAY-10683. In conclusion, baicalin ameliorated CS-induced airway inflammation in rats, and these effects were partially attributed to the modulation of HDAC2/NF-κB/PAI-1 signalling.
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NF-kappa B , Doença Pulmonar Obstrutiva Crônica , Animais , Flavonoides , Histona Desacetilase 2 , Humanos , Inflamação , Inibidor 1 de Ativador de Plasminogênio , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Fumaça/efeitos adversos , Fumar/efeitos adversosRESUMO
During social interactions, people decide whether to trust an actor based on their punitive behaviour. Several empirical studies have indicated that punishment intensity impacts observer trust, yet the underlying mechanism remains to be elucidated. This study included 242 junior high school students and was conducted to investigate the relationship between teachers' punishment intensity and levels of student bystander trust. Additionally, the mediating role of trustworthiness and the moderating role of group relationships were explored. The results showed that the relationship between punishment intensity and observer trust follows an inverted U-shaped pattern. In addition, mild punishment boosts observer trust by improving perceived trustworthiness (ability and integrity) compared to no punishment, while harsh punishment reduces observer trust more than mild punishment by diminishing perceived trustworthiness (ability, benevolence, and integrity). More importantly, group relationships positively moderate the relationship between punishment intensity and observer trust. Specifically, compared to mild or no punishment, harsh punishment decreases trustworthiness (ability, benevolence, and integrity) in close teacher-student relationships but has less impact on neutral relationships. The above findings demonstrate that guiding educators in developing appropriate disciplinary concepts contributes to enhancing student observer trust.
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Trustworthiness is the most significant predictor of trust and has a significant impact on people's levels of trust. Most trustworthiness-related research is empirical, and while it has a long history, it is challenging for academics to get insights that are applicable to their fields of study and to successfully transfer fragmented results into practice. In order to grasp their dynamic development processes through the mapping of network knowledge graphs, this paper is based on the Web of Science database and uses CiteSpace (6.2.R4) software to compile and visualize the 1,463 publications on trustworthy studies over the past 10 years. This paper aims to provide valuable references to theoretical research and the practice of Trustworthiness. The findings demonstrate that: over the past 10 years, trustworthiness-related research has generally increased in volume; trustworthiness research is concentrated in industrialized Europe and America, with American research findings having a bigger global impact; The University of California System, Harvard University, and Yale University are among the high-production institutions; the leading figures are represented by Alexander Todorov, Marco Brambilla, Bastian Jaeger, and others; the core authors are distinguished university scholars; however, the level of cooperation of the core author needs to be improved. The primary journal for publishing research on trustworthiness is the Journal of Personality and Social Psychology and Biology Letters. In addition, the study focuses on three distinct domains, involving social perception, facial clues, and artificial intelligence.
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Dysregulated lipolysis is a risk factor contributing to metabolic diseases and autophagy is known to be important in lipolysis. CTCF is involved in diverse cellular processes including adipogenesis, yet its role in lipolysis or autophagy remains unknown. We identified lipolytic genes were downregulated in CTCF knockdown adipocytes based on the RNA-seq data. Further validation showed that CTCF knockdown restrained adipocyte lipolysis while overexpression of CTCF had opposite effects. Similarly, overexpression and knockdown studies demonstrated that CTCF was a positive regulator of autophagy. Treatment with autophagy inducer relieved the suppression of lipolysis caused by CTCF knockdown, while autophagy inhibitor treatment alleviated lipolysis stimulated by CTCF overexpression, indicating that CTCF regulates adipocyte lipolysis through autophagy. Mechanistically, CTCF interacted with PPARγ to coordinately enhanced lipolytic capacity. Data of chip-seq, chip-qPCR and further experiments confirmed that CTCF and PPARγ separately stimulated transactivation of autophagy regulatory protein Beclin 1, while co-expression of the two displayed synergistic effects to regulate autophagy flux. Expectedly, overexpression of Beclin 1 abolished the blockage of lipolysis and autophagy caused by CTCF knockdown. Collectively, CTCF cooperates with PPARγ to regulate autophagy via directly modulating BECLIN 1 transcription, thereby leading to increased adipocyte lipolysis.
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Lipólise , PPAR gama , Camundongos , Animais , PPAR gama/metabolismo , Proteína Beclina-1/metabolismo , Adipócitos/metabolismo , Adipogenia , Células 3T3-L1RESUMO
During the development of headspace gas chromatography (HSGC) method for assessing residual solvents in rosuvastatin calcium (RSV) drug substance, acetaldehyde (AA) was detected in obtained chromatograms, with a calculated concentration of up to 226 ppm. After a series of experiments, it was established that acetaldehyde originates from matrix interference due to direct degradation of Imp-C, which is accompanied by the formation of impurity at relative retention time (RRT) 2.18, without the involvement of impurity at RRT 2.31. The thermal instability of Imp-C also results in the formation of impurity at RRT 2.31 through dehydration and decarboxylation. In addition, cyclization reaction of degradant at RRT 2.18 further resulted in the generation of impurity at RRT 2.22. The structure of these three degradants, were confirmed by liquid chromatography-mass spectrometry (LC-MS), 1D and 2D nuclear magnetic resonance (NMR) measurement. In order to minimize the said matrix interference, a simple precipitation procedure was proposed as a pretreatment to mitigate the impact of Imp-C. Subsequently, an HSGC method was developed for the simultaneous determination of the degradant AA and the other five residual solvents used in RSV synthetic process. The final method was validated concerning precision, limit of detection (LOD) and limit of quantitation (LOQ), linearity, and accuracy.
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Cromatografia Líquida de Alta Pressão , Cromatografia Líquida de Alta Pressão/métodos , Rosuvastatina Cálcica , Cromatografia Gasosa-Espectrometria de Massas , Limite de Detecção , SolventesRESUMO
[This corrects the article DOI: 10.1016/j.jhepr.2023.100903.].
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The dysregulation of membrane protein expression has been implicated in tumorigenesis and progression, including hepatocellular carcinoma (HCC). In this study, we aimed to identify membrane proteins that modulate HCC viability. To achieve this, we performed a CRISPR activation screen targeting human genes encoding membrane-associated proteins, revealing TMX2 as a potential driver of HCC cell viability. Gain- and loss-of-function experiments demonstrated that TMX2 promoted growth and tumorigenesis of HCC. Clinically, TMX2 was an independent prognostic factor for HCC patients. It was significantly upregulated in HCC tissues and associated with poor prognosis of HCC patients. Mechanistically, TMX2 was demonstrated to promote macroautophagy/autophagy by facilitating KPNB1 nuclear export and TFEB nuclear import. In addition, TMX2 interacted with VDAC2 and VADC3, assisting in the recruitment of PRKN to defective mitochondria to promote cytoprotective mitophagy during oxidative stress. Most interestingly, HCC cells responded to oxidative stress by upregulating TMX2 expression and cell autophagy. Knockdown of TMX2 enhanced the anti-tumor effect of lenvatinib. In conclusion, our findings emphasize the pivotal role of TMX2 in driving the HCC cell viability by promoting both autophagy and mitophagy. These results suggest that TMX2 May serve as a prognostic marker and promising therapeutic target for HCC treatment.Abbreviation: CCCP: Carbonyl cyanide 3-chlorophenylhydrazone; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeat; ER: endoplasmic reticulum; HCC: hepatocellular carcinoma; KPNB1: karyopherin subunit beta 1; PRKN: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; TFEB: transcription factor EB; TMX2: thioredoxin related transmembrane protein 2; VDAC2: voltage dependent anion channel 2; VDAC3: voltage dependent anion channel 3; WB: western blot.
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Third-party punishment (TPP) reflects people's social preference for fairness norms and is fundamental to maintaining fairness norms on a large scale. Several empirical studies have shown that the offender's group membership impacts TPP, but the detailed mechanisms have yet to be fully elucidated. The current study used the third-party punishment game task to explore the relationship between group membership, perceived unfairness, anger, and adolescents' TPP. A total of 306 teenagers aged 12 to 15 were chosen as subjects through cluster sampling. The results showed that group membership (classmate vs. stranger) and gender can affect adolescents' TPP together, which manifests as adolescents enacting significantly harsher punishments on strangers than on classmates, especially for boys. Group membership indirectly affects TPP through the mediating effects of perceived unfairness, anger and through a chain mediation of perceived unfairness and anger. Moreover, gender positively moderate the relationship between group membership and perceived unfairness. Specifically, group membership significantly affects boys' perceived unfairness, but cannot predict girls' perceived unfairness. The above results can be used to guide adolescents toward appropriate justice concepts and moral awareness, thus enhancing TPP.
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Background & Aims: ß-1,4-N-Acetyl-galactosaminyltransferase 1 (B4GALNT1) has been reported to contribute to the development of human malignancies. However, its role in hepatocellular carcinoma (HCC) remains uncharacterised. In this study, we aimed to elucidate the role of B4GALNT1 in HCC stemness and progression. Methods: Immunohistochemical staining was used to evaluate B4GALNT1 expression in HCC tissues and adjacent normal liver tissues. Flow cytometry analysis and sphere formation analysis were performed to investigate the role of B4GALNT1 in HCC stemness. Colony formation, Incucyte, wound-healing, Transwell migration, and invasion assays, and an animal model were used to study the role of B4GALNT1 in HCC progression. RNA-sequencing and co-immunoprecipitation were used to investigate the downstream targets of B4GALNT1. Results: B4GALNT1 was upregulated in HCC and associated with poor clinical outcome of patients with the disease. Moreover, B4GALNT1 promoted HCC stemness, migration, invasion, and growth. Mechanistically, B4GALNT1 not only promoted the expression of the integrin α2ß1 ligand THBS4, but also directly interacted with the ß subunit of integrin α2ß1 ITGB1 to inhibit its ubiquitin-independent proteasomal degradation, resulting in activation of FAK and AKT. Ophiopogonin D inhibited HCC stemness and progression by reducing ITGB1 and THBS4 expression and inhibiting FAK and AKT activation. Conclusions: Our study suggests the B4GALNT1/integrin α2ß1/FAK/PI3K/AKT axis as a therapeutic target for the inhibition of HCC stemness and tumour progression. Impact and implications: The role and regulatory mechanism of B4GALNT1 in HCC have not been studied previously. Here, we reveal that B4GALNT1 has a crucial role in HCC stemness and progression by activating the integrin α2ß1/FAK/PI3K/AKT axis, providing a potential target for HCC therapy. In addition, we find Ophiopogonin D as a potential therapeutic drug for patients with HCC.
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During the COVID-19 pandemic, the use of online learning has become a necessary choice for students, and would increase the probability of cyber aggression (CA). Despite the relationship between Dark Triad and CA previous was explored in previous research, the underlying psychological mechanism of CA in adolescents is still unclear. The current study aimed to examine the mediating role of moral disengagement (MD) and the moderating of gender in the relationship between Dark Triad and CA. A sample consists of 501 Chinese adolescents (246 females; 255 males) between the ages of 11 ~ 20. Participants completed the Dirty Dozen Scale, Moral Disengagement Scale, and Cyber Aggressive Behavior Scale. Results show that higher levels of dark personality were associated with higher levels of MD and CA. Moral disengagement partially mediated this positive effects of dark personality on CA. Moreover, gender moderated the mediation model. Specially, the positive relationship between dark triad personality and CA was stronger among females adolescents. These findings advance the understanding of how dark triad personality induces Chinese adolescents' cyber aggressive behavior.
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People tend to voluntarily sacrifice their own interests to reject unfair proposals, and this behaviour is affected by group affiliation. While group bias is a well-established phenomenon, its direction is still unclear, and little attention has been given to possible moderating factors. In two studies, we manipulate participants' ingroup identification and investigate whether and how individuals with various levels of ingroup identification react differently to unfairness from ingroups and outgroups during an incentivized (Study 1, N = 46) and hypothetical (Study 2, N = 332) ultimatum game. The results show that participants display a strong preference for their own group. High identifiers tend to accept unfair proposals from ingroups compared to outgroups, whereas this effect is nonsignificant for low identifiers, especially for moderately unfair treatment (offer 7:3). Moreover, higher identification tends to be accompanied by higher ingroup positive expectation, which then leads to greater ingroup favouritism for an offer of 7:3. These results imply that ingroup identification can enhance group favouritism during fairness norm enforcement through ingroup positive expectation.
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People show a strong aversion to inequality and are willing to sacrifice their own interests to punish violations of fairness norms. Empirical research has found that group membership could influence the fairness judgment and norm enforcement of the individuals but has shown inconsistent findings and has not focused much on the potential moderators. Here, the two studies aimed to investigate whether victim sensitivity and proposal size moderate the impact of group membership on reactions to unfair proposals. In both studies, the participants with different victim sensitivity (low vs. high group) played the hypothetical (Study 1) and incentivized (Study 2) ultimatum game under the intragroup and intergroup condition and indicated their responses to the different proposals. Results showed that, regardless of the victim sensitivity, ingroup member is often given preferential and positive treatment. Low victim sensitive persons are more likely to accept unfair offers from the ingroup than the outgroup, while this effect was attenuated for those with high victim sensitivity, especially for highly ambiguous unfair offers (offer 6:4 in Study 1 and 8:2 in Study 2). Moreover, the ingroup favoritism score for ambiguous unfair offers was smaller for high compared with the victim sensitivity group. Taken together, the victim sensitivity, and proposal size could moderate the ingroup favoritism on responses to unfairness.
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Although research exists on the relationship between passion and engagement among employees, the mechanisms of academic passion on academic engagement among students needs to be elucidated. Guided by the broaden-and-build and situated cognition theories, we explored the positive effect of academic passion on academic engagement, the mediating effect of academic self-efficacy, and the role of teacher developmental feedback as a moderator in the relationship between academic passion and academic engagement. Based on a sample of 1,029 college students from universities in the Henan Province of China, the results showed that academic passion was positively related to academic engagement, academic self-efficacy partially mediated the relationship between academic passion and academic engagement, and teacher developmental feedback effectively moderated the relationship between academic passion and academic engagement. These findings explained the mechanism underlying the relationship between academic passion and academic engagement. Moreover, the findings highlighted important factors that promote college students' academic engagement.
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Against the scourge of the COVID-19 pandemic, college students' learning engagement has become a key issue in universities and society. Guided by the theories of existential positive psychology and social perception, we explored the positive effect of a growth mindset on learning engagement during the COVID-19 pandemic. A total of 1,040 college students from universities in Henan Province of China effectively completed online questionnaires. The results showed that growth mindset was positively related to learning engagement and negatively associated with perceived COVID-19 event strength and perceived stress; perceived COVID-19 event strength was positively related to perceived stress, while perceived COVID-19 event strength and perceived stress were negatively associated with learning engagement. Growth mindset affected learning engagement through three indirect paths: the mediating role of perceived COVID-19 event strength, the mediating role of perceived stress, and the serial mediating role of both perceived COVID-19 event strength and perceived stress. The results indicated that the growth mindset could contribute to college students' learning engagement through the roles of perceived COVID-19 event strength and perceived stress during the COVID-19 pandemic. This study advances the understanding of the mechanism underlying the relationship between growth mindset and college students' learning engagement during the COVID-19 pandemic. Furthermore, the findings of the study have important implications for promoting college students' learning engagement during the pandemic.
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Gypenosides (Gyps), the major active constituents isolated from Gynostemma pentaphyllum, possess anti-inflammatory and antioxidant activities. Previous studies have demonstrated that Gyps displayed potent ameliorative effects on liver fibrosis and renal fibrosis. In this study, we found that Gyps significantly reduced the mortality of bleomycin-induced pulmonary fibrosis mice (40% mortality rate of mice in the model group versus 0% in the treatment group). Masson staining showed that Gyps could reduce the content of collagen in the lung tissue of pulmonary fibrosis mice Masson staining and immunohistochemistry demonstrated that the expression of the collagen gene α-SMA and fibrosis gene Col1 markedly decreased after Gyps treatment. The active mitosis of fibroblasts is one of the key processes in the pathogenesis of fibrotic diseases. RNA-seq showed that Gyps significantly inhibited mitosis and induced the G2/M phase cell cycle arrest. The mTOR/c-Myc axis plays an important role in the pathological process of pulmonary fibrosis. RNA-seq also demonstrated that Gyps inhibited the mTOR and c-Myc signaling in pulmonary fibrosis mice, which was further validated by Western blot and immunohistochemistry. AKT functions as an upstream molecule that regulates mTOR. Our western blot data showed that Gyps could suppress the activation of AKT. In conclusion, Gyps exerted anti-pulmonary fibrosis activity by inhibiting the AKT/mTOR/c-Myc pathway.
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We theoretically analysis and numerically verify a frequency-quadrupling scheme which is capable of generating millimeter-wave (mm-wave) signals. The scheme is based on dual wavelength feed-forward modulation technique, which circumvents the need for direct modulation at mm-wave frequency band, providing potential for two-tone optical sources. The analytical models for transmission through a dispersive medium are confirmed by numerical simulations. Results of this study demonstrate that such a scheme offer realistic solutions to support future wireless systems.
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We propose and analyze a prototype of a 60 GHz millimeter-wave (mm-wave) generator. In the scheme, two lasers with a 70 GHz frequency interval serve as sources. Then a frequency-quadrupling feed-forward modulation technique is employed to generate two phase correlated sidebands with a 60 GHz interval. The desired sidebands can be selected by using standard optical interleavers. In our work, a 60 GHz mm-wave signal free of phase noise can be achieved. The employed technique can also be extended to frequency 8-tupling.
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We theoretically demonstrate an improved two-step-heterodyne-based, millimeter-wave, radio-over-fiber system. With the millimeter-wave mixer and a fiber Bragg grating located in the base station, two-step heterodyne is achieved. The proposed scheme has the merit of good system performance and high suppression of unwanted frequency tones, which is verified by numerical simulations.
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INTRODUCTION: Non-small cell lung cancer (NSCLC) is a common cause of deaths all over the world. Emerging evidence has indicated that microRNA (miR) play key roles in NSCLC progression. We aimed to determine the functions of miR-129 in NSCLC. miR-129 was dramatically downregulated in NSCLC tissue samples and cells. The decreased miR-129 was found to be associated with poorer prognosis and malefic phenotype of NSCLC patients. We demonstrated that miR-129 upregulation could inhibit NSCLC cell growth. Furthermore, we also sought the molecular mechanism by which miR-129 repressed NSCLC development. METHODS: QRT-PCR was applied to detect the expressions of miR-129 in 51 pairs of NSCLC tissue samples. We further performed the Kaplan-Meier analysis to determine the association between miR-129 expressions and the survival rate of NSCLC patients. We then measured the expression levels of miR-129 in NSCLC cell lines. After that, MTT assays were performed to determine the influence of miR-129 on A549 cell proliferation. Transwell assay was then conducted to explore the biological functions of miR-129 in invasion and migration of NSCLC cells. RESULTS: Results showed that ZEB2 was directly targeted by miR-129 in NSCLC cell lines. Moreover, miR-129 restoration could inhibit EMT and Wnt/ß-catenin in NSCLC cell lines. CONCLUSION: In short, all these results indicated that miR-129/ZEB2 axis maybe a useful diagnostic and prognostic biomarker for NSCLC treatment.
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Liu-Wei-Di-Huang (LW) is a Yin nourishing and kidney tonifying prescription in traditional Chinese medicine with promising pharmacological characteristics that can be further exploited and developed in modern medicine. We provide a comprehensive and detailed literature report on the clinical and experimental pharmacology of LW, including its quality control parameters, phytochemistry, pharmacokinetics, and toxicology. Our literature review indicates that the LW prescription possesses a unique combination of pharmacological characteristics that can be safely used for treating very different diseases. Quality control and pharmacokinetic parameters of LW are mostly based on its major bioactive phytochemical constituents. We postulate that modulating or rebalancing the neuroendocrine immunomodulation network in the body is the underlying mechanism of the multiple pharmacological activities displayed by LW.