While smoking cessation interventions are available, the offer of these by clinicians and uptake by patients remain limited.Hydrocotyle sibthorpioides Lam. (Araliaceae) is a short and edible medicinal herb, which is used in the traditional system of medicines. The review aims to report the current information of H. sibthorpioides on the basis of its botanical and taxonomical description, traditional use, active phytoconstituents, pharmacological use and toxicity. The information on H. sibthorpioides with respect to its journey from traditional uses to scientific validation was gathered based on the online survey. The results from the review signify that the plant is used by the different tribes of the world for the treatment of patients suffering from fever, edema, dysentery, rheumatalgia, whooping cough, jaundice, throat pain, psoriasis, herpes zoster infection, hepatitis-B infection, soothing pain, dysmenorrhoea and carbunculosis. It is also used as a brain tonic, detoxifying agent and hepatoprotective agent. Scientific investigation reported that the plant has a significant pharmacological activity, viz. cognitive agent, anti-cancer, antiviral, antibacterial, anti-fungal and hepatoprotective. Moreover, based on the phytochemical aspects, a total of 50 phytoconstituents was identified and isolated from the plant. In conclusion, the outcome of this review will be useful for (a) developing a comprehensive plant profile; (b) assist investigators for exploring further research; and (c) to fulfil the gaps lacking in terms of clinical studies.In mammals, sperm need to mature in the epididymis to gain fertilization competency. However, the molecular mechanism underlying buffalo sperm maturation remains elusive. Exploring sperm physiology at the posttranslational modification (PTM) level could help to develop our understanding of these mechanisms. Protein phosphorylation and ubiquitination are major PTMs in the regulation of many biological processes. In the present study, to our knowledge, we report the first phosphoproteome and ubiquitylome of sperm collected from the caput, corpus, and cauda segments of the epididymis using liquid chromatography-mass spectrometry combined with affinity purification. In total, 647 phosphorylation sites in 294 proteins and 1063 ubiquitination sites in 446 proteins were characterized. Some of these proteins were associated with cellular developmental processes and energy metabolic pathways. Interestingly, 84 proteins were both phosphorylated and ubiquitinated, simultaneously. Some of these proteins were involved in, for example, spermatogenesis, reproduction, and spermatid development. Taken together, these data provide a theoretical basis for further functional analysis of phosphorylation and ubiquitination in epididymal sperm of buffalo and other mammals, and serve as an important resource for exploring the physiological mechanism underlying sperm maturation.

The prioritized net benefit (Δ) is a measure of the benefit-risk balance in clinical trials, based on generalized pairwise comparisons (GPC) using several prioritized outcomes. Its estimation requires the classification as Wins or Losses of all possible pairs of patients, one from the experimental treatment (E) group and one from the control treatment (C) group. In this simulation study, we assessed the impact of the correlation between prioritized outcomes on Δ, its estimate, bias, size, and power.

The theoretical Δ value was derived for the specific case of two correlated binary outcomes when a normal copula is used. #link# Focusing on one efficacy and one toxicity outcome, two situations frequently met in practice were simulated binary efficacy outcome with binary toxicity outcome, or time to event efficacy outcome with categorical toxicity outcome. Several scenarios of efficacy and toxicity were generated, with various levels of correlation.

When E was more effective than C, positive correlations were mainly associated with a decrease in the proportion of Losses, while negative correlations were associated with a decrease in the proportion of Wins on the toxicity outcome. This resulted in an increase of

Δ

^

with the intensity of the positive correlation without adding any bias. Results were similar whatever the type of outcomes generated but led to power alteration.

Correlations between outcomes analyzed with GPC led to substantial but predictable modifications of Δ and its estimate. Correlations should be taken into consideration when performing sample size estimations in clinical trials.

Correlations between outcomes analyzed with GPC led to substantial but predictable modifications of Δ and its estimate. Correlations should be taken into consideration when performing sample size estimations in clinical trials.Actinobacteria and Proteobacteria are important producers of bioactive natural products (NP), and these phyla dominate in the arid soils of Antarctica, where metabolic adaptations influence survival under harsh conditions. Biosynthetic gene clusters (BGCs) which encode NPs, are typically long and repetitious high G + C regions difficult to sequence with short-read technologies. LY3475070 sequenced 17 Antarctic soil bacteria from multi-genome libraries, employing the long-read PacBio platform, to optimize capture of BGCs and to facilitate a comprehensive analysis of their NP capacity. We report 13 complete bacterial genomes of high quality and contiguity, representing 10 different cold-adapted genera including novel species. Antarctic BGCs exhibited low similarity to known compound BGCs (av. 31%), with an abundance of terpene, non-ribosomal peptide and polyketide-encoding clusters. Comparative genome analysis was used to map BGC variation between closely related strains from geographically distant environments. Results showed the greatest biosynthetic differences to be in a psychrotolerant Streptomyces strain, as well as a rare Actinobacteria genus, Kribbella, while two other Streptomyces spp. were surprisingly similar to known genomes. Streptomyces and Kribbella BGCs were predicted to encode antitumour, antifungal, antibacterial and biosurfactant-like compounds, and the synthesis of NPs with antibacterial, antifungal and surfactant properties was confirmed through bioactivity assays.