Epigenetic regulation during cancer transitions across 11 tumour types.

Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis1-4. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples. With over 1 million cells from each platform analysed through the enrichment of accessible chromatin regions, transcription factor motifs and regulons, we identified epigenetic drivers associated with cancer transitions. Some epigenetic drivers appeared in multiple cancers (for example, regulatory regions of ABCC1 and VEGFA; GATA6 and FOX-family motifs), whereas others were cancer specific (for example, regulatory regions of FGF19, ASAP2 and EN1, and the PBX3 motif). Among epigenetically altered pathways, TP53, hypoxia and TNF signalling were linked to cancer initiation, whereas oestrogen response, epithelial-mesenchymal transition and apical junction were tied to metastatic transition. Furthermore, we revealed a marked correlation between enhancer accessibility and gene expression and uncovered cooperation between epigenetic and genetic drivers. This atlas provides a foundation for further investigation of epigenetic dynamics in cancer transitions.

Differences and commonalities in the genetic architecture of protein quantitative trait loci in European and Arab populations.

Polygenic scores (PGS) can identify individuals at risk of adverse health events and guide genetics-based personalized medicine. However, it is not clear how well PGS translate between different populations, limiting their application to well-studied ethnicities. Proteins are intermediate traits linking genetic predisposition and environmental factors to disease, with numerous blood circulating protein levels representing functional readouts of disease-related processes. We hypothesized that studying the genetic architecture of a comprehensive set of blood-circulating proteins between a European and an Arab population could shed fresh light on the translatability of PGS to understudied populations. We therefore conducted a genome-wide association study with whole-genome sequencing data using 1301 proteins measured on the SOMAscan aptamer-based affinity proteomics platform in 2935 samples of Qatar Biobank and evaluated the replication of protein quantitative traits (pQTLs) from European studies in an Arab population. Then, we investigated the colocalization of shared pQTL signals between the two populations. Finally, we compared the performance of protein PGS derived from a Caucasian population in a European and an Arab cohort. We found that the majority of shared pQTL signals (81.8%) colocalized between both populations. About one-third of the genetic protein heritability was explained by protein PGS derived from a European cohort, with protein PGS performing ~20% better in Europeans when compared to Arabs. Our results are relevant for the translation of PGS to non-Caucasian populations, as well as for future efforts to extend genetic research to understudied populations.

An evolutionary conserved detoxification system for membrane lipid-derived peroxyl radicals in Gram-negative bacteria.

How double-membraned Gram-negative bacteria overcome lipid peroxidation is virtually unknown. Bactericidal antibiotics and superoxide ion stress stimulate the transcription of the Burkholderia cenocepacia bcnA gene that encodes a secreted lipocalin. bcnA gene orthologs are conserved in bacteria and generally linked to a conserved upstream gene encoding a cytochrome b561 membrane protein (herein named lcoA, lipocalin-associated cytochrome oxidase gene). Mutants in bcnA, lcoA, and in a gene encoding a conserved cytoplasmic aldehyde reductase (peroxidative stress-associated aldehyde reductase gene, psrA) display enhanced membrane lipid peroxidation. Compared to wild type, the levels of the peroxidation biomarker malondialdehyde (MDA) increase in the mutants upon exposure to sublethal concentrations of the bactericidal antibiotics polymyxin B and norfloxacin. Microscopy with lipid peroxidation-sensitive fluorescent probes shows that lipid peroxyl radicals accumulate at the bacterial cell poles and septum and peroxidation is associated with a redistribution of anionic phospholipids and reduced antimicrobial resistance in the mutants. We conclude that BcnA, LcoA, and PsrA are components of an evolutionary conserved, hitherto unrecognized peroxidation detoxification system that protects the bacterial cell envelope from lipid peroxyl radicals.

RNA binding protein PRRC2B mediates translation of specific mRNAs and regulates cell cycle progression.

Accumulating evidence suggests that posttranscriptional control of gene expression, including RNA splicing, transport, modification, translation and degradation, primarily relies on RNA binding proteins (RBPs). However, the functions of many RBPs remain understudied. Here, we characterized the function of a novel RBP, Proline-Rich Coiled-coil 2B (PRRC2B). Through photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation and sequencing (PAR-CLIP-seq), we identified transcriptome-wide CU- or GA-rich PRRC2B binding sites near the translation initiation codon on a specific cohort of mRNAs in HEK293T cells. These mRNAs, including oncogenes and cell cycle regulators such as CCND2 (cyclin D2), exhibited decreased translation upon PRRC2B knockdown as revealed by polysome-associated RNA-seq, resulting in reduced G1/S phase transition and cell proliferation. Antisense oligonucleotides blocking PRRC2B interactions with CCND2 mRNA decreased its translation, thus inhibiting G1/S transition and cell proliferation. Mechanistically, PRRC2B interactome analysis revealed RNA-independent interactions with eukaryotic translation initiation factors 3 (eIF3) and 4G2 (eIF4G2). The interaction with translation initiation factors is essential for PRRC2B function since the eIF3/eIF4G2-interacting defective mutant, unlike wild-type PRRC2B, failed to rescue the translation deficiency or cell proliferation inhibition caused by PRRC2B knockdown. Altogether, our findings reveal that PRRC2B is essential for efficiently translating specific proteins required for cell cycle progression and cell proliferation.

Splice factor polypyrimidine tract-binding protein 1 (Ptbp1) primes endothelial inflammation in atherogenic disturbed flow conditions.

NF-κB-mediated endothelial activation drives leukocyte recruitment and atherosclerosis, in part through adhesion molecules Icam1 and Vcam1. The endothelium is primed for cytokine activation of NF-κB by exposure to low and disturbed blood flow (LDF)but the molecular underpinnings are not fully understood. In an experimental in vivo model of LDF, platelets were required for the increased expression of several RNA-binding splice factors, including polypyrimidine tract binding protein (Ptbp1). This was coordinated with changes in RNA splicing in the NF-κB pathway in primed cells, leading us to examine splice factors as mediators of priming. Using Icam1 and Vcam1 induction by tumor necrosis factor (TNF)-α stimulation as a readout, we performed a CRISPR Cas9 knockout screen and identified a requirement for Ptbp1 in priming. Deletion of Ptbp1 had no effect on cell growth or response to apoptotic stimuli, but reversed LDF splicing patterns and inhibited NF-κB nuclear translocation and transcriptional activation of downstream targets, including Icam1 and Vcam1. In human coronary arteries, elevated PTBP1 correlates with expression of TNF pathway genes and plaque. In vivo, endothelial-specific deletion of Ptbp1 reduced Icam1 expression and myeloid cell infiltration at regions of LDF in atherosclerotic mice, limiting atherosclerosis. This may be mediated, in part, by allowing inclusion of a conserved alternative exon in Ripk1 leading to a reduction in Ripk1 protein. Our data show that Ptbp1, which is induced in a subset of the endothelium by platelet recruitment at regions of LDF, is required for priming of the endothelium for subsequent NF-κB activation, myeloid cell recruitment and atherosclerosis.

α-Synuclein phosphorylation at serine 129 occurs after initial protein deposition and inhibits seeded fibril formation and toxicity.

α-Synuclein (α-syn) phosphorylation at serine 129 (pS129­α-syn) is substantially increased in Lewy body disease, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). However, the pathogenic relevance of pS129­α-syn remains controversial, so we sought to identify when pS129 modification occurs during α-syn aggregation and its role in initiation, progression and cellular toxicity of disease. Using diverse aggregation assays, including real-time quaking-induced conversion (RT-QuIC) on brain homogenates from PD and DLB cases, we demonstrated that pS129­α-syn inhibits α-syn fibril formation and seeded aggregation. We also identified lower seeding propensity of pS129­α-syn in cultured cells and correspondingly attenuated cellular toxicity. To build upon these findings, we developed a monoclonal antibody (4B1) specifically recognizing nonphosphorylated S129­α-syn (WT­α-syn) and noted that S129 residue is more efficiently phosphorylated when the protein is aggregated. Using this antibody, we characterized the time-course of α-syn phosphorylation in organotypic mouse hippocampal cultures and mice injected with α-syn preformed fibrils, and we observed aggregation of nonphosphorylated α-syn followed by later pS129­α-syn. Furthermore, in postmortem brain tissue from PD and DLB patients, we observed an inverse relationship between relative abundance of nonphosphorylated α-syn and disease duration. These findings suggest that pS129­α-syn occurs subsequent to initial protein aggregation and apparently inhibits further aggregation. This could possibly imply a potential protective role for pS129­α-syn, which has major implications for understanding the pathobiology of Lewy body disease and the continued use of reduced pS129­α-syn as a measure of efficacy in clinical trials.

Effect of Preoperative Antibiotic Therapy on Operative Culture Yield for Diagnosis of Native Joint Septic Arthritis.

BACKGROUND: Native joint septic arthritis (NJSA) is definitively diagnosed by a positive Gram stain or culture, along with supportive clinical findings. Preoperative antibiotics are known to alter synovial fluid cell count, Gram stain and culture results and are typically postponed until after arthrocentesis to optimize diagnostic accuracy. However, data on the impact of preoperative antibiotics on operative culture yield for NJSA diagnosis are limited. METHODS: We retrospectively reviewed adult cases of NJSA who underwent surgery at Mayo Clinic facilities from 2012-2021 to analyze the effect of preoperative antibiotics on operative culture yield through a paired analysis of preoperative culture (POC) and operative culture (OC) results using logistic regression and generalized estimating equations. RESULTS: Two hundred ninety-nine patients with NJSA affecting 321 joints were included. Among those receiving preoperative antibiotics, yield significantly decreased from 68.0% at POC to 57.1% at OC (p < .001). In contrast, for patients without preoperative antibiotics there was a non-significant increase in yield from 60.9% at POC to 67.4% at OC (p = 0.244). In a logistic regression model for paired data, preoperative antibiotic exposure was more likely to decrease OC yield compared to non-exposure (OR = 2.12; 95% CI = 1.24-3.64; p = .006). Within the preoperative antibiotic group, additional antibiotic doses and earlier antibiotic initiation were associated with lower OC yield. CONCLUSION: In patients with NJSA, preoperative antibiotic exposure resulted in a significant decrease in microbiologic yield of operative cultures as compared to patients in whom antibiotic therapy was held prior to obtaining operative cultures.

Crystalline Polyphenylene Covalent Organic Frameworks.

The synthesis of crystalline polyphenylene covalent organic frameworks (COFs) was accomplished by linking fluorinated tris(4-acetylphenyl)benzene building units using aldol cyclotrimerization. The structures of the two COFs, reported here, were confirmed by powder X-ray diffraction techniques, Fourier transform infrared, and solid-state 13C CP/MAS NMR spectroscopy. The results showed that the COFs were porous and chemically stable in corrosive, harsh environments for at least 1 week. Accordingly, postsynthetically modified derivatives of these COFs using primary amines showed CO2 uptake from air and flue gas.

Harvesting Water from Air with High-Capacity, Stable Furan-Based Metal-Organic Frameworks.

We synthesized two isoreticular furan-based metal-organic frameworks (MOFs), MOF-LA2-1(furan) and MOF-LA2-2(furan) with rod-like secondary building units (SBUs) featuring 1D channels, as sorbents for atmospheric water harvesting (LA = long arm). These aluminum-based MOFs demonstrated a combination of high water uptake and stability, exhibiting working capacities of 0.41 and 0.48 gwater/gMOF (under isobaric conditions of 1.70 kPa), respectively. Remarkably, both MOFs showed a negligible loss in water uptake after 165 adsorption-desorption cycles. These working capacities rival that of MOF-LA2-1(pyrazole), which has a working capacity of 0.55 gwater/gMOF. The current MOFs stand out for their high water stability, as evidenced by 165 cycles of water uptake and release. MOF-LA2-2(furan) is the first aluminum MOF to employ a double 'long arm' extension strategy, which is confirmed through single-crystal X-ray diffraction (SCXRD). The MOFs were synthesized by using a straightforward synthesis route. This study offers valuable insights into the design of durable, water-stable MOFs and underscores their potential for efficient water harvesting.

Water-Enhanced Direct Air Capture of Carbon Dioxide in Metal-Organic Frameworks.

We have developed two series of amine-functionalized zirconium (Zr) metal-organic framework-808 (MOF-808), which were produced by postsynthetic modifications to have either amino acids coordinated to Zr ions (MOF-808-AAs) or polyamines covalently bound to the chloro-functionalized structure (MOF-808-PAs). These MOF variants were comprehensively characterized by liquid-state 1H nuclear magnetic resonance (NMR) measurements and potentiometric acid-base titration to determine the amounts of amines, energy-dispersive X-ray spectroscopy to assess the extent of covalent substitution by polyamines, powder X-ray diffraction analysis to verify the maintenance of the MOF crystallinity and structure after postsynthetic modifications, nitrogen sorption isotherm measurements to confirm retention of the porosity, and water sorption isotherm measurements to find the water uptake in the pores of each member of the series. Evaluation and testing of these compounds in direct air capture (DAC) of CO2 showed improved CO2 capture performance for the functionalized forms, especially under humid conditions: In dry conditions, the l-lysine- and tris(3-aminopropyl)amine-functionalized variants, termed as MOF-808-Lys and MOF-808-TAPA, exhibited the highest CO2 uptakes at 400 ppm, measuring 0.612 and 0.498 mmol g-1, and further capacity enhancement was achieved by introducing 50% relative humidity, resulting in remarkable uptakes of 1.205 and 0.872 mmol g-1 corresponding to 97 and 75% increase compared to the dry uptakes, respectively. The mechanism underlying the enhanced uptake efficiency was revealed by 13C solid-state NMR and temperature-programmed desorption measurements, indicating the formation of bicarbonate species, and therefore a stoichiometry of 1:1 CO2 to each amine site.

Pervasive Selection for Clinically Relevant Resistance and Media Adaptive Mutations at Very Low Antibiotic Concentrations.

Experimental evolution studies have shown that weak antibiotic selective pressures (i.e., when the antibiotic concentrations are far below the minimum inhibitory concentration, MIC) can select resistant mutants, raising several unanswered questions. First, what are the lowest antibiotic concentrations at which selection for de novo resistance mutations can occur? Second, with weak antibiotic selections, which other types of adaptive mutations unrelated to the antibiotic selective pressure are concurrently enriched? Third, are the mutations selected under laboratory settings at subMIC also observed in clinical isolates? We addressed these questions using Escherichia coli populations evolving at subMICs in the presence of either of four clinically used antibiotics: fosfomycin, nitrofurantoin, tetracycline, and ciprofloxacin. Antibiotic resistance evolution was investigated at concentrations ranging from 1/4th to 1/2000th of the MIC of the susceptible strain (MICsusceptible). Our results show that evolution was rapid across all the antibiotics tested, and selection for fosfomycin- and nitrofurantoin-resistant mutants was observed at a concentration as low as 1/2000th of MICsusceptible. Several of the evolved resistant mutants showed increased growth yield and exponential growth rates, and outcompeted the susceptible ancestral strain in the absence of antibiotics as well, suggesting that adaptation to the growth environment occurred in parallel with the selection for resistance. Genomic analysis of the resistant mutants showed that several of the mutations selected under these conditions are also found in clinical isolates, demonstrating that experimental evolution at very low antibiotic levels can help in identifying novel mutations that contribute to bacterial adaptation during subMIC exposure in real-life settings.

Obesity, organ failure, and transplantation: A review of the role of metabolic and bariatric surgery in transplant candidates and recipients.

Obesity is a risk factor for kidney, liver, heart, and pulmonary diseases, as well as failure. Solid organ transplantation remains the definitive treatment for the end-stage presentation of these diseases. Among many criteria for organ transplant, efficient management of obesity is required for patients to acquire transplant eligibility. End-stage organ failure and obesity are 2 complex pathologies that are often entwined. Metabolic and bariatric surgery before, during, or after organ transplant has been studied to determine the long-term effect of bariatric surgery on transplant outcomes. In this review, a multidisciplinary group of surgeons from the Society of American Gastrointestinal and Endoscopic Surgeons and the American Society for Transplant Surgery presents the current published literature on metabolic and bariatric surgery as a therapeutic option for patients with obesity awaiting solid organ transplantation. This manuscript details the most recent recommendations, pharmacologic considerations, and psychological considerations for this specific cohort of patients. Since level one evidence is not available on many of the topics covered by this review, expert opinion was implemented in several instances. Additional high-quality research in this area will allow for better recommendations and, therefore, treatment strategies for these complex patients.

Differentiation and characterization of healthy versus pathological tau using chemical exchange saturation transfer.

Neurofibrillary tangles of tau constitute one of the key biological hallmarks of Alzheimer's disease. Currently, the assessment of regional tau accumulation requires intravenous administration of radioactive tracers for PET imaging. A noninvasive MRI-based solution would have significant clinical implications. Herein, we utilized an MRI technique known as chemical exchange saturation transfer (CEST) to determine the imaging signature of tau in both its monomeric and pathologic fibrillated conformations. Three sets of purified recombinant full-length (4R) tau protein were prepared for collection of CEST spectra using a 9.4 T NMR spectrometer at varying temperatures (25, 37, and 42 °C) and RF intensities (0.7, 1.0, 1.5, and 2.2 µT). Monomeric and fibrillated tau were readily distinguished based on their Z-spectrum profiles. Fibrillated tau demonstrated a less prominent peak at 3.5 ppm with additional peaks near 0.5 and 1.5 ppm. No significant differences were identified between fibrillated tau prepared using heparin versus seed-competent tau. In conclusion, monomeric and fibrillated tau can be readily detected and distinguished based on their CEST-derived Z-spectra, pointing to the potential utility of CEST-MRI as a noninvasive biomarker of regional pathologic tau accumulation in the brain. Further testing and validation in vitro and in vivo will be necessary before this can be applied clinically.

Safety of EUS latex balloon use in patients with a latex allergy.

BACKGROUND AND AIMS: Balloons are used in EUS to improve visualization. However, data on the safety of latex balloons in patients with latex allergies are limited, and nonlatex alternatives can be costly. We investigated the safety of latex balloon use during EUS. METHODS: A retrospective review was conducted at a tertiary center between 2019 and 2022. Patients with reported latex allergies who underwent linear EUS were included. Baseline demographics, EUS characteristics, and adverse events were collected. The primary outcome was the rate of adverse events. RESULTS: Eighty-seven procedures were performed on 57 unique patients (mean age, 65.3 ± 14.5 years). Latex balloons were used in 59 procedures (67.8%), with only 8 procedures (13.6%) using prophylactic medications. No adverse events occurred during or after procedures, regardless of medication use or history of anaphylaxis. CONCLUSIONS: The use of EUS latex balloons in patients with a latex allergy was associated with no adverse events.

Risk of Lymphoma and Leukemia in Thyroid Cancer Patients: A Retrospective Cohort Study in Germany.

Thyroid cancer is the ninth most common cancer worldwide. While differentiated thyroid cancer (DTC) has a high survival rate, concerns arise regarding optimal treatment strategies and potential long-term risks, including second primary malignancies (SPMs), associated with therapies such as radioiodine (RAI). The aim of the present study was to investigate the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia in Germany. This retrospective cohort study used the IQVIA TM Disease Analyzer database and included adults with a first documented diagnosis of thyroid cancer between January 2005 and December 2021 as well as propensity score matched individuals without thyroid cancer in 1284 general practices. Univariate Cox regression models were performed to examine the association between thyroid cancer and the incidence of subsequent lymphoma and leukemia. A total of 4232 thyroid cancer patients (mean age: 54.2 years; 73.6% female) and 21 160 controls (mean age: 54.2 years; 72.6% female) were available for analyses. Thyroid cancer was significantly associated with a higher lymphoma incidence (HR: 3.35, 95% CI: 2.04-5.52), especially in men (HR: 5.37) and those aged 61-70 years. Leukemia incidence was not significantly associated with thyroid cancer (HR: 1.79, 95% CI: 0.91-3.53), although associations were notable in younger age groups. Thyroid cancer is positively associated with a risk of subsequent lymphoma, highlighting the need for vigilant surveillance and tailored treatment strategies. While the association with leukemia is less pronounced, close surveillance remains critical, especially in younger patients.

Efficacy and Clinical Outcomes of mRNA COVID-19 Vaccine in Pregnancy: A Systematic Review and Meta-Analysis.

BACKGROUND: The world has witnessed one of the largest pandemics, dubbed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of December 2020, the USA alone reported 98,948 cases of coronavirus disease 2019 (COVID-19) infection during pregnancy, with 109 related maternal deaths. Current evidence suggests that unvaccinated pregnant women infected with SARS-CoV-2 are at a higher risk of experiencing complications related to COVID-19 compared to nonpregnant women. This review aimed to provide healthcare workers and non-healthcare workers with a comprehensive overview of the available information regarding the efficacy of vaccines in pregnant women. SUMMARY: We performed a systematic review and meta-analysis following PRISMA guidelines. The search through the database for articles published between December 2019 and October 2021 was performed. A comprehensive search was performed in PubMed, Scopus, and EMBASE databases for research publications published between December 2019 and October 2021. We focused on original research, case reports, case series, and vaccination side effect by authoritative health institutions. Phrases used for the Medical Subject Heading [MeSH] search included ("COVID-19" [MeSH]) or ("Vaccine" [MeSH]) and ("mRNA" [MeSH]) and ("Pregnant" [MeSH]). Eleven studies were selected and included, with a total of 46,264 pregnancies that were vaccinated with mRNA-containing lipid nanoparticle vaccine from Pfizer/BioNTech and Moderna during pregnancy. There were no randomized trials, and all studies were observational (prospective, retrospective, and cross-sectional). The mean maternal age was 32.2 years, and 98.7% of pregnant women received the Pfizer COVID-19 vaccination. The local and systemic adverse effects of the vaccination in pregnant women were analyzed and reported. The local adverse effects of the vaccination (at least 1 dose) such as local pain, swelling, and redness were reported in 32%, 5%, and 1%, respectively. The systemic adverse effects such as fatigue, headaches, new onset or worsening of muscle pain, chills, fever, and joint pains were also reported in 25%, 19%, 18%, 12%, 11%, and 8%, respectively. The average birthweight was 3,452 g. Among these pregnancies, 0.03% were stillbirth and 3.68% preterm (<37 weeks) births. KEY MESSAGES: The systemic side effect profile after administering the COVID-19 mRNA vaccine to pregnant women was similar to that in nonpregnant women. Maternal and fetal morbidity and mortality were lowered with the administration of either one or both the doses of the mRNA COVID-19 vaccination.

Testosterone and Covid-19: An update.

There is overwhelming evidence to suggest that male gender is at a higher risk of developing more severe Covid-19 disease and thus having poorer clinical outcomes. However, the relationship between testosterone (T) and Covid-19 remains unclear with both protective and deleterious effects on different aspects of the disease suggested. Here, we review the current epidemiological and biological evidence on the role of testosterone in the process of SARS-CoV-2 infection and in mediating Covid-19 severity, its potential to serve as a biomarker for risk stratification and discuss the possibility of T supplementation as a treatment or preventative therapy for Covid-19.

Machine learning algorithms for prediction of entrapment efficiency in nanomaterials.

Exploitation of machine learning in predicting performance of nanomaterials is a rapidly growing dynamic area of research. For instance, incorporation of therapeutic cargoes into nanovesicles (i.e., entrapment efficiency) is one of the critical parameters that ensures proper entrapment of drugs in the developed nanosystems. Several factors affect the entrapment efficiency of drugs and thus multiple assessments are required to ensure drug retention, and to reduce cost and time. Supervised machine learning can allow for the construction of algorithms that can mine data available from earlier studies to predict performance of specific types of nanoparticles. Comparative studies that utilize multiple regression algorithms to predict entrapment efficiency in nanomaterials are scarce. Herein, we report on a detailed methodology for prediction of entrapment efficiency in nanomaterials (e.g., niosomes) using different regression algorithms (i.e., CatBoost, linear regression, support vector regression and artificial neural network) to select the model that demonstrates the best performance for estimation of entrapment efficiency. The study concluded that CatBoost algorithm demonstrated the best performance with maximum R2 score (0.98) and mean square error (< 10-4). Among the various parameters that possess a role in entrapment efficiency of drugs into niosomes, the results obtained from CatBoost model revealed that the drug:lipid ratio is the major contributing factor affecting entrapment efficiency, followed by the lipid:surfactant molar ratio. Hence, supervised machine learning may be applied for future selection of the components of niosomes that achieve high entrapment efficiency of drugs while minimizing experimental procedures and cost.

The role of pressure on lattice thermal conductivity and its related thermodynamical parameters in In0.53Ga0.47As nanofilms.

Lattice thermal conductivity (LTC) for In0.53Ga0.47As alloy films, with thicknesses ranging from 10 nm to 1.4 µm, was investigated under pressures of up to 11 GPa and temperatures between 1 and 450 K, utilizing the modified Debye-Callaway model. The effects of structural and thermodynamical parameters, as well as phonon interactions, on LTC were examined. The Clapeyron, Murnaghan, and Post equations were applied to determine the pressure dependence of the melting temperature, lattice volume, and Debye temperature, respectively. A novel derivative form of the bulk modulus, suitable for nanomaterials, has been introduced. It was found that decreasing the film thickness increases the Gruneisen parameter, while increasing pressure decreases it. The LTC of nanofilms is significantly affected by their thickness and pressure strength; notably, under 11 GPa, films with a thickness of 10 nm exhibit a substantial decrease in LTC. LTCmax declines due to the greater influence of boundary scattering compared to dislocations. These findings suggest potential applications in managing nanofilm temperature and size, which are key to advancing nanomaterials and enhancing the efficiency of electronic devices.

Design, synthesis, docking, and antiviral evaluation of some novel pyrimidinone-based α-aminophosphonates as potent H1N1 and HCoV-229E inhibitors.

Dialkyl/aryl aminophosphonates, 3a-g and 4a-e were synthesized using the LiClO4 catalyzed Kabachnic Fields-type reaction straightforwardly and efficiently. The synthesized phosphonates structures were characterized using elemental analyses, FT-IR, 1H NMR, 13C NMR, and MS spectroscopy. The new compounds were subjected to in-silico molecular docking simulations to evaluate their potential inhibition against Influenza A Neuraminidase and RNA-dependent RNA polymerase of human coronavirus 229E. Subsequently, the compounds were further tested in vitro using a cytopathic inhibition assay to assess their antiviral activity against both human Influenza (H1N1) and human coronavirus (HCoV-229E). Diphenyl ((2-(5-cyano-6-oxo-4-phenyl-1,6-dihydropyrimidin-2-yl) hydrazinyl) (furan-2-yl) methyl) phosphonate (3f) and diethyl ((2-(5-cyano-6-oxo-4-phenyl-1,6-dihydropyrimidin-2-yl) hydrazinyl) (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) methyl) phosphonate (4e) were demonstrated direct inhibition activity against Influenza A Neuraminidase and RNA-dependent RNA polymerase. This was supported by their highly favorable binding energies in-silico, with top-ranked values of -12.5 kcal/mol and -14.2 kcal/mol for compound (3f), and -13.5 kcal/mol and -9.89 kcal/mol for compound (4e). Moreover, they also displayed notable antiviral efficacy in vitro against both viruses. These compounds demonstrated significant antiviral activity, as evidenced by selectivity indices (SI) of 101.7 and 51.8, respectively against H1N1, and 24.5 and 5.1 against HCoV-229E, respectively.