Mechanisms of Innate Immunity in Polymicrobial Sepsis

Severe bacterial sepsis leads to a pro-inflammatory condition that can manifest as septic shock, multiple organ failure, and death. Neutrophils are critical for the rapid elimination of bacteria, however, the role of neutrophil chemoattractant CXCL1, pattern recognition receptors (PRRs)- NLR protein 3 (NLRP3) and alcohol in bacterial clearance during sepsis remains elusive. We demonstrate that CXCL1 plays a pivotal role in mediating host defense to polymicrobial sepsis following cecal ligation and puncture (CLP) in gene-deficient mice. CXCL1 appears to be essential for restricting bacterial outgrowth and preventing multiple organ failure and death in mice. Moreover, CXCL1 is essential for neutrophil migration, expression of pro-inflammatory mediators, Recombinant interleukin 17 (IL-17) rescued impaired host defenses in cxcl1−/− mice. CXCL1 is important for IL-17A production via Th17 differentiation. CXCL1 is essential for reactive oxygen species production and neutrophil extracellular trap (NET) formation. This study reveals a novel role for CXCL1 in neutrophil recruitment via modulating T cell function and neutrophil-related bactericidal functions. These studies suggest that modulation of CXCL1 levels could reduce bacterial burden and excessive inflammatory injury in sepsis. NLRP3-/- mice or mice treated with NLRP3 inhibitor were protected in response to polymicrobial sepsis. NLRP3-/- mice showed reduced bacterial burden and production of proinflammatory cytokines. Intriguingly, neutrophils obtained from NLRP3-/- or NLRP3-inhibited mice display impaired critical functions of neutrophils, including phagocytosis, bacterial killing, NET formation, autophagy, chemotaxis, and cell death. These unique and novel findings position NLRP3 as a critical linker between neutrophil function and bacterial clearance, highlighting NLRP3 as a therapeutic target to control infection in polymicrobial sepsis. Alcoholics are more susceptible to bacterial sepsis and thus have higher mortality rate as compared to non-alcoholics. In this study, acute alcohol intoxication prior to the induction of polymicrobial sepsis show reduced NETosis. Diminished NETosis was consistent with attenuated ROS production and bacterial clearance in alcohol-challenged CLP-induced mice. Our findings demonstrate that alcohol-suppressed NETosis and NET-mediated extracellular killing of bacteria contribute to the pathogenesis of polymicrobial sepsis, and thus, furthers our understanding on alcohol-induced immune defect during bacterial infection

End-to-End Photo-Sketch Generation via Fully Convolutional Representation Learning

Sketch-based face recognition is an interesting task in vision and multimedia research, yet it is quite challenging due to the great difference between face photos and sketches. In this paper, we propose a novel approach for photo-sketch generation, aiming to automatically transform face photos into detail-preserving personal sketches. Unlike the traditional models synthesizing sketches based on a dictionary of exemplars, we develop a fully convolutional network to learn the end-to-end photo-sketch mapping. Our approach takes whole face photos as inputs and directly generates the corresponding sketch images with efficient inference and learning, in which the architecture are stacked by only convolutional kernels of very small sizes. To well capture the person identity during the photo-sketch transformation, we define our optimization objective in the form of joint generative-discriminative minimization. In particular, a discriminative regularization term is incorporated into the photo-sketch generation, enhancing the discriminability of the generated person sketches against other individuals. Extensive experiments on several standard benchmarks suggest that our approach outperforms other state-of-the-art methods in both photo-sketch generation and face sketch verification.Comment: 8 pages, 6 figures. Proceeding in ACM International Conference on Multimedia Retrieval (ICMR), 201

What is the trend after Covid-19? A Political-Economic Analysis of the Pension Systems in Hong Kong and MACAU

The aging trend of the population in Hong Kong and Macau is evident, so the pension system is especially significant. This research paper uses document analysis and a double-case study as the research method. It uses path dependence and critical moments in historical institutionalism theory as the theoretical tools for political economy analysis. The discussion argues that “the social culture shaped by local politics,” “the combination of local economic development and economic structure,” and “influence from social structure” are the three main factors that influence the pension systems in Hong Kong and Macau, and are the fundamental reasons for the differences between the pension systems in Hong Kong and Macau. We also conclude that the outbreak of COVID-19 is causing the evolution of the pension systems in both regions to be converging.JEL Classification: H7, N9, O2, R5How to Cite:Guo, S., You, L., & Wang, Q. (2023). What is the Trend after Covid-19? A Political-Economic Analysis of the Pension Systems in Hongkong and Macau. Etikonomi, 22(1), 155–174. https://doi.org/10.15408/etk.v22i1.23737

Discrimination experiment of sound distance perception for a real source in near-field

International audienceThe ability of distance perception is quite important for our daily life. For the backward region where the vision cannot cover, listeners perceive objects only via binaural hearing, and the distance perception for a backward sound source is very important. It helps listeners to perceive an approaching sound source and avoid dangerous object especially when the sound source is in the rear. In the free field, the main acoustic distance perception cues for a nearby sound source include intensity variation with distance, binaural cues, dynamic cues, spectrum change and direct-to-reverberant energy ratio (Pavel Zahorik, 2005). Theoretically, all the above mentioned cues can be simulated via virtual auditory display (VAD), and realized by using a real sound source in an anechoic chamber. In comparison, the results based on a real sound source measurement should be more accurate. Previous researches have proved that the sound pressure has a giant influence on the ability of distance discrimination in both near field and far field when source is in front of head (Daniel H. Ashmead, 1990). However, few researches attempt to examine the binaural effect alone in distance perception. The theory was based on a fact that both the sound intensities and spectrums of a nearby sound will be different in two ears due to the head shadow, and these differences will change with distance when the sound source is lateral (PAUL D. COLEMAN, 1963). To verify the impact of binaural effect to distance discrimination, we conducted an experiment to exam the backward sound distance perception thresholds when the sound is presented from different azimuths in the horizontal plane. We used an automatic test system controlled by a computer in an anechoic room, eight listeners participated in the test. A loudness balanced band noise was used as test signals to remove the influence of sound level, and the signal was presented in 75 dBA. One signal was presented in the reference distance (50cm or 100cm), while the other one was presented in a closer distance, and sequence is random. The subjects need to do 2IFC (choose the closer one) between the signals presented in two different distances, and no feedback was given to subjects.The discrimination thresholds of two reference distances (0.5m and 1m) and five source azimuth (0°, 45°, 90°, 135°, 180°, right half plane of head) were examined in the experiment. The result show that subjects distance discrimination thresholds are lower when the sound source is on the side of head (about 20%) compared with front and back (above 30%), distinguishing two signals become quite difficult for participants when signals are presented in azimuth 0° and 180°. Moreover, this phenomenon is more prominent in 50cm compared with 100cm, while the effect of head shadow is more significant in 50cm. The results obtained in this study are consistent with previous studies and reveal that the binaural effect indeed contributes to distance discrimination process of human in a degree. This work is supported by the National Natural Science Foundation of China (Grant No. 11574090) and the Natural Science Foundation of Guangdong Province (Grant No. 2018B030311025)