4-Hydroxyphenylacetic acid (4-HPA) is an active component of Chinese herb Aster tataricus which had been widely used in China for the treatment of pulmonary diseases. The aim of this study is to investigate the effect of 4-HPA on seawater aspiration-induced lung injury. Pulmonary inflammation and edema were assessed by enzyme-linked immunosorbent assay (ELISA), bronchoalveolar lavage fluid (BALF) white cell count, Evans blue dye analysis, wet to dry weight ratios, and histology study. Hypoxia-inducible factor-1α (HIF-1α) siRNA and permeability assay were used to study the effect of 4-HPA on the production of inflammatory cytokines and monolayer permeability in vitro. The results showed that 4-HPA reduced seawater instillation-induced mortality in rats. In lung tissues, 4-HPA attenuated hypoxia, inflammation, vascular leak, and edema, and decreased HIF-1α protein level. In primary rat alveolar epithelial cells (AEC), 4-HPA decreased hypertonicity- and hypoxia-induced HIF-1α protein levels through inhibiting the activations of protein translational regulators and via promoting HIF-1α protein degradation. In addition, 4-HPA lowered inflammatory cytokines levels through suppressing hypertonicity- and hypoxia-induced HIF-1α in NR8383 macrophages. Moreover, 4-HPA decreased monolayer permeability through suppressing hypertonicity and hypoxia-induced HIF-1α, which was mediated by inhibiting vascular endothelial growth factor (VEGF) in rat lung microvascular endothelial cell line (RLMVEC). In conclusion, 4-HPA attenuated inflammation and edema through suppressing hypertonic and hypoxic induction of HIF-1α in seawater aspiration-induced lung injury in rats.

Background: The objective of this study was to investigate the use of ensemble methods to improve the prediction of fetal macrosomia and large for gestational age from prenatal ultrasound imaging measurements. Methods: We evaluated and compared the prediction accuracies of nonlinear and quadratic mixed-effects models coupled with 26 different empirical formulas for estimating fetal weights in predicting large fetuses at birth. The data for the investigation were taken from the Successive Small-for-Gestational-Age-Births study. Ensemble methods, a class of machine learning techniques, were used to improve the prediction accuracies by combining the individual models and empirical formulas. Results: The prediction accuracy of individual statistical models and empirical formulas varied considerably in predicting macrosomia but varied less in predicting large for gestational age. Two ensemble methods, voting and stacking, with model selection, can combine the strengths of individual models and formulas and can improve the prediction accuracy. Conclusions: Ensemble learning can improve the prediction of fetal macrosomia and large for gestational age and have the potential to assist obstetricians in clinical decisions.

Immune checkpoint inhibitors (ICIs) markedly promote the survival outcome of advanced melanoma and non-small cell lung cancer (NSCLC). Clinically, favorable ICI treatment efficacy is noticed only in a smaller proportion of patients. Heparan sulfate proteoglycan 2 (HSPG2) frequently mutates in both tumors. Herein, we aim to investigate the immunotherapeutic and immunological roles of HSPG2 mutations in melanoma and NSCLC. A total of 631 melanoma samples and 109 NSCLC samples with both somatic mutational profiles and clinical immunotherapy data were curated. In addition, by using The Cancer Genome Atlas data, genomic and immunological traits behind HSPG2 mutations were elucidated. Melanoma patients with HSPG2 mutations had a markedly extended ICI outcome than other patients. An association between HSPG2 mutations and the improved outcome was further confirmed in NSCLC. In addition, an elevated ICI response rate was presented in HSPG2-mutated NSCLC patients (81.8% vs. 29.7%, p = 0.002). Subsequent analyses revealed that HSPG2-mutated patients had a favorable abundance of response immunocytes, an inferior abundance of suppression immunocytes, enhanced mutational burden, and interferon response-relevant signaling pathways. We uncovered that HSPG2 mutations were predictive of a better ICI response and associated with preferable immunogenicity, which may be considered as a genomic determinant to customize biotherapy strategies.

Fatty acid synthase (FASN) acts as the central member in fatty acid synthesis and metabolism processes, which regulate oncogenic signals and tumor immunogenicity. To date, no studies have reported the connection of FASN mutations with ICI efficacy. In this study, from 631 melanoma and 109 NSCLC patients who received ICI treatments, we retrospectively curated multiomics profiles and ICI treatment data. We also explored the potential molecular biological mechanisms behind FASN alterations. In melanoma patients, FASN mutations were observed to associate with a preferable immunotherapeutic prognosis and response rate (both p < 0.01). These connections were further corroborated by the NSCLC patients (both p < 0.01). Further analyses showed that a favorable tumor immunogenicity and immune microenvironment were involved in FASN mutations. This work confirms the clinical immunotherapy implications of FASN mutation-mediated fatty acid metabolism and provides a possible indicator for immunotherapy prognosis prediction.

Farmers are considered a high-risk group for intentional and unintentional injuries. This review identified significant risk factors for agricultural injuries in farmers and explored injury prevention countermeasures based on the literature. Therefore, CiteSpace software was used to analyze the relevant literature in this field. Additionally, we identified both key risk factors and countermeasures using the Haddon matrix and the 5 E’s risk reduction strategies conceptual framework, respectively. The risk factors were identified from four categories (host, agent, physical environment, and social environment) corresponding to three phases (pre-event, event, and post-event). Interventions of 5 E’s risk reduction strategies including education, engineering, enforcement, economic, and emergency response have been proven effective in preventing injuries or reducing their severity. Our findings provide a comprehensive foundation and research direction for the study and prevention of injuries among farmers.

Remarkable clinical benefits in several advanced cancers are observed under the treatment of immune checkpoint inhibitor (ICI) agents. However, only a smaller proportion of patients respond to the treatments. Reelin (RELN) is frequently mutated in the cancer genome. In this study, the RELN mutation association with ICI treatment efficacy in melanoma and non-small cell lung cancer (NSCLC) was elucidated. Data from 631 melanoma and 109 NSCLC patients with both ICI treatment data and pre-treatment mutational profiles were collected. In addition, from the Cancer Genome Atlas (TCGA) project, we also obtained both tumors to explore the immunologic features behind RELN mutations. Melanoma patients with RELN mutations exhibited a favorable ICI survival benefit when compared with wild-type patients (HR: 0.66, 95% CI: 0.51–0.87, p = 0.003). A higher response rate was also noticed in RELN-mutated patients (38.9% vs. 28.3%, p = 0.017). The association of RELN mutations with a preferable immunotherapy outcome and response was further confirmed in NSCLC. Further exploration demonstrated that favorable immunocyte infiltration and immune response signaling pathways were found in patients with RELN mutations. In this study, RELN mutations were identified to connect with a better immune microenvironment and an improved ICI efficacy in melanoma and NSCLC, which provides a potential biomarker for immunological feature evaluation and immunotherapeutic outcome prediction at the molecular level.