Strategies for developing retinoic acid receptor alpha-selective antagonists as novel agents for male contraception.

Reported here are the synthesis and in vitro evaluation of a series of 26 retinoic acid analogs based on dihydronaphthalene and chromene scaffolds using a transactivation assay. Chromene amide analog 21 was the most potent and selective retinoic acid receptor α antagonist identified from this series. In vitro evaluation indicated that 21 has favorable physicochemical properties and a favorable pharmacokinetic PK profile in vivo with significant oral bioavailability, metabolic stability, and testes exposure. Compound 21 was evaluated for its effects on spermatogenesis and disruption of fertility in a mouse model. Oral administration of compound 21 at low doses showed reproducibly characteristic albeit modest effects on spermatogenesis, but no effects on fertility were observed in mating studies. The inhibition of spermatogenesis could not be enhanced by raising the dose and lengthening the duration of dosing. Thus, 21 may not be a good candidate to pursue further for effects on male fertility.

Energy generation from bioelectrochemical techniques: Concepts, reactor configurations and modeling approaches.

The process industries play a significant role in boosting the economy of any nation. However, poor management in several industries has been posing worrisome threats to an environment that was previously immaculate. As a result, the untreated waste and wastewater discarded by many industries contain abundant organic matter and other toxic chemicals. It is more likely that they disrupt the proper functioning of the water bodies by perturbing the sustenance of many species of flora and fauna occupying the different trophic levels. The simultaneous threats to human health and the environment, as well as the global energy problem, have encouraged a number of nations to work on the development of renewable energy sources. Hence, bioelectrochemical systems (BESs) have attracted the attention of several stakeholders throughout the world on many counts. The bioelectricity generated from BESs has been recognized as a clean fuel. Besides, this technology has advantages such as the direct conversion of substrate to electricity, and efficient operation at ambient and even low temperatures. An overview of the BESs, its important operating parameters, bioremediation of industrial waste and wastewaters, biodegradation kinetics, and artificial neural network (ANN) modeling to describe substrate removal/elimination and energy production of the BESs are discussed. When considering the potential for use in the industrial sector, certain technical issues of BES design and the principal microorganisms/biocatalysts involved in the degradation of waste are also highlighted in this review.

Hydrothermal carbonization of Typha australis: Influence of stirring rate.

According to existing literature, there are no conclusive results on the impact of stirring on hydrothermal carbonization (HTC); some studies report a significant impact on the product's properties, while others indicate no influence. This study investigates the influence of stirring rate on several responses and properties of HTC products, including solid mass yield, solid carbon fraction, surface area, surface functional groups, morphology, and the fate of inorganic elements during HTC. Waste biomass was introduced as a feedstock to a 2 L HTC reactor, where the effects of temperature (180-250 °C), residence time (4-12 h), biomass to water (B/W) ratio (1-10%), and stirring rate (0-130 rpm) were investigated. The findings of this study conclusively indicated that the stirring rate does not influence any of the studied responses or properties of hydrochar under the selected experimental conditions used in this study. Nevertheless, the results indicated that a low-stirring rate (5 RPM) is enough to slightly enhanced the heating-up phase of the HTC reactor. For future research, it is recommended to examine the impact of stirring rate on the HTC of other types of biomass using the methodology developed in this study.

Nutritional status of under-five aged children of ready-made garment workers in Bangladesh: A cross-sectional study.

BACKGROUND: The ready-made garment (RMG) sector is a significant contributor to the economic growth of Bangladesh, accounting for 10% of the country's GDP and more than 80% of its foreign exchange earnings. The workforce in this sector is predominantly made up of women, with 2.5 million women working in the industry. However, these women face numerous challenges in carrying out their culturally-expected household responsibilities, including childcare, due to severe resource constraints. As a result, the children of these working women have a higher incidence of malnutrition, particularly stunted growth. This study aims to identify the factors that contribute to stunting in children under the age of five whose mothers work in the RMG sector in Bangladesh. METHODS: The study collected data from 267 female RMG workers in the Gazipur district of Bangladesh using a simple random sampling technique. Chi-square tests were used to determine the associations between the factors influencing child stunting, and Multinomial Logit Models were used to estimate the prevalence of these factors. RESULTS: The study found that the prevalence of moderate and severe stunting among the children of RMG workers living in the Gazipur RMG hub was 19% and 20%, respectively. The study identified several significant predictors of child stunting, including the mother's education level, nutritional knowledge, control over resources, receipt of antenatal care, household size, sanitation facilities, and childbirth weight. The study found that improving the mother's education level, increasing household size, and receiving antenatal care during pregnancy were important factors in reducing the likelihood of child stunting. For example, if a mother's education level increased from no education to primary or secondary level, the child would be 0.211 (0.071-0.627) and 0.384 (0.138-1.065) times more likely to have a normal weight and height, respectively, than to be moderately stunted. CONCLUSION: The study highlights the challenges faced by working women in the RMG sector, who often receive minimal wages and have limited access to antenatal care services. To address these challenges, the study recommends policies that support antenatal care for working-class mothers, provide daycare facilities for their children, and implement a comprehensive social safety net program that targets child nutrition. Improving the socioeconomic status of mothers is also critical to reducing child malnutrition in this population.

Evaluation of Senna tora (L.) Roxb. leaves as source of bioactive molecules with antioxidant, anti-inflammatory and antibacterial potential.

Senna tora (L.) Roxb. is an ethno-medicinal herb used by rural and tribal people of the Satpura region of Madhya Pradesh in India and the Phatthalung Province of Thailand for treating rheumatism, bronchitis, ringworm, itches, leprosy, dyspepsia, liver disorders and heart disorders. It is also used in Chinese and Ayurvedic medicine. This study was conducted to investigate the potential of Senna tora (L.) Roxb. as a source of drug candidates against oxidants, inflammation, and bacterial infection. Preliminary phytochemical screening (PPS) and GC-MS were performed to identify the phytochemicals in the ethyl acetate extract of Senna tora (L.) Roxb. leaves (EAESTL). The in vitro antioxidant activity was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH)- and H2O2-scavenging tests; the in vitro anti-inflammatory activity was determined by bovine serum albumin (BSA) denaturation and red blood cell (RBC) hemolysis inhibition; and the antibacterial activity was evaluated by agar-well diffusion methods. Cytotoxicity was estimated by Artemia salina larvae lethality, while acute toxicity was evaluated by oral delivery of the extract to mice. In silico antioxidant, anti-inflammatory, and antibacterial activities were predicted by the Prediction of Activity Spectra for Substances (PASS) program. The pharmacokinetics related to ADME and toxicity tests were determined by the admetSAR2 and ADMETlab2 web servers, and drug-able properties were assessed by the SwissADME server. GC-MS detected fifty-nine phytochemicals that support the types of compounds (phenols, flavonoids, tannins, terpenoids, saponins, steroids, alkaloids, glycosides and reducing sugar) identified by phytochemical screening. EAESTL exhibited dose-dependent antioxidant, anti-inflammatory, and antibacterial activities without any adverse effects or fluctuations in body weight. The PASS program predicted that the identified phytochemicals have antioxidant, anti-inflammatory and antibacterial activities. Among 51 phytochemicals, 16 showed good ADME, and 8 fulfilled drug-able properties without toxicity. Altogether, four phytochemicals, viz., benzyl alcohol, 3-(hydroxy-phenyl-methyl)-2,3-dimethyl-octan-4-one, phenylethyl alcohol and 2,6,6-trimethylbicyclo [3.1.1] heptane-3-ol, showed good pharmacokinetics and drug-able properties without toxicity, along with antioxidant, anti-inflammatory, and antibacterial activities. The obtained results suggest that Senna tora (L.) Roxb. leaves contain bioactive phytochemicals that have the potential to fight against oxidants, inflammation, and bacterial infection as potential drug candidates.

Computational assessment of MCM2 transcriptional expression and identification of the prognostic biomarker for human breast cancer.

Minichromosome maintenance protein 2 (MCM2) is a highly conserved protein from the MCM protein family that plays an important role in eukaryotic DNA replication as well as in cell cycle progression. In addition, it maintains the ploidy level consistency in eukaryotic cells, hence, mutations or alteration of this protein could result in the disintegration of the fine-tuned molecular machinery that can lead to uncontrolled cell proliferation. Moreover, MCM2 has been found to be an important marker for progression and prognosis in different cancers. Therefore, we aimed to analyze the MCM2 expression and the associated outcome in breast cancer (BC) patients based on the publicly available online databases. In this study, server-based gene expression analyses indicate the upregulation of MCM2 (p < 10-6; fold change>2.0) in various BC subtypes as compared to the respective normal tissues. Besides, the evaluation of histological sections from healthy and cancer tissues showed strong staining signals indicating higher expression of MCM2 protein. The overexpression of MCM2 was significantly correlated to promoter methylation and was related to patients' clinical features. Further, mutation analysis suggested missense as the predominant type of mutation (71.4%) with 18 copy-number alterations and 0.2% mutation frequency in the MCM2 gene. This study revealed a significant correlation (Cox p ≤ 0.05) between the higher MCM2 expression and lower patient survival. Finally, we identified the co-expressed genes with gene ontological features and signaling pathways associated in BC development. We believe that this study will provide a basis for MCM2 to be a significant biomarker for human BC prognosis.