Mechanical stress plays a critical role among development, functional maturation, and pathogenesis of pulmonary tissues, especially for the alveolar epithelial cells and vascular endothelial cells located in the microenvironment established with vascular network and bronchial-alveolar network. Alveolar epithelial cells are mainly loaded by cyclic strain and air pressure tension. While vascular endothelial cells are exposed to shear stress and cyclic strain. Currently, the emerging evidences demonstrated that non-physiological mechanical forces would lead to several pulmonary diseases, including pulmonary hypertension, fibrosis, and ventilation induced lung injury. Furthermore, a series of intracellular signaling had been identified to be involved in mechanotransduction and participated in regulating the physiological homeostasis and pathophysiological process. Besides, the communications between alveolar epithelium and vascular endothelium under non-physiological stress contribute to the remodeling of the pulmonary micro-environment in collaboration, including hypoxia induced injuries, endothelial permeability impairment, extracellular matrix stiffness elevation, metabolic alternation, and inflammation activation. In this review, we aim to summarize the current understandings of mechanotransduction on the relation between mechanical forces acting on the lung and biological response in mechanical overloading related diseases. We also would like to emphasize the interplays between alveolar epithelium and vascular endothelium, providing new insights into pulmonary diseases pathogenesis, and potential targets for therapy.

Background Sepsis is a life-threatening condition that induce tens of million death each year, yet early diagnosis remains a formidable challenge. Many studies have focused on the diagnostic accuracy of microRNAs (miRNAs) for sepsis in recent years, particularly miR-155-5p, miR-21, miR-223-3p, miR-146a, and miR-125a. Thus, we conducted this meta-analysis to explore if miRNAs may be used as a biomarker for sepsis detection. Methods We searched PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, and China National Knowledge Infrastructure through May 12, 2022. This meta-analysis was conducted using Meta-disc 1.4 and STATA 15.1 in a fixed/random-effect model. Results The analysis included a total of 50 relevant studies. The overall performance of total miRNAs detection was: pooled sensitivity, 0.76 (95% confidence interval [CI], 0.75 to 0.77); pooled specificity, 0.77 (95%CI, 0.75 to 0.78); and area under the summary receiver operating characteristic curves value (SROC), 0.86. The subgroup analysis suggested that detection in miR-155-5p group had the highest area under the curve (AUC) of SROC among all miRNAs: pooled sensitivity, 0.71 (95%CI, 0.67 to 0.75); pooled specificity, 0.82 (95%CI, 0.76 to 0.86); and SROC, 0.85. MiR-21, miR-223-3p, miR-146a, and miR-125a had SROC values of 0.67, 0.78, 0.69, and 0.74, respectively. The specimen type was found to be a source of heterogeneity in the meta-regression study. The SROC of serum was higher than that of plasma (0.87 and 0.83, respectively). Conclusions Our meta-analysis revealed that miRNAs, specifically miR-155-5p, could be useful biomarkers for detecting sepsis. A clinical serum specimen is also indicated for diagnostic purposes.

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Background PRKAG2 cardiac syndrome is a rare autosomal dominant genetic disorder caused by a PRKAG2 gene variant. There are several major adverse cardiac presentations, including hypertrophic cardiomyopathy (HCM) and life‐threatening arrhythmia. Two cases with pathogenic variants in the PRKAG2 gene are reported here who presents different cardiac phenotypes. Methods Exome sequencing and variant analysis of PRKAG2 were performed to obtain genetic data, and clinical characteristics were determined. Results The first proband was a 9‐month‐old female infant (Case 1), and was identified with severe DCM and resistant heart failure. The second proband was a 10‐year‐old female infant (Case 2), and presented with HCM and ventricular preexcitation. Exome sequencing identified a de novo c.425C > T (p.T142I) heterozygous variant in the PRKAG2 gene for Case 1, and a c.869A > T (p.K290I) for Case 2. The mutated sites in the protein were labeled and identified as p.K290 in the CBS domain and p.T142 in the non‐CBS domain. Differences in the molecular functions of CBS and non‐CBS domains have not been resolved, and variants might lead to the different cardiomyopathy phenotypes. Single‐cell RNA analysis demonstrated similar expression levels of PRKAG2 in cardiomyocytes and conductive tissues. These results suggest that the arrhythmia induced by the PRKAG2 variant was the primary change, and not secondary to cardiomyopathy. Conclusion In summary, this is the first case report to describe a DCM phenotype with early onset in patients possessing a PRKAG2 c.425C > T (p.T142I) pathogenic variant. Our results aid in understanding the molecular function of non‐CBS variants in terms of the disordered sequence of transcripts. Moreover, we used scRNA‐seq to show that electrically conductive cells express a higher level of PRKAG2 than do cardiomyocytes. Therefore, variants in PRKAG2 are expected to also alter the biological function of the conduction system.