Covid-19 impact on air quality in megacities

Air pollution is among the highest contributors to mortality worldwide, especially in urban areas. During spring 2020, many countries enacted social distancing measures in order to slow down the ongoing Covid-19 pandemic. A particularly drastic measure, the "lockdown", urged people to stay at home and thereby prevent new Covid-19 infections. In turn, it also reduced traffic and industrial activities. But how much did these lockdown measures improve air quality in large cities, and are there differences in how air quality was affected? Here, we analyse data from two megacities: London as an example for Europe and Delhi as an example for Asia. We consider data during and before the lockdown and compare these to a similar time period from 2019. Overall, we find a reduction in almost all air pollutants with intriguing differences between the two cities. In London, despite smaller average concentrations, we still observe high-pollutant states and an increased tendency towards extreme events (a higher kurtosis during lockdown). For Delhi, we observe a much stronger decrease of pollution concentrations, including high pollution states. These results could help to design rules to improve long-term air quality in megacities.Comment: 13 pages. Preliminary version of Supplementary Information and open code available here https://osf.io/jfw7n/?view_only=9b1d2320cf2c46a1ad890dff079a2f6

Fraudulent News Headline Detection with Attention Mechanism

E-mail systems and online social media platforms are ideal places for news dissemination, but a serious problem is the spread of fraudulent news headlines. The previous method of detecting fraudulent news headlines was mainly laborious manual review. While the total number of news headlines goes as high as 1.48 million, manual review becomes practically infeasible. For news headline text data, attention mechanism has powerful processing capability. In this paper, we propose the models based on LSTM and attention layer, which fit the context of news headlines efficiently and can detect fraudulent news headlines quickly and accurately. Based on multi-head attention mechanism eschewing recurrent unit and reducing sequential computation, we build Mini-Transformer Deep Learning model to further improve the classification performance

Increased polyphenols and antioxidant activity of rice bean (Vigna umbellata L.) sprouts induced by Methyl Jasmonate: the promotion effect of Methyl Jasmonate on rice bean sprouts

Abstract Rice bean (Vigna umbellata L.) sprouts are richer in metabolites and biological activities after germination. The total polyphenol and total flavonoid contents were analyzed during the sprouting process. The antioxidant activities of the sprouts were tested using 1,1-diphenyl-2- picrylhydrazyl radical (DPPH) screening assay. To determine the reason for increased activity, quantitative analysis of 8 flavonoids, in the germination process of methyl jasmonate (MeJA)-treated and control groups, was performed using high-performance liquid chromatography coupled with diode array detection (HPLC/DAD) and partial least squares discriminant analysis (PLS/DA). The metabolites in MeJA-treated beans shows that addition of 100.0 μmol MeJA significantly increased the total flavonoid and polyphenol contents during the sprouting process. DPPH screening assay and analytical results show that MeJA has a significant influence on the production of secondary metabolites in sprouts between the 4th and 6th days, thereby inducing increased antioxidant activity. Flavonoids rutin, kaempferol-3-O-rutinoside, daidzin, and genistin are further identified as the main contributors to the increased DPPH screening activity

Stimulated Parotid Saliva Is a Better Method for Depression Prediction

Background: Saliva cortisol is considered to be a biomarker of depression prediction. However, saliva collection methods can affect the saliva cortisol level. Objective: This study aims to determine the ideal saliva collection method and explore the application value of saliva cortisol in depression prediction. Methods: 30 depressed patients and 30 healthy controls were instructed to collect saliva samples in the morning with six collection methods. Simultaneous venous blood was collected. Enzyme-linked immunosorbent assay was used to determine the cortisol level. The 24-observerrated Hamilton depression rating scale (HAMD-24) was used to assess the severity of depression. Results: The significant differences in saliva cortisol levels depend on the saliva collection methods. The level of unstimulated whole saliva cortisol was most correlated with blood (r = 0.91). The stimulated parotid saliva cortisol can better predict depression. The area under the curve was 0.89. In addition, the saliva cortisol level of the depression patients was significantly higher than the healthy controls. The correlation between the cortisol level and the HAMD-24 score was highly significant. The higher the saliva cortisol level, the higher the HAMD-24 score. Conclusions: All the above findings point to an exciting opportunity for non-invasive monitoring of cortisol through saliva

Npro of classical swine fever virus enhances HMGB1 acetylation and its degradation by lysosomes to evade from HMGB1-mediated antiviral immunity

Classical swine fever virus (CSFV) can dampen the host innate immunity by destabilizing IRF3 upon its binding with viral Npro. High mobility group box 1 (HMGB1), a non-histone nuclear protein, has diverse functions, including inflammation, innate immunity, etc., which are closely related to its cellular localization. We investigated potential mutual interactions between CSFV and HMGB1 and their effects on virus replication. We found that HMGB1 at the protein level, but not at mRNA level, was markedly reduced in CSFV-infected or Npro-expressing IPEC-J2 cells. HMGB1 in the nuclear compartment is anti-CSFV by promoting IFN-mediated innate immune response, as evidenced by overexpression of nuclear or cytoplasmic dominant HMGB1 mutant in IPEC-J2 cells stimulated with poly(I:C). However, CSFV Npro upregulates HMGB1 acetylation, a modification that promotes HMGB1 translocation into the cytoplasmic compartment where it is degraded by lysosomes. Ethyl pyruvate could downregulate HMGB1 acetylation and prevent Npro-mediated HMGB1 reduction. Inhibition of deacetylase HDAC1 with MS275 or by RNA silencing could promote Npro-mediated HMGB1 degradation. Taken together, our study elucidates the mechanism with which HMGB1 in the nuclei initiates antiviral innate immune response to suppress CSFV replication and elaborates the pathway by which CSFV uses its Npro to evade from HMGB1-mediated antiviral immunity through upregulating HMGB1 acetylation with subsequent translocation into cytoplasm for lysosomal degradation

A Novel Small Molecular Prostaglandin Receptor EP4 Antagonist, L001, Suppresses Pancreatic Cancer Metastasis

Metastatic pancreatic cancer remains a major clinical challenge, emphasizing the urgent need for the exploitation of novel therapeutic approaches with superior response. In this study, we demonstrate that the aberrant activation of prostaglandin E2 (PGE2) receptor 4 (EP4) is a pro-metastatic signal in pancreatic cancer. To explore the therapeutic role of EP4 signaling, we developed a potent and selective EP4 antagonist L001 with single-nanomolar activity using a panel of cell functional assays. EP4 antagonism by L001 effectively repressed PGE2-elicited cell migration and the invasion of pancreatic cancer cells in a dose-dependent manner. Importantly, L001 alone or combined with the chemotherapy drug gemcitabine exhibited remarkably anti-metastasis activity in a pancreatic cancer hepatic metastasis model with excellent tolerability and safety. Mechanistically, EP4 blockade by L001 abrogated Yes-associated protein 1 (YAP)-driven pro-metastatic factor expression in pancreatic cancer cells. The suppression of YAP’s activity was also observed upon L001 treatment in vivo. Together, these findings support the notions that EP4–YAP signaling axis is a vital pro-metastatic pathway in pancreatic cancer and that EP4 inhibition with L001 may deliver a therapeutic benefit for patients with metastatic pancreatic cancer

Reprogramming immunosuppressive myeloid cells facilitates immunotherapy for colorectal cancer

Abstract Immune checkpoint blockade (ICB) has a limited effect on colorectal cancer, underlining the requirement of co‐targeting the complementary mechanisms. Here, we identified prostaglandin E2 (PGE2) receptor 4 (EP4) as the master regulator of immunosuppressive myeloid cells (IMCs), which are the major driver of resistance to ICB therapy. PGE2‐bound EP4 promotes the differentiation of immunosuppressive M2 macrophages and myeloid‐derived suppressor cells (MDSCs) and reduces the expansion of immunostimulated M1 macrophages. To explore the immunotherapeutic role of EP4 signaling, we developed a novel and selective EP4 antagonist TP‐16. TP‐16 effectively blocked the function of IMCs and enhanced cytotoxic T‐cell‐mediated tumor elimination in vivo. Cell co‐culture experiments revealed that TP‐16 promoted T‐cell proliferation, which was impaired by tumor‐derived CD11b+ myeloid cells. Notably, TP‐16 and anti‐PD‐1 combination therapy significantly impeded tumor progression and prolonged mice survival. We further demonstrated that TP‐16 increased responsiveness to anti‐PD‐1 therapy in an IMC‐related spontaneous colorectal cancer mouse model. In summary, this study demonstrates that inhibition of EP4‐expressing IMCs may offer a potential strategy for enhancing the efficacy of immunotherapy for colorectal cancer