BackgroundInflammation is a highly complex biological response evoked by many stimuli. A persistent challenge in modeling this dynamic process has been the (nonlinear) nature of the response that precludes the single-variable assumption. Systems-based approaches offer a promising possibility for understanding inflammation in its homeostatic context. In order to study the underlying complexity of the acute inflammatory response, an agent-based framework is developed that models the emerging host response as the outcome of orchestrated interactions associated with intricate signaling cascades and intercellular immune system interactions.Methodology/Principal FindingsAn agent-based modeling (ABM) framework is proposed to study the nonlinear dynamics of acute human inflammation. The model is implemented using NetLogo software. Interacting agents involve either inflammation-specific molecules or cells essential for the propagation of the inflammatory reaction across the system. Spatial orientation of molecule interactions involved in signaling cascades coupled with the cellular heterogeneity are further taken into account. The proposed in silico model is evaluated through its ability to successfully reproduce a self-limited inflammatory response as well as a series of scenarios indicative of the nonlinear dynamics of the response. Such scenarios involve either a persistent (non)infectious response or innate immune tolerance and potentiation effects followed by perturbations in intracellular signaling molecules and cascades.Conclusions/SignificanceThe ABM framework developed in this study provides insight on the stochastic interactions of the mediators involved in the propagation of endotoxin signaling at the cellular response level. The simulation results are in accordance with our prior research effort associated with the development of deterministic human inflammation models that include transcriptional dynamics, signaling, and physiological components. The hypothetical scenarios explored in this study would potentially improve our understanding of how manipulating the behavior of the molecular species could manifest into emergent behavior of the overall system.

Melanoma is the most dangerous type of skin cancer with high lethal rate. Tumor thickness and tumor-associated vasculature are two key parameters for staging melanoma. Previous techniques for diagnosing melanoma have insurmountable restrictions, such as invasive, low specificity, or inaccurate depth measurement. Here we develop an integrated photoacoustic (PA) and ultrasound (US) imaging system dedicated to overcome these limitations. An integrated detector with sound-light coaxial/confocal design and flexible coupling mode is employed for the combined PA/US imaging strategy. PA imaging results enable a clear characterization of tumor angiogenesis with high resolution and high contrast. Furthermore, accurate thickness measurements of melanoma in different stages can be resolved with the simultaneously obtained PA/US image. Phantom experiments and in vivo animal experimental results demonstrate the integrated PA/US system could provide potential for noninvasive biopsy of melanoma.

We proposed and developed a photoacoustic (PA) dermoscope equipped with an integrated PA probe to achieve quantification and high-resolution, high-contrast deep imaging of human skin. The PA probe, with light-sound confocal excitation and reception, is specially designed, and integrated with an objective lens, an ultrasound transducer, and an inverted-triangle coupling cup to facilitate convenient implementation in a clinical setting. The PA dermoscope was utilized for noninvasive and high-resolution imaging of epidermal and dermal structure in volunteers. The imaging results demonstrated that the characteristic parameters of skin disease, including pigment distribution and thickness, vascular diameter, and depth, can be obtained by the PA dermoscope, confirming that PA dermoscopy can serve as a potential tool for the diagnosis and curative effect evaluation of human skin disease.

The Mariana Trench is the deepest part of Earth's surface, with a maximum depth of close to 11,000 m in the Challenger Deep. Great progress has been made in studying the trench in the past years; however, several basic issues regarding the sedimentology and geochronology of the abyssal surficial sediments in the trench remain unclear. In this study, two gravity cores of Plio‐Pleistocene sediments were retrieved from the southern slope of the Mariana Trench. They were used for an integrated investigation of magnetostratigraphy, authigenic 10Be/9Be dating, and element manganese content. The principal results are as follows. (1) Ten magnetozones are recognized for Core A25, which can be correlated to the geomagnetic polarity time scale from Chrons C1n to C3r. (2) The paleomagnetic and 10Be/9Be‐based ages agree well for both of the two cores, yielding a continuous depositional hiatus since the middle Pleistocene (0.63–0.74 Ma). (3) The sediment accumulation rates prior to ~1.3 Ma are 35–83 cm/Myr and then increased substantially to 167–200 cm/Myr. Based on these results, a sedimentary transition at ~1.3–1.2 Ma is confirmed, which can be potentially correlated to climatic, oceanic, and tectonic changes in the Mid‐Pleistocene transition. In addition, an elemental Mn proxy is derived to reflect changes in bottom‐water ventilation, which is consistent with Lower Circumpolar Deep Water and North Atlantic Deep Water on glacial‐interglacial time scales. We conclude that the sedimentary record of the Mariana Trench provides a unique window for investigating the integrated effects of long‐term climatic, oceanic, and tectonic processes.