The chronology of the SARS outbreak.

<p>From <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1000266#pmed.1000266-World1" target="_blank">[39]</a>.</p

Number of Chinese journal articles per year on non-traditional security issues since 1979.

<p>Number of Chinese journal articles per year on non-traditional security issues since 1979.</p

Learning impairment in naïve rats after intra-hippocampal cycloheximide.

<p>Intra-hippocampal cycloheximide injection (not saline) disrupted the established spatial learning (<b>A</b>: before the injection) in a parallel group of rats without ankle inflammation, as shown in two separate series of the Morris water maze test (<b>B</b>: post-injection day 1-5 and <b>C</b>: post-injection day 15-19). *P< 0.05, as compared with the intra-hippocampal vehicle group.</p

Expression of ChAT in the hippocampus, thalamus, and amygdala.

<p><b>A</b>) ChAT immunoreactivity was decreased in the hippocampus contralateral to ankle inflammation in Aβ group as compared with both naïve and ACSF groups with or without ankle inflammation. Veh: Vehicle. Scale bar: 100 µm. <b>B</b>, <b>C</b>) Western blot showed a substantial downregulation of ChAT expression in the contralateral hippocampus, thalamus, and amygdala of rats in Aβ group with ankle inflammation. * <i>P</i><0.05, as compared with Aβ/vehicle and Aβ/CFA groups; # <i>P</i><0.05, as compared with the ASCF/vehicle group.</p

Expression of NR1 in brain regions.

<p><b>A</b>–<b>C</b>) Immunostaining (A) and Western blot (B, C) showed an upregulation of NR1 on the ipsilateral side (to ankle inflammation) of the hippocampus in rats with the intra-hippocampal Aβ injection. Scale bar: 100 µm. <b>B</b>, <b>C</b>) In these same Aβ-injected rats, NR1 expression was downregulated in the ipsilateral thalamus but not amygdala. * <i>P</i><0.05 and ** <i>P</i><0.01, as compared with the naïve and ACSF group on the same (ipsilateral) side.</p

A schematic presentation of experimental designs.

<p><b>A)</b> Experiment 1 examined the effect of intra-hippocampal Aβ-induced learning impairment on the development of nociceptive behavior following ankle inflammation. <b>B</b>) Experiment 2 examined the effect of intra-hippocampal cycloheximide on the recovery of established nociceptive behavior following ankle inflammation. </p

Morris water maze test and hippocampal Aβ expression.

<p><b>A)</b> No differences were detected among three groups of rats in the hidden-platform test on day 1 and day 2. However, rats in Aβ group showed a longer escape latency than rats in ACSF group on days 3-5 and rats in naïve group on day 4-5. ** <i>P</i><0.01, as compared with ACSF group; # <i>P</i><0.01, as compared with both naïve and ACSF groups. In contrast, no differences in the escape time in visible-platform test on day 7 and 8. <b>B)</b> Immunohistochemical examination of the hippocampal CA1 area showed a substantially increased reactivity of Aβ1-40/1-42 in Aβ group, whereas Aβ immunoreactivity was barely detectable in rats of naïve and ACSF groups at the same hippocampal site. Scale bar: 100 µm. <b>C)</b> Western blot revealed a significant increase in Aβ expression in hippocampus contralateral to ankle inflammation in rats receiving Aβ injection with or without ankle inflammation. * <i>P</i><0.05, as compared with contralateral (contra) side of other groups; #<i>P<</i>0.05, as compared with ipsilateral (ipsi) side of remaining groups.</p

Attenuated nociceptive behavior in rats with learning impairment.

<p><b>A</b>, <b>C</b>) The development of thermal hyperalgesia (A) and mechanical allodynia (C) was attenuated in Aβ-injected rats. <b>B</b>, <b>D</b>) No differences were detected in thermal (B) and mechanical (D) nociceptive threshold on contralateral hind paw in all groups. * <i>P</i><0.05, ** <i>P</i><0.01, as compared with baseline threshold of the same group. FWL: foot-withdrawal latency. #<0.05, # # <i>P</i><0.01, as compared with each of the remaining groups at the same time point.</p

Systems Engineering Approach to Modeling and Analysis of Chronic Obstructive Pulmonary Disease Part II: Extension for Variable Metabolic Rates

Recently, we developed a systems engineering model of the human cardiorespiratory system [Kurian et al. ACS Omega 2023, 8 (23), 20524–20535. DOI: 10.1021/acsomega.3c00854] based on existing models of physiological processes and adapted it for chronic obstructive pulmonary disease (COPD)an inflammatory lung disease with multiple manifestations and one of the leading causes of death in the world. This control engineering-based model is extended here to allow for variable metabolic rates established at different levels of physical activity. This required several changes to the original model: the model of the controller was enhanced to include the feedforward loop that is responsible for cardiorespiratory control under varying metabolic rates (activity level, characterized as metabolic equivalent of the taskRmand normalized to one at rest). In addition, a few refinements were made to the cardiorespiratory mechanics, primarily to introduce physiological processes that were not modeled earlier but became important at high metabolic rates. The extended model is verified by analyzing the impact of exercise (Rm > 1) on the cardiorespiratory system of healthy individuals. We further formally justify our previously proposed adaptation of the model for COPD patients through sensitivity analysis and refine the parameter tuning through the use of a parallel tempering stochastic global optimization method. The extended model successfully replicates experimentally observed abnormalities in COPDthe drop in arterial oxygen tension and dynamic hyperinflation under high metabolic rateswithout being explicitly trained on any related data. It also supports the prospects of remote patient monitoring in COPD

Disruption of persistent nociceptive behavior by cycloheximide.

<p><b>A</b>, <b>C</b>) Thermal hyperalgesia (A) and mechanical allodynia (C) were developed on the ipsilateral hind paw of the rats with ankle inflammation when tested over a 5-day period (designated as day -1 to -5). The statistical significance (ANOVA, P< 0.05; compared to the baseline) was not marked in the figure for the first five days in order to simplify the presentation. Subsequently, rats treated with cycloheximide showed a swift recovery of both thermal hyperalgesia and mechanical allodynia beginning on day 1 after cycloheximide injection. <b>B</b>, <b>D</b>) No differences in the nociceptive threshold were detected between cycloheximide and vehicle groups on the contralateral hind paw of these same rats over the entire experimental period. * <i>P</i><0.05, ** <i>P</i><0.01, as compared with baseline threshold of the same group. #<i>P</i><0.05, # # P<0.01, as compared with the cycloheximide group at the same time point. FWL: foot-withdrawal latency. White arrow: injection of CFA into an ankle; Black arrows: injection of saline (1% DMSO in saline) or cycloheximide into the hippocampus.</p