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Observation-based data of primary and secondary organic carbon in ambient particulate matter (PM) are essential for model evaluation, climate and air quality research, health effect assessments, and mitigation policy development. Since there are no direct measurement tools available to quantify primary organic (POC) and secondary organic carbon (SOC) as separate quantities, their estimation relies on inference approaches using relevant measurable PM constituents. In this study, we measured hourly carbonaceous components and major ions in PM2.5 for a year and a half in suburban Hong Kong from July 2020 to December 2021. We differentiated POC and SOC using a novel Bayesian inference approach. The hourly POC and SOC data allowed us to examine temporal characteristics varying from diurnal and weekly patterns to seasonal variations, as well as their evolution characteristics during individual PM2.5 episodes. A total of 65 city-wide PM2.5 episodes were identified throughout the entire study period, with SOC contributions during individual episodes varying from 10 % to 66 %. In summertime typhoon episodes, elevated SOC levels were observed during daytime hours, and high temperature and NOx levels were identified as significant factors contributing to episodic SOC formation. Winter haze episodes exhibited high SOC levels, likely due to persistent influences from regional transport originating from the northern region to the sampling site. Enhanced SOC formation was observed with increase in the nocturnal NO3 radical (indicated by the surrogate quantity of [NO2][O3]) and under conditions characterized by high water content and strong acidity. These results suggest that both NO3 chemistry and acid-catalyzed aqueous-phase reactions likely make notable contributions to SOC formation during winter haze episodes. The methodology employed in this study for estimating POC and SOC provides practical guidance for other locations with similar monitoring capabilities in place. The availability of hourly POC and SOC data is invaluable for evaluating and improving atmospheric models, as well as understanding the evolution processes of PM pollution episodes. This, in turn, leads to more accurate model predictions and a better understanding of the contributing sources and processes.

Cooking organic aerosol (COA) is one of the major constituents of particulate matter in urban areas. COA is oxidized by atmospheric oxidants such as ozone, changing its physical, chemical and toxicological properties. However, atmospheric chemical lifetimes of COA and its tracers such as oleic acid are typically longer than those that have been estimated by laboratory studies. We tackled the issue by considering temperature. Namely, we hypothesize that increased viscosity of COA at ambient temperature accounts for its prolonged atmospheric chemical lifetimes in wintertime. Laboratory-generated COA particles from cooking oil were exposed to ozone in an aerosol flow tube reactor for the temperature range of −20 to 35 °C. The pseudo-second-order chemical reaction rate constants (k2) were estimated from the experimental data by assuming a constant ozone concentration in the flow tube. The estimated values of k2 decreased by orders of magnitude for lower temperatures. The temperature dependence in k2 was fit well by considering the diffusion-limited chemical reaction mechanism. The result suggested that increased viscosity was likely the key factor to account for the decrease in chemical reactivity at the reduced temperature range, though the idea will still need to be verified by temperature-dependent viscosity data in the future. In combination with the observed global surface temperature, the atmospheric chemical lifetimes of COA were estimated to be much longer in wintertime (> 1 h) than in summertime (a few minutes) for temperate and boreal regions. Our present study demonstrates that the oxidation lifetimes of COA particles will need to be parameterized as a function of temperature in the future for estimating environmental impacts and fates of this category of particulate matter.

Oxygenated organic molecules (OOMs) produced by the oxidation of aromatic compounds are key components of secondary organic aerosol (SOA) in urban environments. The steric effects of substitutions and rings and the role of key reaction pathways in altering the OOM distributions remain unclear because of the lack of systematic multi-precursor study over a wide range of OH exposure. In this study, we conducted flow-tube experiments and used the nitrate adduct time-of-flight chemical ionization mass spectrometer (NO3--TOF-CIMS) to measure the OOMs produced by the photooxidation of six key aromatic precursors under low-NOx conditions. For single aromatic precursors, the detected OOM peak clusters show an oxygen atom difference of one or two, indicating the involvement of multi-step auto-oxidation and alkoxy radical pathways. Multi-generation OH oxidation is needed to explain the diverse hydrogen numbers in the observed formulae. In particular, for double-ring precursors at higher OH exposure, multi-generation OH oxidation may have significantly enriched the dimer formulae. The results suggest that methyl substitutions in precursor lead to less fragmented OOM products, while the double-ring structure corresponds to less efficient formation of closed-shell monomeric and dimeric products, both highlighting significant steric effects of precursor molecular structure on the OOM formation. Naphthalene-derived OOMs however have lower volatilities and greater SOA contributions than the other-type of OOMs, which may be more important in initial particle growth. Overall, the OOMs identified by the NO3--TOF-CIMS may have contributed up to 30.0 % of the measured SOA mass, suggesting significant mass contributions of less oxygenated, undetected semi-volatile products. Our results highlight the key roles of progressive OH oxidation, methyl substitution and ring structure in the OOM formation from aromatic precursors, which need to be considered in future model developments to improve the model performance for organic aerosol.

Abstract The transcription factor MYB plays a pivotal role in haematopoietic homoeostasis and its aberrant expression is involved in the genesis and maintenance of acute myeloid leukaemia (AML). We have previously demonstrated that not all AML subtypes display the same dependency on MYB expression and that such variability is dictated by the nature of the driver mutation. However, whether this difference in MYB dependency is a general trend in AML remains to be further elucidated. Here, we investigate the role of MYB in human leukaemia by performing siRNA-mediated knock-down in cell line models of AML with different driver lesions. We show that the characteristic reduction in proliferation and the concomitant induction of myeloid differentiation that is observed in MLL-rearranged and t(8;21) leukaemias upon MYB suppression is not seen in AML cells with a complex karyotype. Transcriptome analyses revealed that MYB ablation produces consensual increase of MAFB expression in MYB-dependent cells and, interestingly, the ectopic expression of MAFB could phenocopy the effect of MYB suppression. Accordingly, in silico stratification analyses of molecular data from AML patients revealed a reciprocal relationship between MYB and MAFB expression, highlighting a novel biological interconnection between these two factors in AML and supporting new rationales of MAFB targeting in MLL-rearranged leukaemias.

Fine particulate matter (PM2.5) remains a major air pollutant of significant public health concern in urban areas. Long-term monitoring data of PM2.5 chemical composition and source-specific tracers provide essential information for the identification of major sources as well as evaluation and planning of control measures. In this study, we present and analyze a 10-year dataset of PM2.5 major components and source-specific tracers (e.g., levoglucosan, hopanes, K+, Ni, V, Al, and Si) collected over the period of 2008–2017 in an urban site in Hong Kong, China. The time series of pollutants were analyzed by the seasonal and trend decomposition using the locally estimated scatter plot smoothing (LOESS) method and general least squares with the autoregressive moving average method. Bulk PM2.5 and all its major components displayed a significant decline of varying degrees over the decade. PM2.5 was reduced by 40 % at −1.5 µgm-3yr-1. PM2.5 components that are predominantly influenced by local vehicular emissions showed the steepest decline, with nitrate decreasing by −66 %, elemental carbon by −60 %, and hopanes by −75 %, confirming effective control of local vehicular emissions. For components that are significantly impacted by regional transport and secondary formation, they had a notably lower percentage reduction, with sulfate declining by −40 % and organic carbon by −23 %, reflecting complexity in their region-wide contributing sources and formation chemistry. Levoglucosan and K+, two tracers for biomass burning, differed in their reduction extent, with K+ at −60 % and levoglucosan at −47 %, indicating they likely track different biomass burning types. Dust components in PM2.5 also decreased, by −37 % for Al and −46 % for Si. The year of 2011 was an anomaly in the overall trend in having higher concentrations of PM2.5 and components than its adjacent years, and the long time series analysis attributed the anomaly to unusually lower rainfall associated with strong La Niña events. This 10-year trend analysis based on measurements exemplifies the utility of chemical composition data in support of an evidence-based approach for control policy formulation.

Characterization of the spatial distributions of air pollutants on an intracity scale is important for understanding local sources, secondary formation, and human exposure. In this study, we conducted in situ mobile measurements for the chemical composition of fine particles, volatile organic compounds (VOCs), oxygenated VOCs (OVOCs), and common gas pollutants in winter in the megacity of Beijing. The spatial patterns of these pollutants under different pollution conditions were investigated. During the non-haze days all pollutants showed significant spatial variability. Large spatial variations of secondary species including OVOCs and secondary aerosol species highlight the chemical heterogeneity. In particular, the inorganic chemical composition of fine particles varied greatly on the 65 km urban highway, suggesting a wide range of particle neutralization in the megacity of Beijing. Localized sources such as vehicle, cooking, and industrial emissions led to hot spots and nonuniform distributions of primary pollutants in the city. The spatial heterogeneity of air pollutants under less polluted conditions calls for a future need of using fine-resolution models to evaluate human exposure and to develop pollution control strategies. During the haze day the spatial variabilities of secondary gaseous and particulate pollutants were largely reduced, explained by both the elevated urban background of the polluted air mass and the enhanced secondary formation by elevated precursor concentrations and heterogeneous or aqueous pathways. Although localized primary emissions were accumulated under stagnant haze conditions, the chemical composition of fine particles became relatively homogeneous because of the predominant secondary contributions. A uniform spatial pattern of particle neutralization was observed. The concentrations of hydrocarbons and less oxygenated OVOCs showed good positive spatiotemporal correlations during the haze day, while the concentrations of more oxygenated OVOCs showed good positive correlations among themselves but moderate negative correlations with the concentrations of hydrocarbons, less oxygenated OVOCs, and aerosol species. Our results indicate a spatial chemical homogeneity on the megacity scale to promote efficient secondary organic aerosol (SOA) production under haze conditions.

Graph-based deep learning has been proved a promising approach that has an apparent superiority for learning graph data and modeling spatial topological relations between features. In particular, graph attention networks (GATs) are good at efficiently processing the graph-structured hyperspectral data by leveraging masked self-attention layers to address the known shortcomings of previous frameworks based on graph convolutions or their approximations. In this study, we proposed a novel approach that combines localized spectral filtering and GAT for the hyperspectral image classification task. First, we conducted unsupervised t-SNE (t-distributed stochastic neighbor embedding) manifold learning-based feature dimensionality reduction to create localized hyperspectral data cubes. Then, these feature cubes combined with localized adjacent matrices were fed into a shallow graph attention network in a supervised learning manner. Finally, we obtained credible classification results and promising classification performance in distinguishing diversified land covers through reducing the possible redundancy of spectral information and enhancing the expression of local spatial-spectral information. Experiments on two real hyperspectral data sets (that is, Indian Pines-A (IA) and Huanghekou (HH) data sets) demonstrated that the presented approach offers promising classification performance, that is, the GAT using t-SNE acquires superior performance than that of using PCA (principal component analysis), and also proves the great importance of combining spatial- and spectral information for hyperspectral image classification.

The saturated hydraulic conductivity (Ksat) is a key soil hydraulic property governing agricultural production. However, the influence of the conversion from the conventional tillage (CT) to conservation tillage (CS; including no tillage, NT, and reduced tillage, RT) on the Ksat of soils is not well understood and still debated. In this study, we applied a global meta-analysis method to synthesize 227 paired observations for soil Ksat from 69 published studies and investigated factors influencing the effects of conversion to CS on Ksat. Results showed that soil layer, conservation tillage type, soil texture type, and cropping system management did not have significant effects on the influence of conversion to CS on Ksat. When the Ksat was measured by the rainfall simulator, the conversion to CS significantly (p) increased the surface and subsurface soil Ksat by 41.7 % and 36.9 %, respectively. In addition, the subsurface Ksat also tended to increase under CS practices when the Ksat was measured by a tension disc infiltrometer. However, when the Ksat was measured by a hood infiltrometer, ring infiltrometer, constant/falling head, and Guelph permeameter, the conversion to CS had no significant effects on the Ksat. It is observed that, when the conversion period was less than 15 years, the Ksat under CS showed a greater increase for a longer conversion period. Climatic and topographic factors, including the mean annual temperature (MAT) and the mean annual precipitation (MAP), were statistically related to the responses of Ksat to tillage conversion at the global scale. Quadratic polynomials can describe the relationships between them. These findings suggested that quantifying the effects of tillage conversion on soil Ksat needed to consider experimental conditions, especially the measurement technique and conversion period.

Organic aerosol (OA) is a major component of tropospheric submicron aerosol that contributes to air pollution and causes adverse effects on human health. Chemical transport models have difficulties in reproducing the variability in OA concentrations in polluted areas, hindering understanding of the OA budget and sources. Herein, we apply both process-based and observation-constrained schemes to simulate OA in GEOS-Chem. Comprehensive data sets of surface OA, OA components, secondary organic aerosol (SOA) precursors, and oxidants were used for model–observation comparisons. The base models generally underestimate the SOA concentrations in China. In the revised schemes, updates were made on the emissions, volatility distributions, and SOA yields of semivolatile and intermediate-volatility organic compounds (SVOCs and IVOCs) and additional nitrous acid sources. With all the model improvements, both the process-based and observation-constrained SOA schemes can reproduce the observed mass concentrations of SOA and show spatial and seasonal consistency with each other. Our best model simulations suggest that anthropogenic SVOCs and IVOCs are the dominant source of SOA, with a contribution of over 50 % in most of China, which should be considered for pollution mitigation in the future. The residential sector may be the predominant source of SVOCs and IVOCs in winter, despite large uncertainty remaining in the emissions of IVOCs from the residential sector in northern China. The industry sector is also an important source of IVOCs, especially in summer. More SVOC and IVOC measurements are needed to constrain their emissions. Besides, the results highlight the sensitivity of SOA to hydroxyl radical (OH) levels in winter in polluted environments. The addition of nitrous acid sources can lead to over 30 % greater SOA mass concentrations in winter in northern China. It is important to have good OH simulations in air quality models.

The nitrogen-15 (15N) natural abundance composition (δ15N) in soils or plants is a useful tool to indicate the openness of ecosystem N cycling. This study aimed to evaluate the influence of the experimental warming on soil and plant δ15N. We applied a global meta-analysis method to synthesize 79 and 76 paired observations of soil and plant δ15N from 20 published studies, respectively. Results showed that the mean effect sizes of the soil and plant δ15N under experimental warming were −0.524 (95 % CI (confidence interval): −0.987 to −0.162) and 0.189 (95 % CI: −0.210 to 0.569), respectively. This indicated that soil δ15N had negative response to warming at the global scale, where warming had no significant effect on plant δ15N. Experimental warming significantly (p) decreased soil δ15N in Alkali and medium-textured soils, in grassland/meadow, under air warming, for a 4–10-year warming period and for an increase of >3 ∘C in temperature, whereas it significantly (p) increased soil δ15N in neutral and fine-textured soils and for an increase of 1.5–3 ∘C in temperature. Plant δ15N significantly (p) increased with increasing temperature in neutral and fine-textured soils and significantly (p) decreased in alkali soil. Latitude did not affect the warming effects on both soil and plant δ15N. However, the warming effect on soil δ15N was positively controlled by the mean annual temperature, which is related to the fact that the higher temperature can strengthen the activity of soil microbes. The effect of warming on plant δ15N had weaker relationships with environmental variables compared with that on soil δ15N. This implied that soil δ15N was more effective than plant δ15N in indicating the openness of global ecosystem N cycling.

Oxidation of aromatic volatile organic compounds (VOCs) leads to the formation of tropospheric ozone and secondary organic aerosol, for which gaseous oxygenated products are important intermediates. We show, herein, the experimental results of highly oxygenated organic molecules (HOMs) produced by the oxidation of benzene and toluene in a wide range of OH exposure and NOx conditions. The results suggest that multigeneration OH oxidation plays an important role in the product distribution, which likely proceeds more preferably via H subtraction than OH addition for early generation products from light aromatics. More oxygenated products present in our study than in previous flow tube studies, highlighting the impact of experimental conditions on product distributions. The formation of dimeric products, however, was suppressed and might be unfavorable under conditions of high OH exposure and low NOx in toluene oxidation. Under high-NOx conditions, nitrogen-containing multifunctional products are formed, while the formation of other HOMs is suppressed. Products containing two nitrogen atoms become more important as the NOx level increases, and the concentrations of these compounds depend significantly on NO2. The highly oxygenated nitrogen-containing products might be peroxyacyl nitrates, implying a prolonged effective lifetime of RO2 that facilitates regional pollution. Our results call for further investigation on the roles of high-NO2 conditions in the oxidation of aromatic VOCs.

As critical precursors of ozone (O3) and secondary organic aerosols, volatile organic compounds (VOCs) play a vital role in air quality, human health, and climate change. In this study, a campaign of comprehensive field observations and VOC grid sampling was conducted in Xi'an, China, from 20 June to 20 July 2019 to identify the spatiotemporal concentration levels, sources, and secondary transformation potential of VOCs. During the observation period, the average VOC concentrations at the Chanba (CB), Di Huan Suo (DHS), Qinling (QL), and gridded sampling sites were 27.8 ± 8.9, 33.8 ± 10.5, 15.5 ± 5.8, and 29.1 ± 8.4 ppb, respectively. Vehicle exhaust was the primary source of VOC emissions in Xi'an, and the contributions of vehicle exhaust to VOCs at the CB, DHS, and QL sites were 41.3 %, 30.6 %, and 23.6 %–41.4 %, respectively. While industrial emissions were the second-largest source of VOCs in urban areas, contributions from aging sources were high in rural areas. High potential source contribution function values primarily appeared in eastern and southern Xi'an near the sampling site, which indicates that Xi'an exhibits a strong local VOC source. Moreover, alkenes, aromatics, and oxygenated VOCs played a dominant role in secondary transformation, which is a major concern in reducing O3 pollution in Xi'an.

A new capture vaporizer (CV) has been developed and used recently in the Aerodyne aerosol mass spectrometer (AMS) and aerosol chemical speciation monitor (ACSM) instead of the standard vaporizer (SV) to reduce the particle bounce. It is important to characterize the CV performance in different environments. In this study, we characterized specific organic aerosols (OAs) from vehicle, cooking, biomass burning, and coal burning emissions by a time-of-flight ACSM (TOF-ACSM) with the CV. Their corresponding marker ions that have been defined in the previous SV-based analysis are still valid in the CV mass spectra. Spectra of OAs from cooking and vehicle exhaust show similarities in distinct alkyl fragments but different ratios of m∕z 55 and 57. Ions related to polycyclic aromatic hydrocarbons are present in the OA spectra obtained from burning lignite and bituminous coal but not in the spectra obtained from burning anthracite. Although the relative intensities of m∕z 60 and 73 are much lower in the CV spectra than in the SV spectra for biomass burning OA, they are still relatively greater compared with the spectra for other sources. Our data suggest an atmospheric background of f60 of below 0.03 % for CV. Moreover, we deployed the CV TOF-ACSM along with a SV AMS in urban Beijing during the winter of 2017 to characterize ambient OA with strong anthropogenic influences. The CV TOF-ACSM shows a collection efficiency (CE) of about unity. The CV and SV data show consistent mass concentrations of sulfate, nitrate, ammonium, and OA. Six OA factors are identified by the positive matrix factorization (PMF) analysis for both the CV and the SV data. The SV and CV PMF factors show good correlations in mass concentrations. The SV and CV factors related to coal combustion and cooking differ significantly in loadings, explained by the PMF uncertainty and the lack of understanding of the relative ionization efficiency and CE for primary OA. The CV factors related to secondary sources show greater loadings than the SV factors, which may be associated with the changes in signal-to-noise ratios of various ions in the PMF analysis. Our results support improved mass quantification and useful source identification by the CV for ambient particles in the polluted urban environment. The difference in factor loadings between SV and CV should be considered when interpreting or comparing the PMF results among studies.

Superconducting rf cavities are used in particle accelerators to provide energy to the particle beam. Such cavities are mostly fabricated in niobium and often operated in superfluid helium. One of their limits of operation is the appearance of a local quench, initiated by a local field enhancement due to a defect, which leads to a normal conducting transition of the cavity. Localizing the quench area can be achieved with temperature mapping systems. Another method is the use of second sound wave propagation in superfluid helium. Measuring the time of propagation of these waves from quench location to special sensors, called oscillating superleak transducers (OSTs), and using their well-known velocity should allow trilateration. However, most of the experimental measurements on cavities show premature signals, i.e., the second sound signals arrive earlier on the OSTs than expected. This paper presents several quench experiments on cavities equipped with OSTs and temperature mapping quench detection systems. Two hypotheses can explain the observed premature signals. The first one assesses faster propagation in helium. An experimental setup has been developed for testing this hypothesis, where second sound is created by a localized heater in a controlled environment up to 4.3 kW/cm^{2} and 2.8 J. Premature signals could not be verified in this setup. A second hypothesis based on a simple model including several processes in niobium and second sound propagation in helium is discussed. The model improves significantly the prediction of the times of arrival of the second sound waves. The overall study shows that the processes in niobium play a prominent role in the second sound detection for superconducting cavities.

The systematic study related to the interactions between a Stone-Wales (SW) defect pair in axially loaded single-walled carbon nanotubes (SWCNTs) is presented. The results provide insight into the defect-defect interactions quantified by the bond with the highest energy which varies in magnitude with respect to the interdefect distance.

Sawtooth oscillations in tokamaks are defined by their effect on electron temperature: a rapid flattening of the core profile followed by an outward heat pulse and a slow core recovery caused by central heating. Recent high-resolution, multi-chord interferometer measurements on JTEXT extend these studies to particle transport. Sawteeth only partially flatten the core density profile, but enhanced particle diffusion on the time scale of the thermal crash occurs over much of the profile, relevant for impurities. Recovery between crashes implies an inward pinch velocity extending to the center. [ABSTRACT FROM AUTHOR]

A refined molecular life prediction scheme for single-walled carbon nanotubes (SWCNTs), taking into consideration C-C bond rotation and preexisting strain under me-chanical loads, is proposed. The time-dependent fracture behavior of 12 different cases of zigzag (18,0) SWCNT, each embedded with either a single Stone-Wales (SW) defect of different types or two interacting or noninteracting defects, is studied under axially applied tensile load. It is shown that the patterns of atomistic crack propagation and fa-tigue lives of SWCNTs are influenced by the type and orientation of the SW defect(s), inter-defect distance, as well as the magnitude of externally applied stress. For SWCNTs with two SW defects, if the inter-defect distance is within the so called indifference length, defect-defect interaction does exist, and it has pronounced effects on diminishing the lives of the nanotubes. Also, the defect-defect interaction is stronger at shorter inter-defect dis-tance, resulting in shorter fatigue lives. [ABSTRACT FROM AUTHOR]

Imide-containing siloxane-urethane copolymers (1-PU copolymers) were synthesized from 4,4'-diphenylmethane diisocyanate (MDI), OH-terminated polydimethylsiloxane (PDMS) and pyromellitic dianhydride (PMDA). The hard segment consisted of urethane and imide segments and the soft segment was PDMS. The DSC of 1-PU copolymers suggests that they had a high degree of phase separation in their low hard segment contents and phase mixing in high hard segment contents. DMA indicates similar phase behaviour and shows that incorporating imide segments into the copolymers can maintain the high modulus at high temperature. The progress of degradation of I-PU copolymers was determined by TGA and standard kinetics methods and there were three stages at around 250∼425 °C, 425∼560 °C and 560∼700 °C, respectively. The first stage was dominated by the hard-segment structure and content. Incorporating imide segments into PU raises the characteristic temperatures of degradation in the first stage. The second stage resulted from the degradation of the PDMS soft segment to form oligomers by the interchange reaction. The degradation of the imide segment leads to the third stages because the maximum rate of degradation in DTG curves increases with the imide content. [ABSTRACT FROM AUTHOR]

The binding of thyroid hormone to the thyroid hormone receptor (TR) mediates important physiological effects. However, the transcriptional effects of TR mediated by the thyroid response element (TRE) cannot explain many actions of thyroid hormone. We postulate that TR can initiate rapid, non-TRE-mediated effects in the cardiovascular system through cross-coupling to the phosphatidylinositol 3-kinase (PI3-kinase)/protein kinase Akt pathway. In vascular endothelial cells, the predominant TR isoform is TRy1. Treatment of endothelial cells with ʟ-3,S,3′-triiodothyronine (T3) increased the association of TRα1 with the p85α subunit of PI3-kinase, leading to the phosphorylation and activation of Akt and endothelial nitric oxide synthase (eNOS). The activation of Akt and eNOS by T3 was abolished by the PI3-kinase inhibitors, LY294002 and wortmannin, but not by the transcriptional inhibitor, actinomycin D. To determine the physiological relevance of this PI3-kinase/Akt pathway, we administered T3 to mice undergoing transient focal cerebral ischemia. Compared with vehicle, a single bolus infusion of T3 rapidly increased Akt activity in the brain, decreased mean blood pressure, reduced cerebral infarct volume, and improved neurological deficit score. These neuroprotective effects of T3 were greatly attenuated or absent in eNOS-/- and TRα1-/-β-/- mice and were completely abolished in WT mice pretreated with LY294002 or a T3 antagonist, NH-3. These findings indicate that the activation of PI3-kinase/Akt pathways can mediate some of the rapid, non-TRE effects of TR and suggest that the activation of Akt and eNOS contributes to some of the acute vasodilatory and neuroprotective effects of thyroid hormone. [ABSTRACT FROM AUTHOR]

Background: Many determinants for a sustained response to lamivudine therapy have been reported but the role of I cell responsiveness remains unclear. The finding that lyrosine-methionine-aspartate-aspartate (YMDD) motif of the reverse transcriptase domain of hepatitis B virus (HBV) DNA polymerase carries a HLA-A2 restricted cytotoxic T lymphocyte (CII) epitope makes quantitative measurement of the numbers of peptide specific CTLs feasible using MHC tetramer-peptide complex staining. Aim: To investigate the correlation between anti-YMDD motif CTL activity and the efficacy of lamivudine therapy in HLA-A2 positive patients with chronic hepatitis B (CH-B). Methods: The function and phenotype of peptide and interleukin 2 expanded peripheral blood mononuclear cells were quantified by cell lytic assay and immunocytochemical analysis by staining with HLA-A2-peptide tetramer complexes. Results: After in vitro expansion, sustained responders had more potent CL responses against YMDD, YVDD, and YIDD, as well as other epitopes on I-IBV antigens than non-responders. The frequency of YMDD/YVDD/YIDD motif specific CTLs increased significantly with an effective cell lytic function during and after therapy in sustained responders but not in non-responders. YMDD specific CILs cross reacted with YIDD and YVDD mutant epitopes, and shared T cell receptor gene usages with YIDD and YYDD specific CTLs. Conclusions: Sustained responders, at least HLA-A2 patients, elicited a more potent CL immunity against YMDD and its mutants. YMDD specific CTLs are cross reactive with YVDD and YIDD mutant epitopes, which may further contribute to immune clearance of the mutant viruses and a successful response to lamivudine therapy in CH-B patients. [ABSTRACT FROM AUTHOR]

Objective: Minimally invasive mitral valve surgery (mini-MVS) is typically reserved for patients who have not undergone open cardiac surgery. In the reoperative setting, using intrapericardial dissection for crossclamping the aorta through a minimally invasive approach can be difficult and, at times, risky. Cold fibrillatory cardiac arrest (CFCA) with systemic cardiopulmonary bypass without cross-clamping is a well-described technique; however, data about its safety for patients who undergo reoperative mini-MVS are limited. Methods: Data for 34 patients who underwent reoperative mini-MVS with CFCA from March 2017 to March 2022 were reviewed retrospectively. A mini right thoracotomy (n = 30) or robotic (n = 4) approach was used. Systemic hypothermia was induced to a target temperature of 25 °C. Results: Patient mean (SD) age was 64.5 (9.6) years, and 15 of 34 (44.1%) patients were women. Of those 34 patients, 23 (67.6%) had severe regurgitation, and 11 (32.4%) had severe stenosis. Before mini-MVS, 28 patients had undergone valve surgery, and 8 had undergone coronary artery bypass graft surgery. The mitral valve was repaired in 5 of 34 (14.7%) and replaced in 29 of 34 (85.3%) patients. No difference was observed in preoperative and postoperative left ventricular function (P = .82). In 1 patient, kidney failure developed that necessitated dialysis. No postoperative stroke or mortality at 30 days occurred. Conclusion: Mini-MVS with CFCA is well tolerated in patients with prior cardiac surgery. Myocardial function was not impaired, nor was the risk of stroke increased in this cohort, indicating that CFCA is a safe alternative in this high-risk population.

Abstract Predicting the blood–brain barrier (BBB) permeability of small-molecule compounds using a novel artificial intelligence platform is necessary for drug discovery. Machine learning and a large language model on artificial intelligence (AI) tools improve the accuracy and shorten the time for new drug development. The primary goal of this research is to develop artificial intelligence (AI) computing models and novel deep learning architectures capable of predicting whether molecules can permeate the human blood–brain barrier (BBB). The in silico (computational) and in vitro (experimental) results were validated by the Natural Products Research Laboratories (NPRL) at China Medical University Hospital (CMUH). The transformer-based MegaMolBART was used as the simplified molecular input line entry system (SMILES) encoder with an XGBoost classifier as an in silico method to check if a molecule could cross through the BBB. We used Morgan or Circular fingerprints to apply the Morgan algorithm to a set of atomic invariants as a baseline encoder also with an XGBoost classifier to compare the results. BBB permeability was assessed in vitro using three-dimensional (3D) human BBB spheroids (human brain microvascular endothelial cells, brain vascular pericytes, and astrocytes). Using multiple BBB databases, the results of the final in silico transformer and XGBoost model achieved an area under the receiver operating characteristic curve of 0.88 on the held-out test dataset. Temozolomide (TMZ) and 21 randomly selected BBB permeable compounds (Pred scores = 1, indicating BBB-permeable) from the NPRL penetrated human BBB spheroid cells. No evidence suggests that ferulic acid or five BBB-impermeable compounds (Pred scores

Homogeneous dispersion of carbon nanotubes (CNTs) throughout the polymer matrix and their adequate interfacial bonding are critical for load transfer in CNT-polymer composites. However, both cannot be realized simultaneously by either covalent or noncovalent functionalization. A hybrid system integrating both covalent and noncovalent functionalizations is presented for interfacial design of CNT-polymer composites. To investigate the feasibility of this system, examples of the epoxidized single-walled carbon nanotube (SWNT) subsequently wrapped by poly(m-phenylenevinylene- co-2,5-dioctyloxy-p-phenylenevinylene) (PmPV) are studied by means of molecular dynamics simulations. It is shown by our results that PmPV molecules are miscible with epoxy resin and tend to wrap around the epoxidized SWNT, which could be used to weaken the interaction between SWNTs and consequently improve the dispersion of SWNTs into the matrix. The interfacial shear strength of CNT-polymer composites can be improved significantly by properly designed functionalizations, especially the hybrid system. [ABSTRACT FROM AUTHOR]

Recently, indoor positioning becomes a popular issue because of its corresponding location-aware applications. Owing to the limits of the sheltered signal of satellites in indoor environments, one of the alternative scheme is Bluetooth Low Energy (BLE) technology. BLE device broadcasts Received Signal Strength Indicator (RSSI) for distance estimation and further positioning. However, in the complex indoor environment, the reflection, fading, and multipath effect of BLE make the variable RSSI and may lead to poor quality of RSSI. In this study, the concept called Differential Distance Correction (DDC) is similar to the Differential Global Navigation Satellite System (DGNSS). This method can eliminate some residuals and further improve the results with the corrected distance. On the other hand, Pedestrian Dead Reckoning (PDR) is another common indoor positioning method. PDR can propagate the next position from the current position by the implemented of inertial sensors. Despite that, the error of inertial sensors would accumulate with time and walking distance, which position update is required for restraining the drift. Accordingly, the two indoor positioning methods have their strong and weak point. BLE-based positioning is absolute positioning, while PDR is relative positioning. This study proposes a concept that combines the two methods. The pedestrian receives the RSSI and records the information from inertial sensors simultaneously. Through the complementary of two methods, the positioning results would be improved from 29% to 66% according to different travelled distance.

Hypoxia-inducible factors (HIFs) are the master regulators of angiogenesis, a process that is impaired in patients with diabetes mellitus (DM). The transcription factor aryl hydrocarbon receptor nuclear translocator (ARNT, also known as HIF1β) has been implicated in the development and progression of diabetes. Angiogenesis is driven primarily by endothelial cells (ECs), but both global and EC-specific loss of ARNT-cause are associated with embryonic lethality. Thus, we conducted experiments in a line of mice carrying an inducible, EC-specific ARNT-knockout mutation (ArntΔEC, ERT2) to determine whether aberrations in ARNT expression might contribute to the vascular deficiencies associated with diabetes. Mice were first fed with a high-fat diet to induce diabetes. ArntΔEC, ERT2 mice were then adminstrated with oral tamoxifen to disrupt Arnt and peripheral angiogenesis was evaluated by using laser-Doppler perfusion imaging to monitor blood flow after hindlimb ischemia. The ArntΔEC, ERT2 mice had impaired blood flow recovery under both non-diabetic and diabetic conditions, but the degree of impairment was greater in diabetic animals. In addition, siRNA-mediated knockdown of ARNT activity reduced measurements of tube formation, and cell viability in human umbilical vein endothelial cells (HUVECs) cultured under high-glucose conditions. The ArntΔEC, ERT2 mutation also reduced measures of cell viability, while increasing the production of reactive oxygen species (ROS) in microvascular endothelial cells (MVECs) isolated from mouse skeletal muscle, and the viability of ArntΔEC, ERT2 MVECs under high-glucose concentrations increased when the cells were treated with an ROS inhibitor. Collectively, these observations suggest that declines in endothelial ARNT expression contribute to the suppressed angiogenic phenotype in diabetic mice, and that the cytoprotective effect of ARNT expression in ECs is at least partially mediated by declines in ROS production.

Indoor positioning has attracted much attention in recent years due to the trend of Internet of Things (IoT), which is capable of providing numerous applications such as personal tracking, vehicle locator, and Location-Based Service (LBS). To put LBS into practice, positioning and navigation are one of the necessary techniques. Using the smartphone to process indoor positioning also become more and more usual. The most common algorithm in the inertial navigation system is Pedestrian Dead Reckoning (PDR), utilizing sensors built-in the smartphones to conquer the strait of GNSS-denied environment. However, for the purpose of eliminating the error accumulated with time, PDR combining with other algorithms, for instance, updating some geospatial information steadily is a better way to solve this problem. Therefore, this research proposes the imaged based aided algorithm. Moreover, in this study, a novel Artificial Neural Networks (ANN) embedded the system is proposed. The self-designed georeferenced markers and the indoor floor plan will be produced by an Indoor Mobile Mapping System (IMMS) in advance. This research proposed using Cascade-Correlation neural Network (CCN) to estimate the distance between the marker and the smartphone camera. The accuracy using this method can achieve to 0.27 meter. As if at least three coordinates and the distance can be obtained simultaneously, the position of the user can be calculated by the trilateration method. From the experiment, the accuracy of the positioning is about 0.5 meter. This way seems to have the high potential to bring into play on the real-time indoor positioning.

Abstract Charles Darwin viewed eyes as the epitome of evolution by natural selection, describing them as organs of extreme perfection and complication. The visual system is therefore fertile ground for teaching fundamental concepts in optics and biology, subjects with scant representation during the rise and spread of immersive technologies in K-12 education. The visual system is an ideal topic for three-dimensional (3D) virtual reality learning environments (VRLEs), and here we describe a 3D VRLE that simulates the vision of a tarsier, a nocturnal primate that lives in southeast Asia. Tarsiers are an enduring source of fascination for having enormous eyes, both in absolute size and in proportion to the size of the animal. Our motivation for developing a tarsier-inspired VRLE, or Tarsier Goggles, is to demonstrate the optical and selective advantages of hyperenlarged eyes for nocturnal visual predation. In addition to greater visual sensitivity, users also experience reductions in visual acuity and color vision. On a philosophical level, we can never know the visual world of another organism, but advances in 3D VRLEs allow us to try in the service of experiential learning and educational outreach.

Background Regulator of G‐protein signaling 5 (RGS5) is a negative modulator of G‐protein–coupled receptors. The role of RGS5 in brain endothelial cells is not known. We hypothesized that RGS5 in brain microvascular endothelial cells may be an important mediator of blood‐brain barrier function and stroke severity after focal cerebral ischemia. Methods and Results Using a transient middle cerebral artery occlusion model, we found that mice with global and endothelial‐specific deletion of Rgs5 exhibited larger cerebral infarct size, greater neurological motor deficits, and increased brain edema. In our in vitro models, we observed increased Gq activity and elevated intracellular Ca2+ levels in brain endothelial cells. Furthermore, the loss of endothelial RGS5 leads to decreased endothelial NO synthase expression and phosphorylation, relocalization of endothelial tight junction proteins, and increased cell permeability. Indeed, RGS5 deficiency leads to increased Rho‐associated kinase and myosin light chain kinase activity, which were partially reversed in our in vitro model by pharmacological inhibition of Gq, metabotropic glutamate receptor 1, and ligand‐gated ionotropic glutamate receptor. Conclusions Our findings indicate that endothelial RGS5 plays a novel neuroprotective role in focal cerebral ischemia. Loss of endothelial RGS5 leads to hyperresponsiveness to glutamate signaling pathways, enhanced Rho‐associated kinase– and myosin light chain kinase–mediated actin‐cytoskeleton reorganization, endothelial dysfunction, tight junction protein relocalization, increased blood‐brain barrier permeability, and greater stroke severity. These findings suggest that preservation of endothelial RGS5 may be an important therapeutic strategy for maintaining blood‐brain barrier integrity and limiting the severity of ischemic stroke.

OBJECTIVE:Rho-associated kinase (ROCK) signaling pathway has been shown to mediate various cellular functions including cell proliferation, migration, adhesion, apoptosis, and contraction, all of which may be involved in pathogenesis of atherosclerosis. Endogenous nitric oxide (NO) is well known to have an anti-atherosclerotic effect, whereas the exogenous NO-mediated cardiovascular effect still remains controversial. The purpose of this study was to evaluate the effect of exogenous NO on ROCK activity in vascular smooth muscle cells (VSMCs) in vitro and in vivo. METHODS:VSMCs migration was evaluated using a modified Boyden chamber assay. ROCK activities were measured by Western blot analysis in murine and human VSMCs and aorta of mice treated with or without angiotensin II (Ang II) and/or sodium nitroprusside (SNP), an NO donor. RESULTS:Co-treatment with SNP inhibited the Ang II-induced cell migration and increases in ROCK activity in murine and human VSMCs. Similarly, the increased ROCK activity 2 weeks after Ang II infusion in the mouse aorta was substantially inhibited by subcutaneous injection of SNP. CONCLUSIONS:These findings suggest that administration of exogenous NO can inhibit ROCK activity in VSMCs in vitro and in vivo.

Dietary long-chain fatty acids (FA) may influence pathological processes involving endothelial activation, including inflammation and atherosclerosis. We have previously shown that the n–3 FA docosahexaenoate (DHA) inhibits endothelial activation in the range of nutritionally achievable plasma concentrations. The present study assessed structural determinants for this effect. Saturated, monounsaturated, and n–6 and n–3 polyunsaturated FA were incubated with cultured endothelial cells for 24–72 h alone, and then in the presence of interleukin-1, tumor necrosis factor, or bacterial lipopolysaccharide for an additional 24 h before assessing the expression of the vascular cell adhesion molecule-1 (VCAM-1) or other products of endothelial activation. No FA tested per se elicited endothelial activation. While saturated FA did not inhibit cytokine-induced expression of adhesion molecules, a progressively increasing inhibitory activity was observed, for the same chain length, with an increase in double bonds. Comparison of FA with the same length and number of unsaturation and only differing for the double bond position or for the cis/ trans configuration indicated no difference in inhibitory potency, indicating no effect of the double bond position or configuration. As judged by Northern analysis, these latter FA also inhibited VCAM-1 messenger RNA steady state levels to the same extent, indicating a pre-translational site of action attributable to the single double bond. Thus the double bond is the minimum necessary and sufficient requirement for FA inhibition of endothelial activation. These properties are likely relevant to the anti-atherogenic and anti-inflammatory properties ascribed to n–3 FA, which are able to accommodate the highest number of double bonds in a fatty acid of given chain length.—De Caterina, R., W. Bernini, M. A. Carluccio, J. K. Liao, and P. Libby. Structural requirements for inhibition of cytokine-induced endothelial activation by unsaturated fatty acids. J. Lipid Res. 1998. 39: 1062–1070.

Birt-Hogg-Dube (BHD) is a tumor suppressor gene syndrome associated with fibrofolliculomas, cystic lung disease, and chromophobe renal cell carcinoma. In seeking to elucidate the pathogenesis of BHD, we discovered a physical interaction between folliculin (FLCN), the protein product of the BHD gene, and p0071, an armadillo repeat containing protein that localizes to the cytoplasm and to adherens junctions. Adherens junctions are one of the three cell-cell junctions that are essential to the establishment and maintenance of the cellular architecture of all epithelial tissues. Surprisingly, we found that downregulation of FLCN leads to increased cell-cell adhesion in functional cell-based assays and disruption of cell polarity in a three-dimensional lumen-forming assay, both of which are phenocopied by downregulation of p0071. These data indicate that the FLCN-p0071 protein complex is a negative regulator of cell-cell adhesion. We also found that FLCN positively regulates RhoA activity and Rho-associated kinase activity, consistent with the only known function of p0071. Finally, to examine the role of Flcn loss on cell-cell adhesion in vivo, we utilized keratin-14 cre-recombinase (K14-cre) to inactivate Flcn in the mouse epidermis. The K14-Cre-Bhd(flox/flox) mice have striking delays in eyelid opening, wavy fur, hair loss, and epidermal hyperplasia with increased levels of mammalian target of rapamycin complex 1 (mTORC1) activity. These data support a model in which dysregulation of the FLCN-p0071 interaction leads to alterations in cell adhesion, cell polarity, and RhoA signaling, with broad implications for the role of cell-cell adhesion molecules in the pathogenesis of human disease, including emphysema and renal cell carcinoma.

Determining the distribution trends, transport mechanisms, and ecological risks of heavy metals (HMs) in urban river sediments is essential for the government to conduct appropriate remediation work. In this study, we collected sediment cores from the Yayao Waterway in Foshan City, China. The vertical distribution profiles of dissolved and labile Fe, Mn, Cd, Zn, Cu, Cr, Ni, Pb, As, and Co in the sediments were obtained using the thin-film diffusive gradient (DGT) and high-resolution peeper (HR-Peeper) techniques. In addition, the transport rates, contamination levels, and ecological concerns of the HMs were evaluated using the European Community Bureau of Reference (BCR) sequential extraction technique, the DGT-induced sediment fluxes (DIFS) model, and multiple contamination evaluation metrics. The results showed that most of the DGT-labile HMs were associated with Fe/Mn (hydrogen) oxides, and in particular, Zn, Ni, and Cr showed a significant negative correlation with Fe/Mn (p < 0.001). Additionally, Cd had the highest bioavailability (89.17%), and its net diffusive flux at the sediment-water interface (SWI) was positive, which indicated a high release risk from the sediment. However, the R-value of Cd based on the DGT-induced sediment fluxes (DIFS) operation was extremely low, suggesting that although Cd had the biggest supply pool of releases, its release rate was slow. The majority of sampling sites had significantly higher total HM contents in the surface sediments than the background values. The HM contamination in the sediments originated from human activities, primarily from industrial enterprises and with a large contribution from both agricultural and domestic sources. The most polluted HM with the highest ecological danger was Cd, followed by Cu, Zn, Ni, and As when the results of the four pollution evaluation indicators were combined. Consequently, the risk of contamination by HMs in inner-city river sediments should receive more attention., 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 Elsevier Ltd. All rights reserved.)

It is the ultimate goal of this work to foster synergy between quantum chemistry and the flourishing field of quantum information theory. For this, we first translate quantum information concepts, such as entanglement and correlation, into the context of quantum chemical systems. In particular, we establish two conceptually distinct perspectives on 'electron correlation', leading to a notion of orbital and particle correlation. We then demonstrate that particle correlation equals total orbital correlation minimized over all orbital bases. Accordingly, particle correlation resembles the minimal, thus intrinsic, complexity of many-electron wave functions, while orbital correlation quantifies their complexity relative to a basis. We illustrate these concepts of intrinsic and extrinsic correlation complexity in molecular systems, which also manifests the crucial link between the two correlation pictures. Our results provide theoretical justification for the long-favored natural orbitals for simplifying electronic structures, and open new pathways for developing more efficient approaches towards the electron correlation problem.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) is rapidly becoming a major threat to hospitalized children worldwide. The purpose of this study was to summarize etiological characteristics and identify risk factors relevant to CRE bloodstream infection (BSI) and short-term mortality among pediatric patients in China., Methods: In this study, we included 370 inpatients ≤17 years old with BSI caused by Enterobacteriaceae in China from January 2013 to December 2022. By collecting data on demographics, etiological features, and clinical outcomes, we conducted an in-depth analysis., Results: Among the 370 BSI patients with infections caused by Enterobacteriaceae , 35 patients (9.46%) were caused by CRE. Among these CRE strains, Klebsiella pneumoniae (49.46%) was the most important pathogen of BSI in pediatric patients, followed by Escherichia coli (31.62%) and Enterobacter cloacae (5.95%). The most frequent carbapenemase was NDM (23/35, 65.71%), followed by KPC (8/35, 22.86%). The overall 28-day mortality rate of children with an Enterobacteriaceae BSI episode was 1.89% (7/370), of which CRE BSI patients (3/35, 8.57%) were significantly higher than CSE patients (4/335, 1.19%, P < 0.001). Congenital malformation (OR: 8.162, 95% CI: 3.859-16.680, P < 0.001) and catheter-related (OR: 6.645, 95% CI: 3.159-13.28, P: <0.001) were associated with the development of CRE BSI in pediatric patients. A multivariate analysis showed that the infection of CRE (OR 7.758, 95% CI 1.869-29.62, P = 0.021) were independent risk factors for 28-day mortality of Enterobacteriaceae BSI. When the MIC of any carbapenems was ≥8 μg/mL, the mortality rate in the ICU was higher (P < 0.05)., Conclusion: Congenital malformation, previous cephalosporin/carbapenems administration, and catheter-related conditions were closely related to the development of CRE BSI. The mortality rate of CRE BSI was higher. NDM was the predominant carbapenemase-producing mechanism in children., Competing Interests: The authors declare that they have no competing interests., (© 2024 Liang et al.)

Purpose: Tumor-to-background ratio (TBR) is a critical metric in oncologic PET imaging. This study aims to enhance the TBR of [ 18 F]FET in brain tumor imaging by substituting deuterium ("D") for hydrogen ("H"), thereby improving the diagnostic sensitivity and accuracy., Methods: [ 18 F]d 4 -FET was synthesised by two automated radiochemistry modules. Biodistribution studies and imaging efficacy were evaluated in vivo  and ex vivo in rodent models, while metabolic stability and radiation dosimetry were assessed in non-human primates. Additionally, preliminary imaging evaluations were carried out in five brain tumor patients: three glioma patients underwent imaging with both [ 18 F]d 4 -FET and [ 18 F]FET, and two patients with brain metastases were imaged using [ 18 F]d 4 -FET and [ 18 F]FDG., Results: [ 18 F]d 4 -FET demonstrated high radiochemical purity and yield. PET/MRI in rodent models demonstrated superior TBR for [ 18 F]d 4 -FET compared to [ 18 F]FET, and autoradiography showed tumor margins that correlated well with pathological extents. Studies in cynomolgus monkeys indicated comparable in vivo stability and effective dose with [ 18 F]FET. In glioma patients, [ 18 F]d 4 -FET showed enhanced TBR, while in patients with brain metastases, [ 18 F]d 4 -FET displayed superior lesion delineation compared to [ 18 F]FDG, especially in smaller metastatic sites., Conclusion: We successfully synthesized the novel PET radiotracer [ 18 F]d 4 -FET, which retains the advantageous properties of [ 18 F]FET while potentially enhancing TBR for glioma imaging. Preliminary studies indicate excellent stability, efficacy, and sensitivity of [ 18 F]d 4 -FET, suggesting its potential in clinical evaluations of brain tumors., Trial Registration: ChiCTR2400081576, registration date: 2024-03-05, https://www.chictr.org.cn/bin/project/edit?pid=206162., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Heart failure with preserved ejection fraction (HFpEF) is associated with high hospitalization and mortality rates, representing a significant healthcare burden. This study aims to utilize various information including echocardiogram and phonocardiogram to construct and validate a nomogram, assisting in clinical decision-making., Methods: This study analyzed 204 patients (68 HFpEF and 136 non-HFpEF) from the First Affiliated Hospital of Chongqing Medical University. A total of 49 features were integrated and used, including phonocardiogram, echocardiogram features, and clinical parameters. The least absolute shrinkage and selection operator (LASSO) regression was used to select the optimal matching factors, and a stepwise logistic regression was employed to determine independent risk factors and develop a nomogram. Model performance was evaluated by the area under receiver operating characteristic (ROC) curve (AUC), calibration curve, decision curve analysis (DCA), and clinical impact curve (CIC)., Results: The nomogram was constructed using five significant indicators, including NT-proBNP (OR = 4.689, p = 0.015), E/e' (OR = 1.219, p = 0.032), LAVI (OR = 1.088, p < 0.01), D/S (OR = 0.014, p < 0.01), and QM1 (OR = 1.058, p < 0.01), and showed a better AUC of 0.945 (95% CI = 0.908-0.982) in the training set and 0.933 (95% CI = 0.873-0.992) in the testing set compared to conventional nomogram without phonocardiogram features. The calibration curve and Hosmer-Lemeshow test demonstrated no statistical significance in the training and testing sets (p = 0.814 and p = 0.736), indicating the nomogram was well-calibrated. The DCA and CIC results confirmed favorable clinical usefulness., Conclusion: The nomogram, integrating phonocardiogram and echocardiogram features, enhances HFpEF diagnostic efficiency, offering a valuable tool for clinical decision-making., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

Dysfunctional renal tubular epithelial cells, induced by high glucose, are commonly observed in the kidney tissues of diabetic nephropathy (DN) patients. The epithelial-mesenchymal transition (EMT) of these cells often leads to renal interstitial fibrosis and kidney damage in DN. High glucose also triggers mitochondrial damage and apoptosis, contributing further to the dysfunction of renal tubular epithelial cells. Cellular senescence, a recognized characteristic of DN, is primarily caused by high glucose. However, it remains unclear whether high glucose-induced cellular senescence in DN exacerbates the functional impairment of tubular epithelial cells. In this study, we examined the relationship between EMT and cellular senescence in kidney tissues from streptozotocin (STZ)-induced DN and HK-2 cells treated with high glucose (HG). We also investigated the impact of HG concentrations on tubular epithelial cells, specifically mitochondrial dysfunction, cellular senescence and apoptosis. These damages were primarily associated with the secretion of cytokines (such as IL-6, and TNF-α), production of reactive oxygen species (ROS), and an increase of intracellular Ca 2+ . Notably, resveratrol, an anti-aging agent, could effectively attenuate the occurrence of EMT, mitochondrial dysfunction, and apoptosis induced by HG. Mechanistically, anti-aging treatment leads to a reduction in cytokine secretion, ROS production, and intracellular Ca 2+ levels., Competing Interests: Declaration of competing interest All authors declare no competing interests. We declare that neither the entire paper nor any part of its content has been published or has been accepted elsewhere. If accepted, it will not be published elsewhere in the same form, in English or in any other languages, including electronic form without the written consent of the copyright-holder., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The associations between 1-carbon metabolism (OCM) nutrients (methionine, folate, vitamin B-6, and vitamin B-12) and Alzheimer disease (AD) remains inconclusive., Objectives: This study aimed to investigate the association of dietary OCM nutrients with subsequent risk of AD and further assess whether participants with high genetic risk for AD might benefit from dietary OCM nutrients., Methods: We analyzed data from 192,214 participants who completed at least one 24-h dietary questionnaire and had no previous history of AD based on the UK Biobank. Nutrients intake was calculated using McCance and Widdowson's The Composition of Food and USDA's Food and Nutrient Database for Dietary Studies. Cox proportional models with restricted cubic splines were applied to explore the associations., Results: Over a median follow-up of 13.35 y, 959 cases of AD (41 early-onset cases and 918 late-onset cases) were identified. Compared with those in the low-intake OCM group (quartile 1), participants in the high-intake OCM group (quartile 4) had reduced risk of developing AD. The corresponding hazard ratios (HRs) and 95% confidence intervals (CIs) for methionine, folate, vitamin B-6, and vitamin B-12 intake were 0.66 (0.54, 0.80), 0.71 (0.58, 0.87), 0.71 (0.59, 0.87), and 0.77 (0.64, 0.93), respectively. Similar associations were observed in late-onset AD. In early-onset AD, high methionine and vitamin B-12 intake were associated with 70% (HR: 0.30; 95% CI: 0.10, 0.86) and 71% (HR: 0.29; 95% CI: 0.09, 0.96) reduction in risk, respectively. Participants with low genetic risk and high OCM nutrients intake had >75% reduced AD risk compared with high-risk, low-intake participants., Conclusions: In this prospective cohort study, we found that higher intake of OCM nutrients is associated with reduced risk of AD. Participants with high genetic risk of AD are more likely to benefit from dietary OCM nutrients intake., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Both soluble phosphorus (P) deficiency and petroleum hydrocarbon contamination represent challenges in soil environments. While phosphate-solubilizing bacteria and hydrocarbon-degrading bacteria have been identified and employed in environmental bioremediation, the bacteria co-adapted to soluble P deficiency and hydrocarbon contamination has rarely been reported. This study explored the ability of Acinetobacter oleivorans S4 (A. oleivorans S4) to solubilize phosphate using n-hexadecane (H), glucose (G), and a mixed carbon source (HG) in tricalcium phosphate (TCP) medium. A. oleivorans S4 exhibited robust growth in H-TCP, releasing 31 mg L -1 of soluble P. Conversely, A. oleivorans S4 barely grew in G-TCP, releasing 654 mg L -1 of soluble P. In HG-TCP, biomass surpassed that in H-TCP, with phosphate release comparable to that in G-TCP. HPLC analysis revealed a small amount of TCA cycle acids in H-TCP and a large amount of gluconate in G-TCP and HG-TCP. Transcriptomic analysis showed elevated expression of genes associated with alkane degradation, P starvation, N utilization, and trehalose synthesis in H-TCP, revealing the molecular co-adaptation mechanism of A. oleivorans S4. Furthermore, the addition of glucose enhanced alkane degradation, P and N utilization, and reduced trehalose synthesis. It indicated that incomplete glucose metabolism may provide energy for other reactions, and the increase in soluble P mediated by gluconate may alleviate oxidative stress. Overall, A. oleivorans S4 proves promising for remediating soluble P-deficient and hydrocarbon-contaminated environments, and glucose stimulates its transformation into a super phosphate-solubilizing bacterium., 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 Elsevier B.V. All rights reserved.)

Purpose: To investigate the accuracy and reliability of magnetic resonance imaging (MRI) in identifying and grading chondral lesions and explore the optimal imaging technique to image cartilage., Method: A comprehensive search was conducted on Medline, Embase, and Cochrane Library. Eligible cohort studies published before August 2022 were included. The study reports used MRI to diagnose and grade cartilage lesions, with intraoperative findings as the reference standard. Summary estimates of diagnostic performance were obtained. The reliability of MRI interpretation was summarized. Subgroup analyses were performed based on assessed imaging techniques, field strength, and joint surface., Results: Forty-three trials and 3,706 patients were included in the systematic review. The overall area under curve for hierarchical summarized receiver operating characteristics was 0.91 (95% confidence interval [CI] 0.88-0.93). The pooled sensitivity for quantitative MRI, 3-dimensional MRI, and 2-dimensional MRI was 0.82 (95% CI 0.64-0.92), 0.79 (95% CI 0.74-0.83), and 0.63 (95% CI 0.51-0.73), respectively. The pooled sensitivity of 3 Tesla (3T), 1.5 Tesla (1.5T), and <1.5 Tesla MRI was 0.79 (95% CI 0.72-0.85), 0.67 (95% CI 0.60-0.74), and 0.55 (95% CI 0.39-0.71), respectively. There were differences in interobserver consistency across different studies., Conclusions: In general, MRI had high specificity in discriminating normal cartilage, but its sensitivity for identifying chondral lesions is less optimal. Further analysis showed that quantitative MRI, 3D MRI, and 3T MRI demonstrate greater sensitivity compared with 2D MRI, 1.5T MRI, and <1.5 Tesla MRI., Level of Evidence: Level III, systematic review of Level II and III studies., Competing Interests: Disclosures The authors report the following potential conflicts of interest of sources of funding: This work was funded by the Key Research and Development Fund of Sichuan Science and Technology Planning Department, grant number 2022YFS0372 (received by J.L.) and the Youth Research Fund of Sichuan Science and Technology Planning Department, grant number 23NSFSC4894 (received by X.C.). M.Z. is an employee of GE Healthcare. All other authors (M.Y., K.L., L.W., K.Z., G.C.) declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Full ICMJE author disclosure forms are available for this article online, as supplementary material., (Copyright © 2024 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)