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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124725, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38955072

ABSTRACT

Water pollution caused by dyes and industrial wastewater poses a significant threat to ecosystems. The purification of such pollutants presents a major challenge. Photocatalysis based on semiconductor materials is a potential wastewater treatment process due to its safety and cost-effectiveness. In the present work, Zn1-2xCexDyxO (x = 0.01-0.05) semiconductors were prepared by the sol-gel auto-ignition method. The samples are denoted CDZO1, CDZO3, and CDZO5 for x  = 0.01-0.05, respectively. The X-ray diffraction and Raman spectroscopy results revealed the formation of ZnO hexagonal phase wurtzite structure for all synthesized compositions. Different structural properties were determined. It was found that the lattice parameters and the unit cell volume increased, while the crystallite size diminished as x varied from 0.01 to 0.05. Transmission electron microscopy observations confirmed the formation of nanoparticles with the desired chemical compositions. The specific surface area (SSA) values are found to be 39.95 m2/g, 48.62 m2/g, and 51.36 m2/g for CDZO1, CDZO5, and CDZO5 samples, respectively. The reflectance spectra were recorded to examine the optical properties of the different nanoparticles. The values of the optical band gap were 3.221, 3.225, and 3.239 eV for CDZO1, CDZO3, and CDZO5 samples, respectively. In addition, the photocatalytic performance towards RhB dye degradation for the different samples was assessed. It was established that the CDZO3 sample with a moderate SSA value exhibited the superior photocatalytic performance among the other as-prepared samples wherein the percentage of degradation efficiency, and kinetic constant rate attained their maximum values of 98.22 % and 0.0521 min-1, respectively within 75 min. As per the obtained findings, it is evident that the Zn1-2xCexDyxO photocatalyst has prominent potential for use in the degradation of dyes and offers a useful route for impeding the recombination of electron-hole pairs of zinc oxide material.

2.
Mol Ecol Resour ; : e13987, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956928

ABSTRACT

The utility of a universal DNA 'barcode' fragment (658 base pairs of the Cytochrome C Oxidase I [COI] gene) has been established as a useful tool for species identification, and widely criticized as one for understanding the evolutionary history of a group. Large amounts of COI sequence data have been produced that hold promise for rapid species identification, for example, for biosecurity. The fruit fly tribe Dacini holds about a thousand species, of which 80 are pests of economic concern. We generated a COI reference library for 265 species of Dacini containing 5601 sequences that span most of the COI gene using circular consensus sequencing. We compared distance metrics versus monophyly assessments for species identification and although we found a 'soft' barcode gap around 2% pairwise distance, the exceptions to this rule dictate that a monophyly assessment is the only reliable method for species identification. We found that all fragments regularly used for Dacini fruit fly identification >450 base pairs long provide similar resolution. 11.3% of the species in our dataset were non-monophyletic in a COI tree, which is mostly due to species complexes. We conclude with recommendations for the future generation and use of COI libraries. We revise the generic assignment of Dacus transversus stat. rev. Hardy 1982, and Dacus perpusillus stat. rev. Drew 1971 and we establish Dacus maculipterus White 1998 syn. nov. as a junior synonym of Dacus satanas Liang et al. 1993.

3.
PLoS One ; 19(7): e0292413, 2024.
Article in English | MEDLINE | ID: mdl-38959229

ABSTRACT

Salmonella infections pose a significant global public health concern due to the substantial expenses associated with monitoring, preventing, and treating the infection. In this study, we explored the core proteome of Salmonella to design a multi-epitope vaccine through Subtractive Proteomics and immunoinformatics approaches. A total of 2395 core proteins were curated from 30 different isolates of Salmonella (strain NZ CP014051 was taken as reference). Utilizing the subtractive proteomics approach on the Salmonella core proteome, Curlin major subunit A (CsgA) was selected as the vaccine candidate. csgA is a conserved gene that is related to biofilm formation. Immunodominant B and T cell epitopes from CsgA were predicted using numerous immunoinformatics tools. T lymphocyte epitopes had adequate population coverage and their corresponding MHC alleles showed significant binding scores after peptide-protein based molecular docking. Afterward, a multi-epitope vaccine was constructed with peptide linkers and Human Beta Defensin-2 (as an adjuvant). The vaccine could be highly antigenic, non-toxic, non-allergic, and have suitable physicochemical properties. Additionally, Molecular Dynamics Simulation and Immune Simulation demonstrated that the vaccine can bind with Toll Like Receptor 4 and elicit a robust immune response. Using in vitro, in vivo, and clinical trials, our findings could yield a Pan-Salmonella vaccine that might provide protection against various Salmonella species.


Subject(s)
Computational Biology , Epitopes, T-Lymphocyte , Proteomics , Salmonella , Proteomics/methods , Epitopes, T-Lymphocyte/immunology , Salmonella/immunology , Salmonella/genetics , Computational Biology/methods , Humans , Genomics/methods , Molecular Docking Simulation , Salmonella Vaccines/immunology , Animals , Bacterial Proteins/immunology , Bacterial Proteins/genetics , Bacterial Proteins/chemistry , Molecular Dynamics Simulation , Salmonella Infections/prevention & control , Salmonella Infections/immunology , Salmonella Infections/microbiology , Epitopes, B-Lymphocyte/immunology , Immunoinformatics
4.
Bull Environ Contam Toxicol ; 113(1): 1, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38949743

ABSTRACT

Microplastics (MPs) pollution is a profound problem around the world yet it's study on the effect on zooplankton including copepods are very limited. The study was conducted between January 2021 and January 2022 in the Lower Meghna Estuary to investigate MPs ingestion in two different family of copepod: Calanoid and Cyclopoid. A method of acid digestion along with Scanning Electron Microscope (SEM) was used to identify MPs ingested by copepods from the conducted area. However, three types of MPs namely fiber, fragment and foam were extracted from this copepod biomass. Fibers represent highest (> 50%) of the ingested MPs from both group of copepod that exceed fragments and foams in all sampling stations. The overall ingestion rate of Calanoid was found higher (0.084 ± 0.002 particles/individual) compared to the Cyclopoid group (0.077 ± 0.001 particles/individual). The results of the study have effectively illustrated that copepod, obtained from multiple sampling sites within the Lower Meghna Estuary, display a propensity to ingest MPs and subsequently endangering the food security of seafood industry.


Subject(s)
Copepoda , Environmental Monitoring , Estuaries , Microplastics , Water Pollutants, Chemical , Animals , Microplastics/analysis , Water Pollutants, Chemical/analysis , Bangladesh , Eating
5.
J Med Cases ; 15(7): 126-129, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38993809

ABSTRACT

Renal cell carcinoma (RCC) is notorious for spreading to various organs, however, its occurrence in the gastrointestinal (GI) tract is uncommon and poses diagnostic challenges due to vague symptoms. Here, we present the case of a 64-year-old man experiencing recurrent RCC metastasis in the GI tract. He presented with multiple episodes of hematochezia and was found to have masses in the colon, liver, and peritoneum, with histopathology confirming RCC. The patient underwent systemic chemotherapy and palliative radiation therapy, leading to symptom relief. This case emphasizes the rarity of RCC metastasizing to the GI tract and the importance of timely recognition and frequent surveillance during the remission phase to detect recurrence.

6.
bioRxiv ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-39026851

ABSTRACT

Helicases have emerged as promising targets for the development of antiviral drugs; however, the family remains largely undrugged. To support the focused development of viral helicase inhibitors we identified, collected, and integrated all chemogenomics data for all available helicases from the ChEMBL database. After thoroughly curating and enriching the data with relevant annotations we have created a derivative database of helicase inhibitors which we dubbed Heli-SMACC ( Heli case-targeting SMA ll Molecule C ompound C ollection). The current version of Heli-SMACC contains 20,432 bioactivity entries for viral, human, and bacterial helicases. We have selected 30 compounds with promising viral helicase activity and tested them in a SARS-CoV-2 NSP13 ATPase assay. Twelve compounds demonstrated ATPase inhibition and a consistent dose-response curve. The Heli-SMACC database may serve as a reference for virologists and medicinal chemists working on the development of novel helicase inhibitors. Heli-SMACC is publicly available at https://smacc.mml.unc.edu . Highlights: We created a curated Helicase-Targeting SMAll Molecule Compound Collection (Heli-SMACC).Heli-SMACC covers 29 human, viral, and bacterial helicases.Twelve of thirty selected compounds demonstrated inhibitory activity in a SARS-CoV-2 NSP13 ATPase Assay. Heli-SMACC is freely available online at https://smacc.mml.unc.edu .

7.
BMJ Paediatr Open ; 8(1)2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39032935

ABSTRACT

INTRODUCTION: Determining aetiology of severe illness can be difficult, especially in settings with limited diagnostic resources, yet critical for providing life-saving care. Our objective was to describe the accuracy of antemortem clinical diagnoses in young children in high-mortality settings, compared with results of specific postmortem diagnoses obtained from Child Health and Mortality Prevention Surveillance (CHAMPS). METHODS: We analysed data collected during 2016-2022 from seven sites in Africa and South Asia. We compared antemortem clinical diagnoses from clinical records to a reference standard of postmortem diagnoses determined by expert panels at each site who reviewed the results of histopathological and microbiological testing of tissue, blood, and cerebrospinal fluid. We calculated test characteristics and 95% CIs of antemortem clinical diagnostic accuracy for the 10 most common causes of death. We classified diagnostic discrepancies as major and minor, per Goldman criteria later modified by Battle. RESULTS: CHAMPS enrolled 1454 deceased young children aged 1-59 months during the study period; 881 had available clinical records and were analysed. The median age at death was 11 months (IQR 4-21 months) and 47.3% (n=417) were female. We identified a clinicopathological discrepancy in 39.5% (n=348) of deaths; 82.3% of diagnostic errors were major. The sensitivity of clinician antemortem diagnosis ranged from 26% (95% CI 14.6% to 40.3%) for non-infectious respiratory diseases (eg, aspiration pneumonia, interstitial lung disease, etc) to 82.2% (95% CI 72.7% to 89.5%) for diarrhoeal diseases. Antemortem clinical diagnostic specificity ranged from 75.2% (95% CI 72.1% to 78.2%) for diarrhoeal diseases to 99.0% (95% CI 98.1% to 99.6%) for HIV. CONCLUSIONS: Antemortem clinical diagnostic errors were common for young children who died in areas with high childhood mortality rates. To further reduce childhood mortality in resource-limited settings, there is an urgent need to improve antemortem diagnostic capability through advances in the availability of diagnostic testing and clinical skills.


Subject(s)
Cause of Death , Diagnostic Errors , Humans , Infant , Child, Preschool , Female , Male , Diagnostic Errors/statistics & numerical data , Autopsy , Africa/epidemiology , Child Mortality , Infant, Newborn
8.
ACS Appl Mater Interfaces ; 16(28): 36255-36271, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38959094

ABSTRACT

This study delves into enhancing the efficiency and stability of perovskite solar cells (PSCs) by optimizing the surface morphologies and optoelectronic properties of the electron transport layer (ETL) using tungsten (W) doping in zinc oxide (ZnO). Through a unique green synthesis process and spin-coating technique, W-doped ZnO films were prepared, exhibiting improved electrical conductivity and reduced interface defects between the ETL and perovskite layers, thus facilitating efficient electron transfer at the interface. High-quality PSCs with superior ETL demonstrated a substantial 30% increase in power conversion efficiency (PCE) compared to those employing pristine ZnO ETL. These solar cells retained over 70% of their initial PCE after 4000 h of moisture exposure, surpassing reference PSCs by 50% PCE over this period. Advanced numerical multiphysics solvers, employing finite-difference time-domain (FDTD) and finite element method (FEM) techniques, were utilized to elucidate the underlying optoelectrical characteristics of the PSCs, with simulated results corroborating experimental findings. The study concludes with a thorough discussion on charge transport and recombination mechanisms, providing insights into the enhanced performance and stability achieved through W-doped ZnO ETL optimization.

9.
Heliyon ; 10(12): e32694, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38988530

ABSTRACT

Soil salinity is a major threat hindering the optimum growth, yield, and nutritional value of potato. The application of organic composts and micronutrients can effectively ameliorate the salinity-deleterious effects on potato growth and productivity. Herein, the combined effect of banana and soybean composts (BCo and SCo) application alongside foliar supplementation of boron (B), selenium (Se), cobalt (Co), and titanium (Ti) were investigated for improving growth, physiology, and agronomical attributes of potato plants grown in saline alluvial soil. Salinity stress significantly reduced biomass accumulation, chlorophyll content, NPK concentrations, yield attributes, and tuber quality, while inducing malondialdehyde and antioxidant enzymes. Co-application of either BCo or SCo with trace elements markedly alleviated salinity-adverse effects on potato growth and productivity. These promotive effects were also associated with a significant reduction in malondialdehyde content and activities of peroxidase and superoxide dismutase enzymes. The co-application of BCo and B/Se was the most effective among other treatments. Principle component analysis and heatmap also highlighted the efficacy of the co-application of organic composts and micronutrients in improving the salinity tolerance of potato plants. In essence, the co-application of BCo with B and Se can be adopted as a promising strategy for enhancing the productivity of potato crops in salt-affected soils.

10.
Dalton Trans ; 53(25): 10704-10711, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38869436

ABSTRACT

Self-assembly of M(ClO4)2 (M2+ = Ni2+, Cu2+, and Zn2+) with (1S,1'S,1''S,2R,2'R,2''R)-(benzenetricarbonyltris(azanediyl))tris(2,3-dihydro-1H-indene-2,1-diyl) trinicotinate (s,r-L) and the corresponding enantiomer (r,s-L) as a pair of chiral tridentate donors gives rise to the chiral cage pairs [M3(s,r- and r,s-L)2](ClO4)6. For the two pairs of [(Me2CO)(H2O)@M3(r,-s and s,r-L)2](ClO4)6 (M2+ = Ni2+ and Zn2+), the inner cavity is occupied by both an acetone and a single water molecule, whereas for the copper(II) pair of [Me2CO@Cu3(r,s- and s,r-L)2](ClO4)6 under the same conditions, the cavity is filled by only one acetone molecule. Thus, the encapsulation of guest molecules into the cages during self-assembly shows significant metal(II) ion effects. These chiral cages are effective for the enantio-recognition of chiral (S)-2-butanol and (R)-2-butanol via the shifts of the electrochemical oxidation potentials obtained by the linear sweep voltammetry (LSV) technique, density functional theory (DFT) calculations, and the chiral 2-butanol adsorption in the single-crystal-to-single-crystal (SCSC) mode.

11.
J Environ Manage ; 363: 121245, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38843729

ABSTRACT

This study investigates the impact of geopolitical risk on firm-level environmental, social, and governance (ESG) performance. Using a news-based indicator of geopolitical risk across 41 countries and a comprehensive dataset spanning from 2002 to 2021 with 65,354 firm-year observations, we uncover that geopolitical risk is negatively associated with ESG performance. Our findings remain robust even when considering alternative measures of geopolitical risk, ESG components, and sub-samples. Moreover, we address potential endogeneity concerns through two-stage least squares, propensity score matching and entropy balancing approaches. Interestingly, we find that the effect of geopolitical risk is positive for countries with lower geopolitical risk and high peace, indicating that relatively stable environments can incentivize firms to enhance their sustainability practices. We also examine the potential channel effects of cash holding, corporate investment, and cost of capital, and found significant effects. Overall, this paper underscores the significance of geopolitical risk as a macro-level shock that significantly influences ESG performance.


Subject(s)
Politics , Humans , Conservation of Natural Resources
12.
Vaccine ; 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38897895

ABSTRACT

Meningococcal disease is caused by Neisseria meningitidis or meningococcus. Every year globally around 1.2 million people are affected and approximately 120,000 deaths occur due to meningitis. The disease can be prevented by a single dose of meningococcal vaccine. We carried out a randomized observer-blinded non-inferiority trial to evaluate and compare the immunogenicity and safety of a local meningococcal polysaccharide vaccine 'Ingovax ACWY' (test) with Quadri MeningoTM (comparator), an approved meningococcal polysaccharide vaccine in India. A total of 88 healthy adults (18-45 years old) were randomized at a 1:1 ratio in two vaccine groups receiving a single dose vaccine subcutaneously. All participants were followed until three months post-vaccination. Blood for clinical parameters (hematology and biochemistry) and serum bactericidal assay (SBA) was collected prior to vaccination and one-month post-vaccination. Solicited adverse events (AEs) were assessed up to 6 days following vaccination and unsolicited AEs were monitored throughout the follow-up period. There was no significant difference in rates of AE between the two groups. The commonest solicited AE was injection site pain. No serious AEs were reported. There was no significant difference (p<0.05) in seroconversion rate as well as pre and post-vaccination SBA geometric mean titers (GMT)between test and comparator vaccine. The post-vaccination GMT ratio (GMR) of the test and comparator vaccine was found to be 0.9, 1, 1.29, and 0.85 for serogroup A, C, W135, and Y respectively. For all the serogroups, lower limit of 95% CI of the GMR was found to be greater than the pre-defined 0.5 non-inferiority margin suggesting that Ingovax ACWY is similar to Quadri MeningoTM vaccine. We observed the immunogenicity and safety of Ingovax ACWY is non-inferior to comparator vaccine. The development of facilities for manufacturing polysaccharide ACWY vaccines locally will further lead to capacity building in the field of vaccines for Bangladesh.

13.
Cureus ; 16(5): e59738, 2024 May.
Article in English | MEDLINE | ID: mdl-38841032

ABSTRACT

Background Post-acute care (PAC) centers are facilities used for recuperation, rehabilitation, and symptom management in an effort to improve the long-term outcomes of patients. PAC centers include skilled nursing facilities, inpatient rehabilitation facilities, and long-term care hospitals. In the 1990s, Medicare payment reforms significantly increased the discharge rates to PAC centers and subsequently increased the length of stay (LOS) among these patient populations. Over the last several years, there have been national initiatives and multidisciplinary approaches to improve safe discharge rates to home. Multiple studies have shown that patients who are discharged to home have decreased rates of 30-day readmissions, reduced short-term mortality, and an improvement in their activities of daily living.  Objectives This study aimed to investigate how multidisciplinary approaches could improve a single institution's discharge rates to home. In doing so, we aim to lower hospital readmission rates, hospital length of stay, morbidity and mortality rates, and healthcare-associated costs. Methods A retrospective single-institution cohort study was implemented at Jersey Shore University Medical Center (JSUMC). Data from January 2015 to December 2019 served as the control period, compared to the intervention period from January 2020 to January 2024. Patients were either admitted to JSUMC teaching faculty, hospitalists, or "others," which is composed of various medical and surgical subspecialists. Interventions performed to improve home discharge rates can be categorized into the following: physician education, patient education, electronic medical record (EMR) initiatives, accountability, and daily mobility initiatives. All interventions were performed equally across the three patient populations. The primary endpoint was the proportion of patients discharged to home. Results There were 190,699 patients, divided into a pre-intervention group comprising 98,885 individuals and a post-intervention group comprising 91,814 patients. Within the pre-intervention group, the faculty attended to 8,495 patients, hospitalists cared for 39,145 patients, and others managed 51,245 patients. In the post-intervention period, the faculty oversaw 8,014 patients, hospitalists attended to 35,094 patients, and others were responsible for 48,706 patients. After implementing a series of multidisciplinary interventions, there was a significant increase in the proportion of patients discharged home, rising from 74.9% to 80.2% across the entire patient population. Specifically, patients under the care of the faculty experienced a more substantial improvement, with a discharge rate increasing from 73.6% to 84.4%. Similarly, the hospitalists exhibited a rise from 69.4% to 74.3%, and the others demonstrated an increase from 79.3% to 83.7%. All observed changes yielded a p-value < 0.001. Conclusions By deploying a multifaceted strategy that emphasized physician education, patient education, EMR initiatives, accountability measures, and daily mobility, there was a statistically significant increase in the rate of patient discharges to home. These initiatives proved to be cost-effective and led to a tangible reduction in healthcare-associated costs and patient length of stay. Further studies are required to look into the effect on hospital readmission rates and morbidity and mortality rates. The comprehensive approach showcased its potential to optimize patient outcomes.

14.
Brief Bioinform ; 25(4)2024 May 23.
Article in English | MEDLINE | ID: mdl-38877887

ABSTRACT

Neurodegenerative diseases, such as Alzheimer's disease, pose a significant global health challenge with their complex etiology and elusive biomarkers. In this study, we developed the Alzheimer's Identification Tool (AITeQ) using ribonucleic acid-sequencing (RNA-seq), a machine learning (ML) model based on an optimized ensemble algorithm for the identification of Alzheimer's from RNA-seq data. Analysis of RNA-seq data from several studies identified 87 differentially expressed genes. This was followed by a ML protocol involving feature selection, model training, performance evaluation, and hyperparameter tuning. The feature selection process undertaken in this study, employing a combination of four different methodologies, culminated in the identification of a compact yet impactful set of five genes. Twelve diverse ML models were trained and tested using these five genes (CNKSR1, EPHA2, CLSPN, OLFML3, and TARBP1). Performance metrics, including precision, recall, F1 score, accuracy, Matthew's correlation coefficient, and receiver operating characteristic area under the curve were assessed for the finally selected model. Overall, the ensemble model consisting of logistic regression, naive Bayes classifier, and support vector machine with optimized hyperparameters was identified as the best and was used to develop AITeQ. AITeQ is available at: https://github.com/ishtiaque-ahammad/AITeQ.


Subject(s)
Alzheimer Disease , Machine Learning , Alzheimer Disease/genetics , Humans , Algorithms , Gene Expression Profiling/methods , Transcriptome , Computational Biology/methods , RNA-Seq/methods
15.
Mater Horiz ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38919027

ABSTRACT

Cesium lead iodide bromide (CsPbIBr2) perovskite solar cells (PSCs) have improved stability compared to other perovskite compositions. However, they still face significant challenges due to their poor photovoltaic performance parameters, which limit the devices' power conversion efficiencies (PCEs). This study proposes a novel device design to tailor the potential of CsPbIBr2 PSCs by improving their optoelectronic properties. An advanced 3D multiphysics approach was rigorously used to investigate the optics and electrical properties of the proposed CsPbIBr2 PSCs. This approach combines finite-difference time-domain (FDTD) and finite element method (FEM) techniques with the particle swarm optimization (PSO) algorithm. The outcome from the adapted numerical approach is in good agreement with the experimental results. The optimized CsPbIBr2 PSC demonstrates a promising power conversion efficiency (PCE) of over 16.4%, associated VOC of 1.53 V, FF of 80.6%, and JSC of 13.4 mA cm-2. Therefore, the potential of CsPbIBr2 perovskites could be further explored with continued research and development in material science and device physics.

16.
Sci Rep ; 14(1): 12984, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38839768

ABSTRACT

The most rapidly expanding type of solar cells are the Perovskite Solar Cells (PSCs), because of its high device performance, ease of synthesis, high open-circuit voltage, and affordability. Despite these advantages, the development of perovskite-based solar cells continues to be impeded by the issues with perovskite stability and the utilization of the hazardous heavy element lead (Pb). The study emphasizes on the bifacial structure that maintains the conventional absorber layer and electron transport layer (ETL) in the optimized PSC structure. This study employs SCAPS software for device simulation to comprehensively analyze how various parameters affect the performance of solar cells. Additionally, doping concentration variation in both ETL and HTL are explored. The simulation reveals that changing device structure from monofacial to bifacial significantly influences PSC performance, demonstrating that optimizing individual layers effectively enhances overall solar cell performance. The optimized structure achieves impressive PSC performance metrics through parametric analysis, such as voltage (VOC) of 1.18 V, fill factor (FF) of 82.24%, current density (JSC) of 27.12 mA/cm2, power conversion efficiency (PCE) of 27.90% for an incident solar spectrum from the ETL side, and power conversion efficiency (PCE) of 19.86% for an incident solar spectrum from the HTL side, the calculated bifaciality factor (BF) for this structure is 71.18%.

17.
bioRxiv ; 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38915519

ABSTRACT

Despite their widespread impact on human health there are no approved drugs for combating alphavirus infections. The heterocyclic ß-aminomethyl vinyl sulfone RA-0002034 (1a) is a potent irreversible covalent inhibitor of the alphavirus nsP2 cysteine protease with broad spectrum antiviral activity. Analogs of 1a that varied each of three regions of the molecule were synthesized to establish structure-activity relationships for inhibition of Chikungunya (CHIKV) nsP2 protease and viral replication. The covalent warhead was highly sensitive to modifications of the sulfone or vinyl substituents. However, numerous alterations to the core 5-membered heterocycle and its aryl substituent were well tolerated and several analogs were identified that enhanced CHIKV nsP2 binding. For example, the 4-cyanopyrazole analog 8d exhibited a kinact /Ki ratio >10,000 M-1s-1. 3-Arylisoxazole was identified an isosteric replacement for the 5-membered heterocycle, which circumvented the intramolecular cyclization that complicated the synthesis of pyrazole-based inhibitors like 1a. The accumulated structure-activity data was used to build a ligand-based model of the enzyme active site, which can be used to guide the design of covalent nsP2 protease inhibitors as potential therapeutics against alphaviruses.

18.
Article in English | MEDLINE | ID: mdl-38898593

ABSTRACT

OBJECTIVES: To assess the prevalence and severity of periodontal disease of the Rohingya refugees and host community in Bangladesh. METHODS: An unpublished pilot was conducted for the sample size calculation. Two-stage cluster sampling method was used to select 50 participants from refugee camps and 50 from the host community. Structured questionnaire and periodontal examination were completed. Composite measures of periodontal disease were based on the World Workshop (WW) and Centers for Disease Control and Prevention-American Academy of Periodontology. Linear regression models, for clinical attachment level and periodontal pocket depth (PPD) and ordered logistic regression models, for composite measures, were fitted to test the association of periodontal measures and refugee status. RESULTS: Compared to the host community, a smaller percentage of refugees reported good oral health-related behaviours. Refugees exhibited lower levels of bleeding on probing but higher PPD, hence a higher proportion had severe stages of periodontitis. As per the WW, prevalence of periodontal disease was 88% and 100% in the host and refugee groups, respectively. In the unadjusted models, refugees were three times more likely to have severe stages of periodontitis; this association was attenuated when adjusted for confounders (sociodemographic variables and oral health-related behaviours). CONCLUSIONS: Prevalence of periodontitis was high both in the host community and refugees. The refugees exhibited a more severe disease profile. The oral health of both groups is under-researched impacting the response of the health system. Large-scale research systematically exploring the oral health of both groups will inform the design and delivery of community-based interventions.

19.
J Phys Act Health ; : 1-8, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38917992

ABSTRACT

BACKGROUND: There is limited evidence from globally diverse samples on the prevalence and correlates of meeting the global guideline of 180 minutes per day of total physical activity (TPA) among 3- to 4-year-olds. METHODS: Cross-sectional study involving 797 (49.2% girls) 3- to 4-year-olds from 17 middle- and high-income countries who participated in the pilot phases 1 and 2 of the SUNRISE International Study of Movement Behaviours in the Early Years. Daily step count was measured using thigh-worn activPAL accelerometers. Children wore the accelerometers for at least one 24-hour period. Children were categorized as meeting the TPA guideline based on achieving ≥11,500 steps per day. Descriptive analyses were conducted to describe the proportion of meeting the TPA guideline for the overall sample and each of the sociodemographic variables, and 95% CIs were calculated. Multivariable logistic regression was used to determine the sociodemographic correlates of meeting the TPA guideline. RESULTS: Mean daily step count was 10,295 steps per day (SD = 4084). Approximately one-third of the sample (30.9%, 95% CI, 27.6-34.2) met the TPA guideline. The proportion meeting the guideline was significantly lower among girls (adjusted OR [aOR] = 0.70, 95% CI, 0.51-0.96) and 4-year-olds (aOR = 0.50, 95% CI, 0.34-0.75) and higher among rural residents (aOR = 1.78, 95% CI, 1.27-2.49) and those from lower middle-income countries (aOR = 1.35, 95% CI, 0.89-2.04). CONCLUSIONS: The findings suggest that a minority of children might meet the TPA guideline globally, and the risk of not meeting the guideline differed by sociodemographic indicators. These findings suggest the need for more surveillance of TPA in young children globally and, possibly, interventions to improve childhood health and development.

20.
Int J Mol Sci ; 25(9)2024 May 03.
Article in English | MEDLINE | ID: mdl-38732206

ABSTRACT

Breast cancer stands out as one of the most prevalent malignancies worldwide, necessitating a nuanced understanding of its molecular underpinnings for effective treatment. Hormone receptors in breast cancer cells substantially influence treatment strategies, dictating therapeutic approaches in clinical settings, serving as a guide for drug development, and aiming to enhance treatment specificity and efficacy. Natural compounds, such as curcumin, offer a diverse array of chemical structures with promising therapeutic potential. Despite curcumin's benefits, challenges like poor solubility and rapid metabolism have spurred the exploration of analogs. Here, we evaluated the efficacy of the curcumin analog NC2603 to induce cell cycle arrest in MCF-7 breast cancer cells and explored its molecular mechanisms. Our findings reveal potent inhibition of cell viability (IC50 = 5.6 µM) and greater specificity than doxorubicin toward MCF-7 vs. non-cancer HaCaT cells. Transcriptome analysis identified 12,055 modulated genes, most notably upregulation of GADD45A and downregulation of ESR1, implicating CDKN1A-mediated regulation of proliferation and cell cycle genes. We hypothesize that the curcumin analog by inducing GADD45A expression and repressing ESR1, triggers the expression of CDKN1A, which in turn downregulates the expression of many important genes of proliferation and the cell cycle. These insights advance our understanding of curcumin analogs' therapeutic potential, highlighting not just their role in treatment, but also the molecular pathways involved in their activity toward breast cancer cells.


Subject(s)
Breast Neoplasms , Cell Cycle Checkpoints , Curcumin , Cyclin-Dependent Kinase Inhibitor p21 , Gene Expression Regulation, Neoplastic , Humans , Curcumin/pharmacology , Curcumin/analogs & derivatives , Breast Neoplasms/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , MCF-7 Cells , Cyclin-Dependent Kinase Inhibitor p21/metabolism , Cyclin-Dependent Kinase Inhibitor p21/genetics , Cell Cycle Checkpoints/drug effects , Female , Gene Expression Regulation, Neoplastic/drug effects , Up-Regulation/drug effects , Cell Proliferation/drug effects , Cell Survival/drug effects , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Estrogen Receptor alpha/metabolism , Estrogen Receptor alpha/genetics , Antineoplastic Agents/pharmacology , GADD45 Proteins
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