MCPNET: Development of an interpretable deep learning model based on multiple conformations of the compound for predicting developmental toxicity.

The development of deep learning models for predicting toxicological endpoints has shown great promise, but one of the challenges in the field is the accuracy and interpretability of these models. The bioactive conformation of a compound plays a critical role for it to bind in the target. It is a big issue to figure out the bioactive conformation in deep learning without the co-crystal structure or highly precise molecular simulations. In this study, we developed a deep learning framework of Multi-Conformation Point Network (MCPNET) to construct classification and regression models, respectively, based on electrostatic potential distributions on vdW surfaces around multiple conformations of the compound using a dataset of compounds with developmental toxicity in zebrafish embryo. MCPNET applied 3D multi-conformational surface point cloud to extract the molecular features for model training, which may be critical for capturing the structural diversity of compounds. The models achieved an accuracy of 85 % on the classification task and R2 of 0.66 on the regression task, outperforming traditional machine learning models and other deep learning models. The key feature of our model is its interpretability with the component visualization to identify the factors contributing to the prediction and to understand the compound action mechanism. MCPNET may predict the conformation quietly close to the bioactive conformation of a compound by attention-based multi-conformation pooling mechanism. Our results demonstrated the potential of deep learning based on 3D molecular representations in accurately predicting developmental toxicity. The source code is publicly available at https://github.com/Superlit-CC/MCPNET.

Synthesis of 2,3-Fused Quinazolinones via the Radical Cascade Pathway and Reaction Mechanistic Studies by DFT Calculations.

An efficient radical cascade cyclization of unactivated alkenes toward the synthesis of a series of ring-fused quinazolinones has been developed in moderate to excellent yields using commercially available ethers, alkanes, and alcohols, respectively, under a base-free condition in a short time without a transition metal as catalyst. Notably, the transformations can be carried out with the advantages of a broad substrate scope and high atomic economy. Density functional theory calculations and wavefunction analyses were performed to elucidate the radical reaction mechanism.

Whole transcriptome analysis reveals that immune infiltration- lncRNAs are related to cellular apoptosis in liver transplantation.

Introduction: In most instances, liver transplantation (LT) is the only available treatment for end-stage liver diseases. However, LT could also induce serious liver diseases or injury, and the underlying mechanisms of LT-induced complications remain largely unknown, especially the mechanisms of the dysfunction of the immune system mediated by long noncoding RNAs (lncRNAs). Methods: In this study, we globally analyzed the proportion of immune cells by using the transcriptome sequencing data (RNA-seq) of needle-core liver biopsies from pre- and post-transplantation recipients. Dysregulated lncRNAs were found to be correlated with the altered fractions of immune cells. We finally explored the potential targets of dysregulated lncRNAs and analyzed their functions in LT. Results: We found that in the samples, some immune cells changed significantly after LT, including CD4 T cells, NK cells and mast cells. The proportion of macrophages in different polarization states also changed significantly, with M0 macrophages increasing and M2 macrophages decreasing. Through weighted gene co-expression network analysis (WGCNA), 7 gene expression modules related to LT were identified. These modules were related to changes in the proportion of different immune cells. The functions of these modules represent the response modes of different functional genes after LT. Among these modules, MEtan and MEyellow modules were primarily enriched in apoptosis and inflammatory pathways. Twelve immunity-related lncRNAs were identified for the first time, and the regulatory network co-changing with immune cells was also identified. The co-expressed genes of these lncRNAs were highly enriched in apoptosis-related pathways. Many apoptosis-related genes were found to be up-regulated after LT. Discussion: In summary, we speculated that the expression and regulation of these apoptotic genes may be related to the changes in the proportion of immune cells. Some of these lncRNAs and apoptosis-related genes have been reported to be related to cell proliferation and apoptosis. They are also potential biomarkers or therapeutic targets.

Reliable CA-(Q)SAR generation based on entropy weight optimized by grid search and correction factors.

Chromosome aberration (CA) is a serious genotoxicity of a compound, leading to carcinogenicity and developmental side effects. In the present manuscript, we developed a QSAR model for CA prediction using artificial intelligence methodologies. The reliable QSAR model was constructed based on an enlarged data set of 3208 compounds by optimizing machine learning and deep learning algorithms based on hyperparametric iterations and using multiple descriptors of molecular fingerprint in combination with drug-like molecular properties (MP) screened by entropy weight methodology on the open-source Python platform. Furthermore, molecular similarity for returning search and molecular connection index for additional descriptor were additionally introduced to differentiate the compounds with high similarity for correct CA prediction for QSAR model generation. The final generated CA-(Q)SAR model exhibited good prediction accuracy of 80.6%. The bias of the final model is about 0.9793. On the basis of generated QSAR model, data analyses were further performed to analyze the typical structure features in numerical intervals (MPI) of molecular properties MW, XlogP, and TPSA, respectively, for potential CA or non-CA toxicity with a normalized occurrence probability (NOP) more than 70%, which may provide useful clues for drug design of leads or candidate devoid of CA genotoxicity.

How to prevent the infection of contaminated abdominal incisions.

BACKGROUND: Surgical site infection is one of the most common complications of conventional laparoscopic surgery. Preventing infection of the incision is particularly important. OBJECTIVE: To discuss how to prevent the occurrence of surgical site infection after contaminated abdominal surgery. METHODS: Five hundred and fifty-one surgery patients with ``contaminated abdominal incisions'' from January 2011 to May 2013 were analyzed in terms of the preventative treatment, and summarized for surgical site infection. Subcutaneous tissue flushed with normal saline + hydrogen peroxide before suturing in the intervention 1 group; subcutaneous tissue flushed with normal saline + 0.5% povidone-iodine before suturing in the intervention 2 group. RESULTS: When subcutaneous fat was contaminated to a depth of ≤ 2.5 cm, the rates of surgical site infection in the control group and the intervention groups showed no significant difference (P > 0.05). When subcutaneous fat was contaminated to a depth of ≥ 3.0 cm, the rate of surgical site infection in the control group compared with the intervention one group was not statistically different (P > 0.05). The rate of surgical site infection in the control group compared with the intervention two group was statistical significant (P < 0.05). The rate of surgical site infection in the intervention one group compared with the intervention two group was statistical significant (P < 0.05). CONCLUSIONS: Preoperative control of the blood sugar; correction of anemia and the hypoalbuminemia; use of intraoperative the high-frequency electrotome; irrigation of the incision with plenty of physiological saline +$ iodophor before suturing the subcutaneous fat layer were key to effectively preventing infection in contaminated abdominal incisions.

[Method of Remote Sensing Identification for Mineral Types Based on Multiple Spectral Characteristic Parameters Matching].

The traditional mineral mapping methods with remote sensing data, based on spectral reflectance matching techniques, shows low accuracy, for obviously being affected by the image quality, atmospheric and other factors. A new mineral mapping method based on multiple types of spectral characteristic parameters is presented in this paper. Various spectral characteristic parameters are used together to enhanced the stability in the situation of atmosphere and environment background affecting. AVIRIS (Airborne Visible Infrared Imaging Spectrometer) data of Nevada Cuprite are selected to determine the mineral types with this method. Typical mineral spectral data are also obtained from USGS (United States Geological Survey) spectral library to calculate the spectral characteristic parameters. A mineral identification model based on multiple spectral characteristic parameters is built by analyzing the various characteristic parameters, and is applied in the mineral mapping experiment in Cuprite area. The mineral mapping result produced by Clark et al. in 1995 is used to evaluate the effect of this method, results show, that mineral mapping results with this method can obtain a high precision, the overall mineral identification accuracy is 78.96%.

[Study of blood oxygen saturation, heart rate changes and plateau reaction of the Antarctic Kunlun station investigation team in different plateau environments].

OBJECTIVE: To explore the blood oxygen saturation and heart rate changes of the Antarctic explorers. METHODS: During August 2010 to April 2011, the changes in blood oxygen saturation, heart rate and plateau reaction of 16 Antarctic expedition team in different plateau environments (Tibetan plateau versus Antarctic plateau) were monitored with the noninvasive pulse oximeter MD300-C. The extent of acute mountain sickness was determined according to the Lake Louise Consensus acute mountain reaction symptom scores and judgment method. RESULTS: The changes of blood oxygen saturation, heart rate at different altitudes of 110, 3650, 4300 m (96.8% ± 1.2%,89.1% ± 1.2%, 86.1% ± 2.0%, (75.0 ± 5.4) times/min, (104.0 ± 4.3) times/min, (113.0 ± 5.2) times/min,F = 214.155, 240.088,both P < 0.05). With rising latitude and elevation gradient in Antarctic plateau, the changes of blood oxygen saturation, heart rate at different altitudes of 2000, 2500, 3000, 3500 and 4087 m(91.9% ± 1.3%,90.5% ± 1.3%,87.6% ± 1.4%,85.0% ± 1.8%,81.5% ± 2.2%, (85.9 ± 3.2) times/min, (90.6 ± 2.8) times/min, (97.8 ± 4.1) times/min, (102.0 ± 3.4) times/min, (106.3 ± 3.9) times/min, F = 105.418, 90.174, both P < 0.05). Levels of blood oxygen saturation and heart rate were both correlated with the risk of altitude sickness (r = -0.446 and 0.565, both P < 0.05). CONCLUSIONS: As the increases of altitude, there are significant changes in oxygen saturation, heart rate of the Antarctic explorers. And with the increases of altitude, the risk of altitude sickness gradually increases.

[The relationship between systemic inflammatory response syndrome and severity of acute pancreatitis combined with plateau erythrocythemia].

OBJECTIVE: To explore the relationship between systemic inflammatory response syndrome(SIRS) and severity of acute pancreatitis combined with plateau erythrocythemia in the high altitude. METHODS: A retrospective analysis on the clinical data which involved acute pancreatitis combined with plateau erythrocythemia (n = 40) and without plateau erythrocythemia (n = 40) admitted from September 2006 to September 2009 was conducted. According to the unified standards, these cases were divided into plateau erythrocythemia group and no plateau erythrocythemia group. The patients in plateau erythrocythemia group were further divided into severe group and mild group according to scores of APACHEII. The data was analyzed according to the patient with (or without) SIRS, SIRS's standard indicators, diagnostic parameter and relation of severity and duration of SIRS in acute pancreatitis combined with plateau erythrocythemia. RESULTS: There was significantly discrepancy between plateau erythrocythemia group and no plateau erythrocythemia group not only in the incidence of patients who developed SIRS, but also in two items of patients fulfilling or not fulfilling diagnostic criteria of SIRS (P < 0.05). There was significant statistical difference in three items of diagnostic parameter of SIRS between plateau erythrocythemia group and no plateau erythrocythemia group (P < 0.05). Significant difference in two and three diagnostic parameter was found on severity of SIRS in acute pancreatitis combined with plateau erythrocythemia (P < 0.05). The more severity acute pancreatitis combined with plateau erythrocythemia was, the longer duration of SIRS was. CONCLUSION: SIRS is highly correlated with the severity of SIRS in acute pancreatitis combined with plateau erythrocythemia in the high altitude.