Design and Enantioselective Synthesis of Chiral Pyranone Fused Indole Derivatives with Antibacterial Activities against Xanthomonas oryzae pv oryzae for Protection of Rice.

A new class of chiral pyranone fused indole derivatives were prepared by means of N-heterocyclic carbene (NHC) organocatalysis and demonstrated notable antibacterial activity against Xanthomonas oryzae pv oryzae (Xoo). Bioassays showed that compounds (3S,4R)-5b, (3S,4R)-5d, and (3S,4R)-5l exhibited promising in vitro efficacy against Xoo, with EC50 values of 9.05, 9.71, and 5.84 mg/L, respectively, which were superior to that of the positive controls with commercial antibacterial agents, bismerthiazol (BT, EC50 = 27.8 mg/L) and thiodiazole copper (TC, EC50 = 70.1 mg/L). Furthermore, single enantiomer (3S,4R)-5l was identified as an optimal structure displaying 55.3% and 52.0% curative and protective activities against Xoo in vivo tests at a concentration of 200 mg/L, which slightly surpassed the positive control with TC (curative and protective activities of 47.2% and 48.8%, respectively). Mechanistic studies through molecular docking analysis revealed preliminary insights into the distinct anti-Xoo activity of the two single enantiomers (3S,4R)-5l and (3R,4S)-5l, wherein the (3S,4R)-configured stereoisomer could form a more stable interaction with XooDHPS (dihydropteroate synthase). These findings underscore the significant anti-Xoo potential of these chiral pyranone fused indole derivatives, and shall inspire further exploration as promising lead structures for a novel class of bactericides to combat bacterial infections and other plant diseases.

The Racial Disparity Among the Clinical Outcomes Post Stroke and its Intervention Outcomes: A Systematic Review and Meta-analysis.

The Racial disparity between the clinical outcomes poststroke have not been well studied, with limited literature available. We conducted a meta-analysis to evaluate the poststroke outcomes among the White and Black race of patients. We systematically searched all electronic databases from inception until March 1, 2023. The primary endpoint was post stroke in-hospital mortality, and all-cause mortality. Secondary endpoints were poststroke intervention in-hospital mortality, intracerebral hemorrhage, and all-cause mortality (ACM). A total of 1,250,397 patients were included in the analysis, with 1,018,892 (81.48%) patients of the White race and 231,505 (18.51%) patients in the Black race. The mean age of the patients in each group was (73.55 vs 66.28). The most common comorbidity among White and Black patients was HTN (73.92% vs 81.00%), and DM (29.37% vs 43.36%). The odds of in hospital mortality post stroke (OR, 1.45 [95% CI:1.35-1.55], P <0.001), and all-cause mortality (OR, 1.40 [95% CI:1.28-1.54], P < 0.001) were significantly higher among White patients compared with Black patients. Among patients with post stroke intervention the odds of in-hospital mortality (OR, 1.29 (95% CI: 1.05-1.59, P = 0.02), and intracerebral hemorrhage (ICH) (OR, 1.15, [95% CI:1.06-1.26], P < 0.01) were significantly higher among White patients compared with Black patients post intervention. However, all-cause mortality (OR,1.21 [95% CI: 0.87-1.68, P = 0.25] was comparable between both groups. Our study is the most comprehensive and first meta-analysis with the largest sample size thus far, highlighting that White patients are at increased risk of mortality and post intervention intracerebral hemorrhage compared with Black patients.

Early surgery vs conservative management among asymptomatic aortic stenosis: A systematic review and meta-analysis.

Introduction: Although aortic valve replacement in severe symptomatic Aortic Stenosis (AS) are clearly outlined, the role of surgical intervention in asymptomatic severe AS remains unclear with limited evidence. The aim of our meta-analysis is to evaluate the efficacy and safety of early surgical aortic valve repair compared to conservative management. Methods: A systematic literature search was performed in PubMed, Scopus, Embase and Cochrane databases for studies comparing the early surgery versus conservative management among asymptomatic aortic stenosis patients. Unadjusted odds ratios (OR) were pooled using a random-effect model, and a p-value of < 0.05 was considered statistically significant. Results: A total of 5 articles (3 observational studies and 2 randomized controlled trials) were included. At a median followup of 4.1 years, here were significantly lower odds of all-cause mortality [OR = 0.30 (95 %CI:0.17-0.53), p < 0.0001], cardiovascular mortality [OR = 0.35 (95 %CI:(0.17-0.72), p = 0.005], and sudden cardiac death (OR = 0.36 (95 %CI: 0.15-0.89), p = 0.03) among early surgery group compared with conservative care. There was no significant difference between incidence of major bleeding, clinical thromboembolic events, hospitalization due to heart failure, stroke and myocardial infarction between the conservative care groups and early surgery. Conclusion: Among asymptomatic patients with AS, early surgery shows better outcomes in reducing all-cause mortality and cardiovascular mortality compared with conservative management approaches.

Leaf extract of neem (Azadirachta indica) alleviates adverse effects of drought in quinoa (Chenopodium quinoa Willd.) plants through alterations in biochemical attributes and antioxidants.

The influence of varying concentrations (0, 1, 3, 4, 5, 6, 8, and 10 % v/v) of neem (Azadirachta indica) leaf extract on drought stressed (40 % field capacity) quinoa (Chenopodium quinoa Willd.) plants was assessed. During the current study two cultivars of quinoa (V7 and V9) were used. This study revealed that water stress adversely affects the fresh and dry weight of shoots and roots as well as chlorophyll pigments (a and b) of both quinoa cultivars. In contrast, drought stress enhanced glycinebetaine (GB), free proline, phenolic content, hydrogen peroxide (H2O2), activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) enzymes, and relative membrane permeability (RMP). However, application of neem leaf extract improved the accumulation of key osmoprotectants like proline, GB and activities of enzymatic antioxidants. Our findings showed 5 % neem leaf extract is an effective treatment in counteracting the oxidative damage caused by water stress, thereby improving overall plant growth. Of both cultivars of quinoa, the response of cv. V9 to stress as well as foliar applied neem was relatively more promising.

Insights into insecticide-resistance mechanisms in invasive species: Challenges and control strategies.

Threatening the global community is a wide variety of potential threats, most notably invasive pest species. Invasive pest species are non-native organisms that humans have either accidentally or intentionally spread to new regions. One of the most effective and first lines of control strategies for controlling pests is the application of insecticides. These toxic chemicals are employed to get rid of pests, but they pose great risks to people, animals, and plants. Pesticides are heavily used in managing invasive pests in the current era. Due to the overuse of synthetic chemicals, numerous invasive species have already developed resistance. The resistance development is the main reason for the failure to manage the invasive species. Developing pesticide resistance management techniques necessitates a thorough understanding of the mechanisms through which insects acquire insecticide resistance. Insects use a variety of behavioral, biochemical, physiological, genetic, and metabolic methods to deal with toxic chemicals, which can lead to resistance through continuous overexpression of detoxifying enzymes. An overabundance of enzymes causes metabolic resistance, detoxifying pesticides and rendering them ineffective against pests. A key factor in the development of metabolic resistance is the amplification of certain metabolic enzymes, specifically esterases, Glutathione S-transferase, Cytochromes p450 monooxygenase, and hydrolyses. Additionally, insect guts offer unique habitats for microbial colonization, and gut bacteria may serve their hosts a variety of useful services. Most importantly, the detoxification of insecticides leads to resistance development. The complete knowledge of invasive pest species and their mechanisms of resistance development could be very helpful in coping with the challenges and effectively developing effective strategies for the control of invasive species. Integrated Pest Management is particularly effective at lowering the risk of chemical and environmental contaminants and the resulting health issues, and it may also offer the most effective ways to control insect pests.

Mycochemical Screening and Study of Medicinal Properties of Two Amanita Species (Agaricomycetes) from Pakistan.

Fresh basidiocarps of Amanita cinnamomescens and A. pakistanica were collected from Ayubia-Khanspur, Pakistan, during the 2018 monsoon season. Basidiocarps of A. cinnamomescens and A. pakistanica were evaluated for their mycochemicals, mineral composition, and antioxidant and antimicrobial activities. The percentage yield of extracts ranged from 4.13% to 18.20%. The extracts contained noticeable total phenolic contents (0.043 ± 0.02 to 0.046 ± 0.01 mg/g) and total flavonoid contents (0.090 ± 0.004 to 0.0935 ± 0.003 mg/g) and good radical scavenging ability according to the ABTS assay (79.74% ± 0.03% to 85.34% ± 0.02%) and the DPPH radical assay (35.77% ± 0.01% to 44.77% ± 0.003%). In addition, the tested extracts showed substantial antimicrobial activity, which ranged from 10 ± 0.33 to 32.66 ± 0.33 mm. Both mushrooms were also analyzed for their mineral content (sodium, potassium, calcium, nickel, cobalt, copper, zinc, manganese, chromium, and iron). It was concluded that A. cinnamomescens and A. pakistanica can be used as a potential source for formulation of dietary functional foods and pharmaceuticals with antioxidant and antimicrobial effects. To our knowledge, this is the first report on in vitro biological activities and mycochemical analysis of A. pakistanica and A. cinnamomescens from Pakistan.

The Effect of Berberine, a Drug From Chinese Folk Medicine, on Serum and Urinary Uric Acid Levels in Rats With Hyperuricemia.

Background The principal manifestation of hyperuricemia is gout. Many drugs are in use nowadays to treat gout, but they are linked with multiple side effects. The present study observed berberine (from Chinese folk medicine) on serum and urinary uric acid levels in rats with potassium oxonate-induced hyperuricemia. Materials and methods Thirty-six adult healthy female Sprague Dawley rats were randomly divided into six groups of six rats each. To induce hyperuricemia, all the groups except Group A were given potassium oxonate (250 mg/kg) intraperitoneally on days 1, 3, and 7. Group A, the normal control group, was given normal saline for seven consecutive days intraperitoneally. Group C was administered allopurinol (5 mg/kg body weight) intraperitoneally, and Group D, E, and F were given berberine in doses of 0.75 mg/kg, 1.25 mg/kg, and 2.5 mg/kg body weight respectively intraperitoneally for seven consecutive days, one hour after the potassium oxonate injection. On zero, first, third, and seventh day of the experiment, blood and urine samples were taken to estimate the serum and urinary uric acid levels. On days zero and 7, serum uric acid was measured by cardiac puncture, while on days 1 and 3, it was measured by the tail prick method. The uric acid was measured by an enzymatic colorimetric method and creatinine by the Jaffe method. Fractional excretion of urate was also calculated. Results Berberine lowered serum uric acid levels in rats with potassium oxonate-induced hyperuricemia with highly significant results (p-value <0.001) in all three dosages. Berberine increased the urinary uric acid level and the fractional excretion of urate in a time-dependent manner in all three dosages. This effect was maximally shown by low dose berberine with a highly significant result (p-value <0.001). Conclusion Berberine successfully decreased the serum uric acid level of hyperuricemic rats by increasing the urinary uric acid level and fractional excretion of urate.