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To elucidates the mechanism that disulfiram/copper complex (DSF/Cu) treatment activates chloride channels and induces apoptosis in prostate cancer cells.
Cellular membrane currents were measured by membrane clamp technique; western blot to detect protein expression; flow cytometry to detect apoptosis; immunofluorescence to detect target protein co-localization, and further validated by a combination of protein-protein interaction and mock protein molecular docking techniques.
DSF/Cu activated chloride channels and induced apoptosis in LNCaP (a type of androgen-dependent prostate cancer cells) cells. The chloride currents activated by DSF/Cu were significantly reduced after knockdown of CLC3 with siRNA. In addition, DSF/Cu-activated chloride currents were reduced to background current levels after perfusion with genistein, a highly specific tyrosine kinase inhibitor. Conversely, DSF/Cu failed to activate chloride currents in LNCaP cells after 30minutes of pre-incubation with genistein. When genistein was removed, and DSF/Cu was added, the activated currents were small and unstable, and gradually decreased. Immunofluorescence in LNCaP cells also showed co-localization of the CLC3 protein with tyrosine kinase 2β (PTK2B).
DSF/Cu can activate chloride channels and induce apoptosis in LNCaP cells with the involvement of tyrosine kinase. These results provide new insights into the target therapy of prostate cancer.
DSF/Cu can activate chloride channels and induce apoptosis in LNCaP cells with the involvement of tyrosine kinase. These results provide new insights into the target therapy of prostate cancer.The appearance and subsequent evolution of land plants is among the most important events in the earth system. Plant resulted in a change of earth surface albedo and the hydrological cycle, as well as increased rock weatherability thereby causing a persistent change in atmospheric CO2 and O2 . Land plants are, however, themselves dependent on O2 for respiration and long-term survival, something not considered in current geochemical models. In this perspective, we highlight two aspects of land plants' dependency on O2 relevant for the geobiological community (a) fossil root systems can be used as a proxy for minimum levels of past atmospheric O2 consistent with a given fossil root depth; and (b) by identifying a positive feedback mechanism involving atmospheric O2 , root intensity, terrestrial primary production and organic carbon burial. As an example, we consider archaeopterid fossil root systems, resembling those of modern mature conifers. Our soil-plant model suggest that atmospheric O2 with 1 SD probably reached pressures of 18.2 ± 1.9 kPa and 16.8 ± 2.1 kPa by the Middle and Late Devonian, respectively, that is 86 ± 9% and 79 ± 10% of the present-day 21.2 kPa.Identification by NGS of two novel alleles, HLA-A*0201193 and -DQA1*0217, in Greek individuals.
To investigate the mediation/moderation effect between Coping Behaviors (CBs) and Sense of Coherence (SOC) in the prediction of health-related quality of life (HRQoL) in breast cancer patients.
Cross-sectional.
A total of 221 patients were included in this study. The 13-item Orientation to Life Questionnaire, Brief COPE and Functional Assessment of Cancer Therapy-Breast were investigated. Pearson's correlation coefficient and mediation/moderation analysis were performed.
Significant correlations were observed for SOC, active coping, acceptance, positive reframing (PR), planning, use of emotional support (UES), use of instrumental support, behaviour disengagement and self-blame with HRQoL. Except for planning and acceptance, SOC partially mediated the CBs' effect on HRQoL. The UES and PR's effects on HRQoL were significant at lower SOC levels and diminished at higher SOC levels.
Practitioners can incorporate SOC and adaptive CBs, including PR and UES, into the rehabilitation programmes to improve HRQoL in patients.
Practitioners can incorporate SOC and adaptive CBs, including PR and UES, into the rehabilitation programmes to improve HRQoL in patients.The direct synthesis of nitrile from N2 under mild conditions is of great importance and has attracted much interest. Herein, we report a direct conversion of N2 into nitrile via a nitrile-alkyne cross-metathesis (NACM) process involving a N2 -derived Mo nitride. Treatment of the Mo nitride with alkyne in the presence of KOTf afforded an alkyne-coordinated nitride, which was then transformed into MoV carbyne and the corresponding nitrile upon 1 e- oxidation. Both aryl- and alkyl-substituted alkynes underwent this process smoothly. Experiments and DFT calculations have proved that the oxidation state of the Mo center plays a crucial role. This method does not rely on the nucleophilicity of the N2 -derived metal nitride, offering a novel strategy for N2 fixation chemistry.Given the detrimental effects of burnout for individuals and organizations, it is of crucial importance to better understand the self-initiated actions employees take to prevent burnout. While such proactive burnout prevention is likely to reduce burnout complaints, these activities may also be frustrated by high burnout levels. This means that proactive burnout prevention and burnout can negatively affect each other over time. The present study used a four-wave longitudinal panel design to investigate temporal relationships between proactive burnout prevention and burnout over 3, 6 and 9 weeks. Participants were 165 employees in the financial services industry who provided data on all four measurement occasions. The outcomes of structural equation modelling provided support for the hypothesized combined effects model compared to the lagged and reversed effects models. The findings suggest that proactive burnout prevention can help to prevent burnout, while engagement in these behaviours may be hindered by high initial levels of burnout. Employees should therefore intervene before their resource pool becomes too depleted and they lack the energy or mental strength to invest resources, in order to proactively retain or regain resources.
To characterize immune suppression in lymphoma, thymocyte selection-associated high mobility group box protein (TOX) expression and co-expression with programmed cell death receptor-1 (PD-1), T cell immunoglobulin mucin-domain-containing-3 (Tim-3), and CD244 in CD3+, CD4+, CD8+, and regulatory T (Treg) cells from patients with lymphomas were analyzed.
TOX expression and co-expression with PD-1, Tim-3, and CD244 in CD3+, CD4+, Treg, and CD8+ T cells were analyzed by multi-color fluorescent flow cytometry using peripheral blood (PB) from 13 newly diagnosed, untreated lymphoma patients, and 11 healthy individuals.
An increased percentage of TOX+ CD3+, CD4+, and CD8+ T cells was found in PB from patients with B cell non-Hodgkin's lymphoma (B-NHL) in comparison with healthy controls. Moreover, TOX+PD-1+ and TOX+Tim-3+ double-positive T cells increased among the CD3+, CD4+, and CD8+T cell populations in the B-NHL group. There was apparent heterogeneity in TOX expression and co-expression with PD-1, Tim-3, and CD244 in CD3+, CD4+, and CD8+ T cells in different lymphoma patients. In addition, the percentage of CD4+CD25+FoxP3+ T cells (Treg) among the CD3+ and CD4+ T cells significantly increased, and the number of TOX+ and TOX+PD-1+ Treg cells also significantly increased in the B-NHL group.
Higher expression of TOX concurrent with PD-1, Tim-3, and CD244 in T cells from patients with B-NHL may contribute to T cell exhaustion and impair their special anti-tumor T cell activity. TOX may be considered a potential target for reversing T cell exhaustion and improving T cell function in hematological malignancies.
Higher expression of TOX concurrent with PD-1, Tim-3, and CD244 in T cells from patients with B-NHL may contribute to T cell exhaustion and impair their special anti-tumor T cell activity. TOX may be considered a potential target for reversing T cell exhaustion and improving T cell function in hematological malignancies.Self-renewal and differentiation of spermatogonial stem cell (SSC) are critical for male fertility and reproduction, both of which are highly regulated by testicular microenvironment. Exosomal miRNAs have emerged as new components in intercellular communication. However, their roles in the differentiation of SSC remain unclear. Here, we observed miR-486-5p enriched in Sertoli cell and Sertoli cell-derived exosomes. The exosomes mediate the transfer of miR-486-5p from Sertoli cells to SSCs. Exosomes release miR-486-5p, thus up-regulate expression of Stra8 (stimulated by retinoic acid 8) and promote differentiation of SSC. selleckchem And PTEN was identified as a target of miR-486-5p. Overexpression of miR-486-5p in SSCs down-regulates PTEN expression, which up-regulates the expression of STRA8 and SYCP3, promotes SSCs differentiation. In addition, blocking the exosome-mediated transfer of miR-486-5p inhibits differentiation of SSC. Our findings demonstrate that miR-486-5p acts as a communication molecule between Sertoli cells and SSCs in modulating differentiation of SSCs. This provides a new insight on molecular mechanisms that regulates SSC differentiation and a basis for the diagnosis, treatment, and prevention of male infertility.Many studies have reported sex differences in empathy and social skills. In this review, several lines of empirical evidences about sex differences in functions and anatomy of social brain are discussed. The most relevant differences involve face processing, facial expression recognition, response to baby schema, the ability to see faces in things, the processing of social interactions, the response to the others' pain, interest in social information, processing of gestures and actions, biological motion, erotic, and affective stimuli. Sex differences in oxytocin-based parental response are also reported. In conclusion, the female and male brains show several neuro-functional differences in various aspects of social cognition, and especially in emotional coding, face processing, and response to baby schema. An interpretation of this sexual dimorphism is provided in the view of evolutionary psychobiology.
To explore contributors for thriving in nursing homes by evaluating, analysing and synthesizing peer-reviewed qualitative literature on the topic.
Thriving is a positive life-world concept that has been explored by several qualitative studies; however, descriptions of thriving and contributors to thriving have not been compared or contrasted among different studies and contexts, nor have they been reviewed and synthesized.
Qualitative meta-ethnography.
Four electronic databases were searched in October 2019, with sources published between 2000 and 2019 included.
Sources of peer-reviewed literature that employed qualitative methods to explore thriving in nursing homes were evaluated. In total, 1,017 sources were screened at title-level, 95 advanced to abstract-level review and 11 were assessed at full-text level. Each source was evaluated by two researchers independently in relation to methodological quality and relevance to the study aim. Themes pertaining to thriving in nursing homes were extracted, interpreted and synthesized.
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