A comprehensive review and comparison of existing computational methods for protein function prediction.

Protein function prediction is critical for understanding the cellular physiological and biochemical processes, and it opens up new possibilities for advancements in fields such as disease research and drug discovery. During the past decades, with the exponential growth of protein sequence data, many computational methods for predicting protein function have been proposed. Therefore, a systematic review and comparison of these methods are necessary. In this study, we divide these methods into four different categories, including sequence-based methods, 3D structure-based methods, PPI network-based methods and hybrid information-based methods. Furthermore, their advantages and disadvantages are discussed, and then their performance is comprehensively evaluated and compared. Finally, we discuss the challenges and opportunities present in this field.

Establishment of an animal model of immune-related adverse events induced by immune checkpoint inhibitors.

OBJECTIVE: Immunotherapy, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. However, it can also cause immune-related adverse events (irAEs). This study aimed to develop a clinically practical animal model of irAEs using BALB/c mice. METHODS: Subcutaneous tumors of mouse breast cancer 4T1 cells were generated in inbred BALB/c mice. The mice were treated with programmed death-1 (PD-1) and cytotoxic t-lymphocyte antigen 4 (CTLA-4) inhibitors once every 3 days for five consecutive administration cycles. Changes in tumor volume and body weight were recorded. Lung computed tomography (CT) scans were conducted. The liver, lungs, heart, and colon tissues of the mice were stained with hematoxylin-eosin (H&E) staining to observe inflammatory infiltration and were scored. Serum samples were collected, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ferritin, glutamic-pyruvic transaminase (ALT), tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). Mouse liver and lung cell suspensions were prepared, and changes in macrophages, T cells, myeloid-derived suppressor cells (MDSCs), and regulatory (Treg) cells were detected by flow cytometry. RESULTS: Mice treated with PD-1 and CTLA-4 inhibitors showed significant reductions in tumor volume and body weight. The tissue inflammatory scores in the experimental group were significantly higher than those in the control group. Lung CT scans of mice in the experimental group showed obvious inflammatory spots. Serum levels of ferritin, IL-6, TNF-α, IFN-γ, and ALT were significantly elevated in the experimental group. Flow cytometry analysis revealed a substantial increase in CD3+T cells, Treg cells, and macrophages in the liver and lung tissues of mice in the experimental group compared with the control group, and the change trend of MDSCs was opposite. CONCLUSIONS: The irAE-related animal model was successfully established in BALB/c mice using a combination of PD-1 and CTLA-4 inhibitors through multiple administrations with clinical translational value and practical. This model offers valuable insights into irAE mechanisms for further investigation.

MOF-derived high oxygen vacancies CuO/CeO2 catalysts for low-temperature CO preferential oxidation.

The CO preferential oxidation reaction (CO-PROX) is an effective strategy to remove residual poisonous CO in proton exchange membrane fuel cells, in which oxygen vacancies play a critical role in CO adsorption and activation. Herein, a series of CuO/CeO2 catalysts derived from Ce-MOFs precursors were synthesized using different organic ligands via the hydrothermal method and the CO-PROX performance was investigated. The CuO/CeO2-135 catalyst derived from homophthalic tricarboxylic acid (1,3,5-H3BTC) exhibited superior catalytic performance with 100 % CO conversion at a relatively low temperature (T100% = 100 °C), with a wide reaction temperature range and excellent stability. The superior catalytic properties were attributed to the structural improvements provided by the 1,3,5-H3BTC precursors and the promotional effects of oxygen vacancies. Additionally, in-situ Raman spectroscopy was performed to verify the dynamic roles of oxygen vacancies for CO adsorption and activation, while in-situ DRIFTS analysis revealed key intermediates in the CO-PROX reaction, shedding light on the mechanistic aspects of the catalytic process. This work not only demonstrates insights into the effective CuO/CeO2 catalysts for CO preferential oxidation, but also provides a feasible way to synthesize MOF-derived catalysts.

Epidemiological and evolutionary analysis of canine circovirus from 1996 to 2023.

BACKGROUND: Canine circovirus (CanineCV), a non-enveloped virus with a circular DNA genome, has been identified in various avian and mammalian species, including domestic and wild canids. This study aimed to comprehensively analyze the prevalence of CanineCV across diverse animal species in 11 provinces of China. RESULTS: A total of 1,666 serum samples were collected, revealing a 5.82% prevalence of CanineCV in dogs, with the highest rates being observed in southern and eastern China. Phylogenetic analysis of 266 global CanineCV genomes sourced from the NCBI identified six distinct genotypes, elucidating the complex dynamics of their evolution. Evidence suggested a potential bat origin for CanineCV, with positive selection and high rates of evolution being observed. Recombination analysis revealed dynamic genetic exchange, highlighting the intricate nature of CanineCV evolution. Mutational analysis identified key amino acid substitutions likely to influence the virus's adaptation. Additionally, glycosylation, palmitoylation, and SUMOylation sites were predicted, shedding light on crucial functional properties of the virus. CONCLUSIONS: This study provides a global perspective on the origin, genetic diversity, and evolutionary dynamics of CanineCV. Understanding these factors is crucial for elucidating its epidemiology and potential health risks.

Nanometabolomics Elucidated Biological Prospective of Mo4/3B2-x Nanosheets: Toward Metabolic Reprogramming of Amino Acid Metabolism.

Mo4/3B2-x nanosheets are newly developed, and 2D transition metal borides (MBene) were reported in 2021, but there is no report on their further applications and modification; hence, this article sheds light on the significance of potential biological prospects for future biomedical applications. Therefore, elucidation of the biocompatibility, biotoxicology, and bioactivity of Mo4/3B2-x nanosheets has been an urgent need to be fulfilled. Nanometabolomics (also referred as nanomaterials-based metabolomics) was first proposed and utilized in our previous work, which specialized in interpreting nanomaterials-induced metabolic reprogramming through aqueous metabolomics and lipidomics approach. Hence, nanometabolomics could be considered as a novel concept combining nanoscience and metabolomics to provide bioinformation on nanomaterials' biomedical applications. In this work, the safe range of concentration (<50 mg/L) with good biosafety toward human umbilical vein endothelial cells (HUVECs) was discovered. The low concentration (5 mg/L) and high concentration (50 mg/L) of Mo4/3B2-x nanosheets were utilized for the in vitro Mo4/3B2-x-cell interaction. Nanometabolomics has elucidated the biological prospective of Mo4/3B2-x nanosheets via monitoring its biocompatibility and metabolic shift of HUVECs. The results revealed that 50 mg/L Mo4/3B2-x nanosheets could lead to a stronger alteration of amino acid metabolism with disturbance of the corresponding amino acid-related pathways (including amino acid metabolism, amino acid degradation, fatty acid biosynthesis, and lipid biosynthesis and metabolism). These interesting results were closely involved with the oxidative stress and production of excess ROS. This work could be regarded as a pathbreaking study on Mo4/3B2-x nanosheets at a biological level, which also designates their further biochemical, medical, and industrial application and development based on nanometabolomics bioinformation.

Abnormal dynamic functional connectivity and topological properties of cerebellar network in male obstructive sleep apnea.

PURPOSE: To investigate dynamic functional connectivity (dFC) within the cerebellar-whole brain network and dynamic topological properties of the cerebellar network in obstructive sleep apnea (OSA) patients. METHODS: Sixty male patients and 60 male healthy controls were included. The sliding window method examined the fluctuations in cerebellum-whole brain dFC and connection strength in OSA. Furthermore, graph theory metrics evaluated the dynamic topological properties of the cerebellar network. Additionally, hidden Markov modeling validated the robustness of the dFC. The correlations between the abovementioned measures and clinical assessments were assessed. RESULTS: Two dynamic network states were characterized. State 2 exhibited a heightened frequency, longer fractional occupancy, and greater mean dwell time in OSA. The cerebellar networks and cerebrocerebellar dFC alterations were mainly located in the default mode network, frontoparietal network, somatomotor network, right cerebellar CrusI/II, and other networks. Global properties indicated aberrant cerebellar topology in OSA. Dynamic properties were correlated with clinical indicators primarily on emotion, cognition, and sleep. CONCLUSION: Abnormal dFC in male OSA may indicate an imbalance between the integration and segregation of brain networks, concurrent with global topological alterations. Abnormal default mode network interactions with high-order and low-level cognitive networks, disrupting their coordination, may impair the regulation of cognitive, emotional, and sleep functions in OSA.

Microstructural Changes in the Cerebral White Matter After 12 Months of CPAP Treatment for Moderate to Severe Obstructive Sleep Apnoea: A TBSS Study.

Introduction: Continuous positive airway pressure (CPAP) therapy improves clinical symptoms in patients with obstructive sleep apnea (OSA); however, the mechanism of this clinical improvement and how it may be associated with the restoration of white matter (WM) structures in the brain is unclear. Therefore, this study investigated the relationship between the structural recovery of brain WM and improvements in cognitive function and emotion after long-term (12 months) CPAP treatment in patients with OSA. Methods: We collected data from 17 patients with OSA before and 12 months after CPAP treatment, including sleep monitoring, clinical assessment, and diffusion tensor imaging (DTI) magnetic resonance imaging. Results: We observed a partial reversible recovery of brain WM (mean and radial diffusion coefficients) after treatment. This recovery involved the commissural fibers (cingulum, body of corpus callosum), projection fibers (retrolenticular part of the internal capsule, posterior thalamic radiation, posterior limb of the internal capsule, superior corona radiata, posterior corona radiata), association fibers (external capsule, superior longitudinal fasciculus, inferior longitudinal fasciculus), and other regions. In addition, the improvements in WM fibers in one part of the brain significantly were correlated with the Hamilton Anxiety Scale and Hamilton Depression Scale scores. Discussion: Our results suggest that reversible recovery of reduced brain WM integrity due to OSA may require longer CPAP treatment. Moreover, changes in the integrity of the commissural fibers were associated with emotion regulation. These restored WM areas may explain the cognitive and mood improvements observed after OSA treatment.

Regulation of nitrogen metabolism by COE2 under low sulfur stress in Arabidopsis.

The interplay between nitrogen and sulfur assimilation synergistically supports and sustains plant growth and development, operating in tandem to ensure coordinated and optimal outcomes. Previously, we characterized Arabidopsis CHLOROPHYLL A/B-BINDING (CAB) overexpression 2 (COE2) mutant, which has a mutation in the NITRIC OXIDE-ASSOCIATED (NOA1) gene and exhibits deficiency in root growth under low nitrogen (LN) stress. This study found that the growth suppression in roots and shoots in coe2 correlates with decreased sensitivity to low sulfur stress treatment compared to the wild-type. Therefore, we examined the regulatory role of COE2 in nitrogen and sulfur interaction by assessing the expression of nitrogen metabolism-related genes in coe2 seedlings under low sulfur stress. Despite the notable upregulation of nitrate reductase genes (NIA1 and NIA2), there was a considerable reduction in nitrogen uptake and utilization, resulting in a substantial growth penalty. Moreover, the elevated expression of miR396 perhaps complemented growth stunting by selectively targeting and curtailing the expression levels of GROWTH REGULATING FACTOR 2 (GRF2), GRF4, and GRF9. This study underscores the vital role of COE2-mediated nitrogen signaling in facilitating seedling growth under sulfur deficiency stress.

Biomimetic Cancer-Targeting Nanoplatform Boosting AIEgens-Based Photodynamic Therapy and Ferroptosis by Disrupting Redox-Homeostasis.

Photodynamic therapy (PDT) using aggregation-induced emission photosensitizer (AIE-PS) holds tremendous potential but is limited by its inherent disadvantages and the high concentrations of reduced glutathione (GSH) in tumor cells that can neutralize ROS to weaken PDT. Herein, we designed a nanodelivery system (CM-HSADSP@[PS-Sor]) in which albumin was utilized as a carrier for hydrophobic drug AIE-PS and Sorafenib, cross-linkers with disulfide bonds were introduced to form a nanogel core, and then cancer cell membranes were wrapped on its surface to confer homologous tumor targeting ability. A two-way strategy was employed to disturb redox-homeostasis through blocking GSH synthesis by Sorafenib and consuming excess GSH via abundant disulfide bonds, thereby promoting the depletion of GSH, which in turn increased the ROS levels in cancer cells to amplify the efficacy of ferroptosis and PDT, achieving an efficient in vivo antibreast cancer effect. This study brings a new strategy for ROS-based cancer therapy and expands the application of an albumin-based drug delivery system.

A novel nano-drug delivery system of glycyrrhetinic acid-mediated intracellular breakable brucine for enhanced anti-hepatitis B efficacy.

Background: Glycyrrhetinic acid-mediated brucine self-assembled nanomicelles enhance the anti-hepatitis B properties of brucine by improving its water solubility, short half-life, toxicity, and side effects. Brucine (B) is an indole alkaloid extracted from the seeds of Strychnos nux-vomica (Loganiaceae). Purpose: To assess the efficacy of the Brucine-Glycyrrhetnic acid-Polyethylene glycol-3,3'-dithiodipropionic acid-Glycerin monostearate (B-GPSG) in treating hepatitis B, its potential to protect against acute liver injury caused by d-galactosamine and its anti-hepatoma activities were studied. Research Design: The concentration of B-GPSG used in the in vivo and in vitro experiments was 0.63 mg/mL. The rats injected with d-GalN (450 mg/kg) were used as liver injury models. The rats were separated into normal, model, positive, positive control, B-PSG and B-GPSG groups. Hepatoma cells expressing HBV HepG2.2.15 were used for in vitro experiments. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate cloning, Hoechst staining and flow cytometry were conducted to explore the mechanism of B-GPSG against hepatitis B. Results: Compared with the model group, the liver coefficient of B-GPSG group decreased (4.59 ± 0.17 vs 5.88 ± 0.42), the content of MDA in rat liver homogenate decreased (12.54 ± 1.81 vs 23.05 ± 2.98), the activity of SOD increased, the activity of ALT and AST in rat serum decreased. In vitro, the IC50 values of B-GPSG group decreased. B-GPSG group effectively inhibited the proliferation and migration of HepG2.2.15 cells. Conclusions: The hepatoprotective effects of B-GPSG nanomicelles, which are attributed to their GA-mediated liver targeting and synergistic actions with brucine, suggest their therapeutic potential against hepatitis B. This development opens up new possibilities for the application of traditional Chinese medicine and nanomedicine in anti-hepatitis B.

Overlooked shelf sediment reductive sinks of dissolved rhenium and uranium in the modern ocean.

Rhenium (Re) and uranium (U) are essential proxies in reconstructing past oceanic oxygenation evolution. However, their removal in continental shelf sediments, hotspots of early diagenesis, were previously treated as quantitatively unimportant sinks in the ocean. Here we examine the sedimentary reductive removal of Re and U and their coupling with organic carbon decomposition, utilizing the 224Ra/228Th disequilibria within the East China Sea shelf. We identified positive correlations between their removal fluxes and the rates of sediment oxygen consumption or organic carbon decomposition. These correlations enable an evaluation of global shelf reductive sinks that are comparable to (for Re) or higher than (~4-fold for U) previously established suboxic/anoxic sinks. These findings suggest potential imbalances in the modern budgets of Re and U, or perhaps a substantial underestimation of their sources. Our study thus highlights shelf sedimentary reductive removal as critical yet overlooked sinks for Re and U in the modern ocean.

Infarct-related artery only revascularization versus multi-vessel revascularization for patients with Killip I-IV acute myocardial infarction and multivessel disease.

BACKGROUND: The optimal revascularization strategy for non-culprit vessels is still up for debate nowadays, particularly when it comes to individuals with different Killip classes. Therefore, the aim of our study was to investigate whether multivessel revascularization, as compared with infarct-related artery (IRA) alone revascularization, improves long-term prognosis in patients who have experienced an acute myocardial infarction (AMI) and have multivessel coronary artery disease (CAD). METHODS: A retrospective analysis was conducted on clinical data from 646 patients who presented with AMI and multivessel CAD at Beijing Chaoyang hospital between November 2014 and November 2020. Based on various revascularization strategies, patients were categorised into two groups: IRA-only revascularization (n = 416) and multivessel revascularization (n = 230). The primary endpoint was cardiovascular death. RESULTS: In the following 60.6 months (60.6 ± 23.9), the primary endpoint occurred in 3% of the multivessel revascularization group versus 9.6% in the IRA-only revascularization group (HR 0.284, CI 0.120-0.669, p = 0.002). For the Killip I-II patients (n = 533), the primary endpoint occurred in 2.6% of the multivessel revascularization group versus 9.5% in the IRA-only revascularization group (HR 0.236, CI 0.083-0.667, p = 0.003). For Killip III-IV patients (n = 113), there was no significance differences in the primary endpoint. After using the inverse probability weighted method, the benefit of complete revascularization was consistently observed. CONCLUSIONS: Multivessel revascularization significantly reduced the incidence of cardiovascular death for patients presenting with AMI and multivessel CAD, particularly for Killip I-II patients. There were no significant differences in the primary outcome across the groups of patients with Killip III-IV.

Predictive value of CT and 18F-FDG PET/CT features on spread through air space in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma, a leading cause of cancer-related mortality, demands precise prognostic indicators for effective management. The presence of spread through air space (STAS) indicates adverse tumor behavior. However, comparative differences between 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography(PET)/computed tomography(CT) and CT in predicting STAS in lung adenocarcinoma remain inadequately explored. This retrospective study analyzes preoperative CT and 18F-FDG PET/CT features to predict STAS, aiming to identify key predictive factors and enhance clinical decision-making. METHODS: Between February 2022 and April 2023, 100 patients (108 lesions) who underwent surgery for clinical lung adenocarcinoma were enrolled. All these patients underwent 18F-FDG PET/CT, thin-section chest CT scan, and pathological biopsy. Univariate and multivariate logistic regression was used to analyze CT and 18F-FDG PET/CT image characteristics. Receiver operating characteristic curve analysis was performed to identify a cut-off value. RESULTS: Sixty lesions were positive for STAS, and 48 lesions were negative for STAS. The STAS-positive was frequently observed in acinar predominant. However, STAS-negative was frequently observed in minimally invasive adenocarcinoma. Univariable analysis results revealed that CT features (including nodule type, maximum tumor diameter, maximum solid component diameter, consolidation tumor ratio, pleural indentation, lobulation, spiculation) and all 18F-FDG PET/CT characteristics were statistically significant difference in STAS-positive and STAS-negative lesions. And multivariate logistic regression results showed that the maximum tumor diameter and SUVmax were the independent influencing factors of CT and 18F-FDG PET/CT in STAS, respectively. The area under the curve of maximum tumor diameter and SUVmax was 0.68 vs. 0.82. The cut-off value for maximum tumor diameter and SUVmax was 2.35 vs. 5.05 with a sensitivity of 50.0% vs. 68.3% and specificity of 81.2% vs. 87.5%, which showed that SUVmax was superior to the maximum tumor diameter. CONCLUSION: The radiological features of SUVmax is the best model for predicting STAS in lung adenocarcinoma. These radiological features could predict STAS with excellent specificity but inferior sensitivity.

Narrow band imaging-based radiogenomics for predicting radiosensitivity in nasopharyngeal carcinoma.

Objectives: This study aims to assess the efficacy of narrow band imaging (NBI) endoscopy in utilizing radiomics for predicting radiosensitivity in nasopharyngeal carcinoma (NPC), and to explore the associated molecular mechanisms. Materials: The study included 57 NPC patients who were pathologically diagnosed and underwent RNA sequencing. They were categorized into complete response (CR) and partial response (PR) groups after receiving radical concurrent chemoradiotherapy. We analyzed 267 NBI images using ResNet50 for feature extraction, obtaining 2048 radiomic features per image. Using Python for deep learning and least absolute shrinkage and selection operator for feature selection, we identified differentially expressed genes associated with radiomic features. Subsequently, we conducted enrichment analysis on these genes and validated their roles in the tumor immune microenvironment through single-cell RNA sequencing. Results: After feature selection, 54 radiomic features were obtained. The machine learning algorithm constructed from these features showed that the random forest algorithm had the highest average accuracy rate of 0.909 and an area under the curve of 0.961. Correlation analysis identified 30 differential genes most closely associated with the radiomic features. Enrichment and immune infiltration analysis indicated that tumor-associated macrophages are closely related to treatment responses. Three key NBI differentially expressed immune genes (NBI-DEIGs), namely CCL8, SLC11A1, and PTGS2, were identified as regulators influencing treatment responses through macrophages. Conclusion: NBI-based radiomics models introduce a novel and effective method for predicting radiosensitivity in NPC. The molecular mechanisms may involve the functional states of macrophages, as reflected by key regulatory genes.

Altered functional connectivity of cerebellar subregions in male patients with obstructive sleep apnea: A resting-state fMRI study.

PURPOSE: Previous studies have demonstrated impaired cerebellar function in patients with obstructive sleep apnea (OSA), which is associated with impaired cognition. However, the effects of OSA on resting-state functional connectivity (FC) in the cerebellum has not been determined. The purpose of this study was to investigate resting-state FC of the cerebellar subregions and its relevance to clinical symptoms in patients with OSA. METHODS: Sixty-eight patients with OSA and seventy-two healthy controls (HCs) were included in the study. Eight subregions of the cerebellum were selected as regions of interest, and the FC values were calculated for each subregion with other voxels. A correlation analysis was performed to examine the relationship between clinical and cognitive data. RESULTS: Patients with OSA showed higher FC in specific regions, including the right lobule VI with the right posterior middle temporal gyrus and right angular gyrus, the right Crus I with the bilateral precuneus/left superior parietal lobule, and the right Crus II with the precuneus/right posterior cingulate cortex. Furthermore, the oxygen depletion index was negatively correlated with aberrant FC between the right Crus II and the bilateral precuneus / right posterior cingulate cortex in OSA patients (p = 0.004). CONCLUSION: The cerebellum is functionally lateralized and closely linked to the posterior default mode network. Higher FC is related to cognition, emotion, language, and sleep in OSA. Abnormal FC may offer new neuroimaging evidence and insights for a deeper comprehension of OSA-related alterations.

Activating the Intrinsic Zincophilicity of PAM Hydrogel to Stabilize the Metal-Electrolyte Dynamic Interface for Stable and Long-Life Zinc Metal Batteries.

As a potential material to solve rampant dendrites and hydrogen evolution reaction (HER) problem of aqueous zinc metal batteries (AZMB), hydrogel electrolytes usually require additional additives or multi-molecular network strategies to solve existing problems of ionic conductivity, mechanical properties and interface stability. However, the intrinsic zincophilic properties of the gel itself are widely neglected leading to the addition of additional molecules and the complexity of the preparation process. In this work, we innovatively utilize the characteristics of acrylamide's high zincophilic group density, activating the intrinsic zincophilic properties of PAM gel through a simple concentration control strategy which reconstructs a novel zinc-electrolyte interface different from conventional PAM electrolyte. The activated novel gel electrolyte with intrinsic zincophilic properties has high ionic conductivity and effectively suppresses water activity, thereby inhibiting HER corrosion. Meanwhile, it induces uniform deposition of (002) crystal planes, leading to excellent deposition kinetics and long cycle life, thereby ensuring high interfacial stability. Compared with conventional PAM gel electrolytes, the activated zincophilic group-rich hydrogel maintained excellent cycling stability (1 mA/cm2, 1 mAh/cm2) over 2250 hours; The Zn//MnO2 coin cell using novel zincophilic group -rich hydrogel still retains a high specific capacity of more than 170 mAh/g at 0.5 A/g after 1000 cycles.

Education to improve timeliness of shingles diagnosis: Cluster RCT and qualitative study.

BACKGROUND: Herpes zoster (shingles) is normally diagnosed clinically. Timely diagnosis is important so antiviral treatment can be started soon after rash onset. AIM: To assess whether a practice-level educational intervention, aimed at non-clinical patient-facing staff, improves the timely assessment of patients with shingles. DESIGN AND SETTING: Cluster randomised Study Within A Trial (SWAT) with nested qualitative study in General Practices in England. METHODS: Practices were cluster randomised 1:1, stratified by centre and minimised by practice list size and index of multiple deprivation score. Intervention practices were sent educational materials, highlighting the common presenting features of shingles and what action to take if suspected. The primary and secondary outcomes were the mean proportion of patients per practice seen within 72 hours and 144 of rash onset, respectively. Comparison between groups was conducted using linear regression, adjusting for randomisation variables. Semi-structured interviews with practice staff in intervention practices explored views and opinions of the intervention. RESULTS: 67 practices were enrolled; 34 randomised to intervention, 33 to control. The mean difference in proportion of patients seen within 72 and 144 hours was -0.132 (95% CI -0.308, 0.043) and -0.039 (95% CI -0.158, 0.080), respectively. In intervention practices, 90.5% reported distributing the educational materials, however engagement with these was suboptimal. 12 participants were interviewed, and the poster component of the intervention was said to be easiest to implement. CONCLUSION: Our educational intervention did not improve the timely assessment of patients with shingles. This may be the result of poor intervention engagement.

Clinical evaluation of pulmonary quantitative computed tomography parameters for diagnosing eosinophilic chronic obstructive pulmonary disease: Characteristics and diagnostic performance.

Aims: To investigate the characteristics and diagnostic performance of quantitative computed tomography (QCT) parameters in eosinophilic chronic obstructive pulmonary disease (COPD) patients. Methods: High-resolution CT scans of COPD patients were retrospectively analyzed, and various emphysematous parenchyma measurements, including lung volume (LC), lung mean density (LMD), lung standard deviation (LSD), full-width half maximum (FWHM), and lung relative voxel number (LRVN) were performed. The QCT parameters were compared between eosinophilic and noneosinophilic COPD patients, using a definition of eosinophilic COPD as blood eosinophil values ≥ 300 cells·µL-1 on at least three times. Receiver operating characteristic curves and area under the curve (ROC-AUC) and python were used to evaluate discriminative efficacy of QCT. Results: Noneosinophilic COPD patients had a significantly lower TLMD (-846.3 ± 47.9 Hounsfield Unit [HU]) and TFWHM(162.5 ± 30.6 HU) compared to eosinophilic COPD patients (-817.8 ± 54.4, 177.3 ± 33.1 HU, respectively) (p = 0.018, 0.03, respectively). Moreover, the total LC (TLC) and TLSD were significantly lower in eosinophilic COPD group (3234.4 ± 1145.8, 183.8 ± 33.9 HU, respectively) than the noneosinophilic COPD group (5600.2 ± 1248.4, 203.5 ± 20.4 HU, respectively) (p = 0.009, 0.002, respectively). The ROC-AUC values for TLC, TLMD, TLSD, and TFWHM were 0.91 (95% confidence interval [CI], 0.828-0.936), 0.66 (95% CI, 0.546-0.761), 0.64 (95% CI, 0.524-0.742), and 0.63 (95% CI, 0.511-0.731), respectively. When the TLC value was 4110 mL, the sensitivity was 90.7% (95% CI, 79.7-96.9), specificity was 77.8% (95% CI, 57.7-91.4) and accuracy was 86.4%. Notably, TLC demonstrated the highest discriminative efficiency with an F1 Score of 0.79, diagnostic Odds Ratio of 34.3 and Matthews Correlation Coefficient of 0.69, surpassing TLMD (0.55, 3.66, 0.25), TLSD (0.56, 3.95, 0.26), and TFWHM (0.56, 4.16, 0.33). Conclusion: Eosinophilic COPD patients exhibit lower levels of emphysema and a more uniform density distribution throughout the lungs compared to noneosinophilic COPD patients. Furthermore, TLC demonstrated the highest diagnostic efficiency and may serve as a valuable diagnostic marker for distinguishing between the two groups.

Identification of bZIP Transcription Factors That Regulate the Development of Leaf Epidermal Cells in Arabidopsis thaliana by Single-Cell RNA Sequencing.

Epidermal cells are the main avenue for signal and material exchange between plants and the environment. Leaf epidermal cells primarily include pavement cells, guard cells, and trichome cells. The development and distribution of different epidermal cells are tightly regulated by a complex transcriptional regulatory network mediated by phytohormones, including jasmonic acid, and transcription factors. How the fate of leaf epidermal cells is determined, however, is still largely unknown due to the diversity of cell types and the complexity of their regulation. Here, we characterized the transcriptional profiles of epidermal cells in 3-day-old true leaves of Arabidopsis thaliana using single-cell RNA sequencing. We identified two genes encoding BASIC LEUCINE-ZIPPER (bZIP) transcription factors, namely bZIP25 and bZIP53, which are highly expressed in pavement cells and early-stage meristemoid cells. Densities of pavement cells and trichome cells were found to increase and decrease, respectively, in bzip25 and bzip53 mutants, compared with wild-type plants. This trend was more pronounced in the presence of jasmonic acid, suggesting that these transcription factors regulate the development of trichome cells and pavement cells in response to jasmonic acid.

Phthalate metabolites and sex steroid hormones in relation to obesity in US adults: NHANES 2013-2016.

Background: Obesity and metabolic syndrome pose significant health challenges in the United States (US), with connections to disruptions in sex hormone regulation. The increasing prevalence of obesity and metabolic syndrome might be associated with exposure to phthalates (PAEs). Further exploration of the impact of PAEs on obesity is crucial, particularly from a sex hormone perspective. Methods: A total of 7780 adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016 were included in the study. Principal component analysis (PCA) coupled with multinomial logistic regression was employed to elucidate the association between urinary PAEs metabolite concentrations and the likelihood of obesity. Weighted quartiles sum (WQS) regression was utilized to consolidate the impact of mixed PAEs exposure on sex hormone levels (total testosterone (TT), estradiol and sex hormone-binding globulin (SHBG)). We also delved into machine learning models to accurately discern obesity status and identify the key variables contributing most to these models. Results: Principal Component 1 (PC1), characterized by mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) as major contributors, exhibited a negative association with obesity. Conversely, PC2, with monocarboxyononyl phthalate (MCNP), monocarboxyoctyl phthalate (MCOP), and mono(3-carboxypropyl) phthalate (MCPP) as major contributors, showed a positive association with obesity. Mixed exposure to PAEs was associated with decreased TT levels and increased estradiol and SHBG. During the exploration of the interrelations among obesity, sex hormones, and PAEs, models based on Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) algorithms demonstrated the best classification efficacy. In both models, sex hormones exhibited the highest variable importance, and certain phthalate metabolites made significant contributions to the model's performance. Conclusions: Individuals with obesity exhibit lower levels of TT and SHBG, accompanied by elevated estradiol levels. Exposure to PAEs disrupts sex hormone levels, contributing to an increased risk of obesity in US adults. In the exploration of the interrelationships among these three factors, the RF and XGBoost algorithm models demonstrated superior performance, with sex hormones displaying higher variable importance.