Mango peel extracts and mangiferin chromatographic Fourier-transform infrared correlation with antioxidant, antidiabetic, and advanced glycation end product inhibitory potentials using in silico modeling and in vitro assays.

Mangifera indica peels are a rich source of diverse flavonoids and xanthonoids; however, generally these are discarded. Computational studies revealed that mangiferin significantly interacts with amino acid residues of transcriptional regulators 1IK3, 3TOP, and 4f5S. The methanolic extract of Langra variety of mangoes contained the least phenol concentrations (22.6 ± 0.32 mg/gGAE [gallic acid equivalent]) compared to the chloroform (214.8 ± 0.12 mg/gGAE) and ethyl acetate fractions (195.6 ± 0.14 mg/gGAE). Similarly, the methanolic extract of Sindhri variety contained lower phenol concentrations (42.3 ± 0.13 mg/gRUE [relative utilization efficiency]) compared with the chloroform (85.6 ± 0.15 mg/gGAE) and ethyl acetate (76.1 ± 0.32 mg/gGAE) fractions. Langra extract exhibited significant α-glucosidase inhibition (IC50 0.06 mg/mL), whereas the ethyl acetate fraction was highly active (IC50 0.12 mg/mL) in Sindhri variety. Mangiferin exhibited significant inhibition (IC50 0.026 mg/mL). A moderate inhibition of 15-LOX was observed in all samples, whereas mangiferin was least active. In advanced glycation end product inhibition assay, the chloroform fraction of Langra variety exhibited significant inhibition in nonoxidative (IC50 64.4 µg/mL) and oxidative modes (IC50 54.7 µg/mL). It was concluded that both Langra and Sindhri peel extracts and fractions possess significant antidiabetic activities. The results suggest the potential use of peel waste in the management and complications of diabetes.

Patient Outcomes and Management Strategies for Intensive Care Unit (ICU)-Associated Delirium: A Literature Review.

Delirium is a significant public health concern, with tremendous implications for patient outcomes. Intensive care unit (ICU)-related delirium is gaining attention due to the higher prevalence of delirium in ICU-admitted patients. The most common negative outcomes of ICU delirium include cognitive impairments, functional dependence, high incidence of mortality, extended stay in the ICU, and high costs. So far, no single etiological factor has been identified as the sole cause of delirium. Several functional, neurotransmitter, or injury-causing hypotheses have been proposed for ICU delirium. Several risk factors contribute to the development of delirium in patients admitted to the ICU. These are age, gender, types of sedation, physical restraints, medical and surgical interventions, pain, and extended stay in the ICU. The most commonly used assessment modules for ICU delirium are the PREdiction of DELIRium in ICu patients (PRE-DELIRIC), Early PREdiction model for DELIRium in ICu patients (E-PRE-DELERIC), and Lanzhou Model, Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), Intensive Care Delirium Screening Checklist (ICDSC), and Delirium Rating Scale (DRS). There is no proper treatment for ICU delirium; however, it can be managed through various pharmacological and non-pharmacological interventions. Healthcare providers should receive constant education and training on delirium recognition, prevention, and management to enhance patient care and outcomes in the ICU. Further research is needed on the effective prevention and management of ICU delirium.

Epidemiological exploration of fleas and molecular identification of flea-borne viruses in Egyptian small ruminants.

The study aimed to investigate molecularly the presence of flea-borne viruses in infested small ruminants with fleas. It was carried out in Egypt's Northern West Coast (NWC) and South Sinai Governorate (SSG). Three specific primers were used targeting genes, ORF103 (for Capripoxvirus and Lumpy skin disease virus), NS3 (for Bluetongue virus), and Rdrp (for Coronavirus), followed by gene sequencing and phylogenetic analyses. The results revealed that 78.94% of sheep and 65.63% of goats were infested in the NWC area, whereas 49.76% of sheep and 77.8% of goats were infested in the SSG region. Sheep were preferable hosts for flea infestations (58.9%) to goats (41.1%) in the two studied areas. Sex and age of the animals had no effects on the infestation rate (p > 0.05). The season and site of infestation on animals were significantly different between the two areas (p < 0.05). Ctenocephalides felis predominated in NWC and Ctenocephalides canis in SSG, and males of both flea species were more prevalent than females. Molecular analysis of flea DNA revealed the presence of Capripoxvirus in all tested samples, while other viral infections were absent. Gene sequencing identified three isolates as sheeppox viruses, and one as goatpox virus. The findings suggest that Capripoxvirus is adapted to fleas and may be transmitted to animals through infestation. This underscores the need for ongoing surveillance of other pathogens in different regions of Egypt.

A Theoretical Investigation for Exploring the Potential Performance of Non-Fullerene Organic Solar Cells Through Side-Chain Engineering Having Diphenylamino Groups to Enhance Photovoltaic Properties.

The development of ecofriendly fabrication phenomenon is essential requirement for commercialization of non-fullerene acceptors. Recently, end-capped modeling is employed for computational design of five non-fullerene acceptors to elevate various photovoltaic properties. All new molecules are formulated by altering the peripheral acceptors of CH3-2F and DFT methodology is employed to explore the opto-electronic, morphological and charge transfer analysis. From the computational investigation, all reported molecules manifested red shifted absorption with remarkable reduced band gap. Among investigated molecules, FA1-FA3 evinced effectively decreased value of band gaps and designed molecules have low excitation energy justifying proficient charge transference. The lower values of binding energy of FA1 and FA2 suggest their facile exciton dissociation leading to improved charge mobility. By blending with J61 donor, FA4 have sufficiently enhanced value of VOC (1.72 eV) and fill factor (0.9228). Energy loss of the model (R) is 0.57 eV and statistical calculation demonstrate that all our modified molecules except FA3 has profoundly reduced energy loss compelling in its pivotal utilization. From accessible supportive outcomes of recent investigation, it is recommended that our modified chromophore exhibit remarkable noteworthy applications in solar cells for forthcoming innovations.

Coordinated expansion of memory T follicular helper and B cells mediates spontaneous clearance of HCV reinfection.

Introduction: Follicular helper T cells are essential for helping in the maturation of B cells and the production of neutralizing antibodies (NAbs) during primary viral infections. However, their role during recall responses is unclear. Here, we used hepatitis C virus (HCV) reinfection in humans as a model to study the recall collaborative interaction between circulating CD4 T follicular helper cells (cTfh) and memory B cells (MBCs) leading to the generation of NAbs. Methods: We evaluated this interaction longitudinally in subjects who have spontaneously resolved primary HCV infection during a subsequent reinfection episode that resulted in either another spontaneous resolution (SR/SR, n = 14) or chronic infection (SR/CI, n = 8). Results: Both groups exhibited virus-specific memory T cells that expanded upon reinfection. However, early expansion of activated cTfh (CD4+CXCR5+PD-1+ICOS+FoxP3-) occurred in SR/SR only. The frequency of activated cTfh negatively correlated with time post-infection. Concomitantly, NAbs and HCV-specific MBCs (CD19+CD27+IgM-E2-Tet+) peaked during the early acute phase in SR/SR but not in SR/CI. Finally, the frequency of the activated cTfh1 (CXCR3+CCR6-) subset correlated with the neutralization breadth and potency of NAbs. Conclusion: These results underscore a key role for early activation of cTfh1 cells in helping antigen-specific B cells to produce NAbs that mediate the clearance of HCV reinfection.

Innovative Applications of Telemedicine and Other Digital Health Solutions in Pain Management: A Literature Review.

Since the COVID-19 pandemic, healthcare systems are facing extraordinary challenges. Our approaches to medicine have changed and created a whole new generation of people who have chronic pain. Various medical services were postponed. The pandemic significantly impacted the bio-psychosocial model of pain and the management of chronic pain. These new challenges affected millions of patients worldwide, with more burden on patients with chronic pain. Telemedicine and digital health rather than traditional office visits have become essential tools for communications, resulting in an unmatched surge in telehealth adoption. This new approach facilitated the remote treatment and follow-up of patients who have difficulty to access the healthcare services, particularly patients with chronic pain and those who were receiving regular controlled medications. An extensive computer search was conducted, during the period (from January 2014 to March 2024), and included literature from PubMed, Scopus, MEDLINE, and Google scholar. According to preset inclusion and exclusion criteria, a total of 38 articles have been included in this review article. This literature review focuses on the innovation of telemedicine and digital health in pain management, especially in the context of the challenges posed by the COVID-19 pandemic. The manuscript provides a comprehensive overview of telemedicine and digital communications, their evolution, and their significance in healthcare. It also emphasizes the benefits, challenges, limitations, and the ethical concerns of telemedicine in pain management after the COVID-19 pandemic. Furthermore, the document explores the different modes of the telecommunications and discusses the future directions of the digital health technology.

Heterologous maternal antibodies derived from infectious bronchitis vaccines prevent the development of lesions associated with false layer syndrome.

Infectious bronchitis virus (IBV) strains of the Delmarva (DMV)/1639 genotype have been causing false layer syndrome (FLS) in the Eastern Canadian layer operations since the end of 2015. FLS is characterized by the development of cystic oviducts in layer pullets infected at an early age. Currently, there are no homologous vaccines for the control of this IBV genotype. Our previous research showed that a heterologous vaccination regimen incorporating Massachusetts (Mass) and Connecticut (Conn) IBV types protects layers against DMV/1639 genotype IBV. The aim of this study was to investigate the role of maternal antibodies conferred by breeders received the same vaccination regimen in the protection against the development of DMV/1639-induced FLS in pullets. Maternal antibody-positive (MA+) and maternal antibody-negative (MA-) female progeny chicks were challenged at 1 day of age and kept under observation for 16 weeks. Oviductal cystic formations were observed in 3 of 14 birds (21.4 %) in the MA- pullets, while the lesions were notably absent in the MA+ pullets. Milder histopathological lesions were observed in the examined tissues of the MA+ pullets. However, the maternal derived immunity failed to demonstrate protection against the damage to the tracheal ciliary activity, viral shedding, and viral tissue distribution. Overall, this study underscores the limitations of maternal derived immunity in preventing certain aspects of viral pathogenesis, emphasizing the need for comprehensive strategies to address different aspects of IBV infection.

The value and safety of adjuvant radiotherapy (ART) after radical cystectomy in locally advanced urothelial bladder cancer: A controlled randomized study.

BACKGROUND: Adjuvant radiotherapy after radical cystectomy in locally advanced bladder cancer was revived after the advancement in precise radiotherapy that decreased the normal pelvic tissue radiation hazards. However, there are still scarce controlled randomized studies addressing this issue. PATIENTS AND METHODS: One hundred thirty-one cystectomized urothelial bladder cancer patients were enrolled; a hundred and twenty-two were randomized to receive adjuvant radiotherapy (ART) 50 Gy/25 fractions, 4 weeks' post-cystectomy or cystectomy alone (CY). Sixty-two were included in the ART arm and sixty in the CY arm. Twenty-four ART and 30 CY patients received Neoadjuvant chemotherapy. Eleven patients (9%) had cotenant neo-bladder diversion, 6 in ART, and 5 in CY arms. All ART patients were treated with intensity-modulated radiotherapy (IMRT) with daily verification cone-beam CT (CBCT). The median follow-up was 42.7 months. RESULTS: The 3-year adjusted Locoregional relapse-free survival (LRFS) rate was higher in the ART arm, measuring 81% (95%CI: 69-94) compared to 71% (95% CI: 60-80) (p=0.0457). ART significantly improved the locoregional relapse-free rate in the cystectomy bed and the pelvic side wall (p= 0.016 and 0.001, respectively). The overall survival, event-free, and distant metastasis-free survival did not rank to the level of statistical significance in the 2 arms. Even though the acute side effects were slightly higher in ART, the late toxicities were almost equal in the two groups. CONCLUSIONS: Adjuvant radiotherapy is safe and quite tolerable after radical cystectomy when using precise radiation techniques. These techniques significantly improved the LRFS but had insignificant improvement on the overall survival. ART did not affect the distant metastasis-free survival. Similar studies are performed in different centers around the world to confirm the value of ART in urothelial bladder cancer.

Polymer-Based Terbium Complex as a Fluorescent Probe for Cancer Antigen 125 Detection: A Promising Tool for Early Diagnosis of Ovarian Cancer.

A novel photoprobe, Tb-acetylacetone (Tb-ACAC) doped within a modified epoxy cellulose polymer immobilized with CA-125 monoclonal antibody, offers an accurate and highly selective method for early ovarian cancer (OC) diagnosis by detecting cancer antigen 125 (CA-125) in serum samples. This approach leverages quenching of the Tb-ACAC luminescence upon binding to CA-125. Characterization of the photoprobe film through UV-vis and fluorescence measurements confirmed the presence of Tb-ACAC within the polymer matrix. In aqueous solution (pH 6.8, λex = 365 nm), the characteristic emission band of Tb-ACAC at λem = 546.2 nm exhibited significant quenching upon CA-125 binding. This quenching effect enabled the sensitive and specific detection of CA-125 in diverse serum samples from OC patients, demonstrating the applicability, simplicity, and effectiveness of this novel approach.

Native desert plants have the potential for phytoremediation of phytotoxic metals in urban cities: implications for cities sustainability in arid environments.

Arid regions can benefit from using native desert plants, which require minimal freshwater and can aid in remediating soil phytotoxic metals (PTMs) from traffic emissions. In this study, we assessed the ability of three native desert plants-Pennisetum divisum, Tetraena qatarensis, and Brassica tournefortii-to accumulate phytotoxic metals (PTMs) in their different plant organs, including leaves, stems, and roots/rhizomes. The PTMs were analyzed in soil and plant samples collected from Dubai, United Arab Emirates (UAE). The results indicated significantly higher levels of PTMs on the soil surface than the subsurface layer. Brassica exhibited the highest concentrations of Fe and Zn, measuring 566.7 and 262.8 mg kg-1, respectively, while Tetraena accumulated the highest concentration of Sr (1676.9 mg kg-1) in their stems. In contrast, Pennisetum recorded the lowest concentration of Sr (21.0 mg kg-1), while Tetraena exhibited the lowest concentrations of Fe and Zn (22.5 and 30.1 mg kg-1) in their leaves. The roots of Pennisetum, Brassica, and Tetraena demonstrated the potential to accumulate Zn from the soil, with concentration factors (CF) of 1.75, 1.09, and 1.09, respectively. Moreover, Brassica exhibited the highest CF for Sr, measuring 2.34. Pennisetum, however, could not translocate PTMs from its rhizomes to other plant organs, as indicated by a translocation factor (TF) of 1. In contrast, Brassica effectively translocated the studied PTMs from its roots to the stem and leaves (except for Sr in the leaves). Furthermore, Pennisetum exclusively absorbed Zn from the soil into its leaves and stems, with an enrichment factor (EF) greater than 1. Brassica showed the ability to uptake the studied PTMs in its stem and leaves (except for Fe), while Tetraena primarily absorbed Sr and Zn into its stems. Based on the CF and TF results, Pennisetum appears to be a suitable species for phytostabilization of both Fe and Zn, while Brassica is well-suited for Sr and Zn polluted soils. Tetraena shows potential for Zn phytoremediation. These findings suggest that these plants are suitable for PTMs phytoextraction. Furthermore, based on the EF results, these plants can efficiently sequester PTMs.

From yield stress to elastic instabilities: Tuning the extensional behavior of elastoviscoplastic fluids.

In this study, we delve into the intricacies of elastoviscoplastic (EVP) fluids, particularly focusing on how polymer additives influence their extensional behavior. Our findings reveal that polymer additives significantly alter the extensional properties of the EVP fluids, such as relaxation time and extensional stresses while having negligible impact on the shear rheology. Interestingly, the modified fluids exhibit a transition from yield stress-like behavior to viscoelastic-like behavior under high extensional rates, ultimately leading to destabilization under extreme deformation. This research enhances the fundamental understanding of EVP fluids and highlights potential advancements in applications, especially in precision-demanding fields like 3D printing.

Determination of baloxavir marboxil in pharmaceutical preparations and spiked human plasma using its quenching action on acetoxymercuric fluorescein reagent: Assessment of greenness and whiteness.

A straightforward, reliable, and cost-effective spectrofluorimetric approach has been established for the analysis of baloxavir marboxil (BXM) in raw material, tablets, as well as spiked human plasma. The approach relies on BXM's quenching impact on acetoxymercuric fluorescein (AMF) fluorescence intensity. To improve the reaction, factors such as AMF's concentration, solution's pH, diluting solvents, and reaction time were examined and optimized. Linearity, range, accuracy, precision, LOD, and LOQ were all verified in compliance with ICH criteria. The concentration range was shown to be linear between 0.2 and 2 µg/mL. The technique was effectively utilized for BXM analysis in both its tablet as well as spiked human plasma, with mean % recoveries of 101 ± 0.36 and 98.77 ± 0.65, respectively. Two assessment models (AGREE and RGB-12) were used to compare the proposed process's greenness and sustainability to four previously published chromatographic techniques. Higher green and sustainability qualities were declared by the suggested approach than by earlier ones.

Comparative metabolomics study on the secondary metabolites of the red alga, Corallina officinalis and its associated endosymbiotic fungi.

Marine endosymbionts have gained remarkable interest in the last three decades in terms of natural products (NPs) isolated thereof, emphasizing the chemical correlations with those isolated from the host marine organism. The current study aimed to conduct comparative metabolic profiling of the marine red algae Corallina officinalis, and three fungal endosymbionts isolated from its inner tissues namely, Aspergillus nidulans, A. flavipes and A. flavus. The ethyl acetate (EtOAc) extracts of the host organism as well as the isolated endosymbionts were analyzed using ultra-high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-MS/MS)in both positive and negative ion modes, applying both full scan (FS) and all ion fragmentation (AIF) modes. Extensive interpretation of the LC-MS/MS spectra had led to the identification of 76 metabolites belonging to different phytochemical classes including alkaloids, polyketides, sesquiterpenes, butyrolactones, peptides, fatty acids, isocoumarins, quinones, among others. Metabolites were tentatively identified by comparing the accurate mass and fragmentation pattern with metabolites previously reported in the literature, as well as bioinformatics analysis using GNPS. A relationship between the host C. officinalis and its endophytes (A. flavus, A. nidulans, and A. flavipes) was discovered. C. officinalis shares common metabolites with at least one of the three endosymbiotic fungi. Some metabolites have been identified in endophytes and do not exist in their host. Multivariate analysis (MVA) revealed discrimination of A. flavipes from Corallina officinalis and other associated endophytic Aspergillus fungi (A. flavus and A. nidulans).

CD8+ T cell-derived Fgl2 regulates immunity in a cell-autonomous manner via ligation of FcγRIIB.

The regulatory circuits dictating CD8+ T cell responsiveness versus exhaustion during anti-tumor immunity are incompletely understood. Here we report that tumor-infiltrating antigen-specific PD-1+ TCF-1- CD8+ T cells express the immunosuppressive cytokine Fgl2. Conditional deletion of Fgl2 specifically in mouse antigen-specific CD8+ T cells prolongs CD8+ T cell persistence, suppresses phenotypic and transcriptomic signatures of T cell exhaustion, and improves control of the tumor. In a mouse model of chronic viral infection, PD-1+ CD8+ T cell-derived Fgl2 also negatively regulates virus-specific T cell responses. In humans, CD8+ T cell-derived Fgl2 is associated with poorer survival in patients with melanoma. Mechanistically, the dampened responsiveness of WT Fgl2-expressing CD8+ T cells, when compared to Fgl2-deficient CD8+ T cells, is underpinned by the cell-intrinsic interaction of Fgl2 with CD8+ T cell-expressed FcγRIIB and concomitant caspase 3/7-mediated apoptosis. Our results thus illuminate a cell-autonomous regulatory axis by which PD-1+ CD8+ T cells both express the receptor and secrete its ligand in order to mediate suppression of anti-tumor and anti-viral immunity.

Cu-nanoparticles enhance the sustainable growth and yield of drought-subjected wheat through physiological progress.

Drought stress (DS) is a significant abiotic stress that limits agricultural productivity worldwide. In semi-arid climates, one potential solution to alleviate the deleterious effects of drought is the use of soil amendments such as nanoparticles. The current research was conducted out to probe the sway of drought at critical growth stages (CGS) of wheat crop (D0: Control, D1: Drought at tillering stage, and D2: Drought at anthesis stage) and the application of Cu-nanoparticles (T0: 0 mg L-1, T1: 300 mg L-1, T2: 700 mg L-1, and T3: 950 mg L-1) in order to improve drought resilience. Results of the study revealed that DS considerably decreased the wheat growth and yield during CGS. However, Cu-nanoparticles application alleviated the detrimental backlash of DS and led to improvements in various aspects of wheat growth and yield, including plant height, spike length, 1000 grain weight, stomatal conductance, leaf chlorophyll content, water use efficiency, leaf turgor potential, relative water content, and ultimately the grain yield. The use of principal component analysis allowed us to integrate and interpret the diverse findings of our study, elucidating the impact of Cu-nanoparticle treatment on wheat growth and yield under drought. Overall, the study concluded that DS during the anthesis stage had the most significant negative impact on crop yield. However, applying Cu-nanoparticles at the rate of 300 mg L-1 proved to be an effective strategy for improving crop productivity by reducing the harmful effects of drought.

Re-assessment of schistosomiasis in nine endemic districts with cluster sampling in Sierra Leone.

Background: Baseline mapping showed that schistosomiasis was highly/moderately endemic in nine districts in Sierra Leone. Mass drug administration (MDA) with praziquantel started in 2009, and after multiple rounds of treatment, an impact assessment was conducted in 2016 followed by a second re-assessment in 2022 using cluster sampling to provide more granular data for refining chiefdom (sub-district) treatment strategies. Methods: On average, 20 rural villages were systematically selected per district by probability proportional to population size across the nine districts. Surveys were conducted in schools, and 24 school children aged between 5 and 14 years were randomly selected, with an equal number of boys and girls. One stool sample and one urine sample were collected per child. Two Kato-Katz slides were examined per stool for Schistosoma mansoni infection. Hemastix strips were used as a proxy for S. haematobium infection with urine filtration used for egg counts on hematuria-positive samples. Results: In total, 4,736 stool samples and 4,618 urine samples were examined across 200 schools in 125 chiefdoms. Overall, the prevalence of S. mansoni was 16.3% (95% CI: 15.3-17.4%), while the overall prevalence of S. haematobium was 2.0% (95% CI: 1.6-2.4%) by hematuria. The prevalence of heavy infections for S. mansoni and S. haematobium was 1.5% (95% CI: 1.1-1.9%) and 0.02% (95% CI: 0.0-0.14%), respectively. Among 125 chiefdoms surveyed, the overall schistosomiasis prevalence was <10% in 65 chiefdoms, 10-49.9% in 47 chiefdoms, and ≥ 50% in 13 chiefdoms. There was a mixed relationship between schistosomiasis in school children and WASH access in schools. Conclusion: Sierra Leone has made significant progress in reducing schistosomiasis prevalence across the country after a decade of MDA intervention. However, high prevalence remains in some hotspot chiefdoms. The next steps are for the national program to investigate and address any potential issues such as low coverage or poor knowledge of schistosomiasis risk behaviors and, where appropriate, consider broadening to community-wide treatment in hotspot chiefdoms or communities.

Synthesis, Docking, and DFT Studies on Novel Schiff Base Sulfonamide Analogues as Selective COX-1 Inhibitors with Anti-Platelet Aggregation Activity.

Selective COX-1 inhibitors are preferential therapeutic targets for platelet aggregation and clotting responses. In this study, we examined the selective COX-1-inhibitory activities of four newly synthesized compounds, 10-13, along with their abilities to inhibit platelet aggregation against ADP and collagen. The target compounds 10-13 were synthesized using the conventional method, sonication, and microwave-assisted methods. Microanalytical and spectral data were utilized to elucidate the structures of the new compounds 10-13. Additionally, a spectral NMR experiment [NOESY] was conducted to emphasize the configuration around the double bond of the imine group C=N. The obtained results revealed no observed correlation between any of the neighboring protons, suggesting that the configuration at the C=N double bond is E. Biological results revealed that all the screened compounds 10-13 might serve as selective COX-1 inhibitors. They showed IC50 values ranging from 0.71 µM to 4.82 µM against COX-1 and IC50 values ranging from 9.26 µM to 15.24 µM against COX-2. Their COX-1 selectivity indices ranged between 2.87 and 18.69. These compounds show promise as promising anti-platelet aggregation agents. They effectively prevented platelet aggregation induced by ADP with IC50 values ranging from 0.11 µM to 0.37 µM, surpassing the standard aspirin with an IC50 value of 0.49 µM. Additionally, they inhibited the platelet aggregation induced by collagen with IC50 values ranging from 0.12 µM to 1.03 µM, demonstrating superior efficacy compared to aspirin, which has an IC50 value of 0.51 µM. In silico molecular modeling was performed for all the target compounds within the active sites of COX-1 and COX-2 to rationalize their selective inhibitory activities towards COX-1. It was found that the binding interactions of the designed compounds within the COX-1 active site had remained unaffected by the presence of celecoxib. Molecular modeling and DFT calculations using the B3LYP/6-31+G (d,p) level were performed to study the stability of E-forms with respect to Z-forms for the investigated compounds. A strong correlation was observed between the experimental observations and the quantum chemical descriptors.

In Vitro and Randomized Controlled Clinical Study of Natural Constituents' Anti-HPV Potential for Treatment of Plantar Warts Supported with In Silico Studies and Network Analysis.

The aim of this study is to evaluate the anti-HPV potential of a Moringa olifera Lam seed, Nigella sativa L. seed, and Musa Acuminata peel herbal mixture in the form of polymer film-forming systems. A clinical trial conducted in outpatient clinics showed that the most significant outcome was wart size and quantity. Compared to the placebo group, the intervention group's size and number of warts were considerably better according to the results. Chemical profiling assisted by LC-HRMS led to the dereplication of 49 metabolites. Furthermore, network pharmacology was established for the mixture of three plants; each plant was studied separately to find out the annotated target genes, and then, we combined all annotated genes of all plants and filtered the genes to specify the genes related to human papilloma virus. In a backward step, the 24 configured genes related to HPV were used to specify only 30 compounds involved in HPV infection based on target genes. CA2 and EGFR were the top identified genes with 16 and 12 edges followed by PTGS2, CA9, and MMP9 genes with 11 edges each. A molecular docking study for the top active identified compounds of each species was conducted in the top target HPV genes, CA2 and EGFR, to investigate the mode of interaction between these compounds and the targets' active sites.

Idiopathic secondary azoospermia occurrence in men with oligospermia over time.

PURPOSE: To investigate the occurrence of idiopathic secondary azoospermia (ISA) in men with oligospermia over time and identify risk factors for ISA in this population. METHODS: This was a retrospective cohort study conducted in a university-affiliated male infertility clinic. A total of 1056 oligospermic men (concentration < 15 million/ml (M/ml) and no azoospermia) with at least two SA done between 2000 and 2019 were included. The primary outcome was the occurrence of ISA by oligospermia severity. RESULTS: In the entire cohort, 31 patients (2.9%) eventually became azoospermic with time. The ≤ 1 M/ml extremely severe oligospermia (ESO) group (283 patients) had significantly higher rates of ISA in each time period compared to the 1-5 M/ml severe oligospermia (SO) (310 patients) and 5-15 M/ml mild oligospermia (MO) (463 patients) groups (p < 0.05 for all comparisons), with rates of 21.1% in the ESO, 4.8% in the SO, and 0% in the MO group (p = 0.02) after 3-5 years, reaching 32% after 5 years in the ESO group compared to no cases in the other two groups (p = 0.006). Parameters shown to predict ISA were initial concentration < 1 M/ml (OR 22.12, p < 0.001) and time interval of > 3 and 5 years (OR 4.83 and 6.84, p = 0.009 and < 0.001, respectively), whereas testosterone levels were negatively associated with ISA (OR 0.88, p = 0.03). CONCLUSIONS: Men with ≤ 1 M/ml, especially those with low testosterone levels, have a dramatically increased chance of becoming azoospermic with time. Therefore, sperm banking should be recommended in these cases. Men with a sperm concentration above 1 M/ml have low chances of becoming azoospermic, even after 3 or more years.

Elucidating the Environmental and Health Risks of Trace Element Pollution in Red Sea Fish from Nuweiba City, Aqaba Gulf, Egypt.

Trace element bioaccumulation in marine organisms is a rising international issue due to possible health concerns for humans. Thirteen trace elements were analyzed in the sediment, water, and muscular tissue of Red Sea fish. Additionally, the average daily intake (EDI), the cancer risk (CR), the hazard index (HI), and the target hazard quotient (THQ) of those elements have been taken into consideration when evaluating any possible health concerns related to their consumption. All species presented quantifiable values in muscle for all the analyzed elements (arsenic (As), lead (Pb), copper (Cu), aluminum (Al), boron (B), iron (Fe), barium (Ba), manganese (Mn), nickel (Ni), cadmium (Cd), chromium (Cr), zinc (Zn), and mercury (Hg), except for Cd and Hg, being Fe and Zn the most accumulated elements in all species. Conversely, in water samples, most elements were undeleted except for aluminum, boron, iron, and zinc. All Red Sea fish, however, had concentrations of Zn, Ni, Fe, Cu, and Mn below the upper limit allowed, although most species had higher levels of As, Cr, and Pb (0.48 ± 0.83-5.10 ± 0.79, 1.97 ± 0.46-5.25 ± 0.67 and 2.12 ± 1.01-6.83 ± 0.93 µg/g, respectively).The studied Red Sea fish showed contamination degrees (CD) of Mn, Cu, Fe, Ni, Zn, and Pb were ≤ 1, indicating minimal contamination, with As and Cr showing higher contamination degrees. However, the pollution index values (MPI-elements) can be represented according to ascending order: Lethrinus ramak < Cephalopholis hemistiktos < Pagellus affinis < Trachurus japonicus < Cheilinus lunulatus < Siganus luridus < Parupeneus forsskali < Caesio suevica. The study found that edible tissues are safe for human consumption, with HI values for children and adults less than ten, indicating negligible non-cancer hazards. However, fish consumption presents health risks due to chromium, lead, and arsenic, with THQ values several times greater than 1, and CR-Ni, CR-Cr, and CR-As values exceeding the acceptable 10-4 value in all studied species. This study provides critical insights into trace element contamination in marine fish species, highlighting the need for ongoing monitoring and proactive measures to ensure safe marine fish consumption in the Aqaba Gulf.