Downregulation of the Adenosine A2b Receptor by RNA Interference Inhibits Hepatocellular Carcinoma Cell Growth

To investigate the biological effect of adenosine A2b receptor (A2bR) on the human hepatocellular carcinoma cell line HepG2, three A2bR siRNA constructs were transiently transfected into HepG2 cells. The results showed that A2bR siRNA reduced the levels of A2bR mRNA and protein. In order to further detect the function of A2bR, we established a stable hepatocellular carcinoma cell line (HepG2) expressing siRNA targeting the adenosine A2b receptor. Targeted RNAi significantly inhibited tumor cell growth in vitro, and flow cytometry (FCM) showed that significantly more cells expressing A2bR siRNA were in the G0/G1 phase compared to the untransfected group ((89.56% ± 3.15%) versus (56.19% ± 1.58%), P < 0.01). These results indicated that silencing the expression of adenosine A2b receptor in HepG2 cells can suppress cell growth effectively by blocking the cell cycle. Downregulation of adenosine A2b receptor gene expression with RNA interference could be a new approach to hepatocellular carcinoma therapy

Imprint of the stochastic nature of photon emission by electrons on the proton energy spectra in the laser-plasma interaction

The impact of stochasticity effects (SEs) in photon emissions on the proton energy spectra during laser-plasma interaction is theoretically investigated in the quantum radiation-dominated regime, which may facilitate SEs experimental observation. We calculate the photon emissions quantum mechanically and the plasma dynamics semiclassically via two-dimensional particle-in-cell simulations. An ultrarelativistic plasma generated and driven by an ultraintense laser pulse head-on collides with another strong laser pulse, which decelerates the electrons due to radiation-reaction effect and results in a significant compression of the proton energy spectra because of the charge separation force. In the considered regime the SEs are demonstrated in the shift of the mean energy of the protons up to hundreds of MeV. This effect is robust with respect to the laser and target parameters and measurable in soon available strong laser facilities

Spinal toll like receptor 3 is involved in chronic pancreatitis-induced mechanical allodynia of rat

<p>Abstract</p> <p>Background</p> <p>Mechanisms underlying pain in chronic pancreatitis (CP) are incompletely understood. Our previous data showed that astrocytes were actively involved. However, it was unclear how astrocytic activation was induced in CP conditions. In the present study, we hypothesized that toll-like receptors (TLRs) were involved in astrocytic activation and pain behavior in CP-induced pain.</p> <p>Results</p> <p>To test our hypothesis, we first investigated the changes of TLR2-4 in the rat CP model induced by intrapancreatic infusion of trinitrobenzene sulfonic acid (TNBS). Western blot showed that after TNBS infusion, TLR3, but not TLR2 or TLR4, was increased gradually and maintained at a very high level for up to 5 w, which correlated with the changing course of mechanical allodynia. Double immunostaining suggested that TLR3 was highly expressed on astrocytes. Infusion with TLR3 antisense oligodeoxynucleotide (ASO) dose-dependently attenuated CP-induced allodynia. CP-induced astrocytic activation in the spinal cord was also significantly suppressed by TLR3 ASO. Furthermore, real-time PCR showed that IL-1β, TNF-α, IL-6 and monocyte chemotactic protein-1 (MCP-1) were significantly increased in spinal cord of pancreatic rats. In addition, TLR3 ASO significantly attenuated CP-induced up-regulation of IL-1β and MCP-1.</p> <p>Conclusions</p> <p>These results suggest a probable "TLR3-astrocytes-IL-1β/MCP-1" pathway as a positive feedback loop in the spinal dorsal horn in CP conditions. TLR3-mediated neuroimmune interactions could be new targets for treating persistent pain in CP patients.</p

Notch-RBP-J Signaling Regulates the Mobilization and Function of Endothelial Progenitor Cells by Dynamic Modulation of CXCR4 Expression in Mice

Bone marrow (BM)-derived endothelial progenitor cells (EPC) have therapeutic potentials in promoting tissue regeneration, but how these cells are modulated in vivo has been elusive. Here, we report that RBP-J, the critical transcription factor mediating Notch signaling, modulates EPC through CXCR4. In a mouse partial hepatectomy (PHx) model, RBP-J deficient EPC showed attenuated capacities of homing and facilitating liver regeneration. In resting mice, the conditional deletion of RBP-J led to a decrease of BM EPC, with a concomitant increase of EPC in the peripheral blood. This was accompanied by a down-regulation of CXCR4 on EPC in BM, although CXCR4 expression on EPC in the circulation was up-regulated in the absence of RBP-J. PHx in RBP-J deficient mice induced stronger EPC mobilization. In vitro, RBP-J deficient EPC showed lowered capacities of adhering, migrating, and forming vessel-like structures in three-dimensional cultures. Over-expression of CXCR4 could at least rescue the defects in vessel formation by the RBP-J deficient EPC. These data suggested that the RBP-J-mediated Notch signaling regulated EPC mobilization and function, at least partially through dynamic modulation of CXCR4 expression. Our findings not only provide new insights into the regulation of EPC, but also have implications for clinical therapies using EPC in diseases

Longitudinal association between parental involvement and internet gaming disorder among Chinese adolescents: Consideration of future consequences as a mediator and peer victimization as a moderator

Background and aims: Internet gaming disorder (IGD) in adolescents is a concerning issue. Positive parenting has been found to protect against adolescent IGD, but the underlying mechanisms await further investigation. As such, this study examined the longitudinal association between parental involvement (PI) – a specific type of positive parenting understudied in the literature of adolescent gaming disorder – and IGD. Moreover, this study also tested consideration of future consequences (CFC) as a mediator and peer victimization (PV) as a moderator. Methods: A two-wave longitudinal research spanning 6 months apart was conducted. Participants were Chinese adolescents (final N 5 434; 222 females; Mage 5 14.44 years, SD 5 1.56). They provided ratings on PI, PV, and IGD at Wave 1, and CFC-immediate, CFC-future, and IGD at Wave 2. Results: Descriptive statistics showed that the prevalence rate of IGD was 10.81% and 9.45% at Waves 1 and 2, respectively. Moreover, results of moderated mediation model found that after controlling for Wave 1 IGD and covariates, Wave 1 PI was associated with Wave 2 IGD via preventing adolescents who had higher levels of PV from developing a tendence of CFC-immediate and via promoting adolescents who had lower levels of PV to develop a tendence of CFC-future. Discussion and Conclusions: Altogether, these results suggest that facilitative ecological systems (e.g., positive parenting and good relationships with peers) and personal strengths (e.g., positive future orientation) jointly contribute to the mitigation of adolescent IGD

Fascin-1 and Digestive System Carcinoma

Invasion and metastasis are major reason for poor prognosis of digestive system carcinoma patients. Motility and migratory capacity are important in contributing to tumor cells’ invasion and metastasis. Fascin is one of actin cross-linking proteins and can participate in forming parallel actin bundles in cell protrusions. Fascin-1 is consequently involved in cell adhesion, motility, and signaling. In cultured cells, over-expression of fascin-1 can increase migration and invasion capacity of cells. Many studies show up-expressions of fascin-1 are significantly associated with worse prognosis, poor differentiation, TNM stage, positive for lymph node metastasis, and positive for distant metastasis in digestive system carcinoma patients. So fascin-1 may have prognostic value as an early biomarker for more aggressive digestive system carcinoma. This review provides detailed account of preclinical studies conducted to determine the utility of fascin-1 as a therapeutic and predictive agent in invasion and metastasis of carcinomas

Pig Liver Xenotransplantation: A Review of Progress Toward the Clinic

Experience with clinical liver xenotransplantation has largely involved the transplantation of livers from nonhuman primates. Experience with pig livers has been scarce. This brief review will be restricted to assessing the potential therapeutic impact of pig liver xenotransplantation in acute liver failure and the remaining barriers that currently do not justify clinical trials. A relatively new surgical technique of heterotopic pig liver xenotransplantation is described that might play a role in bridging a patient with acute liver failure until either the native liver recovers or a suitable liver allograft is obtained. Other topics discussed include the possible mechanisms for the development of the thrombocytopenis that rapidly occurs after pig liver xenotransplantation in a primate, the impact of pig complement on graft injury, the potential infectious risks, and potential physiologic incompatibilities between pig and human. There is cautious optimism that all of these problems can be overcome by judicious genetic manipulation of the pig. If liver graft survival could be achieved in the absence of thrombocytopenia or rejection for a period of even a few days, there may be a role for pig liver transplantation as a bridge to allotransplantation in carefully selected patients

COVID-19 causes record decline in global CO2 emissions

The considerable cessation of human activities during the COVID-19 pandemic has affected global energy use and CO2 emissions. Here we show the unprecedented decrease in global fossil CO2 emissions from January to April 2020 was of 7.8% (938 Mt CO2 with a +6.8% of 2-{\sigma} uncertainty) when compared with the period last year. In addition other emerging estimates of COVID impacts based on monthly energy supply or estimated parameters, this study contributes to another step that constructed the near-real-time daily CO2 emission inventories based on activity from power generation (for 29 countries), industry (for 73 countries), road transportation (for 406 cities), aviation and maritime transportation and commercial and residential sectors emissions (for 206 countries). The estimates distinguished the decline of CO2 due to COVID-19 from the daily, weekly and seasonal variations as well as the holiday events. The COVID-related decreases in CO2 emissions in road transportation (340.4 Mt CO2, -15.5%), power (292.5 Mt CO2, -6.4% compared to 2019), industry (136.2 Mt CO2, -4.4%), aviation (92.8 Mt CO2, -28.9%), residential (43.4 Mt CO2, -2.7%), and international shipping (35.9Mt CO2, -15%). Regionally, decreases in China were the largest and earliest (234.5 Mt CO2,-6.9%), followed by Europe (EU-27 & UK) (138.3 Mt CO2, -12.0%) and the U.S. (162.4 Mt CO2, -9.5%). The declines of CO2 are consistent with regional nitrogen oxides concentrations observed by satellites and ground-based networks, but the calculated signal of emissions decreases (about 1Gt CO2) will have little impacts (less than 0.13ppm by April 30, 2020) on the overserved global CO2 concertation. However, with observed fast CO2 recovery in China and partial re-opening globally, our findings suggest the longer-term effects on CO2 emissions are unknown and should be carefully monitored using multiple measures