Background Endoplasmic reticulum stress exists within a tumor. Glucose‐regulated protein 94 (GRP94) is a stress‐induced chaperone protein involved in tumor development and progression. Its role in myeloma, colon cancer, and other tumors has been confirmed, but its role in lung cancer is unclear. This study aimed to determine the role of GRP94 in lung cancer progression and prognostic prediction. Methods Immunohistochemical staining of GRP94 in human lung adenocarcinoma (AD) and corresponding normal tissue was performed, and its relationship with FOXP3+ regulatory T‐cell (Treg) infiltration analyzed. We investigated the role of GRP94 in the behavior of lung AD cells by inhibiting GRP94 expression in A549 cells. Western blotting was used to detect the TGF‐β/SMAD2 signaling molecules and explore the possible molecular mechanism of GRP94. Results GRP94 mRNA (encoded by HSP90B1) and protein levels were upregulated and elevated, respectively, in lung AD compared to normal lung tissues. High GRP94 expression was associated with an advanced disease stage and poor survival. There was a positive correlation between GRP94 expression and FOXP3+ Treg infiltration into lung AD tissues. Our results confirm that GRP94 knockdown inhibits cell proliferation and promotes cell apoptosis by increasing caspase‐7 and CHOP levels in lung AD cells. TGF‐β and SMAD2 protein levels were decreased after GRP94 depletion. Conclusions Our study revealed that that GRP94 expression in lung AD favors tumor progression and predicts poor prognosis. The oncogenic role of GRP94 may involve inducing Treg infiltration by promoting the TGF‐β signaling pathway. Key points GRP94 protein levels were elevated in lung AD tissues compared to normal lung tissues. The high expression of GRP94 in lung AD favors tumor progression and predicts poor prognosis. The oncogenic role of the molecule GRP94 may involve the stimulation of Treg infiltration via promotion of the TGF‐β signaling pathway.

This article analyzes 12 semi-structured interviews within the framework of transformational leadership, using a set of open-ended questions addressed to 12 directors (six men and six women) of academic libraries in high-ranking universities in four different countries (Australia, New Zealand, the United Kingdom, and the United States of America). It also investigates the interviewees’ approach to managing and leading their library organizations within the context of the opportunities and challenges facing their organizations as well as their parent institutions. The interpretation of the participants’ responses is based on the four ‘I’s, the four dimensions of the concept of transformational leadership: (1) Idealized influence, (2) Inspirational motivation, (3) Intellectual stimulation, and (4) Individualized consideration. The findings indicated that academic library directors who chose to implement transformational leadership noted its significance as a major contributing factor to the enhancement of inner communication and building mutual trust, and respect within the library organization. This, in turn, has fostered a motivated and creative work environment that has ensured personal and collective success and institutional advancement. Transformational leadership contributes to promoting sustained organizational performance based on adaptability to the rapidly changing environment of academic libraries worldwide.

Decidual macrophages (dMϕs) play critical roles in the establishment of microhomeostasis at the maternal-fetal interface during pregnancy. Impaired macrophage polarization during early pregnancy is associated with recurrent spontaneous abortion (RSA). In the present study, the SEC5 expression level was found to be significantly decreased in primary dMϕs of patients with RSA, and downregulation of SEC5 expression inhibited M2 polarization and STAT6 phosphorylation, whereas SEC5 overexpression in the Mϕs promoted M2 polarization and STAT6 phosphorylation in vitro. We subsequently found that SEC5 interacted with STAT6 in THP-1-derived Mϕs. The abundance of phosphorylated STAT6 (pSTAT6) protein was obviously increased, with a predominant distribution in the nucleus, after M2 polarization of Mϕs, and SEC5 protein was colocalized with pSTAT6. Moreover, a significantly reduced pSTAT6 expression level was observed in the dMϕs of patients with RSA. M2 polarization of Mϕs showed a stimulatory effect on the proliferation and invasion of human extravillous trophoblasts (EVTs) in vitro, and downregulation of SEC5 expression in Mϕs effectively reversed this effect. In a mouse model of LPS-induced early pregnancy loss, the uterine SEC5 expression level and the number of M2-Mϕs at the maternal-fetal interface were significantly reduced. More interestingly, heterozygous SEC5-deficient (SEC5−/+) pregnant mice were more sensitive to LPS-induced pregnancy loss. Taken together, these data indicate that SEC5 participates in the regulation of M2 polarization of Mϕs by interacting with STAT6 and that decreased SEC5 expression inhibits the M2 polarization of dMϕs and results in early pregnancy loss by interfering with the physical activities of EVTs and immunotolerance at the maternal-fetal interface.

Problem We aimed to evaluate potential biomarkers and candidate drugs for recurrent spontaneous abortion (RSA) and explore functional circular RNA pathways involved in regulating RSA. Method of study Expression profiles of placental villus and decidua samples derived from females with RSA and those with healthy pregnancies who underwent induced abortion were analyzed using high‐throughput RNA whole transcriptome sequencing. Abnormally expressed circular RNAs in a larger cohort of samples were validated using real‐time quantitative polymerase chain reaction. Drug discovery and molecular docking were performed using online databases and the Autodock tool, respectively. Results In total, 2103 and 2160 circular RNAs were detected in three pairs of villi and three pairs of decidual tissues, respectively. A total of 22 circular RNAs, 58 miRNAs, and 393 mRNAs with significantly different expression patterns were identified. Five circular RNAs were verified, and the expression of hsa_circ_0088485 was significantly upregulated in the RSA group (P = .041) with a high area under the curve value (.727), sensitivity (76.5%), and specificity (64.7%). GO and KEGG enrichment analyses indicated that differentially expressed genes were associated with angiogenesis and cell adhesion. Drug discovery and molecular docking were analyzed based on 93 differentially expressed mRNAs of the ceRNA network. A total of 36 chemicals were identified as putative bioactive molecules for RSA, and one representative chemical was identified for docking with six proteins. Conclusions These findings provide novel insights into the mechanism of regulation of RSA by circular RNA and its clinical diagnosis and treatment.