Activity prediction of human cytochrome P450 inhibitors based on multiple deep learning and machine learning methods / 中国药科大学学报

@#Inhibition of human cytochrome P450 (CYP) can lead to drug-drug interactions, resulting in serious adverse reactions.It is therefore crucial to accurately predict the inhibitory power of a given compound against a particular CYP isoform.This study compared 11 machine learning methods and 2 deep learning models based on different molecular representations.The experimental results showed that the CatBoost machine learning model based on RDKit_2d+Morgan outperformed other models in terms of accuracy and Mathews coefficient, and even outperformed previously published models.Moreover, the experimental results also showed that the CatBoost model not only had superior performance, but also consumed less computational resources.Finally, this study combined the top 3 performing models as co_model, which slightly outperformed the CatBoost model alone in terms of performance.

Virtual screening of potential ATR kinase inhibitors based on machine learning and molecular docking / 中国药科大学学报

@#Screening potential active compounds from molecular libraries is a common method for drug discovery.However, with the continuous exploration of chemical space, there are already compound libraries with more than billions of molecules, so molecular docking is no longer enough to quickly screen specific target inhibitors from the ultra-large compound libraries.This study proposes a method for screening potential active compounds, which involves filtering and selecting compounds from a candidate compound library containing over 5.5 billion molecules through a series of steps, including calculating physical and chemical property similarities, constructing machine learning prediction models, and molecular docking.In the end, 51 compounds with potential ataxia telangiectasia-mutated and rad3-related (ATR) inhibitory activity were obtained.This method is effective for rapidly screening novel potential active compounds from large compound libraries.

Effect of Reduning Injection， Shenfu Injection Combined with Gefitinib on Proliferation， Stemness Characteristics and Metabolism of Non-small Cell Lung Cancer Cells / 中国实验方剂学杂志

ObjectiveTo compare and observe the effect of Reduning injection （mainly clearing heat）， Shenfu injection （mainly warming Yang） combined with gefitinib on the proliferation， apoptosis， stemness characteristics and metabolism of lung cancer cells. MethodDifferent non-small cell lung cancer （NSCLC） cell lines were selected and intervened with gefitinib （5， 10， 20 μmol·L-1）， Reduning injection （0.6%， 0.9%）， Shenfu injection （0.6%， 0.9%）， gefitinib combined with Reduning injection， and gefitinib combined with Shenfu injection. Cell proliferation in each group was detected by cell counting kit-8 （CCK-8） assay， and cell apoptosis was detected by flow cytometry. The mRNA and protein expressions of lung cancer stem cell markers sex determining region Y-box 2 （Sox2） and aldehyde dehydrogenase family 1 member A1 （ALDH1A1） were determind by real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. The redox ratio of lung cancer cells was observed by femtosecond label-free imaging （FLI） and energy metabolism instrument was used to determine the glycolysis level in cells. ResultCompared with the blank group， Reduning injection reduced the survival rate of lung cancer cells （P<0.05）， increased the apoptosis rate （P<0.05）， down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 （P<0.05）， and up-regulated the redox ratio of cells （P<0.05）， while Shenfu injection exerted no remarkable effect on the above indexes. In addition， compared with gefitinib alone， Reduning injection combined with gefitinib inhibited the survival rate of lung cancer cells （P<0.05）， promoted the cell apoptosis （P<0.05）， down-regulated the mRNA and protein expressions of Sox2 and ALDH1A1 （P<0.05）， up-regulated the redox ratio of cells （P<0.05）， and lowered the proton efflux rate of glycolysis （P<0.05）， while Shenfu injection combined with gefitinib failed to affect these indexes of lung cancer cells significantly. ConclusionReduning injection may inhibit stemness characteristics of tumor cells by regulating their metabolism to enhance the proliferation-inhibiting and pro-apoptotic effects of gefitinib on lung cancer cells， while Shenfu injection had no significant enhancing effect on gefitinib. This indicates that epidermal growth factor receptor tyrosine kinase inhibitors （EGFR-TKIs） should be used in combination with heat-clearing Chinese medicines.

Effect of captopril pretreatment on the dentin bonding durability of self-etch adhesive / 浙江大学学报·医学版

To investigate the effect of captopril on the dentin bonding durability of self-etch adhesive. Different concentrations of captopril ethanol solutions or captopril ethanol/water solutions were prepared to pretreat dentin as primer for the self-etch adhesives. The surface morphology of the dentin was observed with scanning electron microscopy (SEM). Based on the morphology analysis, the pretreatment condition was selected and two self-etch adhesives were employed to evaluate the improvement effect of the captopril pretreatment on the dentin bonding durability. : SEM showed that the pretreatment of captopril ethanol solutions and captopril ethanol/water solutions were able to remove the smear lay and partially expose collagen matrix. According to the SEM results, the pretreating condition of captopril ethanol/water solution with the pretreating time of was selected for further dentin bonding study. For Clearfil SEBOND system, the immediate bonding strength increased from to  (0.05]. For Clearfil S BOND system, there was no significant difference in the immediate bonding strength between the experimental group [(4.07) MPa] and the control group[(4.11) MPa]. But after one-year aging, the bonding strength of the experimental group was higher than that of the control group <0.05]. : The pretreatment with captopril ethanol/water solution increases the dentin bonding strength of the self-etch adhesive systems and also improves the bonding durability.

A potent neutralizing nanobody against SARS-CoV-2 with inhaled delivery potential

The outbreak of COVID-19 has emerged as a global pandemic. The unprecedented scale and severity call for rapid development of effective prophylactics or therapeutics. We here reported Nanobody (Nb) phage display libraries derived from four camels immunized with the SARS-CoV-2 spike receptor-binding domain (RBD), from which 381 Nbs were identified to recognize SARS-CoV-2-RBD. Furthermore, seven Nbs were shown to block interaction of human angiotensin converting enzyme 2 (ACE2) with SARS-CoV-2-RBD-variants, bat-SL-CoV-WIV1-RBD and SARS-CoV-1-RBD. Among the seven candidates, Nb11-59 exhibited the highest activity against authentic SARS-CoV-2 with ND50 of 0.55 g/mL. Nb11-59 can be produced on a large-scale in Pichia pastoris, with 20 g/L titer and 99.36% purity. It also showed good stability profile, and nebulization did not impact its stability. Overall, Nb11-59 might be a promising prophylactic and therapeutic molecule against COVID-19, especially through inhalation delivery. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=154 SRC="FIGDIR/small/242867v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@e4434org.highwire.dtl.DTLVardef@9fee79org.highwire.dtl.DTLVardef@1e15bb1org.highwire.dtl.DTLVardef@4adb0c_HPS_FORMAT_FIGEXP M_FIG C_FIG

Risk factors of recurrence for gastric mucosal lesions after endoscopic submucosal dissection / 中华消化内镜杂志

Objective To investigate the recurrence and risk factors of gastric high-grade intraepithelial neoplasia(HGIN)and early gastric cancer(EGC)after endoscopic submucosal dissection (ESD). Methods The clinical and follow-up data on 444 patients(451 lesion)with HGIN and EGC undergoing ESD in Digestive Endoscopy Center of Chinese PLA General Hospital from November 2006 to January 2016 were summarized, and the risk factors of recurrence were analyzed. Results A total of 410 patients were followed-up, and the recurrence rate was 3.2%(13 patients, 13 lesions), with mean recurrence time of 17.6±9.6 months(6-38 months). Univariate and multivariate analysis revealed that the size of the lesion>4.0 cm was the only risk factor of recurrence(P=0.012,OR=10.855,95%CI:1.673~70.442). Conclusion The rate of recurrence is increasing with the EGC extending, therefore, postoperative monitoring should be strengthened to patients with larger lesion.

BET Bromodomain inhibitors and degraders based on polypharmacology:research advances / 国际药学研究杂志

Bromodomain and extra-terminal domain(BET)Bromodomain has become a new target for the treatment of cancers and other human disorders. Nowadays,several classes of its potent and selective small-molecule inhibitors have been identified,many of which are in clinical trials. Preclinical and clinical data have shown that BET Bromodomain inhibitors have good prospects. Howev-er,there are potential therapeutic deficiencies,such as drug resistance. At present,attempts are being made to develop BET Bromodo-main inhibitors and degraders based on polypharmacology,combining BET Bromodomain with other targets of different mechanisms. In this paper,small-molecule kinase/BET inhibitors,small-molecule histone deacetylases(HDAC)/BET inhibitors and BET protein degraders are reviewed,which may provide guidance for further research on BET protein.

Advances in BET bromodomain protein inhibitors / 中国药科大学学报

@#Recognizing acetyl-lysine of histone is a key process of epigenetic regulation that is mediated by a protein module called bromodomain(BRD). The bromodomain inhibitors of the bromodomains and extra-terminal(BET)family have shown great potential in anti-inflammatory and antiproliferative effects. Through a review of diseases and structures about BET bromodomain, different kinds of inhibitors were analyzed and their structure-activity relationships were summarized. Herenin, the recent advances reported are reviewed for discovering more excellent small molecule inhibitors.

Post-traumatic Diabetes Insipidus / 中国医师杂志

Objective To study the clinical features and diagnosis and therapy of the post-traumatic diabetes insipidus.Methods Forty patients with post-traumatic diabetes insipidus who admitted to our department from June 1990 to June 2000 were analyzed retrospectively.There were 26 cases of male and 14 cases of female.Average age was 21 years old.Results GCS score of twenty nine cases was 8;nine cases:9～12;two cases:13～15 at admission.37 cases survived in which 33 cases had a good recovery,and other 4 cases with persistent diabetes insipidus.The other 3 death after therapy.ConclusionMost post-traumatic diabetes insipidus are temporary,their prognosis are good through early diagonosis and effective treatment.