Tenacissoside H repressed the progression of glioblastoma by inhibiting the PI3K/Akt/mTOR signaling pathway.

Glioblastoma (GBM) is one of the most common intracranial primary malignancies with the highest mortality rate, and there is a lack of effective treatments. In this study, we examined the anti-GBM activity of Tenacissoside H (TH), an active component isolated from the traditional Chinese medicine Marsdenia tenacissima (Roxb.) Wight & Arn (MT), and investigated the potential mechanism. Firstly, we found that TH decreased the viability of GBM cells by inducing cell cycle arrest and apoptosis, and inhibited the migration of GBM cells. Furthermore, combined with the Gene Expression Omnibus database (GEO) and network pharmacology as well as molecular docking, TH was shown to inhibit GBM progression by directly regulating the PI3K/Akt/mTOR pathway, which was further validated in vitro. In addition, the selective PI3K agonist 740 y-p partially restored the inhibitory effects of TH on GBM cells. Finally, TH inhibited GBM progression in an orthotopic transplantation model by inactivating the PI3K/Akt/mTOR pathway in vivo. Conclusively, our results suggest that TH represses GBM progression by inhibiting the PI3K/Akt/mTOR signaling pathway in vitro and in vivo, and provides new insight for the treatment of GBM patients.

The occurrence and sources of PAHs, oxygenated PAHs (OPAHs), and nitrated PAHs (NPAHs) in soil and vegetation from the Antarctic, Arctic, and Tibetan Plateau.

Although the fate of PAHs in the three polar regions (Antarctic, Arctic, and Tibetan Plateau) has been investigated, the occurrence and contamination profiles of PAH derivatives such as oxygenated PAHs (OPAHs) and nitrated PAHs (NPAHs) remain unclear. Some of them are more toxic and can be transformed from PAHs in environment. This study explored and compared the concentrations composition profiles and potential sources of PAHs, OPAHs, and NPAHs in soil and vegetation samples from the three polar regions. The total PAH, OPAH, and NPAH concentrations were 3.55-519, n.d.-101, and n.d.-1.10 ng/g dry weight (dw), respectively. The compounds were dominated by three-ring PAHs, and the most abundant individual PAH and OPAH were phenanthrene (PHE) and 9-fluorenone (9-FO), respectively. The sources of PAHs and their derivatives were qualitatively analyzed by the diagnostic ratios and quantified using the positive matrix factorization (PMF) model. The ratios of PAH derivatives to parent PAHs (9-FO/fluorene and 9,10-anthraquinone/anthracene) were significantly higher in the Antarctic samples than in the Arctic and TP samples, implying a higher occurrence of secondary OPAH and NPAH formation in the Antarctic region. To our knowledge, this is the first comparative study that simultaneously investigated the contamination profiles of PAHs and their derivatives in the three polar regions. The findings of this study provide a scientific basis for the development of risk assessment and pollution control strategies in these fragile regions.

Medical occupation preference under the influence of the COVID-19 pandemic: The role of risk and altruistic preferences.

We examine the influence of the COVID-19 pandemic on medical occupation preference, focusing on Wuhan, China. We conducted a survey of 5686 respondents in China regarding the influence of the COVID-19 pandemic on medical occupation preference. We also conducted a complimentary survey in the UK with 1198 respondents, as well as a field experiment in Wuhan with 428 first and second-year medical students. We find a significant negative impact of the pandemic on the willingness to let a loved one choose a medical occupation. Individuals who were heavily influenced by the pandemic, that is, Wuhan residents, especially medical workers, express significantly lower medical occupation preference. Further analysis from Sobel-Goodman mediation tests reveals that around half of the total negative effect can be mediated by enhanced risk aversion and reduced altruism. The UK survey and the field experiment with medical students in Wuhan reinforce these findings. Our results suggest a shift in medical workers' risk- and altruistic-preferences has led to a reduced medical occupation preference. Non-medical workers and students who are more altruistic and risk-seeking are more likely to choose a medical occupation.

An evaluation of the impact of traffic on the distribution of PAHs and oxygenated PAHs in the soils and moss of the southeast Tibetan Plateau.

Contaminants in high-altitude mountains such as the Tibetan Plateau (TP) have attracted extensive attention due to their potential impact on fragile ecosystems. Rapid development of the economy and society has promoted pollution caused by local traffic emissions in the TP. Among the pollutants emitted by traffic, polycyclic aromatic hydrocarbons (PAHs) and oxygenated PAHs (OPAHs) are of particular concern due to their high toxicity. The TP provides an environment to explore the degree and range of contribution for traffic-induced PAHs and OPAHs. In this study, soils and moss were collected at different altitudes and distances from the G318 highway in the southeast TP. The total concentrations of PAHs (∑16PAHs) and OPAHs (∑6OPAHs) in soils were in the range of 3.29-119 ng/g dry weight (dw) and 0.54-9.65 ng/g dw, respectively. ∑16PAH and ∑6OPAH concentrations decreased logarithmically with increasing distance from traffic. A significantly positive correlation between ∑16PAHs and altitude was found at sampling points closest to traffic. Dominant PAHs constituents in soil and moss included chrysene (CHR), benzo[g,h,i]perylene (BghiP), and benzo[b]fluoranthene (BbF); prevalent OPAH compounds were 9-fluorenone (9-FO) and 9,10-anthraquinone (ATQ). These compounds were related to characteristics of traffic emissions. The multiple diagnosis ratio and correlation analysis showed that exhaust emissions were the main source of the PAHs and OPAHs in the studied environment. PMF modeling quantification of the relative contribution of traffic emissions to PAHs in roadside soils was 45 % on average. The present study characterized the extent and range of traffic-induced PAH and OPAH emissions, providing valuable information for understanding the environmental behaviors and potential risks of traffic-related contaminants in high-altitude areas.

Occurrence, spatial distribution, and sources of PFASs in the water and sediment from lakes in the Tibetan Plateau.

Per-and polyfluoroalkyl substances (PFASs) are omnipresent globally and received increasing attention recently. However, there are limited data on PFASs in the Tibetan Plateau (TP), a remote high-altitude mountain region, which is regard as an important indicator region to study long-range transport behaviors of contaminants. This study investigates the occurrence, distribution, partitioning behavior, and sources of 26 PFASs in water and sediments from the four lakes of TP. The ΣPFAS concentrations ranged from 338 to 9766 pg L-1 in water, and 12.2-414 pg g-1 dry weight in sediments. Perfluorobutanonic acid (PFBA) and perfluorooctane sulfonate (PFOS) were detected in all samples. Qinghai Lake had the highest ΣPFAS concentrations in both water and sediments, while the Ranwu Lake had the lowest. The functional groups and CF2 moiety units were investigated as essential factors influencing the partition behavior. Principal component analysis (PCA) combined back-trajectory was used to infer possible sources of PFASs. The results suggested that the main source of PFASs in Yamdrok Lake, Namco Lake, and Ranwu Lake on southern TP were mainly originated from South Asia via long-range atmospheric transport (LRAT); while for the Qinghai Lake of northern TP, LRAT, local emissions, and tourism activities were the primary sources of PFASs.

Legacy and emerging organic contaminants in the polar regions.

The presence of numerous emerging organic contaminants (EOCs) and remobilization of legacy persistent organic pollutants (POPs) in polar regions have become significant concerns of the scientific communities, public groups and stakeholders. This work reviews the occurrences of EOCs and POPs and their long-range environmental transport (LRET) processes via atmosphere and ocean currents from continental sources to polar regions. Concentrations of classic POPs have been systematically monitored in air at several Arctic stations and showed seasonal variations and declining trends. These chemicals were also the major POPs reported in the Antarctica, while their concentrations were lower than those in the Arctic, illustrating the combination of remoteness and lack of potential local sources for the Antarctica. EOCs were investigated in air, water, snow, ice and organisms in the Arctic. Data in the Antarctica are rare. Reemission of legacy POPs and EOCs accumulated in glaciers, sea ice and snow may alter the concentrations and amplify their effects in polar regions. Thus, future research will need to understand the various biogeochemical and geophysical processes under climate change and anthropogenic pressures.

Positive Sentiment and the Donation Amount: Social Norms in Crowdfunding Donations During the COVID-19 Pandemic.

Public welfare fundraising has been used to collect donations for medical supplies and has played an important role in the fight against the COVID-19 pandemic. This paper studies online crowdfunding donations from the Alumni Association of Wuhan University to North American alumni; donation data are used to investigate how individuals' donation behavior is affected by the previous donation amount and information provided by the fundraising platform. First, our results show that one's donation amount is positively affected by the previous donation amount. Second, the donor's positive sentiment in the message that he or she leaves, as measured by either natural language processing or a manual rating, can affect the subsequent anonymity and messages but not the subsequent donation amount. Third, anonymous donations are much smaller than non-anonymous donations.

2,2'-((1R,3R,4S)-4-methyl-4-vinylcyclohexane-1,3-diyl) bis(prop-2-en-1-amine), a bisamino derivative of ß-Elemene, inhibits glioblastoma growth through downregulation of YAP signaling.

ß-Elemene, a compound extracted from Chinese herb Curcuma wenyujin, has been demonstrated with antitumor effects in various cancers, including glioblastoma (GBM), a primary brain tumor with high morbidity and mortality. In this study, we reported a bisamino derivative of ß-Elemene, 2, 2'-((1R, 3R, 4S)-4-methyl-4-vinylcyclohexane-1, 3-diyl) bis(prop-2-en-1-amine) (compound 1), displayed a better anti-GBM effect than ß-Elemene with lower concentration. GBM cell lines (C6 and U87) were treated with compound 1 and subsequently analyzed by several assays. Compound 1 significantly inhibited the migration of C6 and U87 cells based on wound healing assay, transwell assay and inverted migration assay. Furthermore, colony formation assay, immunostaining and flow cytometry assays revealed that compound 1 significantly inhibited the proliferation of GBM cells. In addition, compound 1 induced the apoptosis of GBM cells. Mechanistically, we found Yes-associated protein (YAP) was down-regulated in compound 1-treated GBM cells, and the overexpression of YAP partially rescued the anti-GBM effects of compound 1. Finally, compound 1 suppresses the GBM growth in xenograft model through inactivation YAP signaling. Taken together, these results reveal that a novel derivative of ß-Elemene, compound 1, exhibits more potent anti-GBM activity than ß-Elemene through inactivating YAP signaling pathway, which will provide novel strategies for the treatment of GBM.

How the onset of the Covid-19 pandemic impacted pro-social behaviour and individual preferences: Experimental evidence from China.

We present experimental evidence on how pro-sociality, trust and attitudes towards risk and ambiguity evolved over the six weeks following the imposition of stringent Covid-19 related lockdown measures in the Hubei province of China. We compare incentivized economic decision-making in a baseline sample, collected pre-epidemic, with a series of repeated cross-sectional samples drawn from the same population between January and March, 2020. We find high rates of altruism, cooperation and aversion to risk taking under ambiguity in the immediate aftermath of the lockdown, while trust is significantly below its baseline level. Risk attitudes also differ in the post-lockdown sample, with decreased risk tolerance in the loss domain and lesser risk aversion in the gain domain. We further uncover significant transitory effects for trust and risk aversion around the date of a high-profile whistleblower's death from Covid-19. Our findings suggest that the onset of a public health crisis may have unintended consequences for economic preferences that determine population compliance with interventions designed to reduce the spread of a novel coronavirus.

Recombinant protein TRAIL-Mu3 enhances the antitumor effects in pancreatic cancer cells by strengthening the apoptotic signaling pathway.

Pancreatic cancer is a highly malignant type of cancer and its treatment remains a major challenge. The novel recombinant protein TNF-related apoptosis-inducing ligand (TRAIL)-Mu3 has been shown to exert stronger tumor inhibitory effects in colon cancer in vitro and in vivo compared with TRAIL. The present study investigated the antitumor effects of TRAIL-Mu3 on pancreatic cancer cells, and the possible mechanisms were further examined. Compared with TRAIL, TRAIL-Mu3 exhibited significantly higher cytotoxic effects on pancreatic cancer cell lines. The inhibitory effect of TRAIL-Mu3 on the viability of PANC-1 cells was shown to be a caspase-dependent process. The affinity of TRAIL-Mu3 to PANC-1 cell membranes was significantly enhanced compared with TRAIL. In addition, TRAIL-Mu3 upregulated death receptor (DR) expression in PANC-1 cells and promoted the redistribution of DR5 in lipid rafts. Western blotting results demonstrated that TRAIL-Mu3 activated the caspase cascade in a faster and more efficient manner compared with TRAIL in PANC-1 cells. Therefore, TRAIL-Mu3 enhanced the antitumor effects in pancreatic cancer cells by strengthening the apoptotic signaling pathway. The present study indicated the potential of TRAIL-Mu3 for the treatment of pancreatic cancer.

A novel TRAIL mutant-TRAIL-Mu3 enhances the antitumor effects by the increased affinity and the up-expression of DR5 in pancreatic cancer.

PURPOSE: Pancreatic cancer is a malignant tumor of the digestive system with poor prognosis and high mortality, and the treatment of pancreatic cancer still remains a major challenge. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis selectively in cancer cells while causing virtually no damage to normal cells, which is promising for cancer therapy. However, many primary tumors and cancer cell lines including various human pancreatic cancer cell lines were found to be resistant to TRAIL-induced apoptosis. Therefore, the purpose of the study was to improve antitumor effect of TRAIL on pancreatic cancer. METHODS: The 114-121 amino acid coding sequence "VRERGPQR" of wild type TRAIL protein that was selected changed into "RRRRRRRR", and the novel membrane-penetrating peptide-alike mutant protein was named TRAIL-Mu3. The antitumor effect of TRAIL-Mu3 was analyzed both in vitro and in vivo. Western blotting, immunofluorescence and flow cytometry were used to investigate the underlying mechanisms. RESULTS: TRAIL-Mu3 could enhance the antitumor effects on pancreatic cancer cell lines, and the antitumor effect of TRAIL-Mu3 was stronger than gemcitabine in vivo. The immunofluorescence results suggested that TRAIL-Mu3 could remarkably enhance the affinity to pancreatic cancer cells. The Western blot results showed that treatment with TRAIL-Mu3 caused a clear cleavage of caspase-3 and caspase-8. In addition, both the Western blot and flow cytometry suggested a significantly up-expression of DR5 in TRAIL-Mu3 group. CONCLUSIONS: Membrane-penetrating peptide-alike mutant-TRAIL-Mu3 induced pancreatic cancer cell death more efficiently than TRAIL, and this effect was supposed to be mediated by the increased affinity to cell membrane, the up-regulation of DR5 and the enhancement of activated caspase.

TRAIL mutant membrane penetrating peptide alike (TMPPA) TRAIL­Mu3 enhances the antitumor effects of TRAIL in vitro and in vivo.

The aim of the present study was to prepare a tumor necrosis factor ligand superfamily member 10 (TRAIL) mutant membrane penetrating peptide alike (TMPPA), TRAIL­Mu3, and to investigate its antitumor effects in colorectal cancer in vitro and in vivo. The pMD19/TRAIL plasmid with designed primers was amplified to construct the target gene; it was ligated with an expression plasmid and the expression was confirmed. Subsequently, TRAIL­Mu3 was purified and further confirmed by western blot analysis. Immunofluorescence analysis was used to detect the distribution of TRAIL­Mu3 in colorectal cancer cells. In addition, the present study investigated the antitumor effects of TRAIL­Mu3 on colorectal cancer in vitro and in vivo. A novel TMPPA, TRAIL­Mu3, was synthesized in the present study. Following a series of detection experiments, it was confirmed that the TRAIL­Mu3 gene was obtained and was able to express TRAIL­Mu3 successfully. The immunofluorescence analysis demonstrated that TRAIL­Mu3 exhibited a markedly enhanced affinity to the colorectal cancer cell surface. In addition, TRAIL­Mu3 exerted stronger antitumor effects, compared with TRAIL, on colorectal cancer in vitro and in vivo.

Generation of a novel TRAIL mutant by proline to arginine substitution based on codon bias and its antitumor effects.

TNF ligand superfamily member 10 (TRAIL) is a member of the tumor necrosis factor superfamily. The present study was performed in an effort to increase the expression of soluble (s)TRAIL by rebuilding the gene sequence of TRAIL. Three principles based on the codon bias of Escherichia coli were put forward to design the rebuild strategy. Relying on these three principles, a P7R mutation near the N­terminal region of sTRAIL, named TRAIL­Mu, was designed. TRAIL­Mu was subsequently cloned into the PTWIN1 plasmid and expressed in E. coli BL21 (DE3). Using a high­level expression system and a three­step purification method, soluble TRAIL­Mu protein reached ~90% of total cellular protein and purity was >95%, demonstrating success in overcoming inclusion body formation. The cytotoxic effect of TRAIL­Mu was evaluated by sulforhodamine B assay in the MD­MB­231, A549, NCI­H460 and L02 cell lines. The results demonstrated that TRAIL­Mu exerted stronger antitumor effects on TRAIL­sensitive tumor cell lines, and was able to partially reverse the resistance of a TRAIL­resistant tumor cell line. In addition, TRAIL­Mu exhibited no notable biological effects in a normal liver cell line. The novel TRAIL variant generated in the present study may be useful for the mass production of this important protein for therapeutic purposes.