Hmgb1, an evolutionarily conserved chromosomal protein, was recently re-discovered to be an innate immune-mediator contributing to both innate and adaptive immune responses. Here, we show a pivotal role for Hmgb1 in acute allograft rejection in a murine cardiac transplantation model. Extracellular Hmgb1 was found to be a potent stimulator for adaptive immune responses. Hmgb1 can be either passively released from damaged cells after organ harvest and ischemia/reperfusion insults, or actively secreted by allograft infiltrated immune cells. After transplantation, allografts show a significant temporal upregulation of Hmgb1 expression accompanied by inflammatory infiltration, a consequence of graft destruction. These data suggest the involvement of Hmgb1 in acute allograft rejection. In line with these observations, treatment of recipients with rA-box, a specific blockade for endogenous Hmgb1, significantly prolonged cardiac allograft survival as compared to those recipients treated with either rGST or control vehicle. The enhanced graft survival is associated with reduced allograft expression of TNFa , IFNc and Hmgb1 and impaired Th1 immune response.

Fear is a negative emotional reaction to or persistent worry over an imminent public health event like COVID-19. The COVID-Fear Scale was developed in many countries, but not in China. The current study aims to examine the psychometric properties of Chinese version of the Fear of COVID-19 Scale. Translation into Chinese and backtranslation into English were conducted firstly. Item analysis and exploratory factor analysis were conducted in Sample 1, followed by validity tests in Sample 2. Likely, test-retest reliability was conducted in sample 3. A bifactor structure of Chinese version of FCV-19S with a general fear factor and two orthogonal group factors with fear thoughts and physical response was confirmed. Besides, it has good internal consistency reliability (α = .92), composite reliability (CR = .92), and validity correlation validity. The results of the present study confirmed that the Chinese version of FCV-19S has good psychometric properties in the Chinese communities. Keywords Fear of COVID-19 Scale. Reliability. Validity Coronavirus disease 2019 (COVID-19) is a novel and highly infectious respiratory disease, which has threatened to become a global public health crisis (Cucinotta and Vanelli 2020). Specifically, the COVID-19 has affected 215 countries till July 13, 2020, and the number of confirmed cases has exceeded 12.95 million with 560,000 registered deaths worldwide (Worldometers 2020). In China, approximately 80,000 individuals have been diagnosed with COVID-19, with over 4600 officially recorded deaths (Chinese National Health Commission 2020). Such substantial negative effects or damage caused by COVID-19 are not simply observed on the global economy (Al-Awadhi et al. 2020; Laing 2020), but this pandemic is also affecting mental health (e.g., depression, anxiety, and fear) across a variety of age groups and cultural backgrounds (Liu et al. 2020; Rajkumar 2020).

Background14,15-epoxyeicosatrienoic acid (14,15-EET) is an important lipid signaling molecule involved in the regulation of tumor metastasis, however, the role and molecular mechanisms of 14,15-EET activity in breast cancer cell epithelial-mesenchymal transition (EMT) and drug resistance remain enigmatic.MethodsThe 14, 15-EET level in serum and in tumor or non-cancerous tissue from breast cancer patients was measured by ELISA. qRT-PCR and western blot analyses were used to examine expression of integrin αvβ3. The role of 14, 15-EET in breast cancer cell adhesion, invasion was explored by adhesion and Transwell assays. The role of 14, 15-EET in breast cancer cell cisplatin resistance in vitro was determined by MTT assay. Western blot was conducted to detect the protein expressions of EMT-related markers and FAK/PI3K/AKT signaling. Xenograft models in nude mice were established to explore the roles of 14, 15-EET in breast cancer cells EMT and cisplatin resistance in vivo.ResultsIn the present study, we show that serum level of 14, 15-EET increases in breast cancer patients and 14, 15-EET level of tumor tissue is higher than that of non-cancerous tissue. Moreover, 14, 15-EET increases integrin αvβ3 expression, leading to FAK activation. 14, 15-EET induces breast cancer cell EMT via integrin αvβ3 and FAK/PI3K/AKT cascade activation in vitro. Furthermore, we find that 14, 15-EET induces breast cancer cells EMT and cisplatin resistance in vivo, αvβ3 integrin and the resulting FAK/PI3K/AKT signaling pathway are responsible for 14, 15-EET induced-breast cancer cells cisplatin resistance.ConclusionsOur findings suggest that inhibition of 14, 15-EET or inactivation of integrin αvβ3/FAK/PI3K/AKT pathway could serve as a novel approach to reverse EMT and cisplatin resistance in breast cancer cells.

Previous studies have shown that miR-203 is a skin-specific microRNA (miRNA) with a profound role in skin cell differentiation. However, emerging microarray and deep sequencing data revealed that miR-203 is also expressed in embryonic skeletal muscle and myoblasts. In this study, we found that miR-203 was transiently upregulated in chicken embryos on days 10 to 16 (E10–E16) and was sharply downregulated and even not expressed after E16 in chicken embryonic skeletal muscle. Histological profiles and weight variations of embryo skeletal muscle revealed that miR-203 expression is correlated with muscle development. In vitro experiments showed that miR-203 exhibited downregulated expression during myoblast differentiation into myotubes. miR-203 overexpression inhibited myoblast proliferation and differentiation, whereas its loss-of-function increased myoblast proliferation and differentiation. During myogenesis, miR-203 can target and inhibit the expression of c-JUN and MEF2C, which were important for cell proliferation and muscle development, respectively. The overexpression of c-JUN significantly promoted myoblast proliferation. Conversely, knockdown of c-JUN by siRNA suppressed myoblast proliferation. In addition, the knockdown of MEF2C by siRNA significantly inhibited myoblast differentiation. Altogether, these data not only suggested that the expression of miR-203 is transitory during chicken skeletal muscle development but also showed a novel role of miR-203 in inhibiting skeletal muscle cell proliferation and differentiation by repressing c-JUN and MEF2C, respectively.