Novel Coumarins Derivatives for A. baumannii Lung Infection Developed by High-Throughput Screening and Reinforcement Learning.

With the increasing resistance of Acinetobacter baumannii (A. baumannii) to antibiotics, researchers have turned their attention to the development of new antimicrobial agents. Among them, coumarin-based heterocycles have attracted much attention due to their unique biological activities, especially in the field of antibacterial infection. In this study, a series of coumarin derivatives were synthesized and screened for their bactericidal activities (Ren et al. 2018; Salehian et al. 2021). The inhibitory activities of these compounds on bacterial strains were evaluated, and the related mechanism of the new compounds was explored. Firstly, the MIC values and bacterial growth curves were measured after compound treatment to evaluate the antibacterial activity in vitro. Then, the in vivo antibacterial activities of the new compounds were assessed on A. baumannii-infected mice by determining the mice survival rates, counting bacterial CFU numbers, measuring inflammatory cytokine levels, and histopathology analysis. In addition, the ROS levels in the bacterial cells were measured with DCFH-DA detection kit. Furthermore, the potential target and detailed mechanism of the new compounds during infection disease therapy were predicted and evidenced with molecular docking. After that, ADMET characteristic prediction was completed, and novel, synthesizable, drug-effective molecules were optimized with reinforcement learning study based on the probed compound as a training template. The interaction between the selected structures and target proteins was further evidenced with molecular docking. This series of innovative studies provides important theoretical and experimental data for the development of new anti-A. baumannii infection drugs.

Phylogenetic trees, conserved motifs and predicted subcellular localization for transcription factor families in pearl millet.

OBJECTIVES: Pearl millet (Pennisetum glaucum) is a cereal crop that is tolerant to a high temperature, a drought and a nutrient-poor condition. Characterizing pearl millet proteins can help to improve productivity of pearl millet and other crops. Transcription factors in general are proteins that regulate transcription of their target genes and thereby regulate diverse processes. Some transcription factor families in pearl millet were characterized in previous studies, but most of them are not. The objective of the data presented was to characterize amino acid sequences for most transcription factors in pearl millet. DATA DESCRIPTION: Sequences of 2395 pearl millet proteins that have transcription factor-associated domains were extracted. Subcellular and suborganellar localization of these proteins was predicted by MULocDeep. Conserved domains in these sequences were confirmed by CD-Search. These proteins were classified into 85 families on the basis of those conserved domains. A phylogenetic tree including pearl millet proteins and their counterparts in Arabidopsis thaliana and rice was constructed for each of these families. Sequence motifs were identified by MEME for each of these families.

Brain metastases: It takes two factors for a primary cancer to metastasize to brain.

Brain metastasis of a cancer is a malignant disease with high mortality, but the cause and the molecular mechanism remain largely unknown. Using the samples of primary tumors of 22 cancer types in the TCGA database, we have performed a computational study of their transcriptomic data to investigate the drivers of brain metastases at the basic physics and chemistry level. Our main discoveries are: (i) the physical characteristics, namely electric charge, molecular weight, and the hydrophobicity of the extracellular structures of the expressed transmembrane proteins largely affect a primary cancer cell's ability to cross the blood-brain barrier; and (ii) brain metastasis may require specific functions provided by the activated enzymes in the metastasizing primary cancer cells for survival in the brain micro-environment. Both predictions are supported by published experimental studies. Based on these findings, we have built a classifier to predict if a given primary cancer may have brain metastasis, achieving the accuracy level at AUC = 0.92 on large test sets.

Changes of bladder mucosal inflammatory factors and prognosis in cystitis glandularis.

Objective: To investigate the relationships of bladder mucosal inflammatory factors, interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) with the occurrence and development of cystitis glandularis (CG), and their effects on the prognosis. Methods: A total of 61 patients with CG from January 2010 to 2014 were randomly selected. Tissue specimens of postoperative patients were collected. 16 cases of normal bladder mucosa during the same period were collected as a control group. Blood specimens and fresh tissue specimens were collected from 6 patients with CG. The messenger ribonucleic acid (mRNA) levels of IL-1, IL-6 and TNF-α were detected via reverse transcription polymerase chain reaction (RT-PCR). The protein levels of IL-1, IL-6 and TNF-α in serum of patients with GC and normal controls were detected via an enzyme-linked immunosorbent assay (ELISA). The protein expressions of IL-1, IL-6 and TNF-α were detected via immunohistochemistry (IHC), and their relationships with the clinical features and prognosis of GC were analyzed. A Cox proportional hazard regression model was used for multivariate analysis on the prognostic factors of CG, and all the tests were performed with 95% confidence interval (CI). Results: The protein expressions of IL-1, IL-6 and TNF-α in patients with CG were obviously higher than those in normal group. The mRNA levels of IL-1, IL-6 and TNF-α in the serum of patients with CG were also significantly higher than those in normal group (P<0.05). The expressions of IL-1, IL-6 and TNF-α in CG were positively correlated. TNF-α is an independent prognostic factor of CG. Conclusion: IL-1, IL-6 and TNF-α are associated with the occurrence and development of CG. TNF-α presents as an independent prognostic factor of CG that can be used for the diagnosis of cystitis glandularis.

[Efficacy and safety of dapoxetine in the treatment of premature ejaculation].

OBJECTIVE: To evaluate the clinical effect and safety of dapoxetine in the treatment of premature ejaculation (PE). METHODS: We randomly assigned 116 PE patients to receive dapoxetine on demand at 30 mg qd (dapoxetine group, n = 60, aged 23-49 years) or oral tamsulosin at 20 mg qd (control group, n = 56, aged 24-46 years). After 4 weeks of medication, we compared the clinical global impression of change (CGIC) , PE profile (PEP) scores, intravaginal ejaculation latency time (IELT) , and adverse reactions between the two groups of patients. RESULTS: Compared with the baseline, the IELT was remarkably prolonged after treatment both in the dapoxetine group ([0.86 ± 0.17] vs [4.32 ± 2.23] min, P < 0.05) and the control ([0.88 ± 0.15] vs [4.17 ± 2.26] min, P < 0.05), with no statistically significant difference between the two groups (P > 0. 05). The post-treatment rate of CGIC in the dapoxetine group had no statistically significant difference from that in the control (85.00% vs 82.14%, P > 0.05). In comparison with pre-treatment, the patients of both the dapoxetine and control groups showed dramatically improved scores after medication in perceived control over ejaculation (0.85 ± 0.23 vs 2.13 ± 0.97 and 0.88 ± 0.21 vs 2.06 ± 0.34, both P < 0.05), ejaculation-related personal distress (1.15 ± 0.64 vs 2.89 ± 0.26 and 1.19 ± 0.53 vs 2.82 ± 0.69, both P < 0.05), satisfaction with sexual intercourse (0.81 ± 0.33 vs 2.58 ± 0.37 and 0.79 ± 0.28 vs 2.45 ± 0.32, both P < 0.05), and ejaculation-related interpersonal difficulty (2.05 ± 0.61 vs 3.24 ± 0.35 and 2.03 ± 0.65 vs 3.18 ± 0.76, both P < 0.05), with no significant differences between the two groups (P > 0.05). The incidence of adverse reactions was significantly lower in the dapoxetine than in the control group (3.33% vs 30.36%, P < 0.05). CONCLUSION: Dapoxetine is effective for the treatment of PE, with its advantages of prolonging the intravaginal ejaculation latency time, improving the quality of sexual life, and low incidence of adverse reactions.

Synthesis of ring-contracted erythromycin A derivatives via microwave-assisted intramolecular transesterification.

The synthesis of ring-contracted derivatives of erythromycin A via intramolecular transesterification under microwave irradiation of 8,9-anhydroerythromycin A 6,9-hemiketal and its derivatives is described. It was found that microwave irradiation could significantly improve the yields and shorten the reaction times under either solvent-containing (method A) or solvent-free (method B) conditions.