Chromatograms and Mass Spectra of High-Mannose and Paucimannose N-Glycans for Rapid Isomeric Identifications.

N-Linked glycosylation is one of the most essential post-translational modifications of proteins. However, N-glycan structural determination remains challenging because of the small differences in structures between isomers. In this study, we constructed a database containing collision-induced dissociation MSn mass spectra and chromatograms of high-performance liquid chromatography for the rapid identification of high-mannose and paucimannose N-glycan isomers. These N-glycans include isomers by breaking of arbitrary numbers of glycosidic bonds at arbitrary positions of canonical Man9GlcNAc2 N-glycans. In addition, some GlcMannGlcNAc2 N-glycan isomers were included in the database. This database is particularly useful for the identification of the N-glycans not in conventional N-glycan standards. This study demonstrated the application of the database to structural assignment for high-mannose N-glycans extracted from bovine whey proteins, soybean proteins, human mammary epithelial cells, and human breast carcinoma cells. We found many N-glycans that are not expected to be generated by conventional biosynthetic pathways of multicellular eukaryotes.

A pH-Sensitive Stretchable Zwitterionic Hydrogel with Bipolar Thermoelectricity.

Amid growing interest in using body heat for electricity in wearables, creating stretchable devices poses a major challenge. Herein, a hydrogel composed of two core constituents, namely the negatively-charged 2-acrylamido-2-methylpropanesulfonic acid and the zwitterionic (ZI) sulfobetaine acrylamide, is engineered into a double-network hydrogel. This results in a significant enhancement in mechanical properties, with tensile stress and strain of up to 470.3 kPa and 106.6%, respectively. Moreover, the ZI nature of the polymer enables the fabrication of a device with polar thermoelectric properties by modulating the pH. Thus, the ionic Seebeck coefficient (Si) of the ZI hydrogel ranges from -32.6 to 31.7 mV K-1 as the pH is varied from 1 to 14, giving substantial figure of merit (ZTi) values of 3.8 and 3.6, respectively. Moreover, a prototype stretchable ionic thermoelectric supercapacitor incorporating the ZI hydrogel exhibits notable power densities of 1.8 and 0.9 mW m-2 at pH 1 and 14, respectively. Thus, the present work paves the way for the utilization of pH-sensitive, stretchable ZI hydrogels for thermoelectric applications, with a specific focus on harvesting low-grade waste heat within the temperature range of 25-40 °C.

Effects of Early Short-Course Corticosteroids on Immune-Related Adverse Events in Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors.

INTRODUCTION: In real-world practice, most non-small cell lung cancer (NSCLC) patients receiving combined immunochemotherapy are exposed to short-course corticosteroids following immune checkpoint inhibitor (ICI) infusion to prevent chemotherapy-related adverse events. However, whether this early short-course corticosteroid use prevents immune-related adverse events (irAEs) remains unknown. METHODS: Between January 1st, 2015, and December 31st, 2020, NSCLC patients who received at least one cycle of ICI with or without chemotherapy were enrolled. Early short-course corticosteroids were defined as corticosteroids administered following ICI injection and before chemotherapy on the same day and no longer than 3 days afterward. The patients were categorized as either "corticosteroid group" or "non-corticosteroid group" depending on their exposure to early short-course corticosteroid. The frequencies of irAEs requiring systemic corticosteroid use and irAEs leading to ICI discontinuation were compared between the two groups, and exploratory survival analyses were performed. RESULTS: Among 252 eligible patients, 137 patients were categorized as "corticosteroid group" and 115 patients as "non-corticosteroid group." The corticosteroid group enriched patients in the first-line setting (n = 75, 54.7%), compared to the non-corticosteroid group (n = 28, 24.3%). Thirty patients (21.9%) in the corticosteroid group and 35 patients (30.4%) in the non-corticosteroid group developed irAEs requiring systemic corticosteroid use (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.35-1.18; p = 0.15). Eight patients (5.8%) in the corticosteroid group, as compared with 18 patients (15.7%) in the non-corticosteroid group, permanently discontinued ICI due to irAEs (OR, 0.34; 95% CI, 0.12-0.85; p = 0.013). CONCLUSION: Early short-course corticosteroids following each ICI injection may reduce the rate of irAEs that lead to ICIs discontinuation, warranting further investigation of its prophylactic use to mitigate clinically significant irAEs.

Using cryoprobes of different sizes combined with cone-beam computed tomography-derived augmented fluoroscopy and endobronchial ultrasound to diagnose peripheral pulmonary lesions: a propensity-matched study.

BACKGROUND: Endobronchial ultrasound (EBUS) and cone-beam computed tomography-derived augmented fluoroscopy (CBCT-AF) are utilized for the diagnosis of peripheral pulmonary lesions (PPLs). Combining them with transbronchial cryobiopsy (TBC) can provide sufficient tissue for genetic analysis. However, cryoprobes of different sizes have varying degrees of flexibility, which can affect their ability to access the target bronchus and potentially impact the accuracy. The aim of this study was to compare the diagnostic efficacy of cryoprobes of varying sizes in CBCT-AF and EBUS for the diagnosis of PPLs. METHODS: Patients who underwent endobronchial ultrasound-guided transbronchial biopsy (EBUS-TBB) and TBC combined with CBCT-AF for PPLs diagnosis between January 2021 and May 2022 were included. Propensity score matching and competing-risks regression were utilized for data analysis. Primary outcome was the diagnostic accuracy of TBC. RESULTS: A total of 284 patients underwent TBC, with 172 using a 1.7-mm cryoprobe (1.7 group) and 112 using a 1.1-mm cryoprobe (1.1 group). Finally, we included 99 paired patients following propensity score matching. The diagnostic accuracy of TBC was higher in the 1.1 group (80.8% vs. 69.7%, P = 0.050), with a similar rate of complications. Subgroup analysis also revealed that the 1.1 group had better accuracy when PPLs were located in the upper lobe (85.2% vs. 66.1%, P = 0.020), when PPLs were smaller than 20 mm (78.8% vs. 48.8%, P = 0.008), and when intra-procedural CBCT was needed to be used (79.5% vs. 42.3%, P = 0.001). TBC obtained larger specimens than TBB in both groups. There is still a trend of larger sample size obtained in the 1.7 group, but there is no statistically different between our two study groups (40.8 mm2 vs. 22.0 mm2, P = 0.283). CONCLUSIONS: The combination of TBC with CBCT-AF and EBUS is effective in diagnosing PPLs, and a thin cryoprobe is preferred when the PPLs located in difficult areas.

Water Adsorption Isotherm and Surface Conductivity of Boroaluminosilicate Glasses.

The surface resistivity of boroaluminosilicate display glasses, which may affect the downstream display panel manufacturing, varies with the relative humidity (RH) of the environment, but the origin of this RH dependence has not been well understood. We have measured the water adsorption behavior on Corning Eagle XG (Glass-E) and Lotus NXT (Glass-L) glass panels using Brewster angle transmission infrared spectroscopy. The IR spectra of adsorbed water were analyzed to obtain the effective thickness of adsorbed water, the distribution of hydrogen-bonding interactions among the adsorbed water molecules, and the isosteric heat of water adsorption. These characteristics were compared with the electrical conductivity (inverse of resistivity) of these two glasses [Appl. Surf. Sci. 2015, 356, 1189]. This comparison revealed the correlation between the conductivity and the water layer structure, which could explain the surface resistivity difference between Glass-E and Glass-L as a function of RH. This study also disputed the previous hypothesis that the water adsorption isotherm would be governed by the areal density of the surface hydroxyl group; instead, it suggested that the network modifier ions may also play a critical role, especially in the intermediate RH regime.

Effects of adding Bacillus subtilis natto NTU-18 in paste feed on growth, intestinal morphology, gastrointestinal microbiota diversity, immunity, and disease resistance of Anguilla japonica glass eels.

Japanese eel, Anguilla japonica, holds significant importance in Taiwanese aquaculture. With the intensification of eel farming, the impact of Edwardsiella tarda has become increasingly severe. Consequently, the abusive use of antibiotics has risen. Bacillus subtilis natto NTU-18, a strain of Bacillus with a high survival rate in feed processing, plays a crucial role in promoting intestinal health through competitive rejection, enhancing immune responses against bacterial pathogens, and improving intestinal health by modulating gastrointestinal microbiota to produce beneficial metabolites of mice and grass carp, Ctenopharyngodon idella. This study investigated the effects of different proportions (control, 0.25 %, 0.5 %, 1 %, and 2 %) of B. subtilis natto NTU-18 added to paste feed on the growth performance, intestinal morphology, and microbiota, expression of immune-related genes, and resistance to E. tarda in Japanese glass eel. The results indicated that the growth performance of all groups with B. subtilis natto NTU-18 added was significantly higher than that of the control group and did not impact the villi morphology. The expression of immune-related genes in the kidney, specifically HSP70 and SOD, was significantly higher from 0.5 % and above than the control; however, no significant differences were observed in CAT, POD, and HSP90. In the liver, significant differences were found in HSP70 and IgM above 0.25 % compared to the control group, with no significant differences in SOD, CAT, POD, and HSP90 among all groups. Additionally, intestinal microbiota analysis revealed that the 2 % additional group had significantly lower diversity than other groups, with Cetobacterium as the dominant species. The challenge test observed that the survival rates of the 0.5 % and 1 % groups were significantly higher. This research suggests that adding 0.5 % and 1 % of B. subtilis natto NTU-18 to the diet is beneficial for Japanese glass eel's immunity, growth performance, and disease resistance.

Differential training benefits and motor unit remodeling in wrist force precision tasks following high and low load blood flow restriction exercises under volume-matched conditions.

BACKGROUND: Blood flow restriction (BFR) resistance training has demonstrated efficacy in promoting strength gains beneficial for rehabilitation. Yet, the distinct functional advantages of BFR strength training using high-load and low-load protocols remain unclear. This study explored the behavioral and neurophysiological mechanisms that explain the differing effects after volume-matched high-load and low-load BFR training. METHODS: Twenty-eight healthy participants were randomly assigned to the high-load blood flow restriction (BFR-HL, n = 14) and low-load blood flow restriction (BFR-LL, n = 14) groups. They underwent 3 weeks of BFR training for isometric wrist extension at intensities of 25% or 75% of maximal voluntary contraction (MVC) with matched training volume. Pre- and post-tests included MVC and trapezoidal force-tracking tests (0-75%-0% MVC) with multi-channel surface electromyography (EMG) from the extensor digitorum. RESULTS: The BFR-HL group exhibited a greater strength gain than that of the BFR-LL group after training (BFR_HL: 26.96 ± 16.33% vs. BFR_LL: 11.16 ± 15.34%)(p = 0.020). However, only the BFR-LL group showed improvement in force steadiness for tracking performance in the post-test (p = 0.004), indicated by a smaller normalized change in force fluctuations compared to the BFR-HL group (p = 0.048). After training, the BFR-HL group activated motor units (MUs) with higher recruitment thresholds (p < 0.001) and longer inter-spike intervals (p = 0.002), contrary to the BFR-LL group, who activated MUs with lower recruitment thresholds (p < 0.001) and shorter inter-spike intervals (p < 0.001) during force-tracking. The discharge variability (p < 0.003) and common drive index (p < 0.002) of MUs were consistently reduced with training for the two groups. CONCLUSIONS: BFR-HL training led to greater strength gains, while BFR-LL training better improved force precision control due to activation of MUs with lower recruitment thresholds and higher discharge rates.

LncRNA SLCO4A1-AS1 suppresses lung cancer progression by sequestering the TOX4-NTSR1 signaling axis.

BACKGROUND: Metastasis is a multistep process involving the migration and invasion of cancer cells and is a hallmark of cancer malignancy. Long non-coding RNAs (lncRNAs) play critical roles in the regulation of metastasis. This study aims to elucidate the role of the lncRNA solute carrier organic anion transporter family member 4A1-antisense 1 (SLCO4A1-AS1) in metastasis and its underlying regulatory mechanisms. METHODS: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify metastasis-associated lncRNAs. Transwell migration and invasion assays, and a tail vein-injection mouse model were used to assess the migration and invasion of cancer cells in vitro and in vivo, respectively. High-throughput screening methods, including MASS Spectrometry and RNA sequencing (RNA-seq), were used to identify the downstream targets of SLCO4A1-AS1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, RNA pull-down, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and chromatin immunoprecipitation (ChIp) assays were conducted to identify and validate the underlying regulatory mechanisms of SLCO4A1-AS1. RESULTS: SLCO4A1-AS1 reduced cancer cell migration and invasion by disrupting cytoskeleton filaments, and was associated with longer overall survival in patients with lung adenocarcinoma. SLCO4A1-AS1 directly interacted with the DNA-binding protein, TOX High Mobility Group Box Family Member 4 (TOX4), to inhibit TOX4-induced migration and invasion. Furthermore, RNA-seq revealed that neurotensin receptor 1 (NTSR1) is a novel and convergent downstream target of SLCO4A1-AS1 and TOX4. Mechanistically, SLCO4A1-AS1 functions as a decoy of TOX4 by interrupting its interaction with the NTSR1 promoter and preventing NTSR1 transcription. Functionally, NTSR1 promotes cancer cell migration and invasion through cytoskeletal remodeling, and knockdown of NTSR1 significantly inhibits TOX4-induced migration and invasion. CONCLUSION: These findings demonstrated that SLCO4A1-AS1 antagonizes TOX4/NTSR1 signaling, underscoring its pivotal role in lung cancer cell migration and invasion. These findings hold promise for the development of novel therapeutic strategies targeting the SLCO4A1-AS1/TOX4/NTSR1 axis as a potential avenue for effective therapeutic intervention in lung cancer.

Regiospecific Cellulose Orientation and Anisotropic Mechanical Property in Plant Cell Walls.

Cellulose microfibrils (CMFs) are a major load-bearing component in plant cell walls. Thus, their structures have been studied extensively with spectroscopic and microscopic characterization methods, but the findings from these two approaches were inconsistent, which hampers the mechanistic understanding of cell wall mechanics. Here, we report the regiospecific assembly of CMFs in the periclinal wall of plant epidermal cells. Using sum frequency generation spectroscopic imaging, we found that CMFs are highly aligned in the cell edge region where two cells form a junction, whereas they are mostly isotropic on average throughout the wall thickness in the flat face region of the epidermal cell. This subcellular-level heterogeneity in the CMF alignment provided a new perspective on tissue-level anisotropy in the tensile modulus of cell wall materials. This finding also has resolved a previous contradiction between the spectroscopic and microscopic imaging studies, which paves a foundation for better understanding of the cell wall architecture, especially structure-geometry relationships.

Photothermal Atomic Force Microscopy Coupled with Infrared Spectroscopy (AFM-IR) Analysis of High Extinction Coefficient Materials: A Case Study with Silica and Silicate Glasses.

Photothermal atomic force microscopy coupled with infrared spectroscopy (AFM-IR) brings significant value as a spatially resolved surface analysis technique for disordered oxide materials such as glasses, but additional development and fundamental understanding of governing principles is needed to interpret AFM-IR spectra, since the existing theory described for organic materials does not work for materials with high extinction coefficients for infrared (IR) absorption. This paper describes theoretical calculation of a transient temperature profile inside the IR-absorbing material considering IR refraction at the interface as well as IR adsorption and heat transfer inside the sample. This calculation explains the differences in peak positions and amplitudes of AFM-IR spectra from those of specular reflectance and extinction coefficient spectra. It also addresses the information depth of the AFM-IR characterization of bulk materials. AFM-IR applied to silica and silicate glass surfaces has demonstrated novel capability of characterizing subsurface structural changes and surface heterogeneity due to mechanical stresses from physical contacts, as well as chemical alterations manifested in surface layers through aqueous corrosion.

Biodegradation of Herbicides by a Plant Nonheme Iron Dioxygenase: Mechanism and Selectivity of Substrate Analogues.

Aryloxyalkanoate dioxygenases are unique herbicide biodegrading nonheme iron enzymes found in plants and hence, from environmental and agricultural point of view they are important and valuable. However, they often are substrate specific and little is known on the details of the mechanism and the substrate scope. To this end, we created enzyme models and calculate the mechanism for 2,4-dichlorophenoxyacetic acid biodegradation and 2-methyl substituted analogues by density functional theory. The work shows that the substrate binding is tight and positions the aliphatic group close to the metal center to enable a chemoselective reaction mechanism to form the C2 -hydroxy products, whereas the aromatic hydroxylation barriers are well higher in energy. Subsequently, we investigated the metabolism of R- and S-methyl substituted inhibitors and show that these do not react as efficiently as 2,4-dichlorophenoxyacetic acid substrate due to stereochemical clashes in the active site and particularly for the R-isomer give high rebound barriers.

Elucidating Interfacial Chain Conformation of Superhydrophilic Polymer Brushes by Vibrational Sum Frequency Generation Spectroscopy.

Surface-tethered macromolecules (polymer brushes) are a potent means to modify surfaces with stimuli-responsive properties while avoiding delamination problems. This vibrational sum frequency generation spectroscopy study describes how the conformation of hydrophilic polymer brushes changes in response to environmental conditions, that is, changes in humidity (in air) and upon exposure to liquid water. Three hydrophilic brushes were prepared on silicon oxide surfaces by surface-initiated reversible deactivation radical polymerization of cationic (quaternary ammonium), anionic (sulfonate), and zwitterionic (containing both) monomers. The average tilt angle of methyl groups was analyzed and used to deduce the chain conformations of the polymer brushes. In air, the brush films absorb water and swell with increasing humidity. This is accompanied by the rotation of interfacial polymer chains. The degree of water uptake and chain conformation vary with the nature of the charged hydrophilic moieties. The hydrophilic polymer brush surfaces appear to remain relatively dry except in near-condensation conditions. In water, the quaternary ammonium groups of cationic and zwitterionic brushes are aligned nearly parallel to the surface. The anionic brush chains appear to assume nearly random conformations in water.

A Data-Driven Model with Feedback Calibration Embedded Blood Pressure Estimator Using Reflective Photoplethysmography.

Ambulatory blood pressure (BP) monitoring (ABPM) is vital for screening cardiovascular activity. The American College of Cardiology/American Heart Association guideline for the prevention, detection, evaluation, and management of BP in adults recommends measuring BP outside the office setting using daytime ABPM. The recommendation to use night-day BP measurements to confirm hypertension is consistent with the recommendation of several other guidelines. In recent studies, ABPM was used to measure BP at regular intervals, and it reduces the effect of the environment on BP. Out-of-office measurements are highly recommended by almost all hypertension organizations. However, traditional ABPM devices based on the oscillometric technique usually interrupt sleep. For all-day ABPM purposes, a photoplethysmography (PPG)-based wrist-type device has been developed as a convenient tool. This optical, noninvasive device estimates BP using morphological characteristics from PPG waveforms. As measurement can be affected by multiple variables, calibration is necessary to ensure that the calculated BP values are accurate. However, few studies focused on adaptive calibration. A novel adaptive calibration model, which is data-driven and embedded in a wearable device, was proposed. The features from a 15 s PPG waveform and personal information were input for estimation of BP values and our data-driven calibration model. The model had a feedback calibration process using the exponential Gaussian process regression method to calibrate BP values and avoid inter- and intra-subject variability, ensuring accuracy in long-term ABPM. The estimation error of BP (ΔBP = actual BP-estimated BP) of systolic BP was -0.1776 ± 4.7361 mmHg; ≤15 mmHg, 99.225%, and of diastolic BP was -0.3846 ± 6.3688 mmHg; ≤15 mmHg, 98.191%. The success rate was improved, and the results corresponded to the Association for the Advancement of Medical Instrumentation standard and British Hypertension Society Grading criteria for medical regulation. Using machine learning with a feedback calibration model could be used to assess ABPM for clinical purposes.

Electrostatic Perturbations from the Protein Affect C-H Bond Strengths of the Substrate and Enable Negative Catalysis in the TmpA Biosynthesis Enzyme.

The nonheme iron dioxygenase 2-(trimethylammonio)-ethylphosphonate dioxygenase (TmpA) is an enzyme involved in the regio- and chemoselective hydroxylation at the C1 -position of the substrate as part of the biosynthesis of glycine betaine in bacteria and carnitine in humans. To understand how the enzyme avoids breaking the weak C2 -H bond in favor of C1 -hydroxylation, we set up a cluster model of 242 atoms representing the first and second coordination sphere of the metal center and substrate binding pocket, and investigated possible reaction mechanisms of substrate activation by an iron(IV)-oxo species by density functional theory methods. In agreement with experimental product distributions, the calculations predict a favorable C1 -hydroxylation pathway. The calculations show that the selectivity is guided through electrostatic perturbations inside the protein from charged residues, external electric fields and electric dipole moments. In particular, charged residues influence and perturb the homolytic bond strength of the C1 -H and C2 -H bonds of the substrate, and strongly strengthens the C2 -H bond in the substrate-bound orientation.

A tongue features fusion approach to predicting prediabetes and diabetes with machine learning.

BACKGROUND: Diabetics has become a serious public health burden in China. Multiple complications appear with the progression of diabetics pose a serious threat to the quality of human life and health. We can prevent the progression of prediabetics to diabetics and delay the progression to diabetics by early identification of diabetics and prediabetics and timely intervention, which have positive significance for improving public health. OBJECTIVE: Using machine learning techniques, we establish the noninvasive diabetics risk prediction model based on tongue features fusion and predict the risk of prediabetics and diabetics. METHODS: Applying the type TFDA-1 Tongue Diagnosis Instrument, we collect tongue images, extract tongue features including color and texture features using TDAS, and extract the advanced tongue features with ResNet-50, achieve the fusion of the two features with GA_XGBT, finally establish the noninvasive diabetics risk prediction model and evaluate the performance of testing effectiveness. RESULTS: Cross-validation suggests the best performance of GA_XGBT model with fusion features, whose average CA is 0.821, the average AUROC is 0.924, the average AUPRC is 0.856, the average Precision is 0.834, the average Recall is 0.822, the average F1-score is 0.813. Test set suggests the best testing performance of GA_XGBT model, whose average CA is 0.81, the average AUROC is 0.918, the average AUPRC is 0.839, the average Precision is 0.821, the average Recall is 0.81, the average F1-score is 0.796. When we test prediabetics with GA_XGBT model, we find that the AUROC is 0.914, the Precision is 0.69, the Recall is 0.952, the F1-score is 0.8. When we test diabetics with GA_XGBT model, we find that the AUROC is 0.984, the Precision is 0.929, the Recall is 0.951, the F1-score is 0.94. CONCLUSIONS: Based on tongue features, the study uses classical machine learning algorithm and deep learning algorithm to maximum the respective advantages. We combine the prior knowledge and potential features together, establish the noninvasive diabetics risk prediction model with features fusion algorithm, and detect prediabetics and diabetics noninvasively. Our study presents a feasible method for establishing the association between diabetics and the tongue image information and prove that tongue image information is a potential marker which facilitates effective early diagnosis of prediabetics and diabetics.

Product Distributions of Cytochrome P450 OleTJE with Phenyl-Substituted Fatty Acids: A Computational Study.

There are two types of cytochrome P450 enzymes in nature, namely, the monooxygenases and the peroxygenases. Both enzyme classes participate in substrate biodegradation or biosynthesis reactions in nature, but the P450 monooxygenases use dioxygen, while the peroxygenases take H2O2 in their catalytic cycle instead. By contrast to the P450 monooxygenases, the P450 peroxygenases do not require an external redox partner to deliver electrons during the catalytic cycle, and also no external proton source is needed. Therefore, they are fully self-sufficient, which affords them opportunities in biotechnological applications. One specific P450 peroxygenase, namely, P450 OleTJE, reacts with long-chain linear fatty acids through oxidative decarboxylation to form hydrocarbons and, as such, has been implicated as a suitable source for the biosynthesis of biofuels. Unfortunately, the reactions were shown to produce a considerable amount of side products originating from Cα and Cß hydroxylation and desaturation. These product distributions were found to be strongly dependent on whether the substrate had substituents on the Cα and/or Cß atoms. To understand the bifurcation pathways of substrate activation by P450 OleTJE leading to decarboxylation, Cα hydroxylation, Cß hydroxylation and Cα-Cß desaturation, we performed a computational study using 3-phenylpropionate and 2-phenylbutyrate as substrates. We set up large cluster models containing the heme, the substrate and the key features of the substrate binding pocket and calculated (using density functional theory) the pathways leading to the four possible products. This work predicts that the two substrates will react with different reaction rates due to accessibility differences of the substrates to the active oxidant, and, as a consequence, these two substrates will also generate different products. This work explains how the substrate binding pocket of P450 OleTJE guides a reaction to a chemoselectivity.

Can a Mononuclear Iron(III)-Superoxo Active Site Catalyze the Decarboxylation of Dodecanoic Acid in UndA to Produce Biofuels?

Decarboxylation of fatty acids is an important reaction in cell metabolism, but also has potential in biotechnology for the biosynthesis of hydrocarbons as biofuels. The recently discovered nonheme iron decarboxylase UndA is involved in the biosynthesis of 1-undecene from dodecanoic acid and using X-ray crystallography was assigned to be a mononuclear iron species. However, the work was contradicted by spectroscopic studies that suggested UndA to be more likely a dinuclear iron system. To resolve this controversy we decided to pursue a computational study on the reaction mechanism of fatty acid decarboxylation by UndA using iron(III)-superoxo and diiron(IV)-dioxo models. We tested several models with different protonation states of active site residues. Overall, however, the calculations imply that mononuclear iron(III)-superoxo is a sluggish oxidant of hydrogen atom abstraction reactions in UndA and will not be able to activate fatty acid residues by decarboxylation at room temperature. By contrast, a diiron-dioxo complex reacts with much lower hydrogen atom abstraction barriers and hence is a more likely oxidant in UndA.

Four-Year Impact of Voiding and Storage Symptoms in Patients with Benign Prostatic Hyperplasia Treated with Prostatic Artery Embolization.

PURPOSE: To study the subscore improvement in International Prostate Symptom Scores (IPSS) after prostatic artery embolization (PAE). MATERIALS AND METHODS: A single-center retrospective study was carried out with follow-up from December 2013 to July 2019 in 37 consecutive patients (66.0 ± 8.8 years old) who underwent PAE, comparing resultant scores before and after PAE. IPSS were divided into storage (IPSS-s) subscores and voiding (IPSS-v) subscores. The changes between IPSS-s and IPSS-v at 1, 3, 6, and 12 months' follow-up as well as the last follow-up were compared with baseline scores. The changes in percentages of IPSS-s and IPSS-v and the changes in average IPSS-s-to-total IPSS ratios (IPSS-s/IPSS-t) and IPSS-v-to-IPSS-t ratios (IPSS-v/IPSS-t) were also analyzed. RESULTS: In the study population, consisting of 37 patients, IPSS-t significantly decreased from 16.5 ± 7.2 at baseline to 8.3 ± 5.7 at the last follow-up (4 years later) (P < .0001). Additionally, the changes in IPSS-v symptoms were greater than the changes in IPSS-s symptoms at 1, 3, 6, and 12 months' follow-up, reaching a statistical significance at 6 months with a decrease of 72.9% ± 42.4% for IPSS-v and a decrease of 50.1% ± 52.2% for IPSS-s (P = .009). CONCLUSIONS: PAE can successfully reduce both IPSS-s and IPSS-v with predominant IPSS-v reduction. The improvements in both subscores were sustained for up to 4 years of follow-up.

Hydroxyl Transfer to Carbon Radicals by Mn(OH) vs Fe(OH) Corrole Complexes.

The transfer of •OH from metal-hydroxo species to carbon radicals (R•) to give hydroxylated products (ROH) is a fundamental process in metal-mediated heme and nonheme C-H bond oxidations. This step, often referred to as the hydroxyl "rebound" step, is typically very fast, making direct study of this process challenging if not impossible. In this report, we describe the reactions of the synthetic models M(OH)(ttppc) (M = Fe (1), Mn (3); ttppc = 5,10,15-tris(2,4,6-triphenyl)phenyl corrolato3-) with a series of triphenylmethyl carbon radical (R•) derivatives ((4-X-C6H4)3C•; X = OMe, tBu, Ph, Cl, CN) to give the one-electron reduced MIII(ttppc) complexes and ROH products. Rate constants for 3 for the different radicals ranged from 11.4(1) to 58.4(2) M-1 s-1, as compared to those for 1, which fall between 0.74(2) and 357(4) M-1 s-1. Linear correlations for Hammett and Marcus plots for both Mn and Fe were observed, and the small magnitudes of the slopes for both correlations imply a concerted •OH transfer reaction for both metals. Eyring analyses of reactions for 1 and 3 with (4-X-C6H4)3C• (X = tBu, CN) also give good linear correlations, and a comparison of the resulting activation parameters highlight the importance of entropy in these •OH transfer reactions. Density functional theory calculations of the reaction profiles show a concerted process with one transition state for all radicals investigated and help to explain the electronic features of the OH rebound process.

Fatigue-related modulation of low-frequency common drive to motor units.

PURPOSE: This study investigated fatigue-related modulation of common neural inputs to motor units (MUs) under 5 Hz, which determines force precision control. METHODS: Twenty-seven adults performed a sequence of fatiguing contractions. The participants were assessed with a static isometric index abduction at 20% maximal voluntary contraction in the pre-test and post-test. Discharge characteristics of MUs of the first dorsal interosseous muscle were analyzed with decomposed EMG signals. RESULTS: Along with increases in the mean (58.40 ± 11.76 ms → 62.55 ± 10.83 ms, P = 0.029) and coefficient of variation (0.204 ± .014 → 0.215 ± 0.017, P = 0.002) in inter-spike intervals, the fatiguing contraction caused reductions in the mean frequency (16.84 ± 3.31 Hz → 15.59 ± 3.21 Hz, P = 0.027) and spectral dispersions (67.54 ± 4.49 → 62.64 ± 6.76 Hz, P = 0.007) of common neural drive, as estimated with smoothed cumulative motor unit spike trains (SCMUSTs). Stabilogram diffusion analysis of SCMUSTs revealed significant fatigue-related reductions in the long-term effective diffusion coefficient (1.91 ± 0.77 Hz2/s → 1.61 ± 0.61 Hz2/s, P = 0.020) and long-term scaling exponent (0.480 ± 0.013 Hz2/s → 0.471 ± 0.017 Hz2/s, P = 0.014). After fatiguing contraction, mutual information of force fluctuations and SCMUSTs was augmented roughly by 12.95% (P = 0.041). CONCLUSIONS: Muscular fatigue could compress and shift the low-frequency common drive to MUs toward lower spectral bands, thereby enhancing transmission of twitch forces through the muscle-tendon complex with a low-pass filter property. The fatigue-induced changes involve increased closed-loop control of the common modulation of MU discharge rates.