Alcohol intake and mortality risk of COVID-19, pneumonia, and other infectious diseases: An analysis of 437191 UK biobank participants

This study aims to investigate the association between alcohol consumption and COVID-19, infectious diseases, and pneumonia mortality. This is a prospective analysis of 437,191 UK Biobank participants (age 56.3 years, 54% female). The main exposure was self-reported alcohol consumption. In addition to never and previous drinkers, we applied quartiles-based and UK guidelines-based criteria to divide current drinkers by weekly consumption into four groups. Outcomes included COVID-19, infectious diseases, and pneumonia mortality, obtained from the national death registries until May 2020. After an 11-year follow-up, compared to never drinkers, previous drinkers had higher mortality risks of infectious diseases and pneumonia (adjusted HR: 1.29 [95% CI 1.06–1.57] and 1.35 [1.07–1.70], respectively), but not COVID-19. There was a curvilinear association of alcohol consumption with infectious diseases and pneumonia mortality. Drinking within-guidelines (<14 UK units/wk) and amounts up to double the recommendation (14 to < 28 UK units/wk) was associated with the lowest mortality risks of infectious diseases (0.70 [0.59–0.83] and 0.70 [0.59–0.83], respectively) and pneumonia (0.71 [0.58–0.87] and 0.72 [0.58–0.88], respectively). Alcohol consumption was associated with lower risks of COVID-19 mortality (e.g., drinking within-guidelines: 0.53 [0.33–0.86]). Drinkers reporting multiples of the recommended alcohol drinking amounts did not have higher mortality risks of COVID-19 and other infectious diseases than never drinkers. Despite the well-established unfavorable effects on general health, we found no deleterious associations between alcohol consumption and the risk of infectious diseases, including COVID-19. Future research with other study designs is needed to confirm the causality

Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer

Increased numbers of myeloid-derived suppressor cells (MDSCs) are positively correlated with poor prognosis and reduced survivals of cancer patients. They play central roles in tumor immune evasion and tumor metastasis. However, limited data are available on phenotypic/transcriptomic characteristics of the different MDSCs subsets in cancer. These cells include immature (I-MDSCs), monocytic (M-MDSCs), and polymorphonuclear/granulocytic (PMN-MDSCs). Phenotypic characterization of myeloid subsets from 27 colorectal cancer (CRC) patients was assessed by flow cytometric analyses. RNA-sequencing of sorted I-MDSCs, PMN-MDSCs, and antigen-presenting cells (APCs) was also performed. We found that the levels of I-MDSCs and PMN-MDSCs were increased in tumor tissues (TT), compared with normal tissues (NT) in colorectal cancer. Our functional annotation analyses showed that genes associated with histone deacetylase (HDAC) activation- and DNA methylation-mediated transcriptional silencing were upregulated, and histone acetyl transferase (HAT)-related genes were downregulated in tumor-infiltrating I-MDSCs. Moreover, pathways implicated in cell trafficking and immune suppression, including Wnt, interleukin-6 (IL-6), and mitogen-activated protein kinase (MAPK) signaling, were upregulated in I-MDSCs. Notably, PMN-MDSCs showed downregulation in genes related to DNA methylation and HDAC binding. Using an ex vivo model, we found that inhibition of HDAC activation or neutralization of IL-6 in CRC tumor tissues downregulates the expression of genes associated with immunosuppression and myeloid cell chemotaxis, confirming the importance of HDAC activation and IL-6 signaling pathway in MDSC function and chemotaxis. This study provides novel insights into the epigenetic regulations and other molecular pathways in different myeloid cell subsets within the CRC tumor microenvironment (TME), giving opportunities to potential targets for therapeutic benefits

Transcriptomic profiling of tumor-infiltrating CD4 + TIM-3 + T Cells reveals their suppressive, exhausted, and metastatic characteristics in colorectal cancer patients

T cell immunoglobulin mucin-3 (TIM-3) is an immune checkpoint identified as one of the key players in regulating T-cell responses. Studies have shown that TIM-3 is upregulated in the tumor microenvironment (TME). However, the precise role of TIM-3 in colorectal cancer (CRC) TME is yet to be elucidated. We performed phenotypic and molecular characterization of TIM-3+ T cells in the TME and circulation of CRC patients by analyzing tumor tissues (TT, TILs), normal tissues (NT, NILs), and peripheral blood mononuclear cells (PBMC). TIM-3 was upregulated on both CD4+ and CD3+CD4− (CD8+) TILs. CD4+TIM-3+ TILs expressed higher levels of T regulatory cell (Tregs)-signature genes, including FoxP3 and Helios, compared with their TIM-3− counterparts. Transcriptomic and ingenuity pathway analyses showed that TIM-3 potentially activates inflammatory and tumor metastatic pathways. Moreover, NF-κB-mediated transcription factors were upregulated in CD4+TIM-3+ TILs, which could favor proliferation/invasion and induce inflammatory and T-cell exhaustion pathways. In addition, we found that CD4+TIM-3+ TILs potentially support tumor invasion and metastasis, compared with conventional CD4+CD25+ Tregs in the CRC TME. However, functional studies are warranted to support these findings. In conclusion, this study discloses some of the functional pathways of TIM-3+ TILs, which could improve their targeting in more specific therapeutic approaches in CRC patients

Evaluation of Dynamic Cell Processes and Behavior Using Video Bioinformatics Tools

Just as body language can reveal a person’s state of well-being, dynamic changes in cell behavior and morphology can be used to monitor processes in cultured cells. This chapter discusses how CL-Quant software, a commercially available video bioinformatics tool, can be used to extract quantitative data on: (1) growth/proliferation, (2) cell and colony migration, (3) reactive oxygen species (ROS) production, and (4) neural differentiation. Protocols created using CL-Quant were used to analyze both single cells and colonies. Time-lapse experiments in which different cell types were subjected to various chemical exposures were done using Nikon BioStations. Proliferation rate was measured in human embryonic stem cell colonies by quantifying colony area (pixels) and in single cells by measuring confluency (pixels). Colony and single cell migration were studied by measuring total displacement (distance between the starting and ending points) and total distance traveled by the colonies/cells. To quantify ROS production, cells were pre-loaded with MitoSOX Red™, a mitochondrial ROS (superoxide) indicator, treated with various chemicals, then total intensity of the red fluorescence was measured in each frame. Lastly, neural stem cells were incubated in differentiation medium for 12 days, and time lapse images were collected daily. Differentiation of neural stem cells was quantified using a protocol that detects young neurons. CLQuant software can be used to evaluate biological processes in living cells, and the protocols developed in this project can be applied to basic research and toxicological studies, or to monitor quality control in culture facilities

The ‘credibility paradox’ in China’s science communication: Views from scientific practitioners

In contrast to increasing debates on China’s rising status as a global scientific power, issues of China’s science communication remain under-explored. Based on 21 in-depth interviews in three cities, this article examines Chinese scientists’ accounts of the entangled web of influence which conditions the process of how scientific knowledge achieves (or fails to achieve) its civic authority. A main finding of this study is a ‘credibility paradox’ as a result of the over-politicisation of science and science communication in China. Respondents report that an absence of visible institutional endorsements renders them more public credibility and better communication outcomes. Thus, instead of exploiting formal channels of science communication, scientists interviewed were more keen to act as ‘informal risk communicators’ in grassroots and private events. Chinese scientists’ perspectives on how to earn public support of their research sheds light on the nature and impact of a ‘civic epistemology’ in an authoritarian state

The role of the ubiquitination-proteasome pathway in breast cancer: Applying drugs that affect the ubiquitin-proteasome pathway to the therapy of breast cancer

The ubiquitin-proteasome pathway is responsible for most eukaryotic intracellular protein degradation. This pathway has been validated as a target for antineoplastic therapy using both in vitro and preclinical models of human malignancies, and is influenced as part of the mechanism of action of certain chemotherapeutic agents. Drugs whose primary action involves modulation of ubiquitin-proteasome activity, most notably the proteasome inhibitor PS-341, are currently being evaluated in clinical trials, and have already been found to have significant antitumor efficacy. On the basis of the known mechanisms by which these agents work, and the available clinical data, they would seem to be well suited for the treatment of breast neoplasms. Such drugs, alone and especially in combination with current chemotherapeutics, may well represent important advances in the therapy of patients with breast cancer

Anatomical and Physiological Plasticity in Leymus chinensis (Poaceae) along Large-Scale Longitudinal Gradient in Northeast China

Although it has been widely accepted that global changes will pose the most important constrains to plant survival and distribution, our knowledge of the adaptive mechanism for plant with large-scale environmental changes (e.g. drought and high temperature) remains limited.An experiment was conducted to examine anatomical and physiological plasticity in Leymus chinensis along a large-scale geographical gradient from 115° to 124°E in northeast China. Ten sites selected for plant sampling at the gradient have approximately theoretical radiation, but differ in precipitation and elevation. The significantly increasing in leaf thickness, leaf mass per area, vessel and vascular diameters, and decreasing in stoma density and stoma index exhibited more obvious xerophil-liked traits for the species from the moist meadow grassland sites in contrast to that from the dry steppe and desert sites. Significant increase in proline and soluble sugar accumulation, K(+)/Na(+) for the species with the increasing of stresses along the gradient showed that osmotic adjustment was enhanced.Obvious xerophytic anatomical traits and stronger osmotic adjustment in stress conditions suggested that the plants have much more anatomical and physiological flexibilities than those in non-stress habitats along the large-scale gradient