All-trans retinoic acid acts as a dual-purpose inhibitor of SARS-CoV-2 infection and inflammation.

Coronavirus disease 2019 (COVID-19) was an epidemic that effected human health caused by SARS-CoV-2 infection. All-trans retinoic acid (ATRA) has anti-inflammatory capability. In this article, we evaluated the effectiveness and revealed the molecular mechanism of ATRA for treating SARS-CoV-2 using deep learning, in vitro studies, multi-scale molecular modeling, and network pharmacology. The DeepDTA model suggested that ATRA would be effective against COVID-19. In vitro studies confirmed the antiviral activity of ATRA. Subsequently, multi-scale molecular modeling indicated that ATRA could binding to angiotensin converting enzyme 2 (ACE2), 3C-like protease (3CLpro), RNA dependent RNA polymerase (RdRp), helicase, and 3'-to-5' exonuclease by non-covalent interactions. Additionally, network pharmacology suggested that ATRA alleviated inflammatory response by regulating the IL-17 signaling pathway and binding with TNF, PTGS2, and MAPK1 directly. In summary, our findings provide the first evidence that ATRA suppresses the entry and replication of SARS-CoV-2, and regulates inflammatory response of host cells.

Multi-stage Unet segmentation and automatic measurement of pharyngeal airway based on lateral cephalograms.

OBJECTIVES: Orthodontic treatment profoundly impact the pharyngeal airway (PA) of patients. Airway examination is an integral part of daily orthodontic diagnosis, and lateral cephalograms (LC) are reliable to reveal PA structures. This study attempted to develop a simple method to help clinicians make a preliminary judgement of patients' PA conditions and assess the impact of orthodontic treatment on their airways. METHODS: LCs of 764 patients were used to train a multistage unit segmentation model. Another 130 images were used to validate the model and more 130 images were used to test the model. RESULTS: Unet was used as the backbone, with a mean dice value of 0.8180, precision of 0.8393, and recall of 0.8188. Furthermore, we identified seven key points and measured related indices. The length of the line separating the nasopharynx and oropharynx and the line separating the oropharynx and hypopharynx were manually measured thrice and the average values was compared. The intraclass correlation coefficient (ICC) for the two lines was 0.599 and 0.855. Then, we performed a single linear regression analysis, which indicated a strong correlation between the predictions and measurements for the two lines. CONCLUSIONS: This method is reliable for segmenting three regions (nasopharynx, oropharynx, and hypopharynx) of the PA and calculating related indices. However, the predictions obtained from this model still have errors, and it is necessary for clinical practitioners to assess and adjust the predictions. CLINICAL SIGNIFICANCE: Our model can help orthodontists formulate personalised treatment plans and evaluate the risk of airway stenosis during orthodontic treatment. This method may mark the beginning of a new and simpler approach for PA obstruction detection, specifically tailored to orthodontic patients.

Clonal evolution characteristics and reduced dimension prognostic model for non-metastatic metachronous bilateral breast cancer.

Background: How to evaluate the prognosis and develop overall treatment strategies of metachronous bilateral breast cancer (MBBC) remains confused in clinical. Here, we investigated the correlation between clonal evolution and clinical characteristics of MBBC; we aim to establish a novel prognostic model in these patients. Methods: The data from Surveillance, Epidemiology, and End Results (SEER) database and the First Hospital of Jilin University were analyzed for breast cancer-specific cumulative mortality (BCCM) by competing risk model. Meanwhile, whole-exome sequencing was applied for 10 lesions acquired at spatial-temporal distinct regions of five patients from our own hospital to reconstruct clonal evolutionary characteristics of MBBC. Then, dimensional-reduction (DR) cumulative incidence function (CIF) curves of MBBC features were established on different point in diagnostic interval time, to build a novel DR nomogram. Results: Significant heterogeneity in genome and clinical features of MBBC was widespread. The mutational diversity of contralateral BC (CBC) was significantly higher than that in primary BC (PBC), and the most effective prognostic MATH ratio was significantly correlated with interval time (R 2 = 0.85, p< 0.05). In SEER cohort study (n = 13,304), the interval time was not only significantly affected the BCCM by multivariate analysis (p< 0.000) but determined the weight of clinical features (T/N stage, grade and ER status) on PBC and CBC in prognostic evaluation. Thus, clinical parameters after DR based on interval time were incorporated into the nomogram for prognostic predicting BCCM. Concordance index was 0.773 (95% CI, 0.769-0.776) in training cohort (n = 8,869), and 0.819 (95% CI, 0.813-0.826) in validation cohort (n = 4,435). Conclusions: Bilateral heterogeneous characteristics and interval time were determinant prognostic factors of MBBC. The DR prognostic nomogram may help clinicians in prognostic evaluation and decision making.

A panel regression analysis for the COVID-19 epidemic in the United States.

This study explored the roles of epidemic-spread-related behaviors, vaccination status and weather factors during the COVID-19 epidemic in 50 U.S. states since March 2020. Data from March 1, 2020 to February 5, 2022 were incorporated into panel model. The states were clustered by the k-means method. In addition to discussing the whole time period, we also took multiple events nodes into account and analyzed the data in different time periods respectively by panel linear regression method. In addition, influence of cluster grouping and different incubation periods were been discussed. Non-segmented analysis showed the rate of people staying at home and the vaccination dose per capita were significantly negatively correlated with the daily incidence rate, while the number of long-distance trips was positively correlated. Weather indicators also had a negative effect to a certain extent. Most segmental results support the above view. The vaccination dose per capita was unsurprisingly proved to be the most significant factor especially for epidemic dominated by Omicron strains. 7-day was a more robust incubation period with the best model fit while weather had different effects on the epidemic spread in different time period. The implementation of prevention behaviors and the promotion of vaccination may have a successful control effect on COVID-19, including variants' epidemic such as Omicron. The spread of COVID-19 also might be associated with weather, albeit to a lesser extent.

Comprehensive Analysis of the COVID-19: Based on the Social-Related Indexes From NUMBEO.

Background: The COVID-19 has been spreading globally since 2019 and causes serious damage to the whole society. A macro perspective study to explore the changes of some social-related indexes of different countries is meaningful. Methods: We collected nine social-related indexes and the score of COVID-safety-assessment. Data analysis is carried out using three time series models. In particular, a prediction-correction procedure was employed to explore the impact of the pandemic on the indexes of developed and developing countries. Results: It shows that COVID-19 epidemic has an impact on the life of residents in various aspects, specifically in quality of life, purchasing power, and safety. Cluster analysis and bivariate statistical analysis further indicate that indexes affected by the pandemic in developed and developing countries are different. Conclusion: This pandemic has altered the lives of residents in many ways. Our further research shows that the impacts of social-related indexes in developed and developing countries are different, which is bounded up with their epidemic severity and control measures. On the other hand, the climate is crucial for the control of COVID-19. Consequently, exploring the changes of social-related indexes is significative, and it is conducive to provide targeted governance strategies for various countries. Our article will contribute to countries with different levels of development pay more attention to social changes and take timely and effective measures to adjust social changes while trying to control this pandemic.

Nanoarchitectonics of Illite-Based Materials: Effect of Metal Oxides Intercalation on the Mechanical Properties.

Clay minerals inevitably interact with colloidal oxides (mainly iron and aluminum oxides) in the evolution of natural geomaterials. However, the interaction between the clay minerals and the colloidal oxides affecting the stability and the strength of geotechnical materials remains poorly understood. In the present work, the interaction between the clay minerals and the colloidal oxides was investigated by reaction molecular dynamics simulations to explore the mechanical properties of illite-based materials. It was found that the metal atoms of the intercalated amorphous iron and aluminum oxides interact with oxygen atoms of the silica tetrahedron at the interface generating chemical bonds to enhance the strength of the illite-based materials considerably. The deformation and failure processes of the hybrid illite-based structures illustrated that the Al-O bonds were more favorable to the mechanical properties' improvement of the hybrid system compared with Fe-O bonds. Moreover, the anisotropy of illite was greatly improved with metal oxide intercalation. This study provides new insight into the mechanical properties' improvement of clay-based materials through metal oxides intercalation.

Seasonal drought events in tropical East Asia over the last 60,000 y.

The cause of seasonal hydrologic changes in tropical East Asia during interstadial/stadial oscillations of the last glaciation remains controversial. Here, we show seven seasonal drought events that occurred during the relatively warm interstadials by phytolith and pollen records. These events are significantly manifested as high percentages of bilobate phytoliths and are consistent with the large zonal sea-surface temperature (SST) gradient from the western to eastern tropical Pacific, suggesting that the reduction in seasonal precipitation could be interpreted by westward shifts of the western Pacific subtropical high triggered by changes of zonal SST gradient over the tropical Pacific and Hadley circulation in the Northern Hemisphere. Our findings highlight that both zonal and meridional ocean-atmosphere circulations, rather than solely the Intertropical Convergence Zone or El Niño-Southern Oscillation, controlled the hydrologic changes in tropical East Asia during the last glaciation.