Pectolinarigenin ameliorated airway inflammation and airway remodeling to exhibit antitussive effect.

Cough is a common symptom of several respiratory diseases. However, frequent coughing from acute to chronic often causes great pain to patients. It may turn into cough variant asthma, which seriously affects people's quality of life. For cough treatment, it is dominated by over-the-counter antitussive drugs, such as asmeton, but most currently available antitussive drugs have serious side effects. Thus, there is a great need for the development of new drugs with potent cough suppressant. BALB/c mice were used to construct mice model with cough to investigate the pharmacological effects of pectolinarigenin (PEC). Hematoxylin-eosin and Masson staining were used to assess lung injury and airway remodeling, and ELISA was used to assess the level of inflammatory factor release. In addition, inflammatory cell counts were measured to assess airway inflammation. Airway hyperresponsiveness assay was used to assess respiratory resistance in mice. Finally, we used Western blotting to explore the potential mechanisms of PEC. We found that PEC could alleviate lung tissue injury and reduce the release of inflammatory factors, inhibit of cough frequency and airway wall collagen deposition in mice model with cough. Meanwhile, PEC inhibited the Ras/ERK/c-Fos pathway to exhibit antitussive effect. Therefore, PEC may be a potential drug for cough suppression.

Intelligent Physical Robots in Health Care: Systematic Literature Review.

BACKGROUND: Intelligent physical robots based on artificial intelligence have been argued to bring about dramatic changes in health care services. Previous research has examined the use of intelligent physical robots in the health care context from different perspectives; however, an overview of the antecedents and consequences of intelligent physical robot use in health care is lacking in the literature. OBJECTIVE: In this paper, we aimed to provide an overview of the antecedents and consequences of intelligent physical robot use in health care and to propose potential agendas for future research through a systematic literature review. METHODS: We conducted a systematic literature review on intelligent physical robots in the health care field following the guidelines of PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Literature searches were conducted in 5 databases (PubMed, Scopus, PsycINFO, Embase, and CINAHL) in May 2021, focusing on studies using intelligent physical robots for health care purposes. Subsequently, the quality of the included studies was assessed using the Mixed Methods Appraisal Tool. We performed an exploratory content analysis and synthesized the findings extracted from the included articles. RESULTS: A total of 94 research articles were included in the review. Intelligent physical robots, including mechanoid, humanoid, android, and animalistic robots, have been used in hospitals, nursing homes, mental health care centers, laboratories, and patients' homes by both end customers and health care professionals. The antecedents for intelligent physical robot use are categorized into individual-, organization-, and robot-related factors. Intelligent physical robot use in the health care context leads to both non-health-related consequences (emotional outcomes, attitude and evaluation outcomes, and behavioral outcomes) and consequences for (physical, mental, and social) health promotion for individual users. Accordingly, an integrative framework was proposed to obtain an overview of the antecedents and consequences of intelligent physical robot use in the health care context. CONCLUSIONS: This study contributes to the literature by summarizing current knowledge in the field of intelligent physical robot use in health care, by identifying the antecedents and the consequences of intelligent physical robot use, and by proposing potential future research agendas in the specific area based on the research findings in the literature and the identified knowledge gaps.

The Influence of Media Information Sources on Preventive Behaviors in China: After the Outbreak of COVID-19 Pandemic.

Background: As announced by the World Health Organization (WHO), since March 2020, the COVID-19 pandemic has become a global pandemic. In order to prevent the spread of COVID-19, Chinese government carried out very strict prevention and control policy. Objective: The study aimed to explore the effect of news reports on COVID-19 vaccine from traditional media and social media on COVID-19 preventive behaviors. Methods: Adults aged between 18 and 58 years old completed an online survey reporting how they gathered media information sources regarding the COVID-19 vaccine, as well as any details relating to risk perception, vaccine efficacy, and preventive behaviors in COVID-19 pandemic. Results: Our results showed that traditional and social media information sources both significantly and positively influenced people's COVID-19 preventive behaviors, with the former showing a stronger effect. COVID-19 contact risk perception and vaccine efficacy awareness of media audiences partly mediate this relationship. Audiences who reported more exposing news reports on COVID-19 vaccine from the media show stronger risk perception and vaccine efficacy awareness. This increases their COVID-19 preventive behaviors. Conclusions: This study found that media information sources have an important impact on people's COVID-19 preventive behaviors. People believe more in the news information of the mainstream media about the COVID-19 pandemic. Moreover, much of the news information of social media is also from the important mainstream media. Media organizations should shoulder greater social responsibility, embed the health-related benefits of COVID-19 vaccination into the values and cultural order of the whole society, find and shape a common space of meaning, and produce forms of internal coupling and value identification.

Activating STAT6 mutations in follicular lymphoma.

Follicular lymphoma (FL) is the second most common non-Hodgkin lymphoma in the Western world. FL cell-intrinsic and cell-extrinsic factors influence FL biology and clinical outcome. To further our understanding of the genetic basis of FL, we performed whole-exome sequencing of 23 highly purified FL cases and 1 transformed FL case and expanded findings to a combined total of 114 FLs. We report recurrent mutations in the transcription factor STAT6 in 11% of FLs and identified the STAT6 amino acid residue 419 as a novel STAT6 mutation hotspot (p.419D/G, p.419D/A, and p.419D/H). FL-associated STAT6 mutations were activating, as evidenced by increased transactivation in HEK293T cell-based transfection/luciferase reporter assays, heightened interleukin-4 (IL-4) -induced activation of target genes in stable STAT6 transfected lymphoma cell lines, and elevated baseline expression levels of STAT6 target genes in primary FL B cells harboring mutant STAT6. Mechanistically, FL-associated STAT6 mutations facilitated nuclear residency of STAT6, independent of IL-4-induced STAT6-Y641 phosphorylation. Structural modeling of STAT6 based on the structure of the STAT1-DNA complex revealed that most FL-associated STAT6 mutants locate to the STAT6-DNA interface, potentially facilitating heightened interactions. The genetic and functional data combined strengthen the recognition of the IL-4/JAK/STAT6 axis as a driver of FL pathogenesis.

Mutations in linker histone genes HIST1H1 B, C, D, and E; OCT2 (POU2F2); IRF8; and ARID1A underlying the pathogenesis of follicular lymphoma.

Follicular lymphoma (FL) constitutes the second most common non-Hodgkin lymphoma in the western world. FL carries characteristic recurrent structural genomic aberrations. However, information regarding the coding genome in FL is still evolving. Here, we describe the results of massively parallel exome sequencing and single nucleotide polymorphism 6.0 array genomic profiling of 11 highly purified FL cases, and 1 transformed FL case and the validation of selected mutations in 102 FL cases. We report the identification of 15 novel recurrently mutated genes in FL. These include frequent mutations in the linker histone genes HIST1H1 B-E (27%) and mutations in OCT2 (also known as POU2F2; 8%), IRF8 (6%), and ARID1A (11%). A subset of the mutations in HIST1H1 B-E affected binding to DNMT3B, and mutations in HIST1H1 B-E and in EZH2 or ARID1A were largely mutually exclusive, implicating HIST1H1 B-E in epigenetic deregulation in FL. Mutations in OCT2 (POU2F2) affected its transcriptional and functional properties as measured through luciferase assays, the biological analysis of stably transduced cell lines, and global expression profiling. Finally, multiple novel mutated genes located within regions of acquired uniparental disomy in FL are identified. In aggregate, these data substantially broaden our understanding of the genomic pathogenesis of FL.

[Relationship between artesunate influence on the process of TGF-beta1 induced alveolar epithelial cells transform into mesenchymal cells and on idiopathic pulmonary fibrosis].

This study is to investigate the effect of artesunate on transforming growth factor-beta1 (TGF-beta1) induced epithelial-mesenchymal transition (EMT) and its possible mechanism. After the in vitro cultured RLE-6TN cells were treated with TGF-beta1 then artesunate intervened on it, after 24 h, expression of the markers of mesenchymal cell was assayed using Western blotting and real-time PCR analysis. Western blotting was also used to detect the effect of TGF-beta1 on the Smad3 and Smad7 expressions of RLE-6TN cells. Morphological alterations were examined by phase-contrast microscope, and ultrastructure changes by electron microscope. Incubation of RLE-6TN cells with TGF-beta1 resulted in the up-regulation of the expression of the mesenchymal cell markers, after artesunate intervened on it, resulted in the down-regulation of the expression. Meanwhile, incubation with artesunate intervened on RLE-6TN cells could lead to the apparent down-regulation of the expression of Smad3 and up-regulation of Samd7 and the transition of RLE-6TN cells to mesenchymal-like by TGF-beta1 induction, after artesunate intervened on it, RLE-6TN cells to epithelial-like. TGF-beta1 induced epithelial-mesenchymal transition process; artesunate can inhibit TGF-beta1-induced epithelial-mesenchymal transition process, the possible mechanism is up-regulation of the expression of Smad7 and down-regulation of the expression of Smad3, meanwhile inhibits phosphorylation of Smad3.

Resveratrol repressed viability of U251 cells by miR-21 inhibiting of NF-κB pathway.

Resveratrol (RSV), a polyphenol, is known to play an important role in inhibiting proliferation and inducing apoptosis of glioma cells. The aim of this study was to explore the mechanism of RSV on U251 cells apoptosis. RSV showed a dose-dependent decrease in U251 cell viability. It could reduce IκB phosphorylation, nuclear P65 protein levels and NF-κB transcriptional activity, which suggested that signaling pathway are involved in RSV-induced apoptosis. In addition, RSV could inhibit miR-21 expression and down-regulation of miR-21 expression could suppress NF-κB activity. Interestingly, over-expression of miR-21 can reverse the effect of RSV on NF-κB activity and apoptosis in U251 cells. These results suggest that RSV can effectively induce apoptosis of U251 cells and modulation of miR-21 possibly contributes to this antitumor action.

Association between admission heart rate and major adverse cardiovascular events in acute myocardial infarction participants with different left ventricular ejection fraction.

BACKGROUND: This study intended to investigate the independent effect of admission heart rate (HR) on the risk of major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI) patients with different left ventricular ejection fraction (LVEF) levels. METHODS: The study was a secondary analysis of the Acute Coronary Syndrome Quality Improvement in Kerela Trial. The relationship between admission HR and 30-day adverse outcomes in AMI patients with different LVEF levels was detected using a Logistic regression model. Interaction tests were used to compare the effects of different subgroups on HR and MACEs. RESULTS: Our study enrolled 18,819 patients. In both partially and fully adjusted models (Model1 and Model2), the risk of MACEs was highest in patients with HR ≥ 120 (OR: 1.62, 95%CI: (1.16, 2.26), P = 0.004, Model1; OR: 1.46, 95%CI: (1.00, 2.12), P = 0.047, Model2). There was a significant interaction between LVEF and HR (P for interaction = 0.003). Meanwhile, the trend test for this association showed that HR was positively and significantly associated with the MACEs in LVEF≥40% group (OR (95%CI): 1.27 (1.12, 1.45), P < 0.001). However, in LVEF<40% group, the trend test was not statistically significant (OR (95%CI): 1.09 (0.93, 1.29), P = 0.269). CONCLUSION: This study found that elevated admission HR was associated with a significantly higher risk for MACEs in patients admitted with AMI. Elevated admission HR was significantly associated with the risk of MACEs in AMI patients without low LVEF but not those with low LVEF (<40%). LVEF levels should be considered when evaluating the association between admission HR and the prognosis of AMI patients in the future.

RORγ Agonists Enhance the Sustained Antitumor Activity through Intrinsic Tc17 Cytotoxicity and Tc1 Recruitment.

Activation of RORγ with synthetic small-molecule agonists has been shown to enhance type 17 effector (CD4+ Th17 and CD8+ Tc17 cells) cell functions and decrease immunosuppressive mechanisms, leading to improved antitumor efficacy in adoptive cell transfer and syngeneic murine tumor models. However, whether Tc17 cells possess intrinsic cytotoxicity and the mechanism they use to lyse target cells is controversial. We report here that Tc17 cells were lytic effectors dependent on perforin and granzyme A. In contrast to Tc1 cells, Tc17 cells resisted activation-induced cell death and maintained granzyme A levels, which conferred the ability to lyse target cells in serial encounters. Thus, although the acute lytic capacity of Tc17 cells could be inferior to Tc1 cells, comparable lysis was achieved over time. In addition to direct lytic activity, Tc17 cells infiltrated early into the tumor mass, recruited other CD8+ T cells to the tumor, and enhanced the survival and lytic capability of these cells during repeated target encounters. Synthetic RORγ agonists further augmented Tc17 survival and lytic activity in vitro and in vivo, controlling tumor growth not only through direct cytotoxicity, but also through recruitment and improved function of other effector cells in the tumor microenvironment, which suggests complementary and cooperate activities for effective immunotherapy.

Positive and negative signaling components involved in TNFalpha-induced NF-kappaB activation.

Tumor Necrosis Factor alpha (TNFalpha) is a pro-inflammatory cytokine that plays important roles in different biological processes, including the induction of other cytokines. One of the most important downstream signaling targets activated by TNFalpha is the NF-kappaB transcription factor, which has been identified to be involved in inflammatory, anti-apoptotic, and immune responses. Stimulation of cells with TNFalpha triggers activation of NF-kappaB through various signaling molecules, including TRAF2, RIP, MAP3K, and the IKK complex. Recently, numerous studies have been performed to explore the detailed mechanism by which NF-kappaB is activated upon TNFalpha stimulation. Current understanding of this pathway has been focused on the identification of signaling components, the role of post-translational modification and the sub-cellular translocation of those components. Additionally, more negative regulators in the TNF-IKK pathway are emerging.

Climatic effects on planning behavior.

What mechanism links climate change and social change? Palaeoanthropological analysis of human remains suggests that abrupt climate change is linked to societal restructuring, but it has been challenging to reliably identify the exact mechanisms underlying this relationship. Here we identify one potential mechanism that can link climate to behavior change, and underpins many of the reported findings on social restructuring. Specifically, we show that daily weather is linked to human planning behavior, and this effect is moderated by climate. Our results demonstrate that as weather gets colder, humans increase their planning in cold regions and decrease planning in warm regions. Since planning has previously been linked to group efficiency, cooperation, and societal organization, our work suggests planning is one mechanism that can link climate change to societal restructuring.

Comparing salt tolerance of beet cultivars and their halophytic ancestor: consequences of domestication and breeding programmes.

Salt tolerance of higher plants is determined by a complex set of traits, the timing and rate of evolution of which are largely unknown. We compared the salt tolerance of cultivars of sugar beet and their ancestor, sea beet, in hydroponic studies and evaluated whether traditional domestication and more recent breeding have changed salt tolerance of the cultivars relative to their ancestor. Our comparison of salt tolerance of crop cultivars is based on values of the relative growth rate (RGR) of the entire plant at various salinity levels. We found considerable salt tolerance of the sea beet and slightly, but significantly, reduced salt tolerance of the sugar beet cultivars. This indicates that traditional domestication by selection for morphological traits such as leaf size, beet shape and size, enhanced productivity, sugar content and palatability slightly affected salt tolerance of sugar beet cultivars. Salt tolerance among four sugar beet cultivars, three of which have been claimed to be salt tolerant, did not differ. We analysed the components of RGR to understand the mechanism of salt tolerance at the whole-plant level. The growth rate reduction at higher salinity was linked with reduced leaf area at the whole-plant level (leaf area ratio) and at the individual leaf level (specific leaf area). The leaf weight fraction was not affected by increased salinity. On the other hand, succulence and leaf thickness and the net assimilation per unit of leaf area (unit leaf rate) increased in response to salt treatment, thus partially counteracting reduced capture of light by lower leaf area. This compensatory mechanism may form part of the salt tolerance mechanism of sea beet and the four studied sugar beet cultivars. Together, our results indicate that domestication of the halophytic ancestor sea beet slightly reduced salt tolerance and that breeding for improved salt tolerance of sugar beet cultivars has not been effective.

How does personality matter? An investigation of the impact of extraversion on individuals' SNS use.

The fast proliferation of social networking sites (SNS) offers Internet users new possibilities for developing and maintaining their social network. Despite a growing interest in SNS, less research attention has been paid to SNS usage from the perspective of personality, that is, the Big Five personality traits. This study develops a model to elucidate how extraversion, an important dimension of personality, affects the perceptions of SNS users and their continuance intention. The research model is empirically tested with answers gained from 221 usable questionnaires. The results indicate that extraversion positively affects perceived satisfaction, supplementary entertainment, and critical mass directly, and indirectly influences both playfulness and SNS continuance intention.

Transferrin modified PEG-PLA-resveratrol conjugates: in vitro and in vivo studies for glioma.

Glioblastoma is one of the most malignant brain tumors with a poor prognosis. In this study, we examined the effects of transferrin (Tf)-modified poly ethyleneglycol-poly lactic acid (PEG-PLA) nanoparticles conjugated with resveratrol (Tf-PEG-PLA-RSV) to glioma therapy in vitro and in vivo. The cell viability of Tf-PEG-PLA-RSV on C6 and U87 glioma cells was determined by the MTT assay. In vivo biodistribution and antitumor activity were investigated in Brain glioma bearing rat model of C6 glioma by i.p. administration of RSV-polymer conjugates. We found that the average diameter of each Tf-PEG-PLA-RSV is around 150 nm with 32 molecules of Tf on surface. In vitro cytotoxicity of PEG-PLA-RSV against C6 and U87 cells was higher than that of free RSV, and further the modification of Tf enhanced the cytotoxicity of the RSV-polymer conjugates as a result of the increased cellular uptake of the RSV-modified conjugates by glioma cells. In comparison with free RSV, RSV conjugates could significantly decrease tumor volume and accumulate in brain tumor, which resulted in prolonging the survival of C6 glioma-bearing rats. These results suggest that Tf-NP-RSV had a potential of therapeutic effect to glioma both in vitro and in vivo and might be a potential candidate for targeted therapy of glioma and worthy of further investigation.

Ubiquitin-specific protease 25 regulates TLR4-dependent innate immune responses through deubiquitination of the adaptor protein TRAF3.

Protein ubiquitination plays a critical role in Toll-like receptor (TLR) signaling and innate immunity. Although several E3 ubiquitin ligases have been identified downstream of TLRs, the regulation of protein deubiquitination in TLR-triggered innate immune responses is poorly understood. We identified ubiquitin-specific protease 25 (USP25) as a regulator of TLR signaling. USP25 was recruited to the TLR4 signaling complex, and it associated with the adaptor proteins tumor necrosis factor receptor-associated factor 3 (TRAF3) and TRAF6 after stimulation of TLR4 with its ligand lipopolysaccharide (LPS). USP25 specifically reversed the Lys(48)-linked ubiquitination of TRAF3 that was mediated by the E3 ubiquitin ligase cIAP2 (cellular inhibitor of apoptosis 2). Deficiency in USP25 enhanced the extent of ubiquitination of TRAF3 and accelerated its degradation after TLR4 activation, which potentiated TLR4-induced activation of NF-κB (nuclear factor κB) and MAPK (mitogen-activated protein kinase) signaling, but inhibited activation of the transcription factor IRF3 (interferon regulatory factor 3). USP25-deficient mice exhibited increased susceptibility to LPS-induced septic shock compared to their wild-type counterparts, which was associated with enhanced production of proinflammatory cytokines and decreased production of interferon-α. Thus, by inhibiting the degradation of TRAF3 during TLR4 activation, USP25 enables a balanced innate immune response.

USP18 inhibits NF-κB and NFAT activation during Th17 differentiation by deubiquitinating the TAK1-TAB1 complex.

Reversible ubiquitin modification of cell signaling molecules has emerged as a critical mechanism by which cells respond to extracellular stimuli. Although ubiquitination of TGF-ß-activated kinase 1 (TAK1) is critical for NF-κB activation in T cells, the regulation of its deubiquitination is unclear. We show that USP18, which was previously reported to be important in regulating type I interferon signaling in innate immunity, regulates T cell activation and T helper 17 (Th17) cell differentiation by deubiquitinating the TAK1-TAB1 complex. USP18-deficient T cells are defective in Th17 differentiation and Usp18(-/-) mice are resistant to experimental autoimmune encephalomyelitis (EAE). In response to T cell receptor engagement, USP18-deficient T cells exhibit hyperactivation of NF-κB and NFAT and produce increased levels of IL-2 compared with the wild-type controls. Importantly, USP18 is associated with and deubiquitinates the TAK1-TAB1 complex, thereby restricting expression of IL-2. Our findings thus demonstrate a previously uncharacterized negative regulation of TAK1 activity during Th17 differentiation, suggesting that USP18 may be targeted to treat autoimmune diseases.

Use of nerve conduits for peripheral nerve injury repair: A Web of Science-based literature analysis.

OBJECTIVE: To identify global research trends in the use of nerve conduits for peripheral nerve injury repair. DATA RETRIEVAL: Numerous basic and clinical studies on nerve conduits for peripheral nerve injury repair were performed between 2002-2011. We performed a bibliometric analysis of the institutions, authors, and hot topics in the field, from the Web of Science, using the key words peripheral nerve and conduit or tube. INCLUSION CRITERIA: peer-reviewed published articles on nerve conduits for peripheral nerve injury repair, indexed in the Web of Science; original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items. EXCLUSION CRITERIA: articles requiring manual searching or telephone access; documents not published in the public domain; and several corrected papers. MAIN OUTCOME MEASURES: (a) Annual publication output; (b) publication type; (c) publication by research field; (d) publication by journal; (e) publication by funding agency; (f) publication by author; (g) publication by country and institution; (h) publications by institution in China; (i) most-cited papers. RESULTS: A total of 793 publications on the use of nerve conduits for peripheral nerve injury repair were retrieved from the Web of Science between 2002-2011. The number of publications gradually increased over the 10-year study period. Articles constituted the main type of publication. The most prolific journals were Biomaterials, Microsurgery, and Journal of Biomedical Materials Research Part A. The National Natural Science Foundation of China supported 27 papers, more than any other funding agency. Of the 793 publications, almost half came from American and Chinese authors and institutions. CONCLUSION: Nerve conduits have been studied extensively for peripheral nerve regeneration; however, many problems remain in this field, which are difficult for researchers to reach a consensus.

CARMA3 is crucial for EGFR-Induced activation of NF-κB and tumor progression.

EGF activates NF-κB, and constitutively activated NF-κB contributes to EGFR mutation-associated tumorigenesis, but it remains unclear precisely how EGFR signaling leads to NF-κB activation. Here we report that CARMA3, a caspase recruitment domain (CARD)-containing scaffold molecule, is required for EGF-induced NF-κB activation. CARMA3 deficiency impaired the activation of the IKK complex following EGF stimulation, resulting in a defect of EGF-induced IκBα phosphorylation and NF-κB activation. We found that CARMA3 and Bcl10 contributed to several characteristics of EGFR-associated malignancy, including proliferation, survival, migration, and invasion. Most importantly, CARMA3 contributed to tumor growth in vivo. Our findings elucidate a crucial link between EGFR-proximal signaling components and the downstream IKK complex, and they suggest a new therapeutic target for treatment of EGFR-driven cancers.

MEKK3 is required for lysophosphatidic acid-induced NF-kappaB activation.

Lysophosphatidic acid (LPA) is a potent agonist that exerts various cellular functions on many cell types through binding to its cognate G protein-coupled receptors (GPCRs). Although LPA induces NF-kappaB activation by acting on its GPCR receptor, the molecular mechanism of LPA receptor-mediated NF-kappaB activation remains to be well defined. In the present study, by using MEKK3-, TAK1-, and IKKbeta-deficient murine embryonic fibroblasts (MEFs), we found that MEKK3 but not TAK1 deficiency impairs LPA and protein kinase C (PKC)-induced IkappaB kinase (IKK)-NF-kappaB activation, and IKKbeta is required for PKC-induced NF-kappaB activation. In addition, we demonstrate that LPA and PKC-induced IL-6 and MIP-2 production are abolished in the absence of MEKK3 but not TAK1. Together, our results provide the genetic evidence that MEKK3 but not TAK1 is required for LPA receptor-mediated IKK-NF-kappaB activation.