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Breast cancer is the main cancer type with more than 2.2 million cases in 2020, and is the principal cause of death in women; with 685000 deaths in 2020 worldwide. The estrogen receptor is involved at least in 70% of breast cancer diagnoses, and the agonist and antagonist properties of the drug in this receptor play a pivotal role in the control of this illness. This work evaluated the agonist and antagonist mechanisms of 30 cannabinoids by employing molecular docking and dynamic simulations. Compounds with docking scores < -8 kcal/mol were analyzed by molecular dynamic simulation at 300 ns, and relevant insights are given about the protein's structural changes, centered on the helicity in alpha-helices H3, H8, H11, and H12. Cannabicitran was the cannabinoid that presented the best relative binding-free energy (-34.96 kcal/mol), and based on rational modification, we found a new natural-based compound with relative binding-free energy (-44.83 kcal/mol) better than the controls hydroxytamoxifen and acolbifen. Structure modifications that could increase biological activity are suggested., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Composting and vermicomposting generate a valuable product rich in plant nutrients and at the same time, reduce environmental pollution. However, along with these processes and in relation to the metabolism of the microorganism and the worms present in the vermicomposting, CO 2 is emitted to the atmosphere, contributing to the greenhouse effect. Taking these issues into account, different masses of fly ash were used to study the control of the CO 2 of the gas coming from a vermicomposting process and to evaluate the possibility of using the adsorbent as fertilizer in the culture of lettuce Lactuca sativa. Along the vermicomposting process, an increase in the concentration of CO 2 emissions was observed, with a maximum level of emission at the day 20 of the process and an average of 770 mg/L in air. After the adsorption process, the CO 2 concentration was lower due to the effect of the fly ash that was able to trap the emitted gas. The percentage of CO 2 adsorption shows maximum values of 55.5, 58.1 and 63.8% with 0.5, 1 and 1.5 kg of fly ash, respectively. The CO 2 uptake capacities of the different loads of fly ash used were 3.39, 7.03 and 6.84 mmol CO 2 /g sorbent with 0.5, 1 and 1.5 kg of fly ash, respectively. After five weeks of sowing L. sativa, it was observed that when no fly ash was used in the soil, the length of the stem was 10.2 cm. Then, the length of the stem was 22 cm, and 16 cm when 10% of fly ash was applied and not applied in the adsorption process, getting a significant correlation between the load of fly ash and the length of the stem. The r when fly ash was used in the adsorption process was 0.9817 and 0.9811 when no ash fly was used in the process., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Treatments for toxoplasmosis such as pyrimethamine have shown numerous side effects. It has been reported that the likelihood of relapse associated with pyrimethamine-based therapy in patients with HIV and toxoplasmic encephalitis (TE) can have significant implications, even for patients who often develop new lesions in areas of the brain previously free of infection. This led us to research for new agents against Toxoplasma gondii. Recent findings have shown the potent biological activity of 4-thiazolidinones. We proposed to design and synthesize a new series of 2-hydrazono-4-thiazolidinones derivatives to evaluate the in vitro growth inhibition effect on T. gondii. The growth rates of T. gondii tachyzoites in Human Foreskin Fibroblast (HFF) cell culture were identified by two in vitro methodologies. The first one was by fluorescence in which green fluorescent RH parasites and cherry-red fluorescent ME49 parasites were used. The second one was a colorimetric methodology using β-Gal parasites of the RH strain constitutively expressing the enzyme beta-galactosidase. The 4-thiazolidinone derivatives 1B, 2B and 3B showed growth inhibition at the same level of Pyrimethamine. These compounds showed IC 50 values of 1B (0.468-0.952 μM), 2B (0.204-0.349 μM) and 3B (0.661-1.015 μM) against T. gondii. As a measure of cytotoxicity the compounds showed a TD 50 values of: 1B (60 μM), 2B (206 μM) and 3B (125 μM). The in vitro assays and molecular modeling results suggest that these compounds could act as possible inhibitors of the Calcium-Dependent Protein Kinase 1 of T. gondii. Further, our results support the fact that of combining appropriate detection technologies, combinatorial chemistry and computational biology is a good strategy for efficient drug discovery. These compounds merit in vivo analysis for anti-parasitic drug detection., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Studies in animals and human muscle have demonstrated differential splicing of the insulin-like growth factor-1 gene in response to mechanical strain and damage. We conducted a study on the expression of insulin-like growth factor-1 splice variants in the levator ani muscle after the first vaginal delivery., Study Design: Ten women were recruited after the first vaginal delivery. Biopsy specimens were taken vaginally of the pubovisceral component of the levator ani muscle. Five nonpregnant women were recruited as control subjects. Samples were processed with real-time quantitative polymerase chain reaction, with specific primers for the insulin-like growth factor-1 splice variants., Results: Insulin-like growth factor splice variants mechano growth factor and insulin-like growth factor-1Ea were significantly up-regulated (100- and 1000-fold) in the delivery population, compared with control subjects (P=.012 and .04, respectively). Statistical analysis indicated a correlation between the expression of the insulin-like growth factor-1 splice variants and the length of the second stage., Conclusion: These results show that damaged levator ani muscle results from stretch and overload after the first vaginal delivery.

The complete assignments of twelve 4-aryl-7-thioaryl-1,5-benzodiazepines 1H and 13C spectra, performed with the use of high resolution variable solvent and temperature 1D and 2D techniques (e.g. HOMOCOSY, NOESY, HMQC and HMBC), lead to the determination of conformational equilibria between two rotamers having the aromatic ring of the thioaryl oriented in a perpendicular or helical orientation toward the benzodiazepine ring. The restricted rotation was evaluated from the population of these conformers.