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Gram-negative bacterial lipopolysaccharide (LPS) increases the susceptibility of cells to pathogenic diseases, including inflammatory diseases and septic syndrome. In our experiments, we examined whether LPS induces epithelial barrier disruption in secretory epithelia and further investigated its underlying mechanism. The activities of Ca2+-activated Cl− channels (CACC) and epithelial Na+ channels (ENaC) were monitored with a short-circuit current using an Ussing chamber. Epithelial membrane integrity was estimated via transepithelial electrical resistance and paracellular permeability assays. We found that the apical application of LPS evoked short-circuit current ( Isc) through the activation of CACC and ENaC. Although LPS disrupted epithelial barrier integrity, this was restored with the inhibition of CACC and ENaC, indicating the role of CACC and ENaC in the regulation of paracellular pathways. We confirmed that LPS, CACC, or ENaC activation evoked apical membrane depolarization. The exposure to a high-K+ buffer increased paracellular permeability. LPS induced the rapid redistribution of zonula occludens-1 (ZO-1) and reduced the expression levels of ZO-1 in tight junctions through apical membrane depolarization and tyrosine phosphorylation. However, the LPS-induced epithelial barrier disruption and degradation of ZO-1 were largely recovered by blocking CACC and ENaC. Furthermore, although LPS-impaired epithelial barrier became vulnerable to secondary bacterial infections, this vulnerability was prevented by inhibiting CACC and ENaC. We concluded that LPS induces the disruption of epithelial barrier integrity through the activation of CACC and ENaC, resulting in apical membrane depolarization and the subsequent tyrosine phosphorylation of ZO-1.

Actomyosin-mediated contractility is required for the majority of force-driven cellular events such as cell division, adhesion, and migration. Under pathological conditions, the role of actomyosin contractility in malignant phenotypes of various solid tumors has been extensively discussed, but the pathophysiological relevance in hematopoietic malignancies has yet to be elucidated. In this study, we found enhanced actomyosin contractility in diverse acute myeloid leukemia (AML) cell lines represented by highly expressed non-muscle myosin heavy chain A (NMIIA) and increased phosphorylation of the myosin regulatory light chain. Genetic and pharmacological inhibition of actomyosin contractility induced multivalent malignancy- suppressive effects in AML cells. In this context, perturbed actomyosin contractility enhances AML cell apoptosis through cytokinesis failure and aryl hydrocarbon receptor activation. Moreover, leukemic oncogenes were downregulated by the YAP/TAZ-mediated mechanotransduction pathway. Our results provide a theoretical background for targeting actomyosin contractility to suppress the malignancy of AML cells.

Mineral trioxide aggregate (MTA) has been introduced as a choice material for regenerative dentistry. To date, the diverse biological activities of MTA, including its anti-inflammatory effects, have been extensively discussed. However, there is limited insight into the link between MTA and immune cell migration. In this study, we report the role of MTA in enhancing both chemotactic and chemokinetic immune cell migration through distinct signaling pathways. By using versatile live imaging techniques, we demonstrated that MTA-mediated CaSR activation induced diverse downstream pathways to govern cell migratory capacity. In this context, Cdc42 generates cytoskeleton-driven cellular protrusions to steer directional cell migration (chemotaxis) whereas Ca2+-calmodulin dependent myosin light chain kinase induces cell contractility that plays an important role in speeding up the average migration speed (chemokinesis). Our findings illuminate an unrecognized role for MTA and the related CaSR signaling network in immune cell migration, providing evidence that can drive development of novel approaches to immunological therapy.

COVID-19 has caused massive disruption on the global economy and presents a considerable risk to human lives. Some countries have successfully controlled the pandemic by adopting strict measures, such as lockdown and travel restriction, but such methods are difficult to be applied widely due to their huge costs. To explore available and low-cost solutions, this study proposes an adaptive transmission model on the basis of a complex network, and gives control simulation method of COVID-19. The suggested model considers adaptive changes such as travel network and people’s travel intention to form a three-level adaptive network transmission model among cities, communities, and people. The improved susceptible–exposed–infectious–recovered–dead transmission process is integrated into the network. Simulation experiments under high-, low-, and conventional-cost controls are performed. In these experiments, the travel restriction and closing cities are considered, and sensitivity analyses of the parameters are conducted to explore low-cost measures. Meanwhile, time duration and application conditions of different controls are discussed. Results show that lockdown is the most effective way, and the contact and infection rates are the two most important factors to control the pandemic. Low-cost combined control measures are feasible and effective for most countries. Finally, several suggestions are given for national and urban preventions and controls of COVID-19 and other infectious diseases in the future.

Data- and knowledge-driven service-oriented smart maintenance decision-making is becoming a current research topic in complex multi-component systems. In it, the comprehensive data and knowledge from different stakeholders such as users, OEMs, and service providers contribute to determining the optimal decision-making schemes. However, the traditional centralized systems or platforms lead to the reluctant cross-organization knowledge sharing for each stakeholder. Meanwhile, although the promising blockchain technology is fit to solve the centralized sharing problems, it little considers the service-oriented maintenance decision-making (SOMD) processes. Moreover, it also ignores the collaborative sharing relationships that generate requests, induce services and respond knowledge among different stakeholders. Thus, in order to solve these problems, this paper focuses on the SOMD processes, and innovatively proposes a decision-making oriented collaborative knowledge sharing framework and multi-channel distributed blockchain network MKShareNet. The network architecture, lifecycle smart contracts, token reward mechanisms, and collaborative knowledge transaction operation logics are all designed. Finally, the prototype system on complex CNC honing machining tools is implemented and the collaborative sharing is verified. It shows that the proposed MKShareNet and system could effectively implement the sequential and incentive knowledge sharing among different stakeholders for maintenance planning.