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Long-term PM2.5 data are essential for the atmospheric environment, human health, and climate change. PM2.5 measurements are sparsely distributed and of short duration. In this study, daily PM2.5 concentrations are estimated using a machine learning method for the period from 1959 to 2022 in the Northern Hemisphere based on near-surface atmospheric visibility. They are extracted from the Integrated Surface Database (ISD). Daily continuous monitored PM2.5 concentration is set as the target, and near-surface atmospheric visibility and other related variables are used as the inputs. A total of 80 % of the samples of each site are the training set, and 20 % are the testing set. The training result shows that the slope of linear regression with a 95 % confidence interval (CI) between the estimated PM2.5 concentration and the monitored PM2.5 concentration is 0.955 [0.955, 0.955], the coefficient of determination (R2) is 0.95, the root mean square error (RMSE) is 7.2 µg m−3, and the mean absolute error (MAE) is 3.2 µg m−3. The test result shows that the slope within a 95 % CI between the predicted PM2.5 concentration and the monitored PM2.5 concentration is 0.864 [0.863, 0.865], the R2 is 0.79, the RMSE is 14.8 µg m−3, and the MAE is 7.6 µg m−3. Compared with a global PM2.5 concentration dataset derived from a satellite aerosol optical depth product with 1 km resolution, the slopes of linear regression on the daily (monthly) scale are 0.817 (0.854) from 2000 to 2021, 0.758 (0.821) from 2000 to 2010, and 0.867 (0.879) from 2011 to 2022, indicating the accuracy of the model and the consistency of the estimated PM2.5 concentration on the temporal scale. The interannual trends and spatial patterns of PM2.5 concentration on the regional scale from 1959 to 2022 are analyzed using a generalized additive mixed model (GAMM), suitable for situations with an uneven spatial distribution of monitoring sites. The trend is the slope of the Theil–Sen estimator. In Canada, the trend is −0.10 µg m−3 per decade, and the PM2.5 concentration exhibits an east–high to west–low pattern. In the United States, the trend is −0.40 µg m−3 per decade, and PM2.5 concentration decreases significantly after 1992, with a trend of −1.39 µg m−3 per decade. The areas of high PM2.5 concentration are in the east and west, and the areas of low PM2.5 concentration are in the central and northern regions. In Europe, the trend is −1.55 µg m−3 per decade. High-concentration areas are distributed in eastern Europe, and the low-concentration areas are in northern and western Europe. In China, the trend is 2.09 µg m−3 per decade. High- concentration areas are distributed in northern China, and the low-concentration areas are distributed in southern China. The trend is 2.65 µg m−3 per decade up to 2011 and −22.23 µg m−3 per decade since 2012. In India, the trend is 0.92 µg m−3 per decade. The concentration exhibits a north–high to south–low pattern, with high-concentration areas distributed in northern India, such as the Ganges Plain and Thar Desert, and the low-concentration area in the Deccan Plateau. The trend is 1.41 µg m−3 per decade up to 2013 and −23.36 µg m−3 per decade from 2014. The variation in regional PM2.5 concentrations is closely related to the implementation of air quality laws and regulations. The daily site-scale PM2.5 concentration dataset from 1959 to 2022 in the Northern Hemisphere is available at the National Tibetan Plateau/Third Pole Environment Data Center (https://doi.org/10.11888/Atmos.tpdc.301127) (Hao et al., 2024).

The Madden–Julian Oscillation (MJO) is a crucial predictability source on a subseasonal-to-seasonal (S2S) timescale. Therefore, the models participating in the World Weather Research Programme and the World Climate Research Programme (WWRP/WCRP) S2S prediction project focus on accurately predicting and analyzing the MJO. This study provides a detailed description of the configuration within the Institute of Atmospheric Physics at the Chinese Academy of Sciences (IAP-CAS) S2S forecast system. We assess the accuracy of the IAP-CAS model's MJO forecast using traditional Real-time Multivariate MJO (RMM) analysis and cluster analysis. Then, we explain the reasons behind any bias observed in the MJO forecast. Comparing the 20-year hindcast with observations, we found that the IAP-CAS ensemble mean has a skill of 24 d. However, the ensemble spread still has potential for improvement. To examine the MJO structure in detail, we use cluster analysis to classify the MJO events during boreal winter into four types: fast-propagating, slow-propagating, standing, and jumping patterns of MJO. The model exhibits biases of overestimated amplitude and faster propagation speed in the propagating MJO events. Upon further analysis, it was found that the model forecasted a wetter background state. This leads to stronger forecasted convection and coupled waves, especially in the fast MJO events. The overestimation of the strength and length of MJO-coupled waves results in a faster MJO mode and quicker dissipation in the IAP-CAS model. These findings show that the IAP-CAS skillfully forecasts signals of MJO and its propagation, and they also provide valuable guidance for improving the current MJO forecast by developing the ensemble system and moisture forecast.

Long-term and high spatial resolution aerosol optical depth (AOD) data are essential for climate change detection and attribution. Global ground-based AOD observations are sparsely distributed, and satellite AOD retrievals have a low temporal frequency as well low accuracy before 2000 over land. In this study, AOD at 550 nm is derived from visibility observations collected at more than 5000 meteorological stations over global land regions from 1959 to 2021. The AOD retrievals (550 nm) of the Moderate Resolution Imaging Spectroradiometer (MODIS) on board the Aqua Earth observation satellite are used to train the machine learning model, and the ERA5 reanalysis boundary layer height is used to convert the surface visibility to AOD. Comparisons with an independent dataset (AERONET ground-based observations) show that the predicted AOD has a correlation coefficient of 0.55 at the daily scale. The correlation coefficients are higher at monthly and annual scales, which are 0.61 and 0.65, respectively. The evaluation shows consistent predictive ability prior to 2000, with correlation coefficients of 0.54, 0.66, and 0.66 at the daily, monthly, and annual scales, respectively. Due to the small number and sparse visibility stations prior to 1980, the global and regional analysis in this study is from 1980 to 2021. From 1980 to 2021, the mean visibility-derived AOD values over global land areas, the Northern Hemisphere, and the Southern Hemisphere are 0.177, 0.178, and 0.175, with a trend of −0.0029 per 10 years, −0.0030 per 10 years, and −0.0021 per 10 years from 1980 to 2021. The regional means (trends) of AOD are 0.181 (−0.0096 per 10 years), 0.163 (−0.0026 per 10 years), 0.146 (−0.0017 per 10 years), 0.165 (−0.0027 per 10 years), 0.198 (−0.0075 per 10 years), 0.281 (−0.0062 per 10 years), 0.182 (−0.0016 per 10 years), 0.133 (−0.0028 per 10 years), 0.222 (0.0007 per 10 years), 0.244 (−0.0009 per 10 years), 0.241 (0.0130 per 10 years), and 0.254 (0.0119 per 10 years) in Eastern Europe, Western Europe, Western North America, Eastern North America, Central South America, Western Africa, Southern Africa, Australia, Southeast Asia, Northeast Asia, Eastern China, and India, respectively. However, the trends decrease significantly in Eastern China (−0.0572 per 10 years) and Northeast Asia (−0.0213 per 10 years) after 2014, with the larger increasing trend found after 2005 in India (0.0446 per 10 years). The visibility-derived daily AOD dataset at 5032 stations over global land from 1959 to 2021 is available from the National Tibetan Plateau/Third Pole Environment Data Center (https://doi.org/10.11888/Atmos.tpdc.300822) (Hao et al., 2023).

Biogenic volatile organic compounds (BVOCs), as a crucial component that impacts atmospheric chemistry and ecological interactions with various organisms, play a significant role in the atmosphere–ecosystem relationship. However, traditional field observation methods are challenging for accurately estimating BVOC emissions in forest ecosystems with high biodiversity, leading to significant uncertainty in quantifying these compounds. To address this issue, this research proposes a workflow utilizing drone-mounted lidar and photogrammetry technologies for identifying plant species to obtain accurate BVOC emission data. By applying this workflow to a typical subtropical forest plot, the following findings were made: the drone-mounted lidar and photogrammetry modules effectively segmented trees and acquired single wood structures and images of each tree. Image recognition technology enabled relatively accurate identification of tree species, with the highest-frequency family being Euphorbiaceae. The largest cumulative isoprene emissions in the study plot were from the Myrtaceae family, while those of monoterpenes were from the Rubiaceae family. To fully leverage the estimation results of BVOC emissions directly from individual tree levels, it may be necessary for communities to establish more comprehensive tree species emission databases and models.

The climate of the Tibetan Plateau (TP) has experienced substantial changes in recent decades as a result of the location's susceptibility to global climate change. The changes observed across the TP are closely associated with regional land–atmosphere interactions. Current models and satellites struggle to accurately depict the interactions; therefore, critical field observations on land–atmosphere interactions outlined here provide necessary independent validation data and fine-scale process insights for constraining reanalysis products, remote sensing retrievals, and land surface model parameterizations. Scientific data sharing is crucial for the TP since in situ observations are rarely available under these harsh conditions. However, field observations are currently dispersed among individuals or groups and have not yet been integrated for comprehensive analysis. This has prevented a better understanding of the interactions, the unprecedented changes they generate, and the substantial ecological and environmental consequences they bring about. In this study, we collaborated with different agencies and organizations to present a comprehensive dataset for hourly measurements of surface energy balance components, soil hydrothermal properties, and near-surface micrometeorological conditions spanning up to 17 years (2005–2021). This dataset, derived from 12 field stations covering a variety of typical TP landscapes, provides the most extensive in situ observation data available for studying land–atmosphere interactions on the TP to date in terms of both spatial coverage and duration. Three categories of observations are provided in this dataset: meteorological gradient data (met), soil hydrothermal data (soil), and turbulent flux data (flux). To assure data quality, a set of rigorous data-processing and quality control procedures are implemented for all observation elements (e.g., wind speed and direction at different height) in this dataset. The operational workflow and procedures are individually tailored to the varied types of elements at each station, including automated error screening, manual inspection, diagnostic checking, adjustments, and quality flagging. The hourly raw data series; the quality-assured data; and supplementary information, including data integrity and the percentage of correct data on a monthly scale, are provided via the National Tibetan Plateau Data Center (https://doi.org/10.11888/Atmos.tpdc.300977, Ma et al., 2023a). With the greatest number of stations covered, the fullest collection of meteorological elements, and the longest duration of observations and recordings to date, this dataset is the most extensive hourly land–atmosphere interaction observation dataset for the TP. It will serve as the benchmark for evaluating and refining land surface models, reanalysis products, and remote sensing retrievals, as well as for characterizing fine-scale land–atmosphere interaction processes of the TP and underlying influence mechanisms.

Photocatalytic reactions during the daytime, alongside aqueous-phase reactions occurring during both daytime and nighttime, are identified as the two primary processes facilitating the conversion of aerosol iron (Fe) from the insoluble state to the soluble state within the atmospheric environment. This study investigated the levels of total Fe (FeT) and soluble Fe (FeS) in PM2.5 samples collected during daytime and nighttime in Qingdao, a coastal city in eastern China, evaluating the distinctive roles of these two pathways in enhancing aerosol Fe solubility (%FeS, defined as the ratio of FeS to FeT). Under clean and humid conditions, characterized by prevailing sea breezes and a relative humidity (RH) typically above 80 %, an average daytime %FeS of 8.7 % was observed, which systematically exceeded the nighttime %FeS (6.3 %). Photochemical conversions involving oxalate contributed to the higher %FeS observed during daytime. Conversely, in scenarios where air masses originated from inland areas and exhibited slightly polluted, daytime %FeS (3.7 %) was noted to be lower than the nighttime %FeS (5.8 %). This discrepancy was attributable to the variations in RH, with nighttime RH averaging around 77 %, conducive to the more efficient generation of acidic compounds, thereby accelerating FeS production compared to the daytime, when RH was only about 62 %. Furthermore, the oxidation rates of sulfur (SOR) displayed a strong correlation with RH, particularly when RH fell below 75 %. A 10 % increase in RH corresponded to a 7.6 % rise in SOR, which served as the primary driver of the higher aerosol acidity and %FeS at night. These findings highlight the RH-dependent activation of aqueous-phase reactions and the augmentation of daytime photocatalysis in the formation of FeS in the coastal moist atmosphere.

This review paper describes the energy-upgraded Continuous Electron Beam Accelerator Facility (CEBAF) accelerator. This superconducting linac has achieved 12 GeV beam energy by adding 11 new high-performance cryomodules containing 88 superconducting cavities that have operated cw at an average accelerating gradient of 20 MV/m. After reviewing the attributes and performance of the previous 6 GeV CEBAF accelerator, we discuss the upgraded CEBAF accelerator system in detail with particular attention paid to the new beam acceleration systems. In addition to doubling the acceleration in each linac, the upgrade included improving the beam recirculation magnets, adding more helium cooling capacity to allow the newly installed modules to run cold, adding a new experimental hall, and improving numerous other accelerator components. We review several of the techniques deployed to operate and analyze the accelerator performance and document system operating experience and performance. In the final portion of the document, we present much of the current planning regarding projects to improve accelerator performance and enhance operating margins, and our plans for ensuring CEBAF operates reliably into the future. For the benefit of potential users of CEBAF, the performance and quality measures for the beam delivered to each of the experimental halls are summarized in the Appendix.

After a long device enhancement phase, scientific operation resumed in 2022. The main new device components are the water cooling of all plasma facing components and the new water-cooled high heat flux divertor units. Water cooling allowed for the first long-pulse operation campaign. A maximum discharge length of 8 min was achieved with a total heating energy of 1.3 GJ. Safe divertor operation was demonstrated in attached and detached mode. Stable detachment is readily achieved in some magnetic configurations but requires impurity seeding in configurations with small magnetic pitch angle within the edge islands. Progress was made in the characterization of transport mechanisms across edge magnetic islands: Measurement of the potential distribution and flow pattern reveals that the islands are associated with a strong poloidal drift, which leads to rapid convection of energy and particles from the last closed flux surface into the scrape-off layer. Using the upgraded plasma heating systems, advanced heating scenarios were developed, which provide improved energy confinement comparable to the scenario, in which the record triple product for stellarators was achieved in the previous operation campaign. However, a magnetic configuration-dependent critical heating power limit of the electron cyclotron resonance heating was observed. Exceeding the respective power limit leads to a degradation of the confinement.

Abstract Fixational eye movements alter the number and timing of spikes transmitted from the retina to the brain, but whether these changes enhance or degrade the retinal signal is unclear. To quantify this, we developed a Bayesian method for reconstructing natural images from the recorded spikes of hundreds of retinal ganglion cells (RGCs) in the macaque retina (male), combining a likelihood model for RGC light responses with the natural image prior implicitly embedded in an artificial neural network optimized for denoising. The method matched or surpassed the performance of previous reconstruction algorithms, and provides an interpretable framework for characterizing the retinal signal. Reconstructions were improved with artificial stimulus jitter that emulated fixational eye movements, even when the eye movement trajectory was assumed to be unknown and had to be inferred from retinal spikes. Reconstructions were degraded by small artificial perturbations of spike times, revealing more precise temporal encoding than suggested by previous studies. Finally, reconstructions were substantially degraded when derived from a model that ignored cell-to-cell interactions, indicating the importance of stimulus-evoked correlations. Thus, fixational eye movements enhance the precision of the retinal representation.

The use of vaporizers to inhale cannabis is a technique that has risen in popularity among the American public. There is a general perception that vaporizers are “safer” when compared to more traditional cannabis smoking via combustion (i.e., cigarettes). The inherent use of heated air in vaporizers might reduce the respiratory toxicants or protein toxins by heating cannabis to a temperature where active compounds form in vapor phase. Yet this temperature is below the point of combustion where smoke and associated toxicants are produced. The elemental impurities are a general concern in all botanical products including cannabis and cannabis-derived products (CCDPs). This study aimed to investigate the potential transfer of those metallic elements from cannabis material to cannabis vapor through the vaporization process. A Volcano Digit Vaporizer (Storz & Bickel) was used as the heating device to perform the vaporization. Three cannabis plant materials were evaluated with varying contents of cannabinoids, including a cannabis placebo (

Introduction Mounting evidence indicates that an individual's humoral adaptive immune response plays a critical role in the setting of SARS-CoV-2 infection, and that the efficiency of the response correlates with disease severity. The relationship between the adaptive immune dynamics in the lower airways with those in the systemic circulation, and how these relate to an individual's clinical response to SARS-CoV-2 infection, are less understood and are the focus of this study. Material and methods We investigated the adaptive immune response to SARS-CoV-2 in paired samples from the lower airways and blood from 27 critically ill patients during the first wave of the pandemic (median time from symptom onset to intubation 11 days). Measurements included clinical outcomes (mortality), bronchoalveolar lavage fluid (BALF) and blood specimen antibody levels, and BALF viral load. Results While there was heterogeneity in the levels of the SARS-CoV-2-specific antibodies, we unexpectedly found that some BALF specimens displayed higher levels than the paired concurrent plasma samples, despite the known dilutional effects common in BALF samples. We found that survivors had higher levels of anti-spike, anti-spike-N-terminal domain and anti-spike-receptor-binding domain IgG antibodies in their BALF (p

Valley magnetic moments play a crucial role in valleytronics in 2D hexagonal materials. Traditionally, insights drawn from the study of quantum states in homogeneous bulks have led to a widespread belief that only materials with broken structural inversion symmetry can exhibit nonvanishing valley magnetic moments. This belief, however, limits the scope of relevant applications, especially for materials with inversion symmetry, such as gapless monolayer graphene, despite its advantage in routine growth and production. This work revisits valley-derived magnetic moments in a broad context covering inhomogeneous structures as well. It generalizes the notion of a valley magnetic moment for a state from an integrated quantity to the local field called the “local valley magnetic moment” with space-varying distribution. It explores the local magnetic moment analytically both within the Dirac model and through a symmetry argument. Numerical investigations are conducted within the tight-binding model. Overall, we demonstrate that the breaking of inversion symmetry in the electron probability distribution leads to nonvanishing local magnetic moments. This probability-based breaking can occur in both structural inversion symmetric and symmetry-broken structures. In suitable inversion-symmetric structures with inhomogeneity, e.g., zigzag nanoribbons of gapless monolayer graphene, it is shown that the local moment of a state can be nonvanishing while the corresponding integrated moment is subject to the broken symmetry constraint. Moreover, it is demonstrated that the local moment can interact with space-dependent magnetic fields, resulting in field effects such as valley Zeeman splitting. Such effects can be exploited for local valley control as a conduit for the implementation of valleytronics.

BackgroundBubble continuous positive airway pressure (bCPAP) is used in resource-limited settings for children with respiratory distress. Low-cost modifications of bCPAP use 100% oxygen and may cause morbidity from oxygen toxicity. We sought to test a novel constructible low-cost entrainment syringe system (LESS) oxygen blender with low-cost modified bCPAP in a relevant clinical setting.MethodsWe conducted a clinical trial evaluating safety of the LESS O2 blender among hospitalized children under five years old in rural Cambodia evaluating the rate of clinical failure within one hour of initiation of the LESS O2 blender and monitoring for any other blender-related complications.FindingsThirty-two patients were included. The primary outcome (clinical failure) occurred in one patient (3.1%, 95% CI = 0.1–16.2%). Clinical failure was defined as intubation, death, transfer to another hospital, or two of the following: oxygen saturation

Latent tuberculosis infection (LTBI) is common in people living with HIV (PLHIV) in high-TB-burden settings. Active TB is associated with specific stool taxa; however, little is known about the stool microbiota and LTBI in PLHIV. We characterised the stool microbiota of PLHIV with [interferon-γ release assay (IGRA)- and tuberculin skin test (TST)-positive] or without (IGRA- and TST-negative) LTBI (n = 25 per group). The 16S rRNA DNA sequences were analysed using QIIME2, Dirichlet-Multinomial Mixtures, DESeq2, and PICRUSt2. No α- or β-diversity differences occurred by LTBI status; however, LTBI-positive people were Faecalibacterium-, Blautia-, Gemmiger-, and Bacteroides-enriched and Moryella-, Atopobium-, Corynebacterium-, and Streptococcus-depleted. Inferred metagenome data showed that LTBI-negative-enriched pathways included several metabolite degradation pathways. Stool from LTBI-positive people demonstrated differential taxa abundance based on a quantitative response to antigen stimulation. In LTBI-positive people, older people had different β-diversities than younger people, whereas in LTBI-negative people, no differences occurred across age groups. Amongst female PLHIV, those with LTBI were, vs. those without LTBI, Faecalibacterium-, Blautia-, Gemmiger-, and Bacteriodes-enriched, which are producers of short-chain fatty acids. Taxonomic differences amongst people with LTBI occurred according to quantitative response to antigen stimulation and age. These data enhance our understanding of the microbiome’s potential role in LTBI.

Liposomes as carriers for CRISPR/Cas9 complexes represent an attractive approach for cardiovascular gene therapy. A critical barrier to this approach remains the efficient delivery of CRISPR-based genetic materials into cardiomyocytes. Echogenic liposomes (ELIP) containing a fluorescein isothiocyanate-labeled decoy oligodeoxynucleotide against nuclear factor kappa B (ELIP-NF-κB-FITC) were used both in vitro on mouse neonatal ventricular myocytes and in vivo on rat hearts to assess gene delivery efficacy with or without ultrasound. In vitro analysis was then repeated with ELIP containing Cas9-sg-IL1RL1 (interleukin 1 receptor-like 1) RNA to determine the efficiency of gene knockdown. ELIP-NF-κB-FITC without ultrasound showed limited gene delivery in vitro and in vivo, but ultrasound combined with ELIP notably improved penetration into heart cells and tissues. When ELIP was used to deliver Cas9-sg-IL1RL1 RNA, gene editing was successful and enhanced by ultrasound. This innovative approach shows promise for heart disease gene therapy using CRISPR technology.

Osteoblasts dysfunction, induced by oxidative stress (OS), is a significant contributor to the pathogenesis of osteoporosis. However, the genes implicated in regulating osteoblast dysfunction remain unclear. Here, we employed the hydrogen peroxide (H 2 O 2 )-induced osteoblast dysfunction model to assess its impact on osteoblast phenotype and to conduct transcriptome and proteome analyses in osteoblasts under OS. We identified 164 genes and 186 proteins with altered expression (differentially expressed genes (DEGs) and differentially expressed proteins (DEPs), respectively). Functional analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed enrichment in pathways associated with apoptosis and osteoblast differentiation. We constructed a protein-protein interaction (PPI) network of DEPs, which comprised 175 DEPs as nodes. Furthermore, seven key DEGs and DEPs with positive correlation (cor-DEGs-DEPs genes) were characterized based on the integrated analysis of mRNA-protein expression. Among these seven genes, Ho-1, Fosl1, and Fosl2 were shown to be upregulated, associated with OS-induced cell differentiation impairment and apoptosis. Conversely, Ccnd2, Col1α1, Col12α1, and Fgfr2 were shown to be downregulated, linked to OS-induced cell cycle delay, apoptosis, impaired mineralization, and differentiation. PPI analysis revealed interactions between these key genes. Lastly, we validated these genes at both mRNA and protein levels using qRT-PCR and Western blot experiments. This study identified seven candidate genes potentially involved in the detrimental effects of OS on MC3T3-E1 apoptosis and dysfunction. These findings offer new insights into how OS disrupts bone formation and may contribute to the development of osteoporosis., 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 Inc. All rights reserved.)

Developing multifunctional materials which could simultaneously possess anti-bacterial ability and electromagnetic (EM) absorption ability during medical care is quite essential since the EM waves radiation and antibiotic-resistant bacteria are threatening people's health. In this work, the multifunctional carbon fiber/Ti 3 C 2 T x MXene (CM) were synthesized through repeated dip-coating and following in-situ growth method. The as-fabricated CF/MXene displayed outstanding EM wave absorption and highly efficient photothermal converting ability. The minimum reflection loss (RL) of -57.07 dB and ultra-broad absorption of 7.74 GHz could be achieved for CM composites. By growth of CoNi-layered double hydroxides (LDHs) sheets onto MXene, the absorption bandwidth for carbon fiber/Ti 3 C 2 T x MXene layered double hydroxides (CML) could be reach 5.44 GHz, which could cover the whole Ku band. The excellent photothermal effect endow the CM composites with excellent antibacterial performance. The antibacterials tests indicated that nearly 100 % bactericidal efficiency against E. acoil and S. aureus was obtained for the CM composite after exposure to near-infrared region (NIR) irradiation. This work provides a promising candidate to combat medical device-related infections and EM pollution., 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 Inc. All rights reserved.)

Phenol-pyranoanthocyanins, a structurally modified type of anthocyanin, has higher stability than anthocyanins. However, their conversion occurs slowly. Therefore, it is crucial to improve the conversion efficiency and production of pyranoanthocyanins. In this study, cranberry anthocyanin (CRAN) was fermented using two Lactobacillus strains along with caffeic acid to form cranberry-derived pyranoanthocyanins (PY-CRAN). PY-CRAN was characterized and identified. The physicochemical properties, antioxidant activity, and tyrosinase inhibitory capacity of PY-CRAN were assessed. The results showed that phenol-pyranoanthocyanins can be rapidly produced through fermentative transformation using Lactiplantibacillus plantarum and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei exhibits a higher propensity for producing phenol-pyranoanthocyanins. PY-CRAN exhibits high stability under light and various pH conditions. Moreover, they possess excellent antioxidant properties and the ability to inhibit tyrosinase. These results suggest that fermentative biotransformation conducted by Lactobacillus is an ideal method for producing cranberry pyranoanthocyanins. The resulting anthocyanins have potential as antioxidant and whitening agents, making them promising bioactive ingredients., 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.)

Particulate organic carbon (POC) plays crucial roles in the global ocean carbon cycle and the oceanic biological pump. Satellite remote sensing has been demonstrated to be an effective technique for the retrieval of surface oceanic POC concentration. However, the complex spatiotemporal variations of the relationships between POC and oceanic optical properties across different waters posed challenges for accurate retrieval of POC concentration from satellite observations. Additionally, interference factors, such as cloud cover and sun glint, resulted in severe data missing problems and impeding daily coverage of the global ocean. With an attempt to generate accurate, seamless and readily available POC products for the global ocean, this study aimed to develop accurate satellite POC retrieval models for the Moderate Resolution Imaging Spectroradiometer (MODIS) data from both Terra and Aqua satellites, and to explore the possibility of using the empirical orthogonal function interpolation technique (DINEOF) to reconstruct satellite-retrieved POC data to generate gap-free global oceanic POC products. Results showed that the eXtreme Gradient Boosting (XGBoost) method could accurately retrieve POC with R 2 approximately 0.80 and RMSE about 0.20 in log10 scale, obviously outperforming the operational blue-to-green band ratio algorithm and the hybrid polynomial algorithm based on two multi-band indices; and the DINEOF method, which could reconstruct approximately 88 % missing pixels for the global ocean, contributed to better revealing the global oceanic POC variations at a daily scale than the satellite-retrieved POC products. Based on the developed models, a suit of long time-series accurate and seamless POC products of the global surface ocean were generated, which is readily available for other applications and should be helpful to investigate the spatiotemporal variations of POC concentrations over global ocean and its roles in the global carbon cycle. The generated seamless products are openly accessible via the DOIs listed in the data availability section., 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.)

Background: To evaluate the new preoperative Changgung classification (CC) system of portal vein thrombosis (PVT) in choosing suitable operative procedures to reconstruct portal veins during liver transplantation (LT) in patients with portal vein cavernous transformation (PVCT)., Methods: This retrospective observational study analyzed data from allograft LTs performed for various liver diseases., Results: The study included 22 males and 4 females with LT indications comprising cirrhosis ( n  = 9), hepatocellular carcinoma ( n  = 12), PVCT ( n  = 2), liver failure from fulminant hepatitis B ( n  = 1), dysfunction of transplanted liver ( n  = 1), and chronic rejection of transplanted liver ( n  = 1). Patients were classified according to Yerdel (21 Yerdel II and 5 Yerdel III) and CC (C1-C5). In total 16 simple operations were performed on C1-C3 cases and 9 complex operations on C4-C5 cases, with one additional simple operation. The distribution according to the Yerdel classification was 16 simple and 5 complex operations in Yerdel II cases and 1 simple and 4 complex operations in Yerdel III cases. The median follow-up time was 27.5 months with overall one-year and three-year OS rates of 88.1% and 83.9% for the cohort. Specifically, the one-year OS rates for patients classified as C1-3 vs. C4-5 were 93.3% and 80.0%, while the three-year OS rates were 86.7% and 80.0%, respectively ( p  = 0.526)., Conclusion: The CC proposed in this study shows comparable potential to the Yerdel classification in preoperatively identifying the need for complex surgical techniques in LT patients with PVCT and may also have predictive power for the survival benefits following LT.

Background: The magnesium depletion score (MDS) is a scoring system developed to predict magnesium deficiency based on pathophysiological factors that affect renal reabsorption. The relationship between systemic magnesium status and arthritis is unclear. The purpose of this study was to determine the association between the MDS and rheumatoid arthritis (RA) as well as osteoarthritis (OA)., Methods: This study was conducted through a cross-sectional survey of 20,513 adults aged ≥ 20 years who participated in NHANES from 2007 to 2018. The four dimensions of the MDS included diuretics, proton pump inhibitors, glomerular filtration rate, and excessive alcohol consumption. Univariate and multivariable-weighted logistic regression were used to assess the associations between MDS and RA/OA, and a test for trend was performed to analyze the presence of a dose-response relationship. Subgroup analyses and interaction tests were performed according to confounders., Results: After adjustment for all covariates, we found a graded dose-response relationship between MDS and RA or OA. When MDS was considered as a continuous variable, each onefold increase in MDS was associated with a 1.21-fold increase in the odds of having RA (OR = 1.21, 1.10, 1.33) and a 1.12-fold increase in the odds of having OA (OR = 1.12, 1.04, 1.21). There was an interaction of sex in the effect of MDS on RA (P interaction  = 0.004) and age in the effect of MDS on OA (P interaction  = 0.006). In addition, these associations were further confirmed in sensitivity and subgroup analyses., Conclusions: Our study identified significant dose-response associations between MDS and both RA and OA. More biological mechanisms are needed in the future to validate and clarify the results of this study., Competing Interests: Compliance with ethical standards. Disclosures: None., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

To address the delamination phenomenon during storage and flavor characteristics of Oyster protein hydrolysates (OPH). In this study, xylo-oligosaccharides (XOS) were selected to covalently graft with OPH through ultrasound-assisted Maillard reaction, and the effect of ultrasound-assisted Maillard reaction on the structure, functional properties, and flavor characteristics of OPH were investigated. The results revealed that the ultrasound treatment led to a 1.46-fold increase in the degree of grafting compared with the conventional wet-heat Maillard reaction methods. Structural analyses at various levels indicated substantial alterations in the OPH structure following the ultrasound-assisted Maillard reaction. More ordered α-helical secondary structures were shifting to random coiling, the tertiary structure showed more stretching changes, and the surface structure was characterized by loose and porous features. Compared with OPH, the solubility of the ultrasound-assisted Maillard reaction products (OPH-U-M) increased from 54.67% to 70.14%, leading to a notable enhancement in storage stability. Flavor profile analysis demonstrated a decrease in unsaturated aldehydes and ketones presenting fishy and bitter aromas, while an increase in presenting meat aroma compounds was observed in OPH-U-M. Furthermore, OPH-U-M exhibited superior antioxidant properties with DPPH and ABTS radical scavenging abilities enhancing 46.05% and 42.09% in comparison with OPH, respectively. The results demonstrated that covalently binding with XOS under ultrasonication pretreatment endowed OPH with superior functional properties (including solubility, storage stability, and antioxidant activity), and the improvement of flavor profile. This study can provide theoretical guidance and practical implications for promoting the processing applications of oyster protein., 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. Published by Elsevier B.V.)

Oral microecological imbalance is closely linked to oral mucosal inflammation and is implicated in the development of both local and systemic diseases, including those caused by viral infections. This review examines the critical role of the interleukin (IL)-17/helper T cell 17 (Th17) axis in regulating immune responses within the oral mucosa, focusing on both its protective and pathogenic roles during inflammation. We specifically highlight how the IL-17/Th17 pathway contributes to dysregulated inflammation in the context of respiratory viral infections. Furthermore, this review explores the potential interactions between respiratory viruses and the oral microbiota, emphasizing how alterations in the oral microbiome and increased production of proinflammatory factors may serve as early, non-invasive biomarkers for predicting the severity of respiratory viral infections. These findings provide insights into novel diagnostic approaches and therapeutic strategies aimed at mitigating respiratory disease severity through monitoring and modulating the oral microbiome., Competing Interests: Declaraion of Competing Interest All other authors declare they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

In theory, there is a trade-off between hydraulic efficiency and safety. However, the strength and direction of this trade-off at the leaf level are not consistent across studies, and habitat climate may impact this trade-off. We compiled a leaf hydraulic efficiency and safety dataset for 362 species from 81 sites world-wide, with 280 paired observations of both traits, and tested whether climate was associated with departure from the proposed trade-off. The leaf hydraulic efficiency-safety trade-off was weak (R 2  = 0.144) at the global scale. Mean annual precipitation and solar radiation (SR) modified the trade-off. Species from dry and high SR habitats (e.g. desert and tropical savanna) were generally located above the trade-off line, indicating that these species tended to have higher leaf hydraulic safety and efficiency than species from wet habitats with low SR (e.g. subtropical monsoon forest and montane rainforest), which were located below the trade-off line. Leaves with high vein density, dry leaf mass per area, and osmotic regulation enhanced safety without compromising hydraulic efficiency. Variation in the hydraulic efficiency-safety trade-off at the leaf level likely facilitates plant survival in specific habitats and allows for a more nuanced view of leaf hydraulic adaption strategies at the global scale., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

This study aimed to identify biomarkers for chronic kidney disease (CKD) by studying serum metabolomics. Serum samples were collected from 194 non-dialysis CKD patients and 317 healthy controls (HC). Using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS), untargeted metabolomics analysis was conducted. A random forest model was developed and validated in separate sets of HC and CKD patients. The serum metabolomic profiles of patients with chronic kidney disease (CKD) exhibited significant differences compared to healthy controls (HC). A total of 314 metabolites were identified as significantly different, with 179 being upregulated and 135 being downregulated in CKD patients. KEGG enrichment analysis revealed several key pathways, including arginine biosynthesis, phenylalanine metabolism, linoleic acid metabolism, and purine metabolism. The diagnostic efficacy of the classifier was high, with an area under the curve of 1 in the training and validation sets and 0.9435 in the cross-validation set. This study provides comprehensive insights into serum metabolism in non-dialysis CKD patients, highlighting the potential involvement of abnormal biological metabolism in CKD pathogenesis. Exploring metabolites may offer new possibilities for the management of CKD.

The Forward Collision Warning (FCW) system has been widely equipped on vehicles to reduce rear-end crashes, which are considered the most common type of crash. However, existing FCW systems have the problem of low response rates, which restrict their safety improvement effects. This study aims to address this issue by building personalized FCW models based on human risk preferences. First, a warning feedback index ranks the gaps between drivers' risk perceptions and FCW models. Then, reward models are developed to characterize the risk perception preferences of each individual driver. After that, the reward models serve as guidelines to fine-tune the benchmark FCW model using the Proximal Policy Optimization (PPO) algorithm. In the empirical analyses, a total of 95,814 warning fragments collected from 74 drivers are used, and the proposed method generates pseudo warning results. By comparing the pseudo and historical warnings, it shows that the precision of pseudo warning results increases from 53.5% to 78.2%. Furthermore, the average differences between the moment of warning and the moment of braking behavior decrease from 2.4 s to 1.6 s. This demonstrates a higher synchronization level in the timing of risk perception between the personalized FCW models and individual drivers, which enhances the driver's trust in the warning system., 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.)

The human brain works as a hierarchical organization that is a continuous axis spanning sensorimotor cortex to transmodal cortex (referring to cortex that integrates multimodal sensory information and participates in complex cognitive functions). Previous studies have demonstrated abnormalities in several specific networks that may account for their multiple behavioral deficits in patients with bulimia nervosa (BN), but whether and how the network hierarchical organization changes in BN remain unknown. This study aimed to investigate alterations of the hierarchy organization in BN network and their clinical relevance. Connectome gradient analyses were applied to depict the network hierarchy patterns of fifty-nine patients with BN and thirty-nine healthy controls (HCs). Then, we evaluated the network- and voxel-level gradient alterations of BN by comparing gradient values in each network and each voxel between patients with BN and HCs. Finally, the association between altered gradient values and clinical variables was explored. In the principal gradient, patients with BN exhibited reduced gradient values in dorsal attention network and increased gradient values in subcortical regions compared to HCs. In the secondary gradient, patients with BN showed decreased gradient values in ventral attention network and increased gradient values in limbic network. Regionally, the areas with altered principal or secondary gradient values in BN group were mainly located in transmodal networks, i.e., the default-mode and frontoparietal network. In BN group, the principal gradient values of right inferior frontal gyrus were negatively associated with external eating behavior. This study revealed the disordered network hierarchy patterns in patients with BN, which suggested a disturbance of brain information integration from attention network and subcortical regions to transmodal networks in these patients. These findings may provide insight into the neurobiological underpinnings of BN., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interests regarding the publication of this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Heavy metal(loid)s (HMs) in agricultural soils not only affect soil function and crop security, but also pose health risks to residents. However, previous concerns have typically focused on only one aspect, neglecting the other. This lack of a comprehensive approach challenges the identification of hotspots and the prioritization of factors for effective management. To address this gap, a novel method incorporating spatial bivariate analysis with random forest was proposed to identify high-risk hotspots and the key influencing factors. A large-scale dataset containing 2995 soil samples and soil HMs (As, Cd, Cr, Cu, Mn, Ni, Pb, Sb, and Zn) was obtained from across Henan province, central China. Spatial bivariate analysis of both health risk and ecological risks revealed risk hotspots. Positive matrix factorization model was initially used to investigate potential sources. Twenty-two environmental variables were selected and input into random forest to further identify the key influencing factors impacting soil accumulation. Results of local Moran's I index indicated high-high HM clusters at the western and northern margins of the province. Hotspots of high ecological and health risk were primarily observed in Xuchang and Nanyang due to the widespread township enterprises with outdated pollution control measures. As concentration and exposure frequency dominated the non-carcinogenic and carcinogenic risks. Anthropogenic activities, particularly vehicular traffic (contributing ∼37.8 % of the total heavy metals accumulation), were the dominant sources of HMs in agricultural soils. Random forest modeling indicated that soil type and PM2.5 concentrations were the most influencing natural and anthropogenic variables, respectively. Based on the above findings, control measures on traffic source should be formulated and implemented provincially; in Xuchang and Nanyang, scattered township enterprises with outdated pollution control measures should be integrated and upgraded to avoid further pollution from these sources., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Pregnancy-induced hypertension remains one of the important types of diseases that affect maternal and infant outcomes; prenatal and perinatal ultrasound examination is an important tool for evaluating fetal development. So, this study aimed to explore the clinical value of applying fetal heart quantification (fetal HQ) measuring left ventricular global longitudinal strain (LVGLS) and left ventricular ejection fraction (LVEF) in mid-to-late fetuses to predict neonatal complications in patients with gestational hypertension., Methods: A retrospective summary of 146 pregnant women with gestational hypertension diagnosed from August 2020 to October 2023 into JinHua Maternal and Child Health Care Hospital was performed. Fetal HQ measured the fetal global spherical index (GSI), left and right ventricular spherical index (SI), left and right ventricular fractional shortening (FS), LVGLS and RVGLS, LVEF, and fractional area change (FAC) of the left and right ventricles. They were divided into complication group and non-complication group based on whether fetal complications occurred 28 days after birth. Multivariate logistic regression was used to screen risk factors to neonatal complications., Results: The 146 neonates were divided into 39 of the complication group and 107 of the non-complication group. Compared with the latter group, pregnant women in the former group had a higher incidence of preeclampsia and eclampsia, increased mean systolic and diastolic blood pressure, significantly lower estimated fetal weight (EFW), left ventricular 24-segment SI, LVGLS, LVEF, and left ventricular FAC values ( p  < .05). Logistic regression showed higher of LVGLS (adjusted OR = 2.281, p  < .001) was risk factors for neonatal complications, while higher LVEF (adjusted OR = 0.600, p  < .001) and left ventricular FAC (adjusted OR = 0.784, p  = .035) were protective factors. Spearman's correlation analysis showed a significant negative correlation between LVGLS and LVEF ( r  = -0.368, p  < .001). Receiver operating curves (ROCs) showed the area under the curve (AUC) for predicting overall neonatal complications was 0.880 for LVGLS and 0.878 for LVEF ( p  < .001)., Conclusions: Fetal HQ for fetal LVGLS and LVEF in mid-to-late pregnancy with gestational hypertension helps to assess the overall neonatal complications risk.

Since microplastics (MPs) were first detected in groundwater, an increasing number of studies have focused on groundwater pollution by MPs. However, knowledge of the global properties of groundwater MPs: distribution, concentration, composition, and morphology remains limited, while potential factors regulating their transport and distribution in groundwater, especially the hydrogeological background and climate warming conditions, have been omitted from most analyses. Furthermore, previous field investigations did not assess the risks posed by groundwater MPs to the environment and to human health, a necessary preliminary to remediation. In this work, to promote future MP pollution studies and remediation policies, we assimilated and synthesized the current knowledge on this topic. We reviewed current data on global groundwater pollution by MPs, analyzed the driving factors of their transport and distribution, and summarized the ecological and health hazards posed by MPs, before discussing current knowledge limits and suggesting perspectives for future work., 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. Published by Elsevier B.V.)

Cuproptosis in antitumor therapy faces challenges from copper homeostasis efflux mechanisms and high glutathione (GSH) levels in tumor cells, hindering copper accumulation and treatment efficacy. Herein, we propose a strategy of "adding fuel to the flames" for potent antitumor therapy through a self-accelerating cycle of ferroptosis-cuproptosis. Disulfiram (DSF) loaded hollow mesoporous copper-iron sulfide (HMCIS) nanoparticle with conjugation of polyethylene glycol (PEG) and folic acid (FA) (i.e., DSF@HMCIS-PEG-FA) was developed to swiftly release DSF, H 2 S, Cu 2+ , and Fe 2+ in the acidic tumor microenvironment (TME). The hydrogen peroxide (H 2 O 2 ) levels and acidity within tumor cells enhanced by the released H 2 S induce acceleration of Fenton (Fe 2+ ) and Fenton-like (Cu 2+ ) reactions, enabling the powerful tumor ferroptosis efficacy. The released DSF acts as a role of "fuel", intensifying catalytic effect ("flame") in tumor cells through the sustainable Fenton chemistry (i.e., "add fuel to the flames"). Robust ferroptosis in tumor cells is characterized by serious mitochondrial damage and GSH depletion, leading to excess intracellular copper that triggers cuproptosis. Cuproptosis disrupts mitochondria, compromises iron-sulfur (Fe-S) proteins, and elevates intracellular oxidative stress by releasing free Fe 3+ . These interconnected processes form a self-accelerating cycle of ferroptosis-cuproptosis with potent antitumor capabilities, as validated in both cancer cells and tumor-bearing mice., 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.)

Background: Surgical site infection (SSI) remains a critical postoperative complication after total hip and knee arthroplasty (THA and TKA). Frailty, a condition characterized by decreased physiological reserve and increased vulnerability to stressors, may influence the risk of SSI in these patients. This meta-analysis aims to evaluate the association between frailty and the incidence of SSI following THA or TKA., Methods: A systematic search of databases including PubMed, EMBASE, Web of Science, Wanfang, and CNKI was conducted to identify relevant studies. Data were extracted and pooled using a random-effects model to calculate the overall risk ratio (RR) and 95 % confidence intervals (CIs)., Results: A total of ten studies comprising 1,036,787 patients met the inclusion criteria. The meta-analysis revealed that frail patients undergoing THA or TKA had a significantly higher risk of developing SSI compared to non-frail patients (RR = 1.64, 95 % CI: 1.39-1.93, p < 0.001, I 2  = 66 %). Subgroup analyses indicated that the type of arthroplasty (hip vs. knee) and the method of frailty assessment did not significantly alter the association. Further subgroup analysis suggested that frailty was significantly associated with a higher incidence of deep SSI including joint infection (RR = 1.77, 95 % CI: 1.27-1.48, p < 0.001), but not the incidence of superficial SSI (RR = 1.57, 95 % CI: 0.45-5.42, p = 0.48). The association between frailty and SSI remains in subgroup of multivariate studies only (RR = 1.56, 95 % CI: 1.34 to 1.80, p < 0.001)., Conclusions: Frailty is a potential predictor of SSI following TKA/THA., Competing Interests: Declaration of competing interest The author declare that they have no potential competing interests., (Copyright © 2024 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Hepatocellular carcinoma (HCC) is an intractable malignant disease with high incidence rate annually. LincRNA PRNCR1 has been confirmed as a tumor supporter, while its functions in HCC remain unclear. This study aims to explore the mechanism of LincRNA PRNCR1 in hepatocellular carcinoma. The qRT-PCR was applied to the quantification of non-coding RNAs. Cell counting Kit-8 (CCK-8), Transwell assay and flow cytometry assay were applied to reflect the change in the phenotype of HCC cells. Moreover, the databases including Targetscan and Starbase and dual-luciferase reporter assay were applied to investigate the interaction of the genes. The western blot was applied to detect the abundance of proteins and the activity of the related pathways. Elevated LincRNA PRNCR1 was dramatically upregulated in HCC pathological samples and cell lines. MiR-411-3p served as a target of LincRNA PRNCR1, and decreased miR-411-3p was found in the clinical samples and cell lines. LincRNA PRNCR1 downregulation could induce the expression of miR-411-3p, and LincRNA PRNCR1 silence could impede the malignant behaviors via increasing the abundance of miR-411-3p. Zinc finger E-box binding homeobox 1 (ZEB1) was confirmed as a target of miR-411-3p, which remarkably upregulated in HCC cells, and ZEB1 upregulation could significantly rescue the effect of miR-411-3p on malignant behaviors of HCC cells. Moreover, LincRNA PRNCR1 was confirmed to involve the Wnt/β-catenin pathway via regulating miR-411-3p/ZEB1 axis. This study suggested that LincRNA PRNCR1 could drive the malignant progression of HCC via regulating miR-411-3p/ZEB1 axis.

KMT2D, a H3K4me1 methyltransferase primarily regulating enhancers, is a leading cause of KABUKI syndrome. This multisystem disorder leads to craniofacial and cognitive abnormalities, possibly through neural crest and neuronal lineages. However, the impacted cell-of-origin and molecular mechanism of KMT2D during the development of KABUKI disease remains unknown. Here we have optimized a brain organoid model to investigate neural crest and neuronal differentiation. To pinpoint KMT2D's enhancer target, we developed a genome-wide cis-regulatory element explorer (GREE) based on single-cell multiomic integration. Single cell RNA-seq revealed that KMT2D-knockout (KO) and patient-derived organoids exhibited neural crest deformities and GABAergic overproduction. Mechanistically, GREE identified that KMT2D targets a roof-plate-like niche cell and activates the niche cell-specific WNT3A enhancer, providing the microenvironment for neural crest and neuronal development. Interestingly, KMT2D-mutated mice displayed decreased WNT3A expression in the diencephalon roof plate, indicating impaired niche cell function. Deleting the WNT3A enhancer in the organoids presented phenotypic similarities to KMT2D-depletion, emphasizing the WNT3A enhancer as the predominant target of KMT2D. Conversely, reactivating WNT signaling in KMT2D-KO rescued the lineage defects by restoring the microenvironment. Overall, our discovery of KMT2D's primary target provides insights for reconciling complex phenotypes of KABUKI syndrome and establishes a new paradigm for dissecting the mechanisms of genetic disorders from genotype to phenotype., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Symmetry lies at the heart of two-dimensional (2D) bioelectronics, determining material properties at the fundamental level. Breaking the symmetry allows emergent functionalities and effects. However, symmetry modulation in 2D bioelectronics and the resultant applications have been largely overlooked. Here, we devise an oxidized architectural MXene, referred to as oxidized MXene (OXene), that couples orbit symmetric breaking with inverse symmetric breaking to entitle the optimized interfacial impedance and Schottky-induced piezoelectric effects. The resulting OXene validates applications ranging from microelectrode arrays, gait analysis, active transistor matrix, and wireless signaling transmission, which enables high-fidelity signal transmission and reconfigurable logic gates. Furthermore, OXene interfaces were investigated in both rodent and porcine myocardium, featuring high-quality and spatiotemporally resolved physiological recordings, while accurate differentiated predictions, enabled via various machine learning pipelines., Competing Interests: Competing interests statement:The authors declare no competing interest.

Bladder cancer (BCa) poses a significant threat to human health, with early-stage diagnosis being particularly valuable yet challenging due to the limited availability of highly efficient targeted contrast agents. In this study, we have developed a novel aptamer-gadolinium conjugate (Apt-Gd) designed as a targeted contrast agent for the magnetic resonance imaging (MRI) of early-stage BCa. The synthesis of Apt-Gd involved the direct conjugation of aptamers with chelating agents through a bioorthogonal reaction, followed by gadolinium chelation. Notably, Apt-Gd exhibited high longitudinal relaxivity, exceptional BCa specificity, and good biocompatibility. Furthermore, our research revealed that intravesical instillation of Apt-Gd effectively enhanced the stability of aptamers and boosted the local contrast enhancement in BCa-bearing mice. The utilization of Apt-Gd yielded a satisfactory signal-to-noise ratio during BCa imaging and significantly prolonged the imaging time window. On the whole, the accurate detection of early-stage BCa using Apt-Gd was achieved for the first time, making a breakthrough in BCa diagnosis with promising potential for practical clinical applications.

Next-generation fabrics with excellent protection and intelligent sensing abilities will be beneficial to protect the elderly from accidents, as the ageing population will be a global challenge in the next decade. However, for widely used techniques such as fabric coating and multi-layer compositing, maintaining a balance between comfortability, stable anti-impact protection, and multi-function such as intelligent monitoring remains elusive. Herein, a full-fiber composite yarn with triboelectric ability was developed, which was then woven into an origami-structured knitted fabric (OSKF). Due to the coaxial torsional structure, the composite yarn exhibited outstanding fracture strength (219.18 MPa). The full-fiber multi-scale structure design endowed the OSKF with significantly improved energy absorption capacity (absorbing > 85% of the applied force) and the desired self-powered sensing performance without affecting the comfortability. The OSKF also had a unique ability to respond to various hazardous situations, such as external mechanical force stimuli, cutting by a sharp object, and accidental falls. This work sheds light on a new path toward the design of next-generation smart protection wearables based on knitted fabric structure design-based full-fiber materials.

Peroxymonosulfate (PMS) is an eco-friendly disinfectant gaining attention. This study examined the influence of metal ions (Co(II), Cu(II), Fe(II)) on PMS disinfection with chloride ions (Cl - ) against waterborne microorganisms, encompassing both bacteria and fungal spores. The findings elucidated that metal ions augment the inactivation of bacteria in the PMS/Cl - system while concurrently impeding the inactivation of fungal spores. Specifically, the PMS/Co(II)/Cl - process increased E. coli inactivation rates by 2.25 and 2.75 times compared to PMS/Co(II) and PMS/Cl - , respectively. Conversely, PMS/Me(II)/Cl - generally exhibited a diminished inactivation capacity against the three fungal spores compared to PMS/Cl - , albeit surpassing the efficacy of PMS/Me(II). For instance, the inactivation levels of A. niger by PMS/Cl - , PMS/Cu(II)/Cl - , and PMS/Cu(II) are 4.47-log, 1.92-log, and 0.11-log, respectively. Notably, fungal spores demonstrated a substantially higher resistance to disinfectants compared to bacteria. Differences in microbial susceptibility were linked to cell wall structure, composition, antioxidant defenses, and reactive species generation, such as hydroxyl radicals (•OH), sulfate radicals (SO 4 •- ), and reactive chlorine species (RCS). This study demonstrated the novel and unique phenomenon of metal ions' dual role in modulating the PMS/Cl - disinfection process, which has not been reported before and has important implications for the field of water treatment., 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.)

We assessed the association between a genome-wide polygenic risk score (PRS) developed for lung adenocarcinoma (LUAD) risk and mutation on the epidermal growth factor receptor (EGFR) gene in 998 East Asian never-smoking female LUAD cases (518 EGFR-positive; 480 EGFR-negative) and 4,544 never-smoking controls using case-case and multinomial regression analyses. We found that the PRS was more strongly associated with EGFR-positive LUAD compared to EGFR-negative LUAD, where the association between the fourth quartile of the PRS and EGFR-positive LUAD (OR=8.63, 95% CI:5.67, 13.14) was significantly higher than the association between the fourth quartile of the PRS with EGFR-negative LUAD (OR=3.50, 95% CI: 2.44, 5.00) (p-heterogeneity=3.66x10 -3 ). Our findings suggest that germline genetic susceptibility may be differentially associated with LUAD in never-smoking female East Asian patients depending on the cancer's mutation status, which may have important public health and clinical implications., (Copyright © 2024. Published by Elsevier Inc.)

Clematis is an excellent vertical greening plant for garden viewing vines, with great ornamental and high medicinal value. To obtain transcriptome information and functional gene data for the Clematis calyx, this study utilized three biological replicates of the calyx from each of the three Clematis varieties: 'Henryi', 'Polish spirit', and 'Mme Julia Correvon' Single-molecule real-time sequencing technology was employed for full-length transcriptome sequencing. The study revealed that 21,673,173 non-chimeric sequences were identified through full-length transcriptome sequencing. After clustering, correction, and redundancy removal, 40,465 high-quality, full-length transcripts were obtained. Among these transcripts, there were 15,488 long non-coding RNA (lncRNA), 9,212 simple sequence repeats (SSR) sites, 1,247 transcription factors (TFs), 1,228 alternative splicing events, and 7,189 selectively polyadenylation sites predicted. In addition, 7,442 primer pairs were designed based on the SSR sites, covering 80.76% of the total SSR. 15 primer pairs were randomly selected for amplification, and 73.3% of them were successfully amplified. Transcript annotation results showed that 38,439, 38,094, 26,815, and 33,407 transcripts were annotated to the Nr, KEGG, KOG, and SwissProt databases, respectively. Among these, the KEGG database identified 137 metabolic pathways, including biosynthesis of secondary metabolites, carbon metabolism, and amino acid biosynthesis. 104 and 7 transcripts are involved in the flavonoid and anthocyanin metabolism pathways, respectively. The above results provide initial insights into the transcriptome information and functional characteristics of Clematis calyx. This critical data supports future research on marker primers for the color mechanism of Clematis calyx, the pathways and regulatory mechanisms of flavonoids and other products, as well as specific trait genes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Tobacco is an agricultural commodity with great economic significance. Producers recognize that the flavor characteristics of filler tobacco clear-out (FTLs) affect the quality of cigar tobacco items. To identify the major volatile organic compounds (VOCs) responsible for differences in FTLs, E-nose, HS-SPME-GC-MS, and HS-GC-IMS were employed for multi-dimensional analysis of nine groups of FTLs at various fermentation stages. The E-nose results indicated a progressive increase in nitrogen-oxygen compounds during fermentation. Coupled with these findings, HS-SPME-GC-MS identified 56 VOCs, and HS-GC-IMS revealed 55 VOCs in the FTLs. Principal component analysis (PCA) suggested that FTLs from various fermentation stages of the Yunxue No 39 tobacco plant exhibit significant differences. Partial least squares discriminant analysis (PLS-DA), along with the variable importance in projection (VIP) method for feature selection, pinpointed 12 VOCs as the essential unmistakable metabolites embroiled within the agrarian fermenting prepare of matured FTLs. During the fermentation process, these crucial metabolites are predominantly enriched in pathways including pyruvate metabolism, phenylalanine metabolism, as well as nicotinate and nicotinamide metabolism. The study provides insights into the differences and diversity of FTLs at agricultural fermentation stages. It offers valuable information for optimizing the quality of agricultural fermentation and guiding the directional fermentation of tobacco leaves., 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.)

Background: Remdesivir, an RNA-polymerase prodrug inhibitor approved for treatment of coronavirus disease 2019 (COVID-19), shortens recovery time and improves clinical outcomes. This prespecified analysis compared remdesivir plus standard of care (SOC) with SOC alone in adults hospitalized with COVID-19 requiring oxygen support in the early stage of the pandemic., Methods: Data for 10-day remdesivir treatment plus SOC from the extension phase of an open-label study (NCT04292899) were compared with real-world, retrospective data on SOC alone (EUPAS34303). Both studies included patients aged ≥18 years hospitalized with severe acute respiratory syndrome coronavirus 2 up to 30 May 2020, with oxygen saturation ≤94% on room air or supplemental oxygen (all forms), and with pulmonary infiltrates. Propensity score weighting was used to balance patient demographics and clinical characteristics across treatment groups. The primary endpoint was time to all-cause mortality or end of study (day 28). Time to discharge, with a 10-day landmark to account for duration of remdesivir treatment, was a secondary endpoint., Results: A total of 1974 patients treated with remdesivir plus SOC, and 1426 with SOC alone, were included after weighting. Remdesivir significantly reduced mortality versus SOC (hazard ratio [HR], 0.46; 95% confidence interval, .39-.54). This association was observed at each oxygen support level, with the lowest HR for patients on low-flow oxygen. Remdesivir significantly increased the likelihood of discharge at day 28 versus SOC in the 10-day landmark analysis (HR, 1.64; 95% confidence interval: 1.43-1.87)., Conclusions: Remdesivir plus early-2020 SOC was associated with a 54% lower mortality risk and shorter hospital stays compared with SOC alone in patients hospitalized with COVID-19 requiring oxygen support. Clinical Trials Registration.  ClinicalTrials.gov NCT04292899 and EUPAS34303., Competing Interests: Potential conflicts of interest. D. F. has served on advisory boards for Gilead Sciences, Inc. and Axcella, and as site principal investigator for clinical trials sponsored by Gilead Sciences, Inc., MetroBiotech, LLC, the National Institutes of Health (NIH; DMID COVAIL), and Regeneron. H. F. G. has received honoraria as a member of DMC or advisory boards for Gilead Sciences, Inc., GSK, Janssen, Johnson and Johnson, Merck, Novartis, and ViiV Healthcare. Furthermore, he has received grants outside of this work from the NIH, Swiss HIV Cohort Study, Swiss National Science Foundation, and Yvonne Jacob Foundation; and has received unrestricted research grants from Gilead Sciences, Inc. All grants were paid to his institution. He has also received a travel grant from Gilead Sciences, Inc. for conference attendance. S. K. G. has received independent grant funding from Indiana University, the NIH, and ViiV Healthcare; and has received consulting/advisory fees from Gilead Sciences, Inc. and ViiV Healthcare. D. K. has received consulting fees from E.R. Squibb & Sons, LLC, and holds stock options in HCA Healthcare. B. B. has received grants from AstraZeneca, Gilead Sciences, Inc., and NIH; has received consulting fees, speaker honoraria, and travel support from Gilead Sciences, Inc.; has participated on a Data Safety Monitoring Board (DSMB) or advisory board for Gilead Sciences, Inc. and is a Gilead Sciences, Inc. speaker for their hepatitis C virus antiviral agent. S. O. has received research funding from HRSA Ryan White Funds. J. A. A. has received institutional research support for clinical trials from Emergent BioSolutions, Frontier Technologies, Gilead Sciences, Inc., GSK, Janssen, Merck, Pfizer, Regeneron, and ViiV Healthcare; has received personal fees for advisory boards from GSK/ViiV Healthcare and Merck; and has participated on a DSMB for Kintor Pharmaceutical, all outside the submitted work. I. M., L. E. T., Y. T., C. B., G. W., R. H., C.-Y. W., A. P. C., and A. O. O. are employees of, and stockholders in, Gilead Sciences, Inc. C.-M. W. has received research funding and travel grants from Gilead Sciences, Inc. for this study; has received research grants or contracts; consulting fees, payment, or honoraria for lectures, presentations, or educational events; and travel support from AbbVie, AstraZeneca, BeiGene, BioNTech, Hoffmann-La Roche, Janssen, and Moderna; and has participated on a Data DSMB or advisory board for AbbVie, AstraZeneca, BeiGene, BioNTech, Hoffmann-La Roche, Janssen, and Moderna. R. L. G. has received grants or contracts to his institution from Eli Lilly, Gilead Sciences, Inc., Johnson & Johnson, Pfizer, Regeneron, and Roivant Sciences (Kinevant Sciences); has received consulting fees from AbbVie, Eli Lilly, Gilead Sciences, Inc., GSK, and Roche; has received payment or honoraria for lectures/speaker fees from Gilead Sciences, Inc. and Pfizer (for an unrelated field); has received travel support from Gilead Sciences, Inc.; has participated on advisory boards for AbbVie, AstraZeneca, Eli Lilly, Gilead Sciences, Inc., GSK, Johnson & Johnson, Kinevant Sciences, and Roche/Genentech; is a de minimis stockholder at AbCellera; and received a gift-in-kind to his institution for an unrelated clinical trial (NCT03383419) from Gilead Sciences, Inc. during the conduct of this study. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The effect of embolization of the middle meningeal artery in patients with subacute or chronic subdural hematoma is uncertain., Methods: We performed a multicenter, open-label, randomized trial in China, involving patients with symptomatic nonacute subdural hematoma with mass effect. Patients were assigned to undergo burr-hole drainage or receive nonsurgical treatment at the surgeon's discretion, and patients in each group were then randomly assigned, in a 1:1 ratio, to undergo middle meningeal artery embolization with liquid embolic material or to receive usual care. Patients whose condition warranted craniotomy were excluded. The primary outcome was symptomatic recurrence or progression of subdural hematoma within 90 days after randomization. Secondary outcomes included clinical and imaging outcomes. The main safety outcome was any serious adverse event (including death)., Results: The analysis included 722 patients, of whom 360 were assigned to the embolization group and 362 to the usual-care group. Burr-hole drainage was performed in 78.3% of the enrolled patients; among the patients who underwent burr-hole drainage, the procedure occurred after embolization in 99.6%. Symptomatic recurrence or progression of subdural hematoma within 90 days occurred in 24 patients (6.7%) in the embolization group and in 36 (9.9%) in the usual-care group (between-group difference, -3.3 percentage points; 95% confidence interval, -7.4 to 0.8; P = 0.10). The incidence of serious adverse events was lower in the embolization group than in the usual-care group (6.7% vs. 11.6%, P = 0.02)., Conclusions: Among patients with symptomatic nonacute subdural hematoma (of whom 78% underwent burr-hole drainage), middle meningeal artery embolization resulted in a 90-day incidence of symptomatic recurrence or progression similar to that with usual care but was associated with a lower incidence of serious adverse events. (Funded by Shanghai Shenkang Hospital Development Center and others; MAGIC-MT ClinicalTrials.gov number, NCT04700345.)., (Copyright © 2024 Massachusetts Medical Society.)

A fundamental understanding of hot carrier relaxation in metal nanostructures is essential for realizing their application potential in energy conversion and photocatalysis. Despite previous investigations of the relaxation of hot carriers generated by surface plasmon resonance (SPR) excitation and interband transitions (IBTs), the hot carrier relaxation lifetimes and their associated mechanisms remain unclear. Herein, we demonstrate two distinct hot carrier relaxation channels in gold plasmonic nanostructures. The experimental observations reveal that the hot carrier relaxation is faster following SPR excitation than that from IBTs in gold nanoparticles and nanorods. The experimental results and theoretical calculations indicate that the numerous plasmon-induced hot carriers undergo surface-mediated carrier-carrier scattering in large gold nanostructures, whereas almost all IBT-induced hot carriers experience bulk carrier-carrier scattering. These findings advance our understanding of hot carrier relaxation and contribute to a clearer microscopic description of scattering channels in plasmonic nanostructures.

Constructing alternating donor-acceptor (D-A) units within g-C 3 N 4 represents an effective strategy for enhancing photocatalytic performance through improved charge carrier separation while concurrently addressing energy shortages and facilitating wastewater remediation. Here, a series of D-A-type conjugated photocatalysts (CNBTC-X) are prepared using g-C 3 N 4 as an acceptor unit and different masses of 5-bromo-2-thiophenecarboxaldehyde (BTC) as a donor unit by a one-step thermal polymerization. CNBTC-50 presents higher photocatalytic properties for CO 2 reduction coupled with tetracycline (TC) removal than those of g-C 3 N 4 , CNBTC-10, CNBTC-30, and CNBTC-70. The introduction of the unique electron-donor-acceptor structure effectively drives the separation and transfer of photoinduced carriers while reducing the internal carrier transfer hindrance. Photocatalytic experiments reveal that the CNBTC-50 photocatalyst achieves up to 94.6% TC removal under visible light irradiation conditions. Compared with that of the pristine g-C 3 N 4 , the photocatalytic degradation reaction rate constant of CNBTC-50 is significantly increased by about 3.87 times. The study examines the influence of various reaction parameters on degradation activity, including catalyst concentration, pH, and TC concentration. Additionally, LC-MS is utilized to perform a comprehensive analysis of the intermediates and pathways involved in TC degradation. Furthermore, CNBTC-50 demonstrates remarkable photocatalytic CO 2 reduction activity, achieving rates of 20.83 μmol g -1 h -1 (CO) and 9.36 μmol g -1 h -1 (CH 4 ), which are 10.68 and 5.98 times more efficient than those of g-C 3 N 4 , respectively. This work aims to offer valuable guidance for the rational design of nonmetal D-A-structured catalysts and effectively integrates reaction systems to couple CO 2 reduction with antibiotic removal.

Myxochelins are a group of catecholate siderophores encoded by mxc biosynthetic gene clusters (BGCs). They are mainly produced by myxobacteria and display a wide variety of bioactivities. Herein, we report a group of new myxochelins produced not by a myxobacterial strain but by an actinobacteria strain, Micromonospora sp. TMD166. They consisted of six new compounds, designated as sporachelins A ( 1 ), A1 ( 2 ), B ( 3 ), C ( 4 ), D ( 5 ), and E ( 6 ), and the known compound myxochelin A ( 7 ). The planar structures were determined by comprehensive analyses of 1D and 2D NMR spectroscopic data, and the absolute configurations were confirmed by Marfey's analysis and chemical synthesis. The six sporachelins are the first examples of acylated derivatives at the primary alcohol of myxochelin A. These molecules were found to inhibit human 5-lipoxygenase. In addition, 1 - 7 exhibited antifibrotic activity in the TGFβ1-induced human hepatic cell line LX-2 by suppressing fibrosis-related genes COL1A1 , ACTA2 , and TGFB1 expression. This is the first report of antifibrotic activity by myxochelins.

In photoacoustic spectroscopy based multicomponent gas analysis, the overlap of the absorption spectra among different gases can affect the measurement accuracy of gas concentrations. We report a multicomponent gas analysis method based on empirical modal decomposition (EMD), convolutional neural networks (CNN), and long short-term memory (LSTM) networks that can extract the exact concentrations of mixed gases from the overlapping wavelength-modulated spectroscopy with second harmonic (WMS-2f) detection. The WMS-2f signals of 25 different concentration combinations of acetylene-ammonia mixtures are detected using a single distributed feedback laser (DFB) at 1531.5 nm. The acetylene concentrations range from 2.5 to 7.5 ppm and the ammonia concentrations from 12.5 to 37.5 ppm. The data set is enhanced by cyclic shifting and adding Gaussian noise. The classification accuracy of the test set reaches 99.89% after tuning. The mean absolute errors of the five additional sets of data measured under different conditions are 0.092 ppm for acetylene and 1.902 ppm for ammonia, within the above concentration ranges.

Background: Multi-material decomposition is an interesting topic in dual-energy CT (DECT) imaging; however, the accuracy and performance may be limited using the conventional algorithms., Purpose: In this work, a novel multi-material decomposition network (MMD-Net) is proposed to improve the multi-material decomposition performance of DECT imaging., Methods: To achieve dual-energy multi-material decomposition, a deep neural network, named as MMD-Net, is proposed in this work. In MMD-Net, two specific convolutional neural network modules, Net-I and Net-II, are developed. Specifically, Net-I is used to distinguish the material triangles, while Net-II predicts the effective attenuation coefficients corresponding to the vertices of the material triangles. Subsequently, the material-specific density maps are calculated analytically through matrix inversion. The new method is validated using in-house benchtop DECT imaging experiments with a solution phantom and a pig leg specimen, as well as commercial medical DECT imaging experiments with a human patient. The decomposition accuracy, edge spreading function, and noise power spectrum are quantitatively evaluated., Results: Compared to the conventional multiple material decomposition (MMD) algorithm, the proposed MMD-Net method is more effective at suppressing image noise. Additionally, MMD-Net outperforms the iterative MMD approach in maintaining decomposition accuracy, image sharpness, and high-frequency content. Consequently, MMD-Net is capable of generating high-quality material decomposition images., Conclusion: A high performance multi-material decomposition network is developed for dual-energy CT imaging., (© 2024 American Association of Physicists in Medicine.)

In recent years, Electronic health records (EHR) has gradually become the mainstream in the healthcare field. However, due to the fact that EHR systems are provided by different vendors, data is dispersed and stored, which leads to the phenomenon of data silos, making medical information too fragmented and bringing some challenges to current medical services. Therefore, in view of the difficulties in sharing EHR between medical institutions, the risk of privacy leakage, and the lack of EHR usage control by patients, an EHR sharing model based on consortium blockchain is proposed in this paper. Firstly, the Interplanetary File System is combined with consortium blockchain, which forms a hybrid storage scheme of EHR, this technology effectively improves data security, privacy protection, and operational efficiency. Secondly, the model combines unidirectional multi-hop conditional proxy re-encryption based on type and identity with distributed key generation technology to achieve secure EHR sharing with fine grained control. At the same time, users are required to link the operation records of EHR, so as to realize the traceability of EHR usage. A dynamic Byzantine fault-tolerant algorithm based on reputation and clustering is then proposed to solve the problems of arbitrary master node selection, high latency and low throughput of PBFT, enabling the nodes to reach consensus more efficiently. Finally, the model is analyzed in terms of security and user control, showing that the model is less energy intensive in terms of communication overhead and time consumption, and can effectively achieve secure sharing between medical data., Competing Interests: Declarations Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)