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Atherosclerosis is the main cause of cardiovascular disease. Systemic inflammation is one important characteristic in atherosclerosis. Pro-inflammatory macrophages can secrete inflammatory factors and promote the inflammation of atherosclerosis. It has a great value for the treatment of atherosclerosis by inhibiting the release of inflammatory factors in macrophages. However, the detailed mechanism of this process is still unclear. In this study, we constructed an APOE-/- mice model of atherosclerosis to research the molecular mechanism of atherosclerosis. Protein tyrosine phosphatase non-receptor type 2 (PTPN2), an anti-inflammatory gene, was dramatically decreased in inflammatory mice. Deletion of PTPN2 could significantly induce monocytes toward M1 phenotype of macrophages, enhance the secretion of IL-12 and IL-1, and promote cell proliferation, invasion and metastasis. Mechanism research showed that PTPN2-mediated p65/p38/STAT3 de-phosphorylation could block the process of macrophage inflammation. In vivo experiments showed that PTPN2 may effectively inhibit the inflammatory response during atherosclerosis. In conclusion, we uncovered the negative role of PTPN2 in the occurrence of atherosclerosis, and this study provides a new potential target for atherosclerosis treatment.

An increasing number of microRNAs (miRs) have been shown to serve crucial roles in intestinal ischemia/reperfusion (II/R) injury. The aim of the present study was to examine the effects of miR-129-5p on II/R injury in vitro and in vivo. It was revealed that the expression level of miR-129-5p was upregulated, whereas SP-D expression was downregulated in the intestinal tissues of I/R mice. Serum levels of diamine oxidase, FD-4 and D-lactic acid, which are commonly used indicators of intestinal mucosal permeability, were significantly decreased following miR-129-5p knockdown. By contrast, ZO-1 and E-cadherin expression levels were increased following miR-129-5p knockdown, as determined using IHC, which improved the function of the epithelial barrier. In addition, Caco-2 cells were exposed to hypoxia/reoxygenation, which can trigger II/R injury. miR-129-5p expression was increased, whereas SP-D expression was decreased by H/R exposure in vitro. Knockdown of miR-129-5p increased ZO-1 and E-cadherin expression in Caco-2 cells. Moreover, overexpression of SP-D improved the function of the epithelial barrier, as indicated by increased transepithelial electrical resistance values and decreased paracellular flux of FD-4. It was also found that liver and lung injury triggered by II/R was attenuated by miR-129-5p knockdown. Collectively, the present study suggested that miR-129-5p knockdown mitigated II/R injury by targeting SP-D.

Hypoxia/reoxygenation (H/R)-induced myocardial cell injury is the main cause of acute myocardial infarction (AMI). Many proofs show that circular RNA plays an important role in the development of AMI. The purpose of this study was to investigate the role of circSAMD4A in H/R-induced myocardial injury. The levels of circular SAMD4A (circSAMD4A) were detected in the heart tissues of AMI mice and H/R-induced H9C2 cells, and the circSAMD4A was suppressed in AMI mice and H/R-induced H9C2 cells to investigate its' function in AMI. The levels of circSAMD4A and miR-138-5p were detected by real-time quantitative PCR, and MTT assay was used to detect cell viability. TUNEL analysis and Annexin V-FITC were used to determine apoptosis. The expression of Bcl-2 and Bax proteins was detected by Western blot. IL-1β, TNF-α and IL-6 were detected by ELISA kits. The study found that the levels of circSAMD4A were up-regulated after H/R induction and inhibition of circSAMD4A expression would reduce the H/R-induced apoptosis and inflammation. MiR-138-5p was down-regulated in H/R-induced H9C2 cells. circSAMD4A was a targeted regulator of miR-138-5p. CircSAMD4A inhibited the expression of miR-138-5p to promote H/R-induced myocardial cell injury in vitro and vivo. In conclusion, CircSAMD4A can sponge miR-138-5p to promote H/R-induced apoptosis and inflammatory response.

Osteoarthritis (OA) is an ageing‐related disease characterized by articular cartilage degradation and joint inflammation. circRNA has been known to involve in the regulation of multiple inflammatory diseases including OA. However, the mechanism underlying how circRNA regulates OA remains to be elucidated. Here, we report circANKRD36 prevents OA chondrocyte apoptosis and inflammation by targeting miR‐599, which specifically degrades Casz1. We performed circRNA sequencing in normal and OA tissues and found the expression of circANKRD36 is decreased in OA tissues. circANKRD36 is also reduced in IL‐1β–treated human chondrocytes. FACS analysis and Western blot showed that the knockdown of circANKRD36 promotes the apoptosis and inflammation of chondrocytes in IL‐1β stress. We then found miR‐599 to be the target of circANKRD36 and correlate well with circANKRD36 both in vitro and in vivo. By database analysis and luciferase assay, Casz1 was found to be the direct target of miR‐599. Casz1 helps to prevent apoptosis and inflammation of chondrocytes in response to IL‐1β. In conclusion, our results proved circANKRD36 sponge miR‐599 to up‐regulate the expression of Casz1 and thus prevent apoptosis and inflammation in OA.

Background: Severe pneumonia caused by Chlamydia psittaci is a rare infectious disease associated with living environment. The causes of thrombocytopenia were infection, leukemia, idiopathic thrombocytopenia and many other factors. The determination of platelet parameters could reflect the compensatory situation of bone marrow and provide a basis reason of thrombocytopenia identification. Case presentation: Based on the patient’s symptoms, exposure history, computerized tomography（CT）and next-generation sequencing, a preliminary diagnosis of the patient were made, at the same time other infections are excluded. We reported a case of severe pneumonia with severe thrombocytopenia caused by Chlamydia psittaci. During the treatment, he was diagnosed as parrot fever and secondary immune thrombocytopenia. Anti-infection and rising platelet with Doptelet treatment were in effect. The presence of high fever, feeling faint, gastrointestinal symptoms, images of chest CT and platelet reduction, Chlamydia psittaci might be considered as a priority reason of this case, other infections and hematology disorders excluded.Conclusion: This is the first reported case of Chlamydia psittaci-induced thrombocytopenia associated with bone marrow changes and treatment. The efficacy of mokexin in the treatment of thrombocytopenia may be further generalized.

Background: Infection of Chlamydia psittaci (C. psittaci) could lead to serious clinical manifestations in humans, including severe pneumonia with rapid progression, adult respiratory distress syndrome (ARDS), sepsis, multiple organ dysfunction syndromes (MODS), and probably death. Implementation of extracorporeal membrane oxygenation (ECMO) in the patient with severe ARDS gives a promising new method for recovery.Case Presentation: We report our successful use of venovenous (VV) ECMO in a 48-year-old man who manifested with severe respiratory distress syndrome, acute kidney injury, and septic shock caused by a diagnosis of pneumonia. After the combination of therapy including anti-infection, mechanical ventilation, and continuous renal replacement therapy (CRRT), acute inflammatory syndrome developed. However, his respiratory status rapidly deteriorated. Then, venoarterial (VA)-ECMO support was placed on the patient as suddenly slowing of the heart rate. Harlequin (North-South) syndrome occurred after ECMO initiation. A series of the process could not relieve hypoxia in the upper body. At last, transition to VV-ECMO improved hypoxia. The duration of VV-ECMO was 7 days and the mechanical ventilation was weaned on the next day. On the day of ECMO weaning, nanopore targeted sequencing (NTS) of bronchoalveolar lavage fluid (BALF) reported the presence of C. psittaci. After 19 days of critical systemic rehabilitation and combination therapy, the patient fully recovered from C. psittaci.Conclusion: This is the first reported case of the patient receiving ECMO for C. psittaci pneumonia. ECMO puts the lungs on temporary rest, promotes the recovery of pulmonary function, and also wins time for finding the pathogens, which is crucial in the treatment of rare pathogens.

ObjectiveThe adoption of hearts from donation after circulatory death (DCD) is a promising approach for the shortage of suitable organs in heart transplantation. However, DCD hearts suffer from serious ischemia/reperfusion injury (IRI). Recent studies demonstrate that nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis is a novel target to ameliorate myocardial IRI. Melatonin is shown to inhibit NLRP3 inflammasome-mediated pyroptosis. Therefore, this study is designed to verify the hypothesis that melatonin can protect the heart graft preserved with ex vivo heart perfusion (EVHP) against myocardial IRI via inhibiting NLRP3 inflammasome-mediated pyroptosis in a rat model of DCD.MethodsDonor-heart rats were randomly divided into three groups: (1) Control group: non-DCD hearts were harvested from heart-beating rats and immediately preserved with allogenic blood-based perfusate at constant flow for 105 min in the normothermic EVHP system; (2) DCD-vehicle group; and (3) DCD-melatonin group: rats were subjected to the DCD procedure with 25 min of warm ischemia injury and preserved by the normothermic EVHP system for 105 min. Melatonin (200 μmol/L) or vehicle was perfused in the cardioplegia and throughout the whole EVHP period. Cardiac functional assessment was performed every 30 min during EVHP. The level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis of heart grafts submitted to EVHP were evaluated.ResultsTwenty five-minute warm ischemia injury resulted in a significant decrease in the developed pressure (DP), dP/dtmax, and dP/dtmin of left ventricular of the DCD hearts, while the treatment with melatonin significantly increased the DP, dP/dtmax of the left ventricular of DCD hearts compared with DCD-vehicle group. Furthermore, warm ischemia injury led to a significant increase in the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis in the hearts preserved with EVHP. However, melatonin added in the cardioplegia and throughout the EVHP period significantly attenuated the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis compared with DCD-vehicle group.ConclusionEVHP combined with melatonin post-conditioning attenuates myocardial IRI in DCD hearts by inhibiting NLRP3 inflammasome-mediated pyroptosis, which might expand the donor pool by the adoption of transplantable DCD hearts.

Sepsis is one of the main causes of death in critically ill patients. Despite the continuous development of medical technology in recent years, its morbidity and mortality are still high. This is mainly related to the delay in starting treatment and non-adherence of clinical guidelines. Artificial intelligence (AI) is an evolving field in medicine, which has been used to develop a variety of innovative Clinical Decision Support Systems. It has shown great potential in predicting the clinical condition of patients and assisting in clinical decision-making. AI-derived algorithms can be applied to multiple stages of sepsis, such as early prediction, prognosis assessment, mortality prediction, and optimal management. This review describes the latest literature on AI for clinical decision support in sepsis, and outlines the application of AI in the prediction, diagnosis, subphenotyping, prognosis assessment, and clinical management of sepsis. In addition, we discussed the challenges of implementing and accepting this non-traditional methodology for clinical purposes.

This paper investigates a dual-channel supply chain in which a manufacturer sells the product via an offline retailer or online store. The manufacturer sets the wholesale and online price, and the retailer decides the retail price with the retailer’s fairness preference and consumer’s online channel preference. Through investigating the combined impacts of fairness preference and channel preference on the enterprises’ operational strategies, this paper obtains some meaningful results. If a manufacturer thinks over the fairness preference, he decreases the wholesale price to mitigate a loss of retailer and benefit the supply chain design. The manufacturer intends to set up the online channel with a lower acceptance as the fairness preference grows. However, the gains from enhanced online channel acceptance cannot compensate for the manufacturer’s loss by the fairness effect that benefits the retailer. Moreover, the manufacturer cannot neglect the retailer’s fairness preference generating a “lose-lose” case for both members.

Sepsis is a severe disease, which results from the excessive inflammatory response to the infection. Dysfunction of intestinal barrier is a crucial problem in various pathological conditions. Meanwhile, microRNAs exhibit significant roles in the modulation of many diseases, including sepsis. Multiple investigations indicate that miR-199a-5p participates in different human diseases. Nevertheless, little is known on the roles of miR-199a-5p in sepsis. Herein, we evaluated the mechanism of miR-199a-5p on the intestinal barrier dysfunction in sepsis. Intestinal mucosa permeability indicators including D-lactic acid, DAO, and FD-40 levels were determined, and they were greatly increased in sepsis. Then, we proved that miR-199a-5p was induced in sepsis mice tissues and isolated intestinal epithelial cells. Moreover, miR-199a-5p increased D-lactic acid, DAO, and FD-40 while inhibition of miR-199a-5p exhibited a reversed process. Additionally, we observed that miR-199a-5p affected the oxidative damage and inflammation in the intestine tissues from sepsis mice. The content of MDA was elevated whereas SOD was remarkably repressed in the miR-199a-5p mimic group. IL-6, IL-1β, and TNF-α were induced by miR-199a-5p overexpression while IL-10 was reduced by miR-199a-5p. Subsequently, surfactant protein D (SP-D) was predicted as the target of miR-199a-5p. The activation of NF-κB has been identified in sepsis. Herein, we demonstrated that inhibitor of miR-199a-5p contributed to IEC injury via targeting SP-D and inactivating the NF-κB pathway. These revealed miR-199a-5p exacerbated the intestinal barrier dysfunction via inhibiting SP-D and activating the NF-κB pathway in sepsis.

The severity of sepsis may be associated with excessive inflammation, thus leading to acute liver injury. MicroRNA-21 is highly expressed in the liver of a variety of inflammation-related diseases, and PPARα is also proved to participate in regulating inflammation. In the present study, the LPS-induced sepsis model was established. We found that microRNA-21 expression was upregulated in the liver of sepsis mice, and microRNA-21 inhibition significantly reduced the liver injury. The expression of liver injury markers, inflammation cytokines, and PPARα in the septic mice was higher than in antagomir-21 treated septic mice. In addition, we also found that PPARα is the target gene of microRNA-21; PPARα antagonist GW6471 could reverse the effect of antagomir-21. In conclusion, our study illustrated that microRNA-21 exacerbate acute liver injury in sepsis mice by inhibiting PPARα expression.

Previous studies have confirmed that reference prices play an essential role in consumer purchasing decisions, and some researchers have suggested that reference prices are positively influenced by innovation. Therefore, we construct an interactive effect of innovation and reference price to study their combined impact on supply chain decisions. We model a supply chain, where a manufacturer determines the innovation level and the wholesale price while the retailer controls the retail price, as a dynamic Stackelberg game. We show that the interactive effect causes the steady-state wholesale and retail prices to increase, thus motivating the manufacturer to increase innovation investment. We see that the retail price and the level of innovation increase in reference price effect whereas they decrease in consumer memory. The centralized firm has a higher steady-state innovation level and innovation/price ratio and lower steady-state retail price compared to the decentralized supply chain. Consumers also benefit from the interactive effect as well as from centralization. Finally, we use numerical analysis to demonstrate our results and offer some managerial implications.

Innate immune molecule surfactant protein D (SP-D), a member of the C-type lectin protein family, plays an indispensable role in host defense and the regulation of inflammation in the lung and other tissues. Osteoarthritis (OA) is a degenerative disease of cartilage, with inflammation that causes pathologic changes and tissue damage. However, it is unknown whether there exist SP-D expression and its potential role in the pathogenesis of OA. In this study, we examined SP-D expression and explored its biological function in a sodium nitroprusside (SNP)-stimulated rat chondrocytes and surgically-induced rat OA model. We found SP-D expression in both human and rat articular chondrocytes, with higher level in normal chondrocytes compared to in OA chondrocytes. Furthermore, In vivo study demonstrated that recombinant human SP-D (rhSP-D) ameliorated cartilage degeneration in surgically-induced rat OA model. In vitro cell culture study showed that rhSP-D markedly inhibited the expression of caspase-3 as an apoptosis biomarker, and decreased phosphorylation of p38 mitogen-activated protein kinase (MAPK), which resulted in maintaining normal nuclear morphology and increasing mitochondrial membrane potential in SNP-stimulated rat chondrocytes. Collectively, these findings indicate that SP-D expresses in articular chondrocytes and suppresses SNP-stimulated chondrocyte apoptosis and ameliorates cartilage degeneration via suppressing p38 MAPK activity.

Background/Aims: LINC00037 has previously been reported to be up-regulated in clear cell renal cell carcinoma (ccRCC), however, the underlying mechanism remained unknown. In this study, we designed to investigate the functional role of LINC00037 in ccRCC Methods: LINC00037 knockdown and re-expressing 786-O and A498 cells were established. CCK8 assay and EdU assay were performed to evaluate the proliferation rates of ccRCC cells. Flow cytometry assay was performed to detect the cell apoptosis and cell cycle. Subcutaneous injection xenotransplantation mouse model was used to observe the role of LINC00037 in tumor growth in vivo. Mass spectrometry (MS) was performed to find the interacting partner of LINC00037 and RNA immunoprecipitation (RIP) was carried out to validate their interaction. Results: We found that knockdown of LINC00037 resulted in inhibited cell proliferation with activated apoptosis and cell cycle arrest in vitro. Over-expression of LINC00037 in LINC00037 knockdown cells restored and enhanced cell proliferation. In vivo mouse model indicated reduced tumor progression by LINC00037 depletion and promoted tumor progression by LINC00037 overexpression. LINC00037 could bind to epidermal growth factor receptor (EGFR) and increase the protein level of EGFR. Conclusion: LINC00037 could inhibit proliferation of ccRCC in an epidermal growth factor receptor-dependent way.

Overconfidence is a common, pervasive cognitive bias that is of great practical importance in decision-making and widely recognized as an influential factor to consider in operations management. In this paper, we consider overconfidence bias in a supply chain innovation scenario, which consists of an innovative upstream supplier and an overconfident downstream manufacturer overestimating the impact of innovation to enhance demand. We investigate the influence of the manufacturer’s overconfidence on supplier innovation and supply chain profits under the wholesale price contract and the cost-sharing contract settings. Our results suggest that while the overconfidence is detrimental to the supplier’s innovation under a wholesale price contract, it is beneficial to the supplier’s innovation under a cost-sharing contract, and even more beneficial than in the centralized case. We also find that, under a wholesale price contract the manufacturer’s profit can be higher than under a cost-sharing contract when the level of overconfidence exceeds a certain threshold. Interestingly, we further find that the supplier’s unawareness of overconfidence benefits both biased supply chain members under a wholesale price contract but shows the opposite effect for a cost-sharing contract. Our results offer insights into overconfidence bias in operations management and provide practical decision-making advice for supply chain members.

CRISPR/Cas9, as a new genome-editing tool, offers new approaches to understand and treat diseases, which is being rapidly applied in various areas of biomedical research including sepsis field. The type II prokaryotic CRISPR/Cas system uses a single-guide RNA (sgRNA) to target the Cas9 nuclease to a specific genomic sequence, which is introduced into disease models for functional characterization and for testing of therapeutic strategies. This incredibly precise technology can be used for therapeutic research of gene-related diseases and to program any sequence in a target cell. Most importantly, the multifunctional capacity of this technology allows simultaneous editing of several genes. In this review, we focus on the basic principles, advantages and limitations of CRISPR/Cas9 and the use of the CRISPR/Cas9 system as a powerful tool in sepsis research and as a new strategy for the treatment of sepsis.

Sepsis is a severe disease, which results from the excessive inflammatory response to the infection. Dysfunction of intestinal barrier is a crucial problem in various pathological conditions. Meanwhile, microRNAs exhibit significant roles in the modulation of many diseases, including sepsis. Multiple investigations indicate that miR-199a-5p participates in different human diseases. Nevertheless, little is known on the roles of miR-199a-5p in sepsis. Herein, we evaluated the mechanism of miR-199a-5p on the intestinal barrier dysfunction in sepsis. Intestinal mucosa permeability indicators including D-lactic acid, DAO, and FD-40 levels were determined, and they were greatly increased in sepsis. Then, we proved that miR-199a-5p was induced in sepsis mice tissues and isolated intestinal epithelial cells. Moreover, miR-199a-5p increased D-lactic acid, DAO, and FD-40 while inhibition of miR-199a-5p exhibited a reversed process. Additionally, we observed that miR-199a-5p affected the oxidative damage and inflammation in the intestine tissues from sepsis mice. The content of MDA was elevated whereas SOD was remarkably repressed in the miR-199a-5p mimic group. IL-6, IL-1β, and TNF-α were induced by miR-199a-5p overexpression while IL-10 was reduced by miR-199a-5p. Subsequently, surfactant protein D (SP-D) was predicted as the target of miR-199a-5p. The activation of NF-κB has been identified in sepsis. Herein, we demonstrated that inhibitor of miR-199a-5p contributed to IEC injury via targeting SP-D and inactivating the NF-κB pathway. These revealed miR-199a-5p exacerbated the intestinal barrier dysfunction via inhibiting SP-D and activating the NF-κB pathway in sepsis.

Sepsis and intestinal injury triggered by sepsis are common in intensive care units, which can contribute to a high mortality. lncRNAs can modulate gene expression, and they are closely involved in multiple diseases, including sepsis. In our present study, we investigated the biological function of MEG3 in sepsis, especially during the intestinal injury. Currently, we observed that in LPS-induced sepsis mouse models, the intestinal injury was triggered. Meanwhile, we reported that MEG3 was greatly decreased in vivo, with an increase of miR-129-5p and inhibition of SP-D. Then, MEG3 was overexpressed, and we found that its overexpression repressed the intestinal injury via downregulating miR-129-5p in sepsis mice. Moreover, TNF-α and IL-6 expression was elevated in intestinal tissues compared to the control groups. MEG3 restrained the activation of TNF-α and IL-6, in sepsis models. Subsequently, to induce the inflammatory injury of sepsis, human colorectal Caco2 cells were treated with 10 ng/ml LPS. 10 ng/ml LPS significantly inhibited Caco2 cell proliferation and increased the apoptosis. Additionally, MEG3 was decreased whereas miR-129-5p was obviously increased in Caco2 cells incubated with LPS. Interestingly, we showed that MEG3 repressed cell apoptosis partly and enhanced Caco2 cell proliferation. miR-129-5p overexpression could reverse the effect of MEG3 in vitro. Previously, we proved SP-D was reduced in sepsis and it depressed the intestinal injury in vivo. Finally, the correlation among MEG3, miR-129-5p, and SP-D was predicted and confirmed in our investigation. These findings indicated that MEG3 might be a potential target for intestinal damage caused by sepsis via regulating miR-129-5p and SP-D.

Background: Cardiopulmonary resuscitation (CPR) strategies in COVID-19 patients differ from those in patients suffering from cardiogenic cardiac arrest. During CPR, both healthcare and non-healthcare workers who provide resuscitation are at risk of infection. The Working Group for Expert Consensus on Prevention and Cardiopulmonary Resuscitation for Cardiac Arrest in COVID-19 has developed this Chinese Expert Consensus to guide clinical practice of CPR in COVID-19 patients. Main recommendations: 1) A medical team should be assigned to evaluate severe and critical COVID-19 for early monitoring of cardiac-arrest warning signs. 2) Psychological counseling and treatment are highly recommended, since sympathetic and vagal abnormalities induced by psychological stress from the COVID-19 pandemic can induce cardiac arrest. 3) Healthcare workers should wear personal protective equipment (PPE). 4) Mouth-to-mouth ventilation should be avoided on patients suspected of having or diagnosed with COVID-19. 5) Hands-only chest compression and mechanical chest compression are recommended. 6) Tracheal-intubation procedures should be optimized and tracheal-intubation strategies should be implemented early. 7) CPR should be provided for 20-30 min. 8) Various factors should be taken into consideration such as the interests of patients and family members, ethics, transmission risks, and laws and regulations governing infectious disease control. Changes in management: The following changes or modifications to CPR strategy in COVID-19 patients are proposed: 1) Healthcare workers should wear PPE. 2) Hands-only chest compression and mechanical chest compression can be implemented to reduce or avoid the spread of viruses by aerosols. 3) Both the benefits to patients and the risk of infection should be considered. 4) Hhealthcare workers should be fully aware of and trained in CPR strategies and procedures specifically for patients with COVID-19.

Staphylococcus aureus pneumonia is an important cause of sepsis which causes gut injury, inflammation, and apoptosis. The surfactant proteins surfactant protein A (SP-A) and surfactant protein D (SP-D) bind bacterial pathogens and facilitate clearance of pathogens, apoptotic bodies, and modulate immune responses. SP-A and SP-D are expressed in both lung and gut epithelia. We hypothesize SP-A and SP-D regulate pneumonia severity and gut injury during pneumonia.Wild-type (WT) and SP-A and SP-D double knockout (SP-A/D KO) mice were subjected to S. aureus or sham pneumonia. Bronchoalveolar lavage and tissue harvest were performed 24 h later. Pneumonia severity, gut mucosal injury, inflammation, and apoptosis were measured using a combination of histology, immunohistochemistry, cytokine assay, TUNEL assay, quantitative real-time polymerase chain reaction, and Western blot analyses.Pneumonia increased gut inflammation, apoptosis, and mucosal injury in both groups. Pneumonia histology and bacterial growth in bronchoalveolar lavage fluid demonstrate more severe infection in SP-A/D KO mice compared with WT controls. SP-A/D KO mice with pneumonia also demonstrate more severe histologic gut mucosal injury, increased gut apoptosis, elevated caspase-3 levels, and Bax/Bcl-2 mRNA expression compared with WT pneumonia mice. Nuclear factor κB (NF-κB) p65 expression and its nuclear translocation, gut levels of tumor necrosis factor α and interleukin-1β were all increased in SP-A/D KO mice with pneumonia compared with WT controls.These data provide evidence SP-A and SP-D attenuate S. aureus pneumonia severity resulting in decreased intestinal mucosal injury, apoptosis, and inflammation. Improved pulmonary clearance of S. aureus decreased caspase-3 and Bax/Bcl-2 expressions and decreased activation of the NF-κB signaling pathway in intestine represent potential mechanisms for the effects of SP-A and SP-D on gut injury during pneumonia.

Incumbent firms often reposition themselves in response to entrants, but when doing so they incur repositioning costs. Incumbent repositioning costs and the associated decision biases have been identified in the economics, operations and strategy literatures as critical aspects of the competitive interactions between incumbents and entrants, but they have received limited attention in game-theoretic treatments at the strategy level. To fill this gap, we develop a strategic mental model to analytically characterize the impacts of repositioning costs and decision biases on firms’ equilibrium strategies and profits. Including these costs and biases changes the nature of strategic dynamics as well as introduces new implications for strategic choice.

High mobility group box 1 protein (HMGB1) plays an important role in myocardial ischemia-reperfusion (I/R) injury. Rosuvastatin (RS) preconditioning has been reported to reduce myocardial I/R injury. The aim of this study was to investigate whether postconditioning with RS is able to reduce myocardial I/R injury by inhibiting HMGB1 expression in rats. Anesthetized male rats were subjected to ischemia for 30 min and treated once with RS (10 mg/kg, i.v.) 5 min prior to reperfusion for 4 h. Lactate dehydrogenase (LDH), creatine kinase (CK) and superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels and infarct size were measured. HMGB1 expression was assessed by immunoblotting. The results showed that RS postconditioning significantly decreased the infarct size and the activities of LDH and CK following 4 h reperfusion (all P