Background To determine the diagnostic value of hematologic markers for coronavirus disease 2019 (COVID‐19) and explore their relationship with disease severity. Methods Subjects included 190 COVID‐19 patients, 190 healthy subjects, and 105 influenza pneumonia (IP) patients. COVID‐19 patients were divided into the ARDS and non‐ARDS groups. Routine blood examination, biochemistry indicator, days in hospital, body temperature, pneumonia severity index (PSI), CURB‐65, and MuLBSTA were recorded. Correlations between variables were assessed using Spearman's correlation analysis. Receiver operating characteristic (ROC) curves were used to study the accuracy of the various diagnostic tests. Results Compared with healthy subjects, COVID‐19 patients had lower white blood cell (WBC), lymphocyte, platelet, and hemoglobin levels; higher percentages of neutrophils and monocytes; lower percentages of lymphocytes and higher neutrophil‐to‐lymphocyte ratio (NLR), monocyte‐to‐lymphocyte ratio (MLR), and platelet‐to‐lymphocyte ratio (PLR) values (P < .05). COVID‐19 patients had higher WBC and neutrophil levels and lower percentages of lymphocytes compared to IP (P < .05). ROC curve analysis revealed that MLR had a high diagnostic value in differentiating COVID‐19 patients from healthy subjects, but not from IP patients. NLR showed significant positive correlations with PSI, CURB‐65, and MuLBSTA. Lymphocyte count was lower in the ARDS group and yielded a higher diagnostic value than the other variables. Conclusions Monocyte‐to‐lymphocyte ratio showed an acceptable efficiency to separate COVID‐19 patients from healthy subjects, but failed to rule out IP patients. NLR may be a reliable marker to evaluate the disease severity of COVID‐19. Lymphocyte count may be useful to establish the early diagnosis of ARDS in the COVID‐19 patients.

Organic crystals are easily cracked into pieces or powders under applied stress because of their intrinsic brittle nature. This undesired mechanical property directly limits their application in flexible optical and optoelectronic devices. Herein, we developed a compact single-benzene molecule dimethyl 2,5-bis((2-hydroxyethyl)amino)terephthalate, which was easily crystallized to form two polymorphs, A and B. Featuring a single-benzene π-system, both polymorphs A and B display red fluorescence in crystals. More importantly, crystals of polymorph A are flexible and can be elastically bent under mechanical force. Given these advantages, a flexible optical waveguide has been realized in the crystal of polymorph A with a bent shape, highlighting its potential application in flexible devices. In addition, the thermal transformation of crystals from polymorph A to polymorph B, which was accompanied by the change of optical property as well as mechanical elasticity, has been observed.

Background

Acute respiratory distress syndrome (ARDS) is characterized by increased pulmonary inflammation and endothelial barrier permeability. Omentin has been shown to benefit obesity-related systemic vascular diseases; however, its effects on ARDS are unknown. In the present study, the level of circulating omentin in patients with ARDS was assessed to appraise its clinical significance in ARDS. Mice were subjected to systemic administration of adenoviral vector expressing omentin (Ad-omentin) and one-shot treatment of recombinant human omentin (rh-omentin) to examine omentin's effects on lipopolysaccharide (LPS)-induced ARDS. Pulmonary endothelial cells (ECs) were treated with rh-omentin to further investigate its underlying mechanism. We found that a decreased level of circulating omentin negatively correlated with white blood cells and procalcitonin in patients with ARDS. Ad-omentin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and endothelial barrier injury in mice, accompanied by Akt/eNOS pathway activation. Treatment of pulmonary ECs with rh-omentin attenuated inflammatory response and restored adherens junctions (AJs), and cytoskeleton organization promoted endothelial barrier after LPS insult. Moreover, the omentin-mediated enhancement of EC survival and differentiation was blocked by the Akt/eNOS pathway inactivation. Therapeutic rh-omentin treatment also effectively protected against LPS-induced ARDS via the Akt/eNOS pathway. Collectively, these data indicated that omentin protects against LPS-induced ARDS by suppressing inflammation and promoting the pulmonary endothelial barrier, at least partially, through an Akt/eNOS-dependent mechanism. Therapeutic strategies aiming to restore omentin levels may be valuable for the prevention or treatment of ARDS.

Background17β-estradiol can suppress acute lung injury (ALI) and regulate alveolar epithelial sodium channel (ENaC). However the relationship between these two functions remains unclear. This study is conducted to assess the role of ENaC and the PI3K/Akt/SGK1 signaling pathway in 17β-estradiol therapy in attenuating LPS-induced ALI.MethodsALI was induced in C57BL/J male mice by intratracheal administration of lipopolysaccharide (LPS). Concurrent with LPS administration, 17β-estradiol or sterile saline was administered to ALI model with or without the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin. The lung histological changes, inflammatory mediators in bronchoalveolar lavage fluid (BALF), wet/dry weight ratio (W/D) and alveolar fluid clearance (AFC) were measured 4 hours after LPS challenge in vivo. For in vitro studies, LPS-challenged MLE-12 cells were pre-incubated with or without wortmannin for 30 minutes prior to 17β-estradiol treatment. Expression of ENaC subunits was assessed by reverse transcriptase PCR, western blot, cell surface biotinylation, and immunohistochemistry. The levels of phosphorylated Akt and SGK1 in lung tissue and lung cell lines were investigated by western blot.Results17β-estradiol suppressed LPS-mediated ALI in mice by diminishing inflammatory mediators and enhancing AFC. 17β-estradiol promoted the expression and surface abundance of α-ENaC, and increased the levels of phosphorylated-Akt and phosphorylated-SGK1 following LPS challenge. This induction was abolished by the PI3K inhibitor wortmannin in vivo and in vitro.Conclusion17β-estradiol attenuates LPS-induced ALI not only by repressing inflammation, but also by reducing pulmonary edema via elevation of α-ENaC expression and membrane abundance. These effects were mediated, at least partially, via activation of the PI3K/Akt/SGK1 signaling pathway.

The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.202200471.Applications in extreme conditions, such as those encountered in space exploration, require lightweight materials that can retain their elasticity in extremely cold environments. However, cryogenic treatment of most soft polymeric and elastomeric materials results in complete loss of their ability for elastic flow, whereby such materials that are normally ductile become stiff, brittle, and prone to cracking. Here, a facile method for preparation of hybrid organic crystalline materials that are not only cryogenically robust but are also capable of large, recoverable, and reversible deformation at low temperatures is reported. To that end, flexible organic crystals are first mechanically reinforced by a polymer coating and combined with a thermally responsive polymer. The resulting hybrid materials respond linearly and reversibly to temperatures from −15 to −120 °C without fatigue in air as well as in cold vacuum. The approach proposed here not only circumvents one of the main drawbacks that are inherent to the amorphous nature and has thus far limited the applications of polymeric materials at low temperatures, but it also provides a cost-effective access to a myriad of lightweight sensing, electronic, optical or actuating devices that can operate in low-temperature environmental settings.

Acute respiratory distress syndrome (ARDS) is characterized by uncontrolled extravasation of protein-rich fluids, which is caused by disruption and dysfunction of the barrier of pulmonary endothelial cells (ECs). Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a novel adipokine with pleiotropic properties, which has been reported to exert beneficial effects against obesity-associated systemic vascular diseases; however, its effects on ARDS remain unknown. In the present study, mice were subjected to systemic administration of adenoviral vector expressing vaspin (Ad-vaspin) to examine its effects on lipopolysaccharide (LPS)-induced ARDS in vivo. Histological analysis was then conducted, and cytokine [tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10] levels, and intercellular cell adhesion molecule-1 (ICAM-1) and adherens junctions (AJs) expression were detected. In addition, human pulmonary microvascular ECs (HPMECs) were treated with recombinant human (rh)-vaspin to further investigate its molecular basis and underlying mechanism. The mRNA expression levels of inflammatory cytokines (TNF-α and IL-6) and endothelial-specific adhesion markers [vascular cell adhesion molecule-1 and E-selectin], activation of nuclear factor-κB, and cell viability and apoptosis were then examined. Furthermore, the expression of AJs and organization of the cytoskeleton, as well as expression and activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and generation of reactive oxygen species (ROS) were determined. The results indicated that Ad-vaspin protected against LPS-induced ARDS by alleviating the pulmonary inflammatory response and pulmonary EC barrier dysfunction in mice, which was accompanied by activation of the protein kinase B (Akt)/glycogen synthase kinase (GSK)-3β pathway. In addition, pretreatment of HPMECs with rh-vaspin attenuated inflammation, apoptosis and ROS generation without alterations in AJs and cytoskeletal organization following LPS insult, which was accompanied by activation of the Akt/GSK3β pathway. In conclusion, the present study demonstrated that vaspin protects against LPS-induced ARDS by reversing EC barrier dysfunction via the suppression of inflammation, apoptosis and ROS production in pulmonary ECs, at least partially via activation of the Akt/GSK3β pathway. These findings provide evidence of a causal link between vaspin and EC dysfunction in ARDS, and suggest a potential therapeutic intervention for patients with ARDS.

Mechanical ventilation (MV) is the main supportive treatment of acute respiratory distress syndrome (ARDS), but it may lead to ventilator-induced lung injury (VILI). Large epidemiological studies have found that obesity was associated with lower mortality in mechanically ventilated patients with acute lung injury, which is known as “obesity paradox.” However, the effects of obesity on VILI are unknown. In the present study, wild-type mice were fed a high-fat diet (HFD) and ventilated with high tidal volume to investigate the effects of obesity on VILI in vivo, and pulmonary microvascular endothelial cells (PMVECs) were subjected to 18% cyclic stretching (CS) to further investigate its underlying mechanism in vitro. We found that HFD protects mice from VILI by alleviating the pulmonary endothelial barrier injury and inflammatory responses in mice. Adipose-derived exosomes can regulate distant tissues as novel adipokines, providing a new mechanism for cell-cell interactions. We extracted three adipose-derived exosomes, including HFD mouse serum exosome (S-Exo), adipose tissue exosome (AT-Exo), and adipose-derived stem cell exosome (ADSC-Exo), and further explored their effects on MV or 18% CS-induced VILI in vivo and in vitro. Administration of three exosomes protected against VILI by suppressing pulmonary endothelial barrier hyperpermeability, repairing the expression of adherens junctions, and alleviating inflammatory response in vivo and in vitro, accompanied by transient receptor potential vanilloid 4 (TRPV4)/Ca2+ pathway inhibition. Collectively, these data indicated that HFD-induced obesity plays a protective role in VILI by alleviating the pulmonary endothelial barrier injury and inflammatory response via adipose-derived exosomes, at least partially, through inhibiting the TRPV4/Ca2+ pathway.