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In this study, machine learning (ML) algorithms were employed to predict the pseudo-1st-order reaction rate constants for the sonochemical degradation of aqueous organic pollutants under various conditions. A total of 618 sets of data, including ultrasonic, solution, and pollutant characteristics, were collected from 89 previous studies. Considering the difference between the electrical power (P ele ) and calorimetric power (P cal ), the collected data were divided into two groups: data with P ele and data with P cal . Eight input variables, including frequency, power density, pH, temperature, initial concentration, solubility, vapor pressure, and octanol-water partition coefficient (K ow ), and one target variable of the degradation rate constant, were selected for ML. Statistical analysis was conducted, and outliers were determined separately for the two groups. ML models, including random forest (RF), extreme gradient boosting (XGB), and light gradient boosting machine (LGB), were used to predict the pseudo-1st-order reaction rate constants for the removal of aqueous pollutants. The prediction performance of the ML models was evaluated using different metrics, including the root mean squared error (RMSE), mean absolute error (MAE), and R squared (R 2 ). A significantly higher prediction performance was obtained using data without outliers and augmented data. Consequently, all the applied ML models could be used to predict the sonochemical degradation of aqueous pollutants, and the XGB model showed the highest accuracy in predicting the rate constants. In addition, the power density and frequency were the most influential factors among the eight input variables in prediction with the Shapley additive explanation (SHAP) values method. The degradation rate constants of the two pollutants over a wide frequency range (20-1,000 kHz) were predicted using the trained ML model (XGB) and the prediction results were analyzed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Gregarines are a large and diverse subgroup of Apicomplexa, a lineage of obligate animal symbionts including pathogens such as Plasmodium , the malaria parasite. Unlike Plasmodium , however, gregarines are poorly studied, despite the fact that as early-branching apicomplexans they are crucial to our understanding of the origin and evolution of all apicomplexans and their parasitic lifestyle. Exemplifying this, the earliest branch of gregarines, the archigregarines, are particularly poorly studied: around 80 species have been described from marine invertebrates, but almost all of them were assigned to a single genus, Selenidium . Most are known only from light micrographs and largely unresolved rDNA phylogenies, where they exhibit a great deal of sequence variation, and fall into four subclades. To resolve the relationships within archigregarines, we sequenced 12 single-cell transcriptomes from species representing all four known subclades, as well as one blastogregarine (which frequently branch with Selenidium ). A 190-gene phylogenomic tree confirmed four maximally supported individual clades of archigregarines and blastogregarines. These clades are discrete and distantly related, and also correlate with host identity. We propose the establishment of three novel genera of archigregarines to reflect their phylogenetic diversity and host range, and nine novel species isolated from a range of marine invertebrates.

The 20-kHz probe-type sonicator systems were investigated for the enhancement of the cavitational oxidation activity under various geometric conditions including vertical and horizontal probe positions and vessel sizes/volumes as a following study to our previous study. The sonochemical oxidation activity (mass-based I 3 - ion generation rate) increased significantly for all vessel size conditions as the probe was placed close to the vessel bottom, owing to the expansion of the sonochemical active zone induced by the reflections of ultrasound at the bottom and the reactor wall. A concentric circular active zone is observed at positions close to the bottom. The highest sonochemical activity was obtained at 1 cm (vertical position) in the 20 cm vessels (input power: 50 %). At the vertical positions of 11 cm to 7 cm, no significant difference in the sonochemical activity was observed for all input power conditions (25, 50, and 75 %) because no meaningful reflections occurred. Higher sonochemical activities were obtained at an input power of 75 % owing to the increased power and strong reflection. The highest cavitational yield considering the energy efficiency was obtained at 6 cm (vertical position) for 75 % of all power and geometric conditions. Horizontal probe position tests showed that the asymmetric formation of the sonochemical active zone could significantly enhance the sonochemical activity. The highest activity was obtained at 1 cm (vertical position) and 2.5 cm (horizontal position) in the 20 cm vessel., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Crosstalk, the exchange of chemical species between battery electrodes, significantly accelerates thermal runaway (TR) of lithium-ion batteries. To date, the understanding of their main mechanisms has centered on single-directional crosstalk of oxygen (O 2 ) gas from the cathode to the anode, underestimating the exothermic reactions during TR. However, the role of multidirectional crosstalk in steering additional exothermic reactions is yet to be elucidated due to the difficulties of correlative in situ analyses of full cells. Herein, the way in which such crosstalk triggers self-amplifying feedback is elucidated that dramatically exacerbates TR within enclosed full cells, by employing synchrotron-based high-temperature X-ray diffraction, mass spectrometry, and calorimetry. These findings reveal that ethylene (C 2 H 4 ) gas generated at the anode promotes O 2 evolution at the cathode. This O 2 then returns to the anode, further promoting additional C 2 H 4 formation and creating a self-amplifying loop, thereby intensifying TR. Furthermore, CO 2 , traditionally viewed as an extinguishing gas, engages in the crosstalk by interacting with lithium at the anode to form Li 2 CO 3 , thereby accelerating TR beyond prior expectations. These insights have led to develop an anode coating that impedes the formation of C 2 H 4 and O 2 , to effectively mitigate TR., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Aging manifests as many phenotypes, among which age-related changes in brain vessels are important, but underexplored. Thus, in the present study, we constructed a model to predict age using cerebrovascular morphological features, further assessing their clinical relevance using a novel pipeline. Age prediction models were first developed using data from a normal cohort (n = 1181), after which their relevance was tested in two stroke cohorts (n = 564 and n = 455). Our novel pipeline adapted an existing framework to compute generic vessel features for brain vessels, resulting in 126 morphological features. We further built various machine learning models to predict age using only clinical factors, only brain vessel features, and a combination of both. We further assessed deviation from healthy aging using the age gap and explored its clinical relevance by correlating the predicted age and age gap with various risk factors. The models constructed using only brain vessel features and those combining clinical factors with vessel features were better predictors of age than the clinical factor-only model (r = 0.37, 0.48, and 0.26, respectively). Predicted age was associated with many known clinical factors, and the associations were stronger for the age gap in the normal cohort. The age gap was also associated with important factors in the pooled cohort atherosclerotic cardiovascular disease risk score and white matter hyperintensity measurements. Cerebrovascular age, computed using the morphological features of brain vessels, could serve as a potential individualized marker for the early detection of various cerebrovascular diseases., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Apicomplexans are a diverse phylum of unicellular eukaryotes that share obligate relationships with terrestrial and aquatic animal hosts. Many well-studied apicomplexans are responsible for several deadly zoonotic and human diseases, most notably malaria caused by Plasmodium. Interest in the evolutionary origin of apicomplexans has also spurred recent work on other more deeply-branching lineages, especially gregarines and sister groups like squirmids and chrompodellids. But a full picture of apicomplexan evolution is still lacking several lineages, and one major, diverse lineage that is notably absent is the adeleorinids. Adeleorina apicomplexans comprises hundreds of described species that infect invertebrate and vertebrate hosts across the globe. Although historically considered coccidians, phylogenetic trees based on limited data have shown conflicting branch positions for this subgroup, leaving this question unresolved. Phylogenomic trees and large-scale analyses comparing cellular functions and metabolism between major subgroups of apicomplexans have not incorporated Adeleorina because only a handful of molecular markers and a couple organellar genomes are available, ultimately excluding this group from contributing to our understanding of apicomplexan evolution and biology. To address this gap, we have generated complete genomes from mitochondria and plastids, as well as multiple deep-coverage single-cell transcriptomes of nuclear genes from two Adeleorina species, Klossia helicina and Legerella nova, and inferred a 206-protein phylogenomic tree of Apicomplexa. We observed distinct structures reported in species descriptions as remnant host structures surrounding adeleorinid oocysts. Klossia helicina and L. nova branched, as expected, with monoxenous adeleorinids within the Adeleorina and their mitochondrial and plastid genomes exhibited similarity to published organellar adeleorinid genomes. We show with a phylogeneomic tree and subsequent phylogenomic analyses that Adeleorina are not closely related to any of the currently sampled apicomplexan subgroups, and instead fall as a sister to a large clade encompassing Coccidia, Protococcidia, Hematozoa, and Nephromycida, collectively. This resolves Adeleorina as a key independently-branching group, separate from coccidians, on the tree of Apicomplexa, which now has all known major lineages sampled., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Increasing lithium contents within the lattice of positive electrode materials is projected in pursuit of high-energy-density batteries. However, it intensifies the release of lattice oxygen and subsequent gas evolution during operations. This poses significant challenges for managing internal pressure of batteries, particularly in terms of the management of gas evolution in composite electrodes-an area that remains largely unexplored. Conventional assumptions postulate that the total gas evolution is estimated by multiplying the total particle count by the quantities of gas products from an individual particle. Contrarily, this investigation on overlithiated materials-a system known to release the lattice oxygen-demonstrates that loading densities and inter-particle spacing in electrodes significantly govern gas evolution rates, leading to distinct extents of gas formation despite of an equivalent quantity of released lattice oxygen. Remarkably, this study discoveres that O 2 and CO 2 evolution rates are proportional to 1 O 2 concentration by the factor of second and first-order, respectively. This indicates an exceptionally greater change in the evolution rate of O 2 compared to CO 2 depending on local 1 O 2 concentration. These insights pave new routes for more sophisticated approaches to manage gas evolution within high-energy-density batteries., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Many proteins lack stable 3D structures. These intrinsically disordered proteins (IDPs) or hybrid proteins containing ordered domains with intrinsically disordered protein regions (IDPRs) often carry out regulatory functions related to molecular recognition and signal transduction. IDPs/IDPRs constitute a substantial portion of the human proteome and are termed "the unfoldome". Herein, we probe the human breast cancer unfoldome and investigate relations between IDPs and key disease genes and pathways. We utilized bottom-up proteomics, MudPIT (Multidimensional Protein Identification Technology), to profile differentially expressed IDPs in human normal (MCF-10A) and breast cancer (BT-549) cell lines. Overall, we identified 2271 protein groups in the unfoldome of normal and cancer proteomes, with 148 IDPs found to be significantly differentially expressed in cancer cells. Further analysis produced annotations of 140 IDPs, which were then classified to GO (Gene Ontology) categories and pathways. In total, 65% (91 of 140) IDPs were related to various diseases, and 20% (28 of 140) mapped to cancer terms. A substantial portion of the differentially expressed IDPs contained disordered regions, confirmed by in silico characterization. Overall, our analyses suggest high levels of interactivity in the human cancer unfoldome and a prevalence of moderately and highly disordered proteins in the network.

Introduction: We aimed to predict platinum sensitivity using routine baseline multimodal magnetic resonance imaging (MRI) and established clinical data in a radiomics framework., Methods: We evaluated 96 patients with ovarian cancer who underwent multimodal MRI and routine laboratory tests between January 2016 and December 2020. The patients underwent diffusion-weighted, contrast-enhanced T1-weighted, and T2-weighted MRI. Subsequently, 293 radiomic features were extracted by manually identifying tumor regions of interest. The features were subjected to the least absolute shrinkage and selection operators, leaving only a few selected features. We built the first prediction model with a tree-based classifier using selected radiomics features. A second prediction model was built by combining the selected radiomic features with four established clinical factors: age, disease stage, initial tumor marker level, and treatment course. Both models were built and tested using a five-fold cross-validation., Results: Our radiomics model predicted platinum sensitivity with an AUC of 0.65 using a few radiomics features related to heterogeneity. The second combined model had an AUC of 0.77, confirming the incremental benefits of the radiomics model in addition to models using established clinical factors., Conclusion: Our combined radiomics-clinical data model was effective in predicting platinum sensitivity in patients with advanced ovarian cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Na, Noh, Kim, Lee and Park.)

Proteins play a crucial role in many biological processes, where their interaction with other proteins are integral. Abnormal protein-protein interactions (PPIs) have been linked to various diseases including cancer, and thus targeting PPIs holds promise for drug development. However, experimental confirmation of the peculiarities of PPIs is challenging due to their dynamic and transient nature. As a complement to experimental technologies, multiple computational molecular docking (MD) methods have been developed to predict the structures of protein-protein complexes and their dynamics, still requiring further improvements in several issues. Here, we report an improved MD method, namely three-software docking (3SD), by employing three popular protein-peptide docking software (CABS-dock, HPEPDOCK, and HADDOCK) in combination to ensure constant quality for most targets. We validated our 3SD performance in known protein-peptide interactions (PpIs). We also enhanced MD performance in proteins having intrinsically disordered regions (IDRs) by applying the modified 3SD strategy, the three-software docking after removing random coiled IDR (3SD-RR), to the comparable crystal PpI structures. At the end, we applied 3SD-RR to the AlphaFold2-predicted receptors, yielding an efficient prediction of PpI pose with high relevance to the experimental data regardless of the presence of IDRs or the availability of receptor structures. Our study provides an improved solution to the challenges in studying PPIs through computational docking and has the potential to contribute to PPIs-targeted drug discovery. SIGNIFICANCE STATEMENT: Protein-protein interactions (PPIs) are integral to life, and abnormal PPIs are associated with diseases such as cancer. Studying protein-peptide interactions (PpIs) is challenging due to their dynamic and transient nature. Here we developed improved docking methods (3SD and 3SD-RR) to predict the PpI poses, ensuring constant quality in most targets and also addressing issues like intrinsically disordered regions (IDRs) and artificial intelligence-predicted structures. Our study provides an improved solution to the challenges in studying PpIs through computational docking and has the potential to contribute to PPIs-targeted drug discovery., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The phylum Phoronida comprises filter-feeding invertebrates that live in a protective tube sometimes reinforced with particulate material from the surrounding environments. Animals with these characteristics make promising candidate hosts for symbiotic bacteria, given the constant interactions with various bacterial colonizers, yet phoronids are one of the very few animal phyla with no available microbiome data whatsoever. Here, by sequencing the V4 region of the 16S rRNA gene, we compare bacterial microbiomes in whole phoronids, including both tube and living tissues, with those associated exclusively to the isolated tube and/or the naked animal inside. We also compare these communities with those from the surrounding water. Phoronid microbiomes from specimens belonging to the same colony but collected a month apart were significantly different, and bacterial taxa previously reported in association with invertebrates and sediment were found to drive this difference. The microbiomes associated with the tubes are very similar in composition to those isolated from whole animals. However, just over half of bacteria found in whole specimens are also found both in tubes and naked specimens. In conclusion, phoronids harbour bacterial microbiomes that differ from those in the surrounding water, but the composition of those microbiomes is not stable and appears to change in the same colony over a relatively short time frame. Considering individual spatial/anatomical compartments, the phoronid tube contributes most to the whole-animal microbiome., (© 2023. The Author(s).)

Radical prostatectomy (RP) is the main treatment of prostate cancer (PCa). Biochemical recurrence (BCR) following RP remains the first sign of aggressive disease; hence, better assessment of potential long-term post-RP BCR-free survival is crucial. Our study aimed to evaluate a combined clinical-deep learning (DL) model using multiparametric magnetic resonance imaging (mpMRI) for predicting long-term post-RP BCR-free survival in PCa. A total of 437 patients with PCa who underwent mpMRI followed by RP between 2008 and 2009 were enrolled; radiomics features were extracted from T2-weighted imaging, apparent diffusion coefficient maps, and contrast-enhanced sequences by manually delineating the index tumors. Deep features from the same set of imaging were extracted using a deep neural network based on pretrained EfficentNet-B0. Here, we present a clinical model (six clinical variables), radiomics model, DL model (DLM-Deep feature), combined clinical-radiomics model (CRM-Multi), and combined clinical-DL model (CDLM-Deep feature) that were built using Cox models regularized with the least absolute shrinkage and selection operator. We compared their prognostic performances using stratified fivefold cross-validation. In a median follow-up of 61 months, 110/437 patients experienced BCR. CDLM-Deep feature achieved the best performance (hazard ratio [HR] = 7.72), followed by DLM-Deep feature (HR = 4.37) or RM-Multi (HR = 2.67). CRM-Multi performed moderately. Our results confirm the superior performance of our mpMRI-derived DL algorithm over conventional radiomics.

Herein, we report the design, synthesis and evaluation of novel (E)-3-(3-oxo-4-substituted-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-N-hydroxypropenamides (4 a-i, 7 a-g) targeting histone deacetylases. Three human cancer cell lines were used to test the cytotoxicity of the synthesized compounds (SW620, colon; PC-3, prostate; NCI-H23, lung cancer); inhibitory activity towards HDAC; anticancer activity; as well as their impact on the cell cycle and apoptosis. As a result, compounds 4 a-i bearing the alkyl substituents seemed to be less potent than the benzyl-containing compounds 7 a-g in all biological assays. Compounds 7 e-f were found to be the most active HDAC inhibitors with IC 50 of 1.498±0.020 μM and 1.794±0.159 μM, respectively. In terms of cytotoxicity and anticancer assay, 7 e and 7 f also showed good activity with IC 50 values in the micromolar range. In addition, the cell cycle and apoptosis of SW620 were affected by compound 7 f in almost a similar manner to that of reference compound SAHA. Docking assays were carried out for analysis the binding mode and selectivity of this compound toward 8 HDAC isoforms. Overall, our data confirmed that the inhibition of HDAC plays a pivotal role in their anticancer activity., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Apicomplexans and related lineages comprise many obligate symbionts of animals; some of which cause notorious diseases such as malaria. They evolved from photosynthetic ancestors and transitioned into a symbiotic lifestyle several times, giving rise to species with diverse non-photosynthetic plastids. Here, we sought to reconstruct the evolution of the cryptic plastids in the apicomplexans, chrompodellids, and squirmids (ACS clade) by generating five new single-cell transcriptomes from understudied gregarine lineages, constructing a robust phylogenomic tree incorporating all ACS clade sequencing datasets available, and using these to examine in detail, the evolutionary distribution of all 162 proteins recently shown to be in the apicoplast by spatial proteomics in Toxoplasma. This expanded homology-based reconstruction of plastid proteins found in the ACS clade confirms earlier work showing convergence in the overall metabolic pathways retained once photosynthesis is lost, but also reveals differences in the degrees of plastid reduction in specific lineages. We show that the loss of the plastid genome is common and unexpectedly find many lineage- and species-specific plastid proteins, suggesting the presence of evolutionary innovations and neofunctionalizations that may confer new functional and metabolic capabilities that are yet to be discovered in these enigmatic organelles., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.)

Natural killer (NK) cell-based therapy has been studied for the treatment of patients with cancers, but the inadequate infiltration of NK cells into solid tumors remains a big challenge to its clinical application. In this study, we examined the interaction between NK cells and endothelial cells, which might play a major role in NK cell homing to solid tumors. We found that endothelial cells were activated by TNF-α and IL-1β, which were produced by tumor-associated CD11b + cells, which included F4/80 + macrophages. TNF-α-treated endothelial cells increased NK cell migration by producing CCL2 and CCL7, which was proved by transwell and imaging assays. TNF-α-treated endothelial cells adhered well to NK cells, which was due to a TNF-α-induced increase in ICAM-1 and VCAM-1 expression on endothelial cells. Imaging data confirmed that TNF-α-treated endothelial cells transfected with ICAM-1 or VCAM-1 siRNAs did not establish stable contacts with NK cells. Taken together, our data suggest that CCL2, CCL7, ICAM-1, and VCAM-1 expressed by endothelial cells will be potential targets to guide adequate interaction with NK cells, which is a crucial step for NK cell homing to the tumor microenvironment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Falls are common in older adults and increase in recent years. This study aimed to examine the risk of falls associated with long-acting benzodiazepines (BZDs) or tricyclic antidepressants (TCAs) use in community-dwelling older adults., Methods: A nationwide population-based case-crossover design was used. We screened information on 6,370,275 fall or fall fracture cases among community-dwelling elderly patients from the database of the national health insurance data warehouse in South Korea. We extracted the data of elderly patients who visited the hospital for a fall and were diagnosed with the first fall or fall fracture after prescription of long-acting BZDs ( n = 1805) or TCAs ( n = 554). The study used conditional logistic regression analysis to analyze the associations and stratified analysis by gender and age group to control for their confounding effects., Results: Risk of falls or fall fractures increased by more than two times after taking long-acting BZDs (odds ratio [OR] = 2.16; 95% confidence interval [CI] = 1.85-2.52) or TCAs (OR = 2.13; 95% CI = 1.62-2.83). The longer the prescription period of both, the higher the risk of falls or fall fractures was (≥49 days for long-acting BZDs vs. ≥ 56 days for TCAs)., Conclusions: Long-acting BZDs or TCAs should be avoided or prescribed for a shorter duration based on these adverse effects. Health care providers should focus on fall prevention practices in older adults who take such drugs.

Aims: Absence from work or school in patients with congenital heart disease (CHD) is an understudied domain. Illness identity, which is the degree to which a chronic illness is integrated into one's identity, could be hypothesized to be a predictor for absenteeism. This study determined the proportion of young adults with CHD absent from work or school and examined if illness identity dimensions were related to absenteeism., Methods and Results: In a cross-sectional study, we included 255 patients with CHD. Data on absence from work or school over the past 12 months were obtained using self-report. The Illness Identity Questionnaire was used, which comprises four illness identity dimensions: rejection, engulfment, acceptance, and enrichment. Linear models with doubly robust estimations were computed after groups were balanced using propensity weighting. Absence from work/school occurred in 69% of young adults with CHD. Absence because of CHD specifically was present in 15% of the patients. Engulfment was significantly related to both all-cause absence and absence for CHD reasons., Conclusions: Patients who strongly define themselves in terms of their heart disease were more likely to be absent from work or school than those who did not. If this finding can be confirmed in future research, it has the potential to be a target for intervention to influence work/school absence., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Sonochemical oxidation activity may be significantly enhanced by optimizing the geometric factors of a sonoreactor and implementing additional physical actions, such as mechanical mixing and gas sparging. This study investigates the effects of liquid recirculation flow on sonochemical oxidation reactions. This was carried out through experimental testing with a 28 kHz bath-type sonoreactor under various liquid heights and flow rates, ranging from 1λ to 4.0λ and 1.5-6.0 L/min, respectively. The potassium iodide (KI) dosimetry and sonochemiluminescence methods were used in the experiment. With an increase in the liquid height/volume, the pseudo zero-order kinetic constant and the mass of triiodide (I 3 - ) ions fluctuated. The optimal liquid height was 2.0λ, 2.5λ, and 3.0λ, based on the appropriate formation of a cavitation active zone in the reactor. The introduction of a liquid recirculation flow led to a large reduction in sonochemical activity due to the shrinkage of the cavitation active zone. However, the sonochemical activity increased at higher flow rates through the capture of ultrasonic energy at the bottom zone. This increase was attributed to the formation of a strong and expanded active zone limited to the reactor bottom to the height of the recirculation flow. The results demonstrate that applying a high rate liquid flow adjacent to the transducer module may be beneficial for enhanced sonochemical activity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Medical devices with antimicrobial properties are a potential long-term solution to the high rate of multi-drug-resistant healthcare-associated infections. Silver nanoparticles (AgNPs) are an established agent for effectively eliminating a wide range of microbial strains. AgNPs have been commonly incorporated into traditional plastic materials; however, recently, there has been increased interest in using AgNPs combined with 3D-printing technology for medical devices due to the accessibility and customizability of 3D-printed products. This study reports a novel method of utilizing acetone to partially dissolve 3D-printed polymer acrylonitrile butadiene styrene (ABS) plastic to attach a layer of AgNPs. The antimicrobial properties of this AgNP-coated surface were tested against several microbial strains prevalent in healthcare-associated infections. AgNP-coated ABS (AgNP-ABS) plastic demonstrated significant elimination of viable bacteria within 4 h for all tested bacterial species ( Acinetobacter baumannii , non-pathogenic and pathogenic Escherichia coli , Pseudomonas aeruginosa , and methicillin-resistant Staphylococcus aureus ) and within 19 h for the tested fungus Candida albicans . The longevity of adhesion of AgNPs to the ABS plastic was assessed by checking antibacterial activity against A. baumannii after repeat use cycles. AgNP-ABS plastic showed decreased antibacterial efficacy with repeated use but maintained the ability to eliminate microbes within 3 h for up to eight use cycles. The AgNP-coated ABS plastic showed efficacy as an antimicrobial surface, and future studies will consider its applicability in the production of medical devices.

The Asp233-Asp246 pair is highly conserved in Class A β-lactamases, which hydrolyze β-lactam antibiotics. Here, we characterize its function using CTX-M-14 β-lactamase. The D233N mutant displayed decreased activity that is substrate-dependent, with reductions in k cat /K m ranging from 20% for nitrocefin to 6-fold for cefotaxime. In comparison, the mutation reduced the binding of a known reversible inhibitor by 10-fold. The mutant structures showed movement of the 213-219 loop and the loss of the Thr216-Thr235 hydrogen bond, which was restored by inhibitor binding. Mutagenesis of Thr216 further highlighted its contribution to CTX-M activity. These results demonstrate the importance of the aspartate pair to CTX-M hydrolysis of substrates with bulky side chains, while suggesting increased protein flexibility as a means to evolve drug resistance., (© 2021 Federation of European Biochemical Societies.)

Tuberculosis drug resistance continues to threaten global health but the underline molecular mechanisms are not clear. Ethambutol (EMB), one of the well-known first - line drugs in tuberculosis treatment is, unfortunately, not free from drug resistance problems. Genomic studies have shown that some genetic mutations in Mycobacterium tuberculosis (Mtb) EmbR, and EmbC/A/B genes cause EMB resistance. EmbR-PknH pair controls embC/A/B operon, which encodes EmbC/A/B genes, and EMB interacts with EmbA/B proteins. However, the EmbR binding site on PknH was unknown. We conducted molecular simulation on the EmbR- peptides binding structures and discovered phosphorylated PknH 273-280 (N'-HEALS P DPD-C') makes β strand with the EmbR FHA domain, as β-MoRF (MoRF; molecular recognition feature) does at its binding site. Hydrogen bond number analysis also supported the peptides' β-MoRF forming activity at the EmbR FHA domain. Also, we discovered that previously known phosphorylation residues might have their chronological order according to the phosphorylation status. The discovery validated that Mtb PknH 273-280 (N'-HEALSDPD-C') has reliable EmbR binding affinity. This approach is revolutionary in the computer-aided drug discovery field, because it is the first trial to discover the protein-protein interaction site, and find binding partner in nature from this site., Competing Interests: This manuscript has not been published and is not under consideration for publication elsewhere. We have no conflicts of interest to disclose, all authors read the manuscript and agreed to submit to Signal Transduction and Targeted Therapy., (© 2021 The Authors.)

SiO x ( x ≈ 1) is one of the most promising anode materials for application in secondary lithium-ion batteries because of its high theoretical capacity. Despite this merit, SiO x has a poor initial Coulombic efficiency, which impedes its widespread use. To overcome this limitation, in this work, we successfully demonstrate a novel synthesis of Mg-doped SiO x via a mass-producible physical vapor deposition method. The solid-state reaction between Mg and SiO x produces Si and electrochemically inert magnesium silicate, thus increasing the initial Coulombic efficiency. The Mg doping concentration determines the phase of the magnesium silicate domains, the size of the Si domains, and the heterogeneity of these two domains. Detailed electron microscopy and synchrotron-based analysis revealed that the nanoscale homogeneity of magnesium silicates driven by cycling significantly affected the lifetime. We found that 8 wt % Mg is the most optimized concentration for enhanced cyclability because MgSiO 3 , which is the dominant magnesium silicate composition, can be homogeneously mixed with silicon clusters, preventing their aggregation during cycling and suppressing void formation.