Bioactivity and In Silico Studies of Isoquinoline and Related Alkaloids as Promising Antiviral Agents: An Insight

Viruses are widely recognized as the primary cause of infectious diseases around the world. The ongoing global pandemic due to the emergence of SARS-CoV-2 further added fuel to the fire. The development of therapeutics becomes very difficult as viruses can mutate their genome to become more complex and resistant. Medicinal plants and phytocompounds could be alternative options. Isoquinoline and their related alkaloids are naturally occurring compounds that interfere with multiple pathways including nuclear factor-κB, mitogen-activated protein kinase/extracellular-signal-regulated kinase, and inhibition of Ca²⁺-mediated fusion. These pathways play a crucial role in viral replication. Thus, the major goal of this study is to comprehend the function of various isoquinoline and related alkaloids in viral infections by examining their potential mechanisms of action, structure-activity relationships (SAR), in silico (particularly for SARS-CoV-2), in vitro and in vivo studies. The current advancements in isoquinoline and related alkaloids as discussed in the present review could facilitate an in-depth understanding of their role in the drug discovery process

The spatial distribution and spectral characteristics of the diffuse soft X-ray background

The diffuse emission in soft X-rays (0.1-2.5 keV) was measured over half the sky with 5° (FWHM) spatial resolution during a sky survey experiment. X-ray intensity maps in galactic coordinates are presented in B(0.1-0.19 keV), L(0.1-0.28KeV), and M(0.4-0.9 keV) energy bands. The maps contain observations from part of the sky bounded by galactic longitudes l=180° to 270° and galactic latitudes b=40° to 80°, which is poorly studied in other surveys. Regions of excess soft X-ray emission are found to be associated with an edge of Loop I and its extension in the Southern galactic hemisphere, the northern HI hole and other features in HI and radio continuum surveys. No quantitative correlation is observed between the X-ray intensity and natural hydrogen column density (NH). The energy spectra observed from some regions otside the Loop I are best fitted with thermal emission spectra of a hot plasma with cosmic elemental abundances, negligible interstellar absorption and temperature 106.2-106.3K. The observed emission measures over several regions of sky are in the range of (0.27-1.0) 10−2 cm−6 pc. Present data support the local origin for the soft X-ray background from a thermal plasma of presure ≳4600 cm−3 K, temperature ~106 K and size ≲330 pc. A spread in the temperature of the local hot plasma with cosmic elemental abundances, is necessary to explain the observed variation in the hardness ratio

Detection of a very low hard X-ray pulse fraction in the bright state of GX 1+4

We have observed the Galactic center hard X-ray pulsar GX 1+4 on 1993 December 11, in the energy range of 20 - 100 keV with a balloon-borne Xenon filled Multi-cell Proportional Counter (XMPC) telescope. The source was detected in a bright state, the average observed source count rate being 10.1 ±0.2 s-1 per detector. X-ray pulsations with a period of 121.0 ± 0.4 s were detected in the source at a very high significance level. This, compared with the Burst and Transient Source Experiment (BATSE) observations, gives a spin down rate of dot-P = 1.6 ± 1.4 s yr -1. The pulse fraction in the hard X-ray range is low (35%), and the observed spectrum is very hard (power law energy index 0.54 ± 0.18). The observed source luminosity in the 20 - 100 keV range is 7.9 ± 0.3 x 1037 erg/s. These properties are similar to those seen during high luminosity spin up state of early 1970s and suggest that the source should revert back to a a spin-up episode

Attitudes towards risk-reducing early salpingectomy with delayed oophorectomy for ovarian cancer prevention: a cohort study

OBJECTIVE: To determine risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) acceptability and effect of surgical prevention on menopausal sequelae/satisfaction/regret in women at increased ovarian cancer (OC) risk. DESIGN: Multicentre, cohort, questionnaire study (IRSCTN:12310993). SETTING: United Kingdom (UK). POPULATION: UK women without OC ≥18 years, at increased OC risk, with/without previous RRSO, ascertained through specialist familial cancer/genetic clinics and BRCA support groups. METHODS: Participants completed a 39-item questionnaire. Baseline characteristics were described using descriptive statistics. Logistic/linear regression models analysed the impact of variables on RRESDO acceptability and health outcomes. MAIN OUTCOMES: RRESDO acceptability, menopausal sequelae, satisfaction/regret. RESULTS: In all, 346 of 683 participants underwent risk-reducing salpingo-oophorectomy (RRSO). Of premenopausal women who had not undergone RRSO, 69.1% (181/262) found it acceptable to participate in a research study offering RRESDO. Premenopausal women concerned about sexual dysfunction were more likely to find RRESDO acceptable (odds ratio [OR] = 2.9, 95% CI 1.2-7.7, P = 0.025). Women experiencing sexual dysfunction after premenopausal RRSO were more likely to find RRESDO acceptable in retrospect (OR = 5.3, 95% CI 1.2-27.5, P < 0.031). In all, 88.8% (143/161) premenopausal and 95.2% (80/84) postmenopausal women who underwent RRSO, respectively, were satisfied with their decision, whereas 9.4% (15/160) premenopausal and 1.2% (1/81) postmenopausal women who underwent RRSO regretted their decision. HRT uptake in premenopausal individuals without breast cancer (BC) was 74.1% (80/108). HRT use did not significantly affect satisfaction/regret levels but did reduce symptoms of vaginal dryness (OR = 0.4, 95% CI 0.2-0.9, P = 0.025). CONCLUSION: Data show high RRESDO acceptability, particularly in women concerned about sexual dysfunction. Although RRSO satisfaction remains high, regret rates are much higher for premenopausal women than for postmenopausal women. HRT use following premenopausal RRSO does not increase satisfaction but does reduce vaginal dryness. TWEETABLE ABSTRACT: RRESDO has high acceptability among premenopausal women at increased ovarian cancer risk, particularly those concerned about sexual dysfunction

Gapless Assembly of Maize Chromosomes Using Long-Read Technologies

Creating gapless telomere-to-telomere assemblies of complex genomes is one of the ultimate challenges in genomics. We use two independent assemblies and an optical map-based merging pipeline to produce a maize genome (B73-Ab10) composed of 63 contigs and a contig N50 of 162 Mb. This genome includes gapless assemblies of chromosome 3 (236 Mb) and chromosome 9 (162 Mb), and 53 Mb of the Ab10 meiotic drive haplotype. The data also reveal the internal structure of seven centromeres and five heterochromatic knobs, showing that the major tandem repeat arrays (CentC, knob180, and TR-1) are discontinuous and frequently interspersed with retroelements