Mimicking lightning-induced electrochemistry on the early Earth.

To test the hypothesis that an abiotic Earth and its inert atmosphere could form chemically reactive carbon- and nitrogen-containing compounds, we designed a plasma electrochemical setup to mimic lightning-induced electrochemistry under steady-state conditions of the early Earth. Air-gap electrochemical reactions at air-water-ground interfaces lead to remarkable yields, with up to 40 moles of carbon dioxide being reduced into carbon monoxide and formic acid, and 3 moles of gaseous nitrogen being fixed into nitrate, nitrite, and ammonium ions, per mole of transmitted electrons. Interfaces enable reactants (e.g., minerals) that may have been on land, in lakes, and in oceans to participate in radical and redox reactions, leading to higher yields compared to gas-phase-only reactions. Cloud-to-ground lightning strikes could have generated high concentrations of reactive molecules locally, establishing diverse feedstocks for early life to emerge and survive globally.

Stability of nucleic acid bases in concentrated sulfuric acid: Implications for the habitability of Venus' clouds.

What constitutes a habitable planet is a frontier to be explored and requires pushing the boundaries of our terracentric viewpoint for what we deem to be a habitable environment. Despite Venus' 700 K surface temperature being too hot for any plausible solvent and most organic covalent chemistry, Venus' cloud-filled atmosphere layers at 48 to 60 km above the surface hold the main requirements for life: suitable temperatures for covalent bonds; an energy source (sunlight); and a liquid solvent. Yet, the Venus clouds are widely thought to be incapable of supporting life because the droplets are composed of concentrated liquid sulfuric acid-an aggressive solvent that is assumed to rapidly destroy most biochemicals of life on Earth. Recent work, however, demonstrates that a rich organic chemistry can evolve from simple precursor molecules seeded into concentrated sulfuric acid, a result that is corroborated by domain knowledge in industry that such chemistry leads to complex molecules, including aromatics. We aim to expand the set of molecules known to be stable in concentrated sulfuric acid. Here, we show that nucleic acid bases adenine, cytosine, guanine, thymine, and uracil, as well as 2,6-diaminopurine and the "core" nucleic acid bases purine and pyrimidine, are stable in sulfuric acid in the Venus cloud temperature and sulfuric acid concentration range, using UV spectroscopy and combinations of 1D and 2D 1H 13C 15N NMR spectroscopy. The stability of nucleic acid bases in concentrated sulfuric acid advances the idea that chemistry to support life may exist in the Venus cloud particle environment.

Mitigating cold stress in rice: a study of genotype performance and sowing time.

Rice (Oryza sativa L.) is an essential food for half of the global population and is vital in maintaining global food security. Climate change, increasing population and recent incident of COVID pandemic has generated financial burden and threaten the global food security. Due to theses factors rice cultivation also has to face significant challenges. frequent weather changes pose a considerable challenge to agricultural planning, which was previously relaying on consistent seasonal variations. In this context, rice cultivation is particularly sensitive to cold, where its development and productivity inhibited by low temperatures (< 18 °C). Developing rice varietes with low temprature tolerence and good yield potential is one of the major goals of current breeding efforts of plant scientists. For this purpose, short duration and early rice varieties are most favorable to avoid cold stress and yield more in less number of days. this study was designed to investigate the effect of low temperatures on different rice varieties. the study was designed to identify low temprature tolerent genotypes with early and regular cultivation. For this, thirty-four genotypes were evaluated in two gorwing seasons (2018-2019) with four different sowing times. Statistically sowing time showed significant interaction between all yield contributing parameters. The data indicate that exposure to low temperatures during the reproductive phase prolongs the maturation period of the crop, also length of the panicle and the fertility of the spikelets drops, resulting in a significant decrease in the production of sensitive varieties. Some varieties are more sensitive to cold stress compared to others. In the Egyptian context, Giza176, Sakha104, and Sakha107 are recommended for early cultivation, while the genotypes Giza 179, Sakha101, Sakha104, and GZ 9730-1-1-1-1 are indicated for the normal cultivation period. The Sakha104 variety is particularly notable, as it is recommended for both purposes. In addition, the data obtained in this study provide valuable information for selecting rice varieties suitable for double cropping in the North Delta of Egypt. This study also contributes to the existing literature, providing insights into the resilience of rice cultivation in the face of climate change.

The Effect of Neoadjuvant Therapy on Esophagectomy for cT2N0M0 Esophageal Adenocarcinoma.

BACKGROUND: For cT2N0M0 esophageal adenocarcinomas, the effects of neoadjuvant chemoradiotherapy (NT) on surgical outcomes and the oncological benefits to the patients are debatable. In this study, we investigated the optimal management for cT2N0M0 adenocarcinoma (1) assessing the perioperative impact of NT on esophagectomy and (2) evaluating the oncologic effect of NT in a homogeneous group of patients with clinical stage IIA. We hypothesized that NT does not negatively affect perioperative outcomes and provides an oncologic benefit to selected patients with cT2N0M0 disease. METHODS: The National Cancer Database was queried (2010-2019) for patients with cT2N0M0 esophageal adenocarcinoma undergoing esophagectomy. After propensity-matching to adjust for differences in patient and tumor characteristics, we compared postoperative outcomes (logistic regression) and survival (Kaplan-Meier and Cox regression) among those who underwent NT vs upfront surgery (S). RESULTS: This study included 3413 patients, of whom 2359 (69%) received NT, and 1054 (31%) S. In contrast to those who underwent S, in the matched cohort, patients treated with NT had comparable conversion rates (8% vs11.1%, p = 0.06), length of stay (9 vs 10 days, p = 0.078), unplanned readmission (5.4% vs 8.8%, p = 0.109), and 30- (3.9% vs 3.7%, p = 0.90) and 90-day mortality (5.7% vs 4.7%, p = 0.599). In addition, NT associated with improved survival in patients with cT2N0M0 tumors > 5 cm (HR 0.30, 95% CI 0.17-0.36). CONCLUSIONS: NT does not appear to increase technical complexity or to adversely affect postoperative outcomes after esophagectomy. Furthermore, minimally invasive esophagectomy is feasible following NT, with comparable conversion rates to those who had upfront surgery. Lastly, NT was selectively associated with improved survival in patients with cT2N0M0 esophageal cancer.

Characterizing barriers and facilitators of metabolic bariatric surgery tourism: a systematic review.

BACKGROUND: Metabolic bariatric surgery tourism continues to rise and has become a growing concern for bariatric surgeons globally. With varying degrees of regulation, counselling and success, those that develop complications may have to deal with a multitude of challenges often distant from their country of operation. The aim of this study was to characterize the barriers and facilitators influencing individuals to undergo metabolic bariatric surgery tourism, in order to better understand the implications to the National Health Service and other healthcare systems. METHODS: A systematic literature search, restricted to the English language, was performed to identify relevant studies. All studies were included until December 2022, the last search date. Study quality was assessed with the validated mixed-methods appraisal tool. A Braun and Clarke thematic analysis was undertaken to identify themes and subthemes. RESULTS: A total of five studies met the inclusion criteria. Identified themes included: availability, accessibility, cost, eligibility, reputation, and stigma; the available evidence was of varying quality. CONCLUSION: This work identifies a series of subthemes influencing the decision to undertake metabolic bariatric surgery tourism. The results highlight the limited literature available in understanding the complex motivational insights; the scale of the problem in the current healthcare system; cost and long-term outcomes. A National Emergency Bariatric Surgery audit would allow generation of more robust data to explore further the issues of clinical relationships and networks and to guide policy making.

Prevalence and viral suppression of hepatitis B virus infection among people living with HIV on antiretroviral therapy in Sierra Leone.

OBJECTIVE: Sub-Saharan Africa is one of the regions with the highest burdens of HIV and hepatitis B virus (HBV), but data on the impact of antiretroviral therapy (ART) on HBV DNA suppression is limited. In this study, we aimed to determine the prevalence and associated factors of a positive hepatitis B surface antigen (HBsAg) among people living with HIV, and assess the suppression of ART on HBV replication in people living with HIV in Sierra Leone. METHODS: A cross-sectional study was designed to recruit people living with HIV aged 18 years or older in ten public hospitals in Sierra Leone between August 2022 and January 2023. Statistical analyses were performed using R software. Logistic regression analysis was used to assess factors independently associated with positive HBsAg and HBV DNA suppression. RESULTS: Of the 3106 people living with HIV recruited in this study, 2311 (74.4%) were women. The median age was 36 years, 166 (5.3%) had serological evidence of HBV vaccination. The overall prevalence of HBsAg positivity was 12.0% (95% CI: 10.9% to 13.2%). Male sex (adjusted OR (aOR) 2.11, 95% CI: 1.67 to 2.68; p<0.001) and being separated (aOR 1.83, 95% CI: 1.06 to 3.16, p=0.031; reference group: being married) were independent predictors of HBsAg seropositivity. Among 331 people living with HIV and HBV receiving ART, 242 (73.1%) achieved HBV DNA suppression (below 20 IU/mL). HBV suppression rate was higher in HIV-virally suppressed patients than those with unsuppressed HIV viral load (p<0.001). In addition, the male sex was more likely to have unsuppressed HBV DNA (aOR 1.17, 95% CI: 1.17 to 3.21; p=0.010). CONCLUSIONS: We reported a high prevalence of HBsAg seropositivity and low HBV immunisation coverage in people living with HIV in Sierra Leone. In addition, we observed that ART can efficiently result in a viral suppression rate of HBV infection. Therefore, achieving the global target of eliminating HBV infection by 2030 requires accelerated access to care for people living with HIV and HBV, including HBV testing, antiviral treatment and hepatitis B vaccination.

Imaging after Pancreatic Surgery: Expected Findings and Postoperative Complications.

Pancreatic surgery is considered one of the most technically challenging surgical procedures, despite the evolution of modern techniques. Neoplasms remain the most common indication for pancreatic surgery, although inflammatory conditions may also prompt surgical evaluation. The choice of surgical procedure depends on the type and location of the pathologic finding because different parts of the pancreas have separate vascular supplies that may be shared by adjacent organs. The surgical approach could be conventional or minimally invasive (laparoscopic, endoscopic, or robotic assisted). Because of the anatomic complexity of the pancreatic bed, perioperative complications may be frequently encountered and commonly involve the pancreatic-biliary, vascular, lymphatic, or bowel systems, irrespective of the surgical technique used. Imaging plays an important role in the assessment of suspected postoperative complications, with CT considered the primary imaging modality, while MRI, digital subtraction angiography, and molecular imaging are considered ancillary diagnostic tools. Accurate diagnosis of postoperative complications requires a solid understanding of pancreatic anatomy, surgical indications, normal postoperative appearance, and expected postsurgical changes. The practicing radiologist should be familiar with the most common perioperative complications, such as anastomotic leak, abscess, and hemorrhage, and be able to differentiate these entities from normal anticipated postoperative changes such as seroma, edema and fat stranding at the surgical site, and perivascular soft-tissue thickening. In addition to evaluation of the primary operative fossa, imaging plays a fundamental role in assessment of the adjacent organ systems secondarily affected after pancreatic surgery, such as vascular, biliary, and enteric complications. Published under a CC BY 4.0 license. Test Your Knowledge questions are available in the supplemental material. See the invited commentary by Winslow in this issue.

Bandwidth of quantized surface plasmons: competition between radiative and nonradiative damping effects.

We investigate the damping effects of coherent electron oscillations on the bandwidth of a quantized nanoparticle plasmon resonance. The nanoparticle (NP) is treated as a two-level quantum system, and the total relaxation time involves both the population relaxation time associated with radiative processes and the collisional relaxation time associated with nonradiative processes that result in dephasing/decoherence of electron oscillations. We describe the optical response of NPs to an external electromagnetic field by the optical Bloch equations employing the density matrix formalism to capture the quantum description nature of dipolar plasmon resonance and suggest a generalized criterion for the validity of dipole approximation. Then we explore the competition between the radiative and nonradiative damping in determining the plasmon bandwidth of two typical NP models; metallic nanospheres and dielectric core-metal shell NPs (nanoshells). We show that the frequency of plasmon resonance, in addition to the NP size, plays an important role in the competition between the damping mechanisms. Consequently, the damping processes are significantly influenced by the factors that determine the resonance frequency, such as the core size, the dielectric constant of the medium, and the shell thickness (for nanoshells). For both models of NPs, we identify the optimum parameters that achieve a narrower plasmon bandwidth (minimal damping), which is a prerequisite for advanced sensing and medical applications. We demonstrate excellent agreement of the simulated spectral features of the plasmon resonance with previously reported experimental results for a single NP where the inhomogeneous broadening of the plasmon line is excluded. For NP ensembles where inhomogeneous broadenings and interface chemical effects are significant, our theoretical approach successfully predicts the overall trend of size-dependent damping rates.

Plasmon resonances of GZO core-Ag shell nanospheres, nanorods, and nanodisks for biosensing and biomedical applications in near-infrared biological windows I and II.

There is currently a great deal of interest in realizing localized surface plasmon resonances (LSPRs) in two distinct windows in the near-infrared (NIR) spectrum for in vivo biosensing and medical applications, the biological window (BW) I and II (BW I, 700-900 nm; BW II, 1000-1700 nm). This study aims to demonstrate that LSPRs of Ga-doped ZnO (GZO) core-silver (Ag) shell structures exhibit promising features for biological applications in the NIR BW I and II. Here, we study three different shapes for nanoshells: the core-shell nanosphere, nanorod, and nanodisk. In the calculation of the optical response of these nanoshells, an effective medium approach is first used to reduce the dielectric function of a nanoshell to that of an equivalent homogenous NP with an effective dielectric function. Then, the LSPR spectra of nanoshells are calculated using the modified long-wavelength approximation (MLWA), which corrects the polarizability of the equivalent NP as obtained by Gans theory. Through numerical investigations, we examine the impacts of the core and shell sizes of the proposed nanoshells as well as the medium refractive index on the position and line width of the plasmon resonance peaks. It is shown that the plasmon resonances of the three proposed nanoshells exhibit astonishing resonance tunability in the NIR region by varying their geometrical parameters. Specifically, the improved spectrum characteristics and tunability of its plasmon resonances make the GZO-Ag nanosphere a more viable platform for NIR applications than the spherical metal colloid. Furthermore, we demonstrate that the sensitivity and figure of merit (FOM) of the plasmon resonances may be significantly increased by using GZO-Ag nanorods and nanodisks in place of GZO-Ag nanospheres. It is found that the optical properties of the transverse plasmon resonance of the GZO-Ag nanodisk are superior to all plasmon resonances produced by the GZO-Ag nanorods and GZO-Ag nanospheres in terms of sensitivity and FOM. The FOM of the transverse plasmon mode of the GZO-Ag nanodisk is almost two orders of magnitude higher than that of the longitudinal and transverse plasmon modes of the GZO-Ag nanorod in BW I and BW II. And it is 1.5 and 2 times higher than the plasmon resonance FOM of GZO-Ag nanospheres in BW I and BW II, respectively.

Fenamates and ibuprofen as foundational components in the synthesis of innovative, targeted COX-2 anti-inflammatory drugs, undergoing thorough biopharmacological assessments and in-silico computational studies.

Cyclooxygenase-2 plays a vital role in inflammation by catalyzing arachidonic acid conversion toward prostaglandins, making it a prime therapeutic objective. Selective COX-2 inhibitors represent significant progress in anti-inflammatory therapy, offering improved efficacy and fewer side effects. This study describes the synthesis of novel anti-inflammatory compounds from established pharmaceutically marketed agents like fenamates III-V and ibuprofen VI. Through rigorous in vitro testing, compounds 7b-c, and 12a-b demonstrated substantial in vitro selective inhibition, with IC50 values of 0.07 to 0.09 µM, indicating potent pharmacological activity. In vivo assessment, particularly focusing on compound 7c, revealed significant anti-inflammatory effects. Markedly, it demonstrated the highest inhibition of paw thickness (58.62 %) at the 5-hr mark compared to the carrageenan group, indicating its potency in mitigating inflammation. Furthermore, it exhibited a rapid onset of action, with a 54.88 % inhibition observed at the 1-hr mark. Subsequent comprehensive evaluations encompassing analgesic efficacy, histological characteristics, and toxicological properties indicated that compound 7c did not induce gastric ulcers, in contrast to the ulcerogenic tendency associated with mefenamic acid. Moreover, compound 7c underwent additional investigations through in silico methodologies such as molecular modelling, field alignment, and density functional theory. These analyses underscored the therapeutic potential and safety profile of this novel compound, warranting further exploration and development in the realm of pharmaceutical research.

Novel imidazo[2,1-b]thiazoles and imidazo[1,2-a]pyridines tethered with indolinone motif as VEGFR-2 inhibitors and apoptotic inducers: Design, synthesis and biological evaluations.

The current study investigates the anticancer and VEGFR-2 inhibitory activities of 16 novel indolinone-grafted imidazo[2,1-b]thiazole and imidazo[1,2-a]pyridine derivatives (6a-h and 10a-h). The structures of these target compounds were confirmed using elemental and spectral analyses. All compounds were evaluated for their VEGFR-2 inhibitory activity in vitro, with eight compounds demonstrating promising results, exhibiting IC50 values in the sub-micromolar range (0.22 µM - 0.95 µM). Additionally, the anticancer potential of these compounds was assessed using an MTT assay against two breast cancer cell lines, MCF-7 and MDA-MB-231. Compounds 6a, 6f, 6 h, and 10f showed superior performance (IC50 = 9.79, 8.78, 8.35, and 10.88 µM, respectively) compared to the reference drug cisplatin (IC50 = 11.50 µM) against MDA-MB-231 cells. Based on their consistent VEGFR-2 inhibitory activity, compounds 6a, 6 h, and 10f were selected for further analysis. Molecular docking studies with VEGFR-2 (PDB ID: 4AGD) revealed binding behaviors similar to the co-crystallized ligand sunitinib. Among the reported target molecules, compound 10f exhibited the most desirable characteristics in terms of efficacy and safety and was further analyzed using density-functional theory (DFT) simulations to better understand its physical properties.

Novel indolinone-tethered benzothiophenes as anti-tubercular agents against MDR/XDR M. tuberculosis: Design, synthesis, biological evaluation and in vivo pharmacokinetic study.

Joining the global effort to eradicate tuberculosis, one of the deadliest infectious killers in the world, we disclose in this paper the design and synthesis of new indolinone-tethered benzothiophene hybrids 6a-i and 7a-i as potential anti-tubercular agents. The MICs were determined in vitro for the synthesized compounds against the sensitive M. tuberculosis strain ATCC 25177. Potent compounds 6b, 6d, 6f, 6h, 7a, 7b, 7d, 7f, 7h and 7i were furtherly assessed versus resistant MDR-TB and XDR-TB. Structure activity relationship investigation of the synthesized compounds was illustrated, accordingly. Superlative potency was unveiled for compound 6h (MIC = 0.48, 1.95 and 7.81 µg/mL for ATCC 25177 sensitive TB strain, resistant MDR-TB and XDR-TB, respectively). Moreover, validated in vivo pharmacokinetic study was performed for the most potent derivative 6h revealing superior pharmacokinetic profile over the reference drug. For further exploration of the anti-tubercular mechanism of action, molecular docking was carried out for the former compound in DprE1 active site as one of the important biological targets of TB. The binding mode and the docking score uncovered exceptional binding when compared to the co-crystallized ligand suggesting that it maybe the underlying target for its outstanding anti-tubercular potency.

Factor XI as a new target for prevention of thromboembolism in cardiovascular disease: a meta-analysis of randomized controlled trials.

Anticoagulant therapy is a mainstay in the management of patients with cardiovascular disease. The use of conventional anticoagulants carries potential side effects, mainly bleeding. Drugs targeting Factor XI (FXI) have been investigated in randomized controlled trials as a new option with more favorable outcomes. A comprehensive literature search was conducted to identify relevant studies comparing FXI inhibitors to placebo or standard therapy. The primary outcomes were incidence of all bleeding events, major bleeding, and thromboembolism. Secondary outcomes included incidence of all adverse events (AE), serious AE, and all-cause mortality. A total of 11 studies involving 10,536 patients were included. FXI inhibitors were associated with a trend toward reduction of bleeding events and incidence of thromboembolism compared to the control group (placebo/standard therapy). There was no statistically significant difference between both groups in terms of adverse events and all-cause mortality. When compared to enoxaparin, FXI inhibitors significantly reduced the risk of bleeding events (RR = 0.42, 95% CI: 0.23-0.76, P = 0.004) and thromboembolism (RR = 0.59, 95% CI: 0.44-0.77, P = 0.001). On the other hand, when compared to DOACs, FXI inhibitors were associated with a significant reduction in bleeding events but not thromboembolism. Whereas, compared to placebo, FXI inhibitors did not increase the risk of bleeding events, adverse events, or all-cause mortality (P > 0.05). FXI inhibitors could be a safer and more potent option for prevention of thromboembolism than conventional therapy.

A multidisciplinary approach to the antioxidant and hepatoprotective activities of Arbutus pavarii Pampan fruit; in vitro and in Vivo biological evaluations, and in silico investigations.

The Libyan Strawberry, Arbutus pavarii Pampan (ARB), is an endemic Jebel Akhdar plant used for traditional medicine. This study presents the antioxidant and hepatoprotective properties of ARB fruit-extract. ARB phytochemical analysis indicated the presence of 354.54 GAE and 36.2 RE of the phenolics and flavonoids. LC-MS analysis identified 35 compounds belonging to phenolic acids, procyanidins, and flavonoid glycosides. Gallic acid, procyanidin dimer B3, ß-type procyanidin trimer C, and quercetin-3-O-glucoside were the major constituents of the plant extract. ARB administration to paracetamol (PAR)-intoxicated rats reduced serum ALT, AST, bilirubin, hepatic tissue MDA and proinflammatory markers; TNF-α and IL-6 with an increase in tissue GSH level and SOD activity. Histological and immunohistochemical studies revealed that ARB restored the liver histology and significantly reduced the tissue expression of caspase 3, IL-1B, and NF-KB in PAR-induced liver damage. Docking analysis disclosed good binding affinities of some compounds with XO, COX-1, 5-LOX, and PI3K.

Treatment of large intracranial aneurysms using the Woven EndoBridge (WEB): a propensity score-matched analysis.

The Woven EndoBridge (WEB) device is primarily used for treating wide-neck intracranial bifurcation aneurysms under 10 mm. Limited data exists on its efficacy for large aneurysms. We aim to assess angiographic and clinical outcomes of the WEB device in treating large versus small aneurysms. We conducted a retrospective review of the WorldWide WEB Consortium database, from 2011 to 2022, across 30 academic institutions globally. Propensity score matching (PSM) was employed to compare small and large aneurysms on baseline characteristics. A total of 898 patients were included. There was no significant difference observed in clinical presentations, smoking status, pretreatment mRS, presence of multiple aneurysms, bifurcation location, or prior treatment between the two groups. After PSM, 302 matched pairs showed significantly lower last follow-up adequate occlusion rates (81% vs 90%, p = 0.006) and higher retreatment rates (12% vs 3.6%, p < 0.001) in the large aneurysm group. These findings may inform treatment decisions and patient counseling. Future studies are needed to further explore this area.

Dual Layer vs Single Layer Woven EndoBridge Device in the Treatment of Intracranial Aneurysms: A Propensity Score-Matched Analysis.

BACKGROUND: The Woven EndoBridge (WEB) devices have been used for treating wide neck bifurcation aneurysms (WNBAs) with several generational enhancements to improve clinical outcomes. The original device dual-layer (WEB DL) was replaced by a single-layer (WEB SL) device in 2013. This study aimed to compare the effectiveness and safety of these devices in managing intracranial aneurysms. METHODS: A multicenter cohort study was conducted, and data from 1,289 patients with intracranial aneurysms treated with either the WEB SL or WEB DL devices were retrospectively analyzed. Propensity score matching was utilized to balance the baseline characteristics between the two groups. Outcomes assessed included immediate occlusion rate, complete occlusion at last follow-up, retreatment rate, device compaction, and aneurysmal rupture. RESULTS: Before propensity score matching, patients treated with the WEB SL had a significantly higher rate of complete occlusion at the last follow-up and a lower rate of retreatment. After matching, there was no significant difference in immediate occlusion rate, retreatment rate, or device compaction between the WEB SL and DL groups. However, the SL group maintained a higher rate of complete occlusion at the final follow-up. Regression analysis showed that SL was associated with higher rates of complete occlusion (OR: 0.19; CI: 0.04 to 0.8, p = 0.029) and lower rates of retreatment (OR: 0.12; CI: 0 to 4.12, p = 0.23). CONCLUSION: The WEB SL and DL devices demonstrated similar performances in immediate occlusion rates and retreatment requirements for intracranial aneurysms. The SL device showed a higher rate of complete occlusion at the final follow-up.

In Silico and In Vitro Screening of Some Pregnane Glycosides Isolated from Certain Caralluma Species as SARS-COV-2 Main Protease Inhibitors.

SARS-CoV-2 caused pandemic represented a major risk for the worldwide human health, animal health and economy, forcing extraordinary efforts to discover drugs for its prevention and cure. Considering the extensive interest in the pregnane glycosides because of their diverse structures and excellent biological activities, we investigated them as antiviral agents against SARS-COV-2. We selected 21 pregnane glycosides previously isolated from the genus Caralluma from Asclepiadaceae family to be tested through virtual screening molecular docking simulations for their potential inhibition of SARS-CoV-2 Mpro. Almost all target compounds showed a more or equally negative docking energy score relative to the co-crystallized inhibitor X77 (S=-12.53 kcal/mol) with docking score range of (-12.55 to -19.76 kcal/mol) and so with a potent predicted binding affinity to the target enzyme. The activity of the most promising candidates was validated by in vitro testing. Arabincoside C showed the highest activity (IC50=35.42 µg/ml) and the highest selectivity index (SI=9.9) followed by Russelioside B (IC50=50.80 µg/ml), and Arabincoside B (IC50=53.31 µg/ml).

Machine learning prediction of hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the United States.

BACKGROUND AND PURPOSE: Predicting patient recovery and discharge disposition following mechanical thrombectomy remains a challenge in patients with ischemic stroke. Machine learning offers a promising prognostication approach assisting in personalized post-thrombectomy care plans and resource allocation. As a large national database, National Inpatient Sample (NIS), contain valuable insights amenable to data-mining. The study aimed to develop and evaluate ML models predicting hospital discharge disposition with a focus on demographic, socioeconomic and hospital characteristics. MATERIALS AND METHODS: The NIS dataset (2006-2019) was used, including 4956 patients diagnosed with ischemic stroke who underwent thrombectomy. Demographics, hospital characteristics, and Elixhauser comorbidity indices were recorded. Feature extraction, processing, and selection were performed using Python, with Maximum Relevance - Minimum Redundancy (MRMR) applied for dimensionality reduction. ML models were developed and benchmarked prior to interpretation of the best model using Shapley Additive exPlanations (SHAP). RESULTS: The multilayer perceptron model outperformed others and achieved an AUROC of 0.81, accuracy of 77 %, F1-score of 0.48, precision of 0.64, and recall of 0.54. SHAP analysis identified the most important features for predicting discharge disposition as dysphagia and dysarthria, NIHSS, age, primary payer (Medicare), cerebral edema, fluid and electrolyte disorders, complicated hypertension, primary payer (private insurance), intracranial hemorrhage, and thrombectomy alone. CONCLUSION: Machine learning modeling of NIS database shows potential in predicting hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the NIS database. Insights gained from SHAP interpretation can inform targeted interventions and care plans, ultimately enhancing patient outcomes and resource allocation.

Design, Synthesis, and Biological Evaluation of Novel Phenoxy Acetic Acid Derivatives as Selective COX-2 Inhibitors Coupled with Comprehensive Bio-Pharmacological Inquiry, Histopathological Profiling, and Toxicological Scrutiny.

COX-2 plays a key role in converting arachidonic acid into prostaglandins. This makes it a significant target for treating inflammation. Selective COX-2 inhibitors have marked a new phase in inflammatory treatment, providing significant effectiveness while reducing negative side effects. Herein, we aimed at the design and synthesis of new anti-inflammatory agents 5a-f, 7a-b, 10a-f, and 13a-b with expected selective inhibition for COX-2. Compounds 5d-f, 7b, and 10c-f showed significant COX-2 inhibition with IC50 in the range of 0.06-0.09 µM, indicating powerful pharmacological potential. In light of this, eight compounds were selected for further testing in vivo to assess their selectivity toward COX-1/COX-2 enzymes with the ability to reduce paw thickness. Compounds 5f and 7b showed significant anti-inflammatory effects without causing stomach ulcers, as they showed significant in vivo inhibition for paw thickness at 63.35% and 46.51%, as well as paw weight at 68.26% and 64.84%. Additionally, the tested compounds lowered TNF-α by 61.04% and 64.88%, as well as PGE-2 by 60.58% and 57.07%, respectively. Furthermore, these potent compounds were thoroughly analyzed for their pain-relieving effects, histological changes, and toxicological properties. Assessing renal and stomach function, as well as measuring liver enzymes AST and ALT, together with kidney indicators creatinine and urea, offered valuable information on their safety profiles. Molecular modeling studies explain the complex ways in which the strong interacts with the COX-2 enzyme. This comprehensive strategy emphasizes the therapeutic potential and safety profiling of these new analogues for managing inflammation.

Optimization of ultrasound- and enzymatic-assisted extractions of polyphenols from dried red onion peels and evaluation of their antioxidant activities.

There is a recognized need for exploring new natural antioxidants that have high antioxidant potential. Thus, the aim of this study was to optimize the extraction process of onion peels using ultrasound- and enzymatic-assisted extractions (UAE and EAE) methods to utilize the optimal extracts as natural antioxidants. Box-Behnken Design (BBD) was implemented to reach the optimal extracts with the highest simultaneous content of total phenolic content (TPC) and total flavonoid content (TFC). The optimal UAE and EAE extracts were subjected to High Performance Liquid Chromatography (HPLC) analysis to identify their chemical profile. The antioxidant activities of optimal extracts obtained by UAE and EAE were evaluated in vitro using DPPH and FRAP assays and their abilities to increase the oxidative stability of sunflower oil were studied using Rancimat test. The optimal conditions for UAE were 34.02 W, 26.87 mL/g solid, and 45.43 min, meanwhile they were 30.00 mL/g solid, 45.43 min at enzyme concentration of 0.52% for EAE method. DPPH and FRAP assays results revealed that EAE optimal extract show superior antioxidant activity over UAE optimal extract. The protection factor of optimal EAE extract against sunflower oil oxidation was close to that of butylated hydroxytoluene (BHT).