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Accounts of Chemical Research Jun 2024ConspectusNature's prototypical hydrogen-forming catalysts─hydrogenases─have attracted much attention because they catalyze hydrogen evolution at near zero...
ConspectusNature's prototypical hydrogen-forming catalysts─hydrogenases─have attracted much attention because they catalyze hydrogen evolution at near zero overpotential and ambient conditions. Beyond any possible applications in the energy sphere, the hydrogenases feature complicated active sites, which implies novel biosynthetic pathways. In terms of the variety of cofactors, the [FeFe]-hydrogenase is among the most complex.For more than a decade, we have worked on the biosynthesis of the active site of [FeFe] hydrogenases. This site, the H-cluster, is a six-iron ensemble consisting of a [4Fe-4S] cluster linked to a [2Fe] cluster that is coordinated to CO, cyanide, and a unique organic azadithiolate ligand. Many years ago, three enzymes, namely, HydG, HydE, and HydF, were shown to be required for the biosynthesis and the in vitro maturation of [FeFe] hydrogenases. The structures of the maturases were determined crystallographically, but still little progress was made on the biosynthetic pathway. As described in this Account, the elucidation of the biosynthetic pathway began in earnest with the identification of a molecular iron-cysteinate complex produced within HydG.In this Account, we present our most recent progress toward the molecular mechanism of [2Fe] biosynthesis using a collaborative approach involving cell-free biosynthesis, isotope and element-sensitive spectroscopies, as well as inorganic synthesis of purported biosynthetic intermediates. Our study starts from the radical SAM enzyme HydG that lyses tyrosine into CO and cyanide and forms an Fe(CO)(CN)-containing species. Crystallographic identification of a unique auxiliary 5Fe-4S cluster in HydG leads to a proposed catalytic cycle in which a free cysteine-chelated "dangler" Fe serves as the platform for the stepwise formation of a [4Fe-4S][Fe(CO)(CN)(cysteinate)] intermediate, which releases the [Fe(CO)(CN)(cysteinate)] product, Complex B. Since Complex B is unstable, we applied synthetic organometallic chemistry to make an analogue, syn-B, and showed that it fully replaces HydG in the in vitro maturation of the H-cluster. Syn-B serves as the substrate for the next radical SAM enzyme HydE, where the low-spin Fe(II) center is activated by 5'-dAdo to form an adenosylated Fe(I) intermediate. We propose that this Fe(I) species strips the carbon backbone and dimerizes in HydE to form a [Fe(SH)(CO)(CN)] product. This mechanistic scenario is supported by the use of a synthetic version of this dimer complex, syn-dimer, which allows for the formation of active hydrogenase with only the HydF maturase. Further application of this semisynthesis strategy shows that an [Fe(SCHNH)(CO)(CN)] complex can activate the apo hydrogenase, marking it as the last biosynthetic intermediate en route to the H-cluster. This combined enzymatic and semisynthetic approach greatly accelerates our understanding of H-cluster biosynthesis. We anticipate additional mechanistic details regarding H-cluster biosynthesis to be gleaned, and this methodology may be further applied in the study of other complex metallocofactors.
PubMed: 38937148
DOI: 10.1021/acs.accounts.4c00231 -
Journal of Physics. Condensed Matter :... Jun 2024The magnetic properties of a circular graphene nanoribbon (carbon belt) in a magnetic field parallel to its central axis is studied using a tight-binding model. Orbital...
The magnetic properties of a circular graphene nanoribbon (carbon belt) in a magnetic field parallel to its central axis is studied using a tight-binding model. Orbital magnetic susceptibility is calculated using an analytical expression of the energy eigenvalues as a function of the magnetic flux density for any size, and its temperature dependence is considered. In the absence of electron hopping parallel to the magnetic field, the orbital magnetic susceptibility diverges at absolute zero if the chemical potential is zero and the number of atoms is a multiple of four. As the temperature increases, the magnitude of susceptibility decreases according to the power law, whose exponent depends on the size. In the presence of electron hopping parallel to the magnetic field, the divergence of the susceptibility near absolute zero disappears, and the sign changes with the transfer integral parallel to the magnetic field and the temperature. .
PubMed: 38936393
DOI: 10.1088/1361-648X/ad5cb8 -
Medical Physics Jun 2024Gold nanoparticles (GNPs) accumulated within tumor cells have been shown to sensitize tumors to radiotherapy. From a physics point of view, the observed GNP-mediated...
BACKGROUND
Gold nanoparticles (GNPs) accumulated within tumor cells have been shown to sensitize tumors to radiotherapy. From a physics point of view, the observed GNP-mediated radiosensitization is due to various downstream effects of the secondary electron (SE) production from internalized GNPs such as GNP-mediated dose enhancement. Over the years, numerous computational investigations on GNP-mediated dose enhancement/radiosensitization have been conducted. However, such investigations have relied mostly on simple cellular geometry models and/or artificial GNP distributions. Thus, it is at least desirable, if not necessary, to conduct further investigations using cellular geometry models that properly reflect realistic cell morphology as well as internalized GNP distributions at the nanoscale.
PURPOSE
The primary aim of this study was to develop a nanometer-resolution geometry model of a GNP-laden tumor cell for computational investigations of GNP-mediated dose enhancement/radiosensitization. The secondary aim was to demonstrate the utility of this model by quantifying GNP-induced SE tracks/dose distribution at sub-cellular levels for further validation of a nanoscopic dose point kernel (nDPK) method against full-fledged Geant4 Monte Carlo (MC) simulation.
METHODS
A transmission electron microscopy (TEM) image of a single cell showing cytoplasm, cellular nucleus, and internalized GNPs in the cellular endosome was segmented into sub-cellular levels based on pixel value thresholding. A corresponding material density was allocated to each pixel, and, by adding a thickness, each pixel was transformed to a geometric voxel and imported as a Geant4-acceptable input geometry file. In Geant4-Penelope MC simulation, a clinical 6 MV photon beam was applied, vertically or horizontally to the cell surface, and energy deposition to the cellular nucleus and cytoplasm, due to SEs emitted by internalized GNPs, was scored. Next, nDPK calculations were performed by generating virtual electron tracks from each GNP voxel to all nucleus and cytoplasm voxels. Subsequently, another set of Geant4 simulation was performed with both Penelope and DNA physics models under the geometry closely mimicking in vitro cell irradiation with a clinical 6 MV photon beam, allowing for derivation of nDPK specific to this geometry and further comparison between Gean4 simulation and nDPK method.
RESULTS
The Geant4-calculated SE tracks and associated energy depositions showed significant dependence on photon incidence angle. For perpendicular incidence, nDPK results showed good agreement (average percentage pixel-to-pixel difference of 0.4% for cytoplasm and 0.5% for nucleus) with Geant4 results, while, for parallel incidence, the agreement became worse (-1.7%-0.7% for cytoplasm and -5.5%-0.8% for nucleus). Under the 6 MV cell irradiation geometry, nDPK results showed reasonable agreement (pixel-to-pixel Pearson's product moment correlation coefficient of 0.91 for cytoplasm and 0.98 for nucleus) with Geant4 results.
CONCLUSIONS
The currently developed TEM-based model of a GNP-laden cell offers unprecedented details of realistic intracellular GNP distributions for nanoscopic computational investigations of GNP-mediated dose enhancement/radiosensitization. A benchmarking study performed with this model showed reasonable agreement between Geant4- and nDPK-calculated intracellular dose deposition by SEs emitted from internalized GNPs, especially under perpendicular incidence - a popular cell irradiation geometry and when the Geant4-Penelope physics model was used.
PubMed: 38935922
DOI: 10.1002/mp.17275 -
Environmental Science and Pollution... Jun 2024Urban heat islands (UHIs) are a significant environmental problem, exacerbating the urban climate and affecting human health in the Asir region of Saudi Arabia. The need...
Urban heat islands (UHIs) are a significant environmental problem, exacerbating the urban climate and affecting human health in the Asir region of Saudi Arabia. The need to understand the spatio-temporal dynamics of UHI in the context of urban expansion is crucial for sustainable urban planning. The aim of this study was to quantify the changes in land use and land cover (LULC) and urbanization, assess the expansion process of UHI, and analyze its connectivity in order to develop strategies to mitigate UHI in an urban context over a 30-year period from 1990 to 2020. Using remote sensing data, LULC changes were analyzed with a random forest model. LULC change rate (LCCR), land cover intensity (LCI), and landscape expansion index (LEI) were calculated to quantify urbanization. The land surface temperature for the study period was calculated using the mono-window algorithm. The UHI effect was analyzed using an integrated radius and non-linear regression approach, fitting SUHI data to polynomial curves and identifying turning points based on the regression derivative for UHI intensity belts to quantify the expansion and intensification of UHI. Landscape metrics such as the aggregation index (AI), landscape shape index (LSI), and four other matrices were calculated to assess UHI morphology and connectivity of the UHI. In addition, the LEI was adopted to measure the extent of UHI growth patterns. From 1990 to 2020, the study area experienced significant urbanization, with the built-up area increasing from 69.40 to 338.74 km, an increase of 1.923 to 9.385% of the total area. This expansion included growth in peripheral areas of 129.33 km, peripheral expansion of 85.40 km, and infilling of 3.80 km. At the same time, the UHI effect intensified with an increase in mean LST from 40.55 to 46.73 °C. The spatial extent of the UHI increased, as shown by the increase in areas with an LST above 50 °C from 36.58 km in 1990 to 133.52 km in 2020. The connectivity of the UHI also increased, as shown by the increase in the AI from 38.91 to 41.30 and the LSI from 56.72 to 93.64, reflecting a more irregular and fragmented urban landscape. In parallel to these urban changes, the area classified as UHI increased significantly, with the peripheral areas expanding from 23.99 km in the period 1990-2000 to 80.86 km in the period 2000-2020. Peripheral areas also grew significantly from 36.42 to 96.27 km, contributing to an overall more pronounced and interconnected UHI effect by 2020. This study provides a comprehensive analysis of urban expansion and its thermal impacts. It highlights the need for integrated urban planning that includes strategies to mitigate the UHI effect, such as improving green infrastructure, optimizing land use, and improving urban design to counteract the negative effects of urbanization.
PubMed: 38935284
DOI: 10.1007/s11356-024-34051-w -
In Vitro Cellular & Developmental... Jun 2024Decellularized tissues are an attractive scaffolds for 3D tissue engineering. Decellularized animal tissues have certain limitations such as the availability of tissue,...
Decellularized tissues are an attractive scaffolds for 3D tissue engineering. Decellularized animal tissues have certain limitations such as the availability of tissue, high costs and ethical concerns related to the use of animal sources. Plant-based tissue decellularized scaffolds could be a better option to overcome the problem. The leaves of different plants offer a unique opportunity for the development of tissue-specific scaffolds, depending on the reticulate or parallel veination. Herein, we decellularized spinach leaves and employed these for the propagation and osteogenic differentiation of dental pulp stem cells (DPSCs). DPSCs were characterized by using mesenchymal stem cell surface markers CD90, CD105 and CD73 and CD34, CD45 and HLA-DR using flow cytometry. Spinach leaves were decellularized using ethanol, NaOH and HCL. Cytotoxicity of spinach leaf scaffolds were analysed by MTT assay. Decellularized spinach leaves supported dental pulp stem cell adhesion, proliferation and osteogenic differentiation. Our data demonstrate that the decellularized spinach cellulose scaffolds can stimulate the growth, proliferation and osteogenic differentiation of DPSCs. In this study, we showed the versatile nature of decellularized plant leaves as a biological scaffold and their potential for bone regeneration in vitro.
PubMed: 38935255
DOI: 10.1007/s11626-024-00937-9 -
Journal of Clinical Sleep Medicine :... Jun 2024To examine the effects of nurse-led brief behavioral treatment for insomnia (BBTI) on insomnia severity, sleep status, daytime function, quality of life (QoL),...
STUDY OBJECTIVES
To examine the effects of nurse-led brief behavioral treatment for insomnia (BBTI) on insomnia severity, sleep status, daytime function, quality of life (QoL), psychological distress levels, treatment response, and insomnia remission in young and middle-aged Asian adults with insomnia symptoms.
METHODS
This two-parallel, randomized controlled trial recruited 42 participants with insomnia symptoms randomly allocated to the nurse-led BBTI group or sleep hygiene (SH) group. The outcome measurements included the Insomnia Severity Index, sleep diary, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Brief Fatigue Inventory, RAND-36 Health Status Inventory, and the Depression, Anxiety and Stress Scale-21. The measurement time points included baseline, the end of each week of the intervention period, and one-month follow-up.
RESULTS
Compared with the SH group, participants in the BBTI group significantly improved insomnia severity, sleep onset latency, sleep efficiency, sleep quality, daytime sleepiness, and the mental components of QoL after completing nurse-led BBTI immediately and one month later ( < 0.05). In addition, 52.4% and 71.4% of the participants achieved remission after completing nurse-led BBTI immediately and one month later, which were significantly higher than the SH group (14.3%, = 0.02; 14.3%, < 0.001, respectively).
CONCLUSIONS
We suggested the relative effects of BBTI on declined insomnia severity and improved sleep status among young and middle-aged Asian adults with insomnia symptoms and confirmed the benefits of nurse-led BBTI in alleviating insomnia. Nurses should incorporate BBTI into insomnia care further to enhance the daytime function and quality of life of the population with insomnia symptoms.
CLINICAL TRIAL REGISTRATION
Registry: ClinicalTrials.gov; Name: Effects of Nurse-led Brief Behavioral Treatment for Insomnia: A Feasibility Randomized Controlled Trial; URL: https://clinicaltrials.gov/study/NCT05310136; Identifier: NCT05310136.
PubMed: 38935053
DOI: 10.5664/jcsm.11256 -
The Journal of Hand Surgery Jun 2024The research outlines anatomical landmarks that may help surgeons in identifying the lateral antebrachial cutaneous nerve (LABCN) to minimize nerve damage during...
PURPOSE
The research outlines anatomical landmarks that may help surgeons in identifying the lateral antebrachial cutaneous nerve (LABCN) to minimize nerve damage during procedures in the cubital fossa.
METHODS
Twenty-eight fresh cadaveric upper extremities were dissected. The course of the LABCN was followed from the emerging point at the biceps brachii tendon (BT) to the mid-forearm. The nerve's relationships with the BT, lateral epicondyle (LE), antebrachial vein, and brachioradialis (BR) muscle were measured and documented.
RESULTS
The LABCN emerged lateral to the BT in all specimens and crossed medially at the top of the BT in 50% of the cadavers. It was deep to the forearm superficial fascia in all cadavers. At the level of the LE, the nerve was located at a mean of 6.3 ± 3.1 mm medial to the BR. The LABCN aligns with the medial border of the BR at a mean of 68 mm distal to the interepicondylar line. The mean distance from the LE to the LABCN at the interepicondylar line was 24.5 ± 7.2 mm. The LABCN and antebrachial vein are in the same deep fascia plane, on average 47.6 ± 5 mm (37-55) from the LE. At the elbow joint level, 82.1% of the specimens have two branches for the LABCN, whereas 17.9% demonstrated only a single branch.
CONCLUSIONS
Lateral antebrachial cutaneous nerve was situated approximately 6.8 cm distal to the interepicondyle line, positioned at the ulnar edge of the BR, and runs parallel with the antebrachial vein deep to the forearm fascia plane. The nerve crossed over the biceps tendon in 50% of the specimens. These findings suggest that the nerve should be identified 6-7 cm distal to the LE, followed by a proximal dissection.
CLINICAL RELEVANCE
This study may help surgeons in identifying LABCN, and reducing the potential risk of LABCN injury.
PubMed: 38934998
DOI: 10.1016/j.jhsa.2024.04.018 -
Ankle mechanics during jump landings across different foot positions in professional ballet dancers.Sports Biomechanics Jun 2024This study aimed to investigate the effect foot position on ankle joint mechanics and vertical ground reaction forces (vGRF) across jump landings in professional ballet...
This study aimed to investigate the effect foot position on ankle joint mechanics and vertical ground reaction forces (vGRF) across jump landings in professional ballet dancers. Twenty-seven professional ballet dancers (men: 14; women: 13) attended one data collection session, completing five maximal countermovement jumps in parallel, first, second, fourth, and fifth positions. Three-dimensional ankle mechanics, landing vGRF variables, and jump height were recorded via a seven-camera motion capture system and one force platform. A repeated measures multivariate analysis of variance was used to assess the main effects foot position across all target variables. A linear discriminate analysis was conducted to investigate target variables across foot positions. Frontal and transverse plane ankle mechanics had the largest impact when discriminating between foot positions. Ankle power in the transverse plane during jump landing in fourth was double that of all other positions. Our findings suggest that ankle range of motion should be restored before returning to jumps in fourth and fifth positions following distal lower extremity injury. The multiplanar energy transfer observed indicates a need for specific exercises to develop multiplanar force and rate of force development of local structures around the ankle.
PubMed: 38934793
DOI: 10.1080/14763141.2024.2369913 -
MSystems Jun 2024Airway microbiota are known to contribute to lung diseases, such as cystic fibrosis (CF), but their contributions to pathogenesis are still unclear. To improve our...
Airway microbiota are known to contribute to lung diseases, such as cystic fibrosis (CF), but their contributions to pathogenesis are still unclear. To improve our understanding of host-microbe interactions, we have developed an integrated analytical and bioinformatic mass spectrometry (MS)-based metaproteomics workflow to analyze clinical bronchoalveolar lavage (BAL) samples from people with airway disease. Proteins from BAL cellular pellets were processed and pooled together in groups categorized by disease status (CF vs. non-CF) and bacterial diversity, based on previously performed small subunit rRNA sequencing data. Proteins from each pooled sample group were digested and subjected to liquid chromatography tandem mass spectrometry (MS/MS). MS/MS spectra were matched to human and bacterial peptide sequences leveraging a bioinformatic workflow using a metagenomics-guided protein sequence database and rigorous evaluation. Label-free quantification revealed differentially abundant human peptides from proteins with known roles in CF, like neutrophil elastase and collagenase, and proteins with lesser-known roles in CF, including apolipoproteins. Differentially abundant bacterial peptides were identified from known CF pathogens (e.g., ), as well as other taxa with potentially novel roles in CF. We used this host-microbe peptide panel for targeted parallel-reaction monitoring validation, demonstrating for the first time an MS-based assay effective for quantifying host-microbe protein dynamics within BAL cells from individual CF patients. Our integrated bioinformatic and analytical workflow combining discovery, verification, and validation should prove useful for diverse studies to characterize microbial contributors in airway diseases. Furthermore, we describe a promising preliminary panel of differentially abundant microbe and host peptide sequences for further study as potential markers of host-microbe relationships in CF disease pathogenesis.IMPORTANCEIdentifying microbial pathogenic contributors and dysregulated human responses in airway disease, such as CF, is critical to understanding disease progression and developing more effective treatments. To this end, characterizing the proteins expressed from bacterial microbes and human host cells during disease progression can provide valuable new insights. We describe here a new method to confidently detect and monitor abundance changes of both microbe and host proteins from challenging BAL samples commonly collected from CF patients. Our method uses both state-of-the art mass spectrometry-based instrumentation to detect proteins present in these samples and customized bioinformatic software tools to analyze the data and characterize detected proteins and their association with CF. We demonstrate the use of this method to characterize microbe and host proteins from individual BAL samples, paving the way for a new approach to understand molecular contributors to CF and other diseases of the airway.
PubMed: 38934598
DOI: 10.1128/msystems.00929-23 -
Journal of Clinical Microbiology Jun 2024This study compared the performance of two commercial molecular assays, the STANDARD M10 assay (M10) and the Xpert assay (Xpert), for detecting toxigenic in stool...
This study compared the performance of two commercial molecular assays, the STANDARD M10 assay (M10) and the Xpert assay (Xpert), for detecting toxigenic in stool specimens. A total of 487 consecutive stool specimens submitted for routine testing between June and November 2023 were included. Following routine testing using C. DIFF QUIK CHEK COMPLETE (QCC), M10 and Xpert were tested in parallel, alongside toxigenic culture (reference standard). Additionally, two-step algorithms, using QCC on the first step and either M10 or Xpert on the second step, were assessed. Both M10 and Xpert demonstrated a sensitivity and negative predictive value (NPV) of 100%. M10 exhibited significantly higher specificity and positive predictive value (PPV; 91.9% and 64.2%, respectively) than Xpert (90.3% and 59.8%, respectively). Both two-step algorithms showed a sensitivity and NPV of 98.4% and 99.8%, respectively. The specificity and PPV of the two-step algorithm using M10 (95.2% and 75.0%, respectively) were slightly higher than those of the one using Xpert (94.8% and 73.2%, respectively), without statistical significance. Receiver operating characteristic curve analysis, assessing the predictive ability of cycle threshold (Ct) values for the detection of free toxin, exhibited an area under the curve of 0.825 for M10 and 0.843 for Xpert. This indicates the utility of Ct values as predictors for the detection of free toxin in both assays. In conclusion, M10 proves to be an effective diagnostic tool with performance comparable to Xpert, whether utilized independently or as part of a two-step algorithm.
PubMed: 38934589
DOI: 10.1128/jcm.00524-24