Dual Delivery of Tetramethylpyrazine and miR-194-5p Using Soft Mesoporous Organosilica Nanoparticles for Acute Lung Injury Therapy.

Background: The respiratory system is intensely damaged by acute lung injury (ALI). The anti-inflammatory effects of tetramethylpyrazine (TMP) against ALI have been confirmed, but it exhibits a short half-life. miR-194-5p could directly target Rac1, but the internalization rate of miRNA cells was low. Purpose: To explore the potential of the soft mesoporous organic silica nanoplatform (NPs) as carriers for delivery of TMP and miR-194-5p through the tail vein. Methods: NPs@TMP and NPs@PEI@miR-194-5p were added to the HUVEC cell-lines, in vitro, to observe the cell uptake and cytotoxic effects. In vivo experiments were conducted by injecting fluorescently labeled NPs through the tail vein and tracking distribution. Therapeutic and toxic side-effects were analyzed systemically. Results: In vitro study exhibited that NPs have no toxic effect on HUVECs within the experimental parameters and have excellent cellular uptake. The IVIS Spectrum Imaging System shows that NPs accumulate mainly in the lungs. NPs@TMP treatment can improved oxidative stress and inflammation levels in ALI mice and inhibited the TLR4/NLRP3/caspase 1 pathway. NPs@PEI@miR-194-5p can inhibit the Rac1/ZO-1/occludin pathway and improved endothelial cell permeability in ALI mice. The co-treatment of NPs@TMP and NPs@PEI@miR-194-5p can significantly improved the survival rates of the mice, reduced pulmonary capillary permeability and improved pathological injury in ALI mice. Innovation: This study combined traditional Chinese medicine, bioinformatics, cellular molecular biology and nanobiomedicine to study the pathogenesis and treatment of ALI. The rate of cellular internalization was improved by changing the shape and hardness of nanoparticles. NPs@TMP and NPs@PEI@miR-194-5p combined application can significantly improve the survival condition and pathological injury of mice. Conclusion: NPs loaded with TMP and miR-194-5p showed a greater therapeutic effect in ALI mice.

Navigating the Decision to Disclose Mental Illness in the Workplace: The Role of Leader Motivating Language and Perceived Organizational Support.

Mental health disclosure in the workplace has drawn much attention as it comes with multiple benefits such as reducing financial burden, facilitating relationships, and counteracting related stress. Drawing on insights from the disclosure decision-making model, motivating language theory, and organizational support theory, the study presents a model that pictures the underlying mechanisms of the disclosure decision-making process. The findings from a survey of 416 participants suggested that the direction-giving and empathic language strategy can lead to employees' perceived organizational support. Such perception can help them reduce anticipated negative outcomes when considering disclosure and increase their disclosure efficacy, which in turn increases their disclosure intention.

Enhancing Employee Engagement via Leaders' Motivational Language in times of crisis: Perspectives from the COVID-19 outbreak.

By bridging theoretical perspectives from diverse disciplines including public relations, organizational communication, psychology, and management, this study advances a sequential mediation process model that links leaders' motivational communication-specifically, direction-giving, empathetic, and meaning-making language-to employees' organizational engagement during times of crisis. The model incorporates employees' psychological needs satisfaction and their subsequent crisis coping strategies so as to explain the process that underlies the effects of leader communication on employee engagement. We tested the model in a unique yet underexplored crisis context: organizational crises triggered by the global pandemic of COVID-19. The results of an online survey of 490 full-time U.S. employees provide strong support to the model's predictions. Our research extends internal crisis communication scholarship in public relations by addressing what types of leader communication strategies as well as how these strategies contribute to employee engagement in a holistic fashion. It also advances theoretical development of the motivational language theory, self-determination theory, transactional model of stress and coping, and organizational engagement-the four theoretical bases of our study-in the context of organizational crises. Lastly, the study results provide timely practical insights on effective internal crisis communication.

Tetramethylpyrazine ameliorates acute lung injury by regulating the Rac1/LIMK1 signaling pathway.

Acute lung injury (ALI) is a respiratory disorder characterized by severe inflammation of the alveoli and lung parenchyma. Tetramethylpyrazine (TMP), the main active compound in Ligusticum chuanxiong Hort (LC), can protect against lipopolysaccharide (LPS)-induced ALI. Our study aimed to investigate how TMP protects the endothelial cell barrier in pulmonary capillaries. We administered TMP intraperitoneally at different doses and found that acute lung injury in mice was improved, but not in a dose-dependent manner. TMP toxicity was tested in vitro. We observed that LPS-induced cytoskeletal remodeling was inhibited by TMP. Murine ALI was induced as follows: For the 1st hit, LPS (2 mg/kg) was injected intraperitoneally; after 16 h, for the 2nd hit, LPS (4 mg/kg) was instilled intratracheally. The mice in treatment groups had TMP or dexamethasone administered intraperitoneally 30 min prior to the 1st hit and 30 min past the 2nd hit. Mice were euthanized 24 h after the last injecting. We measured protein and mRNA levels using enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase real-time PCR (RT-qPCR), respectively. The ultrastructural analysis was performed with transmission electron microscopy (TEM) and the cytoskeleton was observed by immunofluorescence. Immunohistochemistry and Western blotting were used to detect protein expression in the Rac1/LIMK1/ZO-1/occludin signal pathway. The results showed that TMP treatment decreased inflammatory cell infiltration and alleviated LPS-induced damage in lung tissue. Also, TMP significantly inhibited the Rac1/LIMK1/ZO-1/occludin signaling pathway. Our findings show that using TMP during sepsis can protect the pulmonary microvascular endothelial cell barrier and suppress inflammation. Therefore, TMP may have a promising therapeutic role in preventing acute lung injury from sepsis.

Employee coping with organizational change in the face of a pandemic: The role of transparent internal communication.

The COVID-19 pandemic has caused many businesses and organizations to implement changes to manage operational and economic challenges. Understanding how employees manage such changes during the process is critical to the success of organizations. Integrating the literature from transparent internal communication, the transactional theory of stress and coping, and organizational change research, this study proposes a theoretical model to understand the role of internal communication and its effects on employees' management of organizational change. An online survey was conducted with 490 full-time employees in the U.S. during the second and third weeks of April 2020. The findings of this study demonstrate that transparent internal communication can help encourage problem-focused control coping, reduce uncertainty, and foster employee-organization relationships during organizational change. Theoretical and practical implications are discussed.