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Peanut (Arachis hypogaea L.) is an important oil crop. Oleic acid is a major factor that determines the quality of peanuts. Therefore, the high oleic and high oleic to linoleic acid ratio are the target traits in an advanced peanut breeding program. This study provided an extensive evaluation of the genetic and physical characteristics as well as disease resistance of 220 high oleic peanut varieties in China. Notably, these varieties clustered into five major categories based on their traits. A majority of these varieties have been bred using interspecific hybridization or selected from mutants of self-crossed parents, with the main parent varieties being Kaixuan 016 and CTWE. Analysis of disease resistance showed that most high oleic peanut varieties could resist two or three diseases. However, those varieties with resistance to multiple diseases were relatively scarce. Moreover, some high oleic peanut varieties showed no disease resistance or inadequate testing. The results further indicate that the genetic basis for high oleic peanut breeding is insufficient, highlighting the need for its further development. Importantly, our findings lay a critical foundation for future high oleic peanut breeding and promote better understanding of the genetic and trait diversity offered by these varieties.

Abstract Background Invasive pulmonary aspergillosis (IPA) is a serious fungal infection. However, current diagnostic methods have limitations. The purpose of this study was to use artificial intelligence to achieve a more accurate diagnosis of IPA. Methods Totally 263 patients (148 cases of IPA, 115 cases of non-IPA) were retrospectively enrolled from a single institution and randomly divided into training and test sets at a ratio of 7:3. Clinic-radiological independent risk factors for IPA were screened using univariate analysis and multivariate logistic regression analysis, after which a clinic-radiological model was constructed. The optimal radiomics features were extracted and screened based on CT images to construct the radiomics label score (Rad-score) and radiomics model. The optimal DL features were extracted and screened using four pre-trained convolutional neural networks, respectively, followed by the construction of the DL label score (DL-score) and DL model. Then, the radiomics-DL model was constructed. Finally, the combined model was constructed based on clinic-radiological independent risk factors, the Rad-score, and the DL-score. LR was adopted as the classifier. Receiver operating characteristic (ROC) curves were drawn, and the areas under the curve (AUC) were calculated to evaluate the efficacy of each model in predicting IPA. Additionally, based on the best-performing model on the LR classifier, four other machine learning (ML) classifiers were constructed to evaluate the predictive value for IPA. Results The AUC of the clinic-radiological model for predicting IPA in the training and test sets was 0.845 and 0.765, respectively. The AUC of the radiomics-DL and combined models in the training set was 0.871 and 0.932, while in the test set was 0.851 and 0.881, respectively. The combined model showed better predictive performance than all other models. DCA showed that taking 0.00–1.00 as the threshold, the clinical benefit of the combined model was higher than that of all other models. Then, the combined model was trained on four other machine learning classifiers, all of which achieved AUC values above 0.80 in the test set, showing good performance in predicting IPA. Conclusion Clinic, CT radiomics, and DL combined model could be used to predict IPA effectively.

[Objective] The Belt and Road Initiative is the core of China’s foreign policy and future opening-up and international cooperation. It is of great significance to analyze the pattern and efficiency of fossil energy trade between China and countries along the Belt and Road to promote the high-quality development of energy along the Belt and Road and ensure China’s energy security. [Methods] Based on the fossil energy trade data of China’s import countries along the Belt and Road from 2000 to 2020 in the CHRTD resource trade database, this study explored the spatial and temporal change patterns and efficiency of fossil energy trade between China and these countries based on the ordered clustering method, survival analysis model, and stochastic frontier gravity model. [Results] The main results are as follows: From 2000 to 2020, China’s fossil energy import experienced obviously different stages, the number of trading countries was increasing, and the import volume was increasing year by year. Among them, the proportion of natural gas imports increased significantly; energy trade was relatively stable, and the survival rate of trade relations was high, but there were still some low energy trade activities. GDP, economic structure, and spatial distance were important factors that affected China’s energy imports. Energy import efficiency was generally low, and high-value countries was in small number and spatially scattered. Among the energy sources where the time-varying model is applicable, the trade efficiency of coal imports was decreasing year by year, while the import value and volume of natural gas were on the rise. [Conclusion] China’s fossil energy import trade cooperation with countries along the Belt and Road has gradually deepened, but the overall trade efficiency is still low. Further improving regional connectivity and formulating more refined trade management policies are important ways to reduce energy trade risks.

Abstract Metabolic-associated steatohepatitis (MASH) and ulcerative colitis (UC) exhibit a complex interconnection with immune dysfunction, dysbiosis of the gut microbiota, and activation of inflammatory pathways. This study aims to identify and validate critical butyrate metabolism-related shared genes between both UC and MASH. Clinical information and gene expression profiles were sourced from the Gene Expression Omnibus (GEO) database. Shared butyrate metabolism-related differentially expressed genes (sBM-DEGs) between UC and MASH were identified via various bioinformatics methods. Functional enrichment analysis was performed, and UC patients were categorized into subtypes using the consensus clustering algorithm based on sBM-DEGs. Key genes within sBM-DEGs were screened through Random Forest, Support Vector Machines-Recursive Feature Elimination, and Light Gradient Boosting. The diagnostic efficacy of these genes was evaluated using receiver operating characteristic (ROC) analysis on independent datasets. Additionally, the expression levels of characteristic genes were validated across multiple independent datasets and human specimens. Forty-nine shared DEGs between UC and MASH were identified, with enrichment analysis highlighting significant involvement in immune, inflammatory, and metabolic pathways. The intersection of butyrate metabolism-related genes with these DEGs produced 10 sBM-DEGs. These genes facilitated the identification of molecular subtypes of UC patients using an unsupervised clustering approach. ANXA5, CD44, and SLC16A1 were pinpointed as hub genes through machine learning algorithms and feature importance rankings. ROC analysis confirmed their diagnostic efficacy in UC and MASH across various datasets. Additionally, the expression levels of these three hub genes showed significant correlations with immune cells. These findings were validated across independent datasets and human specimens, corroborating the bioinformatics analysis results. Integrated bioinformatics identified three significant biomarkers, ANXA5, CD44, and SLC16A1, as DEGs linked to butyrate metabolism. These findings offer new insights into the role of butyrate metabolism in the pathogenesis of UC and MASH, suggesting its potential as a valuable diagnostic biomarker.

Traffic data imputation is crucial for the reliability and efficiency of intelligent transportation systems (ITSs), forming the foundation for downstream tasks like traffic prediction and management. However, existing deep learning-based imputation methods struggle with two significant challenges: poor performance under high missing data rates and the limited incorporation of external traffic-related factors. To address these challenges, we propose a novel knowledge graph-enhanced generative adversarial network (KG-GAN) for traffic data imputation. Our approach uniquely integrates external knowledge with traffic spatiotemporal dependencies to improve data imputation quality. Specifically, we construct a fine-grained knowledge graph (KG) that differentiates attributes and relationships of external factors such as points of interest (POI) and weather conditions, facilitating more robust knowledge representation learning. We then introduce a knowledge-aware embedding cell (EM-cell) that merges traffic data with these learned external representations, providing richer inputs for the spatiotemporal GAN. Extensive experiments on a large-scale real-world traffic dataset demonstrate that KG-GAN significantly outperforms state-of-the-art methods under various missing data scenarios. Additionally, ablation studies confirm the superior performance gained from incorporating external knowledge, underscoring the importance of this approach in addressing complex missing data patterns.

Ice, water, and sediment represent three interconnected habitats in lake ecosystems, and bacteria are crucial for maintaining ecosystem equilibrium and elemental cycling across these habitats. However, the differential characteristics and driving mechanisms of bacterial community structures in the ice, water, and sediments of seasonally frozen lakes remain unclear. In this study, high-throughput sequencing technology was used to analyze and compare the structure, function, network characteristics, and assembly mechanisms of bacterial communities in the ice, water, and sediment of Wuliangsuhai, a typical cold region in Inner Mongolia. The results showed that the bacterial communities in the ice and water phases had similar diversity and composition, with Proteobacteria, Bacteroidota, Actinobacteria, Campilobacterota, and Cyanobacteria as dominant phyla. The bacterial communities in sediments displayed significant differences from ice and water, with Chloroflexi, Proteobacteria, Firmicutes, Desulfobacterota, and Acidobacteriota being the dominant phyla. Notably, the bacterial communities in water exhibited higher spatial variability in their distribution than those in ice and sediment. This study also revealed that during the frozen period, the bacterial community species in the ice, water, and sediment media were dominated by cooperative relationships. Community assembly was primarily influenced by stochastic processes, with dispersal limitation and drift identified as the two most significant factors within this process. However, heterogeneous selection also played a significant role in the community composition. Furthermore, functions related to nitrogen, phosphorus, sulfur, carbon, and hydrogen cycling vary among bacterial communities in ice, water, and sediment. These findings elucidate the intrinsic mechanisms driving variability in bacterial community structure and changes in water quality across different media phases (ice, water, and sediment) in cold-zone lakes during the freezing period, offering new insights for water environmental protection and ecological restoration efforts in such environments.

Abstract Chromoblastomycosis (CBM), a chronic fungal infection affecting the skin and subcutaneous tissues, is predominantly caused by dematiaceous fungi in tropical and subtropical areas. Characteristically, CBM presents as plaques and nodules, often leading to scarring post-healing. Besides traditional diagnostic methods such as fungal microscopy, culture, and histopathology, dermatoscopy and reflectance confocal microscopy can aid in diagnosis. The treatment of CBM is an extended and protracted process. Imiquimod, acting as an immune response modifier, boosts the host’s immune response against CBM, and controls scar hyperplasia, thereby reducing the treatment duration. We present a case of CBM in Guangdong with characteristic reflectance confocal microscopy manifestations, effectively managed through a combination of itraconazole, terbinafine, and imiquimod, shedding light on novel strategies for managing this challenging condition.

Our case demonstrated unique cytomegalovirus (CMV) encephalitis post-haploidentical donor hematopoietic stem cell transplantation (HID-HSCT), with early findings on diffusion-weighted brain magnetic resonance imaging (MRI) in the absence of any neurologic symptoms. A 54-year-old Chinese man with acute lymphoblastic leukemia (Philadelphia chromosome-negative) underwent HID-HSCT. After HSCT, the patient developed CMV viremia and severe acute graft-versus-host disease. Recurrence of CMV viremia was observed. On day 129, brain MRI was performed to determine the cause for the intermittent fever. Diffusion-weighted imaging (DWI) revealed several bright spots in the cortex of the frontal lobes and anterior angle of the left lateral ventricle. Subsequently, he developed transplant-associated thrombotic microangiopathy, posterior reversible encephalopathy syndrome, and enlargement of lesions alongside the ventricular wall on a brain MRI series. Metagenomic next-generation sequencing (NGS) of the cerebrospinal fluid (CSF) led to the final diagnosis of CMV encephalitis. Although ganciclovir combined with foscarnet was administered, the patient’s consciousness deteriorated, followed by respiratory failure. The patient died on day 198. Additionally, we performed a systematic review to comprehensively analyze this disease. Regarding treatment, immunological therapies, including virus-specific T cells from a third donor and CMV-cytotoxic T lymphocytes, may be more effective. This case report and systematic review underscores the complexities of managing CMV ventriculoencephalitis in HSCT recipients and emphasizes the importance of early diagnosis by brain MRI and CSF polymerase chain reaction or NGS and ongoing research in improving outcomes.

Background: Chromoblastomycosis (CMB) is a chronic granulomatous fungal infection that affect the skin and subcutaneous tissues. It is clinically problematic due to limited treatment options, low cure rates, and high rates of relapse. This underscores the necessity for innovative treatment approaches. In this study, potassium iodide (KI) combined with Methylene Blue (MB) mediated antimicrobial photodynamic therapy (PDT) were assessed in the treatment of Fonsecaea monophora (F. monophora) both in vitro and in vivo. And the underlying mechanism that contributes to the efficacy of this treatment approach was investigated. Methods: In vitro experiments were conducted using different combinations and concentrations of MB, KI, and 660 nm light (60 mW/cm2) to inhibit F. monophora. The study was carried out using colony-forming unit (CFU) counts and scanning electron microscopy (SEM). The production of singlet oxygen (1O2), free iodine (I2), hydrogen peroxide (H2O2), and superoxide anion during the KI combined MB-mediated antimicrobial PDT process was also detected. In vivo experiments were developed using a Balb/c mouse paw infection model with F. monophora and treated with PBS, 10 mM KI, 2 mM MB +100 J/cm² and 10 mM KI+2 mM MB +100 J/cm² respectively. Inflammatory swelling, fungal load and histopathological analyses of the mouse footpads were assessed. Results: KI enhanced the killing effect of MB-mediated antimicrobial PDT on the conidial spores of F. monophora at the cell and infected animal model level. During the process, the main antimicrobial agents in KI combined with MB- mediated antimicrobial PDT could produce stronger toxic active species including free I2 and H2O2. Conclusion: KI combined with MB-mediated antimicrobial PDT could be an effective adjunct therapy for treating CBM.

ObjectiveThe applications of personalized abutments and abutment crown bridge products have increased year by year, but there is no clear requirement for clinical evaluation of the same variety of such products. This study mainly introduces the clinical evaluation concerns of personalized abutments and abutment crown bridge products, in order to provide reference for the declaration and registration of such products. MethodsThe clinical evaluation of personalized abutments and crown bridge products are summarized, and the research content of clinical evaluation is clarified. ResultsThe clinical evaluation requirements that need to be considered by enterprises are introduced. ConclusionPersonalized abutment and abutment crown bridge products can refer to this study when they are launched in China, mainly using in vitro performance comparison tests for equivalence verification.

As people’s consumption levels and health awareness have risen, the consumer demand for functional foods is steadily increasing. Medium-chain fatty acids (MCFAs), an important class of dietary fatty acids, have been regarded as high-value functional foods due to their unique transportation system and the fact that they can be metabolized rapidly in the body while producing high energy. Beginning with an overview of the types and structures of MCFAs, this paper goes on to elaborate the metabolic pathway of MCFAs in the human body and then summarize recent research on MCFAs in the adjuvant treatment of different diseases. This article focuses on the positive role of MCFAs in the adjuvant treatment of Alzheimer’s disease, epilepsy, cancer, diabetes, obesity, and other diseases, and expounds their action mechanism. Finally, an outlook on the future development of MCFAs is given. Overall, this review provides a theoretical basis for promoting the application of MCFAs in the fields of food and medicine.

Cardiovascular diseases (CVD) are the leading cause of death worldwide, despite advances in understanding cardiovascular health. Significant barriers still exist in effectively preventing and managing these diseases. Vascular smooth muscle cells (VSMCs) are crucial for maintaining vascular integrity and can switch between contractile and synthetic functions in response to stimuli such as hypoxia and inflammation. These transformations play a pivotal role in the progression of cardiovascular diseases, facilitating vascular modifications and disease advancement. This article synthesizes the current understanding of the mechanisms and signaling pathways regulating VSMC phenotypic transitions, highlighting their potential as therapeutic targets in cardiovascular disease interventions.

Abstract Background Cranio-lenticulo-sutural dysplasia (CLSD) is a rare dysmorphic syndrome characterized by skeletal dysmorphism, late-closing fontanels, and cataracts. CLSD is caused by mutations in the SEC23A gene (OMIM# 607812) and can be inherited in either an autosomal dominant or autosomal recessive pattern. To date, only four mutations have been reported to cause CLSD. This study aims to identify the disease-causing variants in a large cohort of congenital cataract patients, to expand the genotypic and phenotypic spectrum of CLSD, and to confirm the association between SEC23A and autosomal recessive CLSD (ARCLSD). Methods We collected detailed medical records and performed comprehensive ocular examinations and whole-exome sequencing (WES) on 115 patients with congenital cataracts. After suspecting that a patient may have CLSD based on the sequencing results, we proceeded to conduct transmission electron microscopy (TEM) on the cultured skin fibroblasts. The clinical validity of the reported gene-disease relationships for the gene and the disease was evaluated using the ClinGen gene curation framework. Results Two novel compound heterozygous variants (c.710A > C p.Asp237Ala, c.1946T > C p.Leu649Pro) of the SEC23A gene, classified as variant of uncertain significance, were identified in the proband with skeletal, cardiac, ocular, and hearing defects. The observation of typical distended endoplasmic reticulum cisternae further supported the diagnosis of CLSD. Application of the ClinGen gene curation framework confirmed the association between SEC23A and ARCLSD. Conclusion This study expands the genotypic and phenotypic spectrum of CLSD, proposes TEM as a supplemental diagnostic method, and indicates that congenital cataracts are a typical sign of ARCLSD.

Mercury and arsenic are two highly toxic pollutants, and many researchers have explored the effects of the two substances on the environment. However, the research content of toxic substances in frozen periods is relatively small. To explore the spatial and vertical distribution of mercury and arsenic in the ice, water, and sediments of Wuliangsuhai Lake under ice conditions, and to assess the harm degree of the two toxic substances to human beings. We collected the ice, water, and sediments of the lake in December 2020, and tested the contents of Hg and As. The single-factor pollution index method, the local cumulative index method, and the ecological risk coding method were used to assess the pollution status in these three environmental media, and the Monte Carlo simulation combined with the quantitative model recommended by USEPA was used to assess the population health risk. The results showed that (1) The average single-factor pollution values of Hg and As in water were 0.367 and 0.114, both pollutants were at clean levels during the frozen period. (2) The mean Igeo values of Hg and As were 0.657 and −0.948. The bioavailability of Hg in the sediments of Wuliangsuhai Lake during the frozen period was high, and its average value was 7.8%, which belonged to the low-risk grade. The bioavailability of As ranged from 0.2% to 3.7%, with an average value of 1.3%. (3) Monte Carlo simulation results indicate acceptable levels of health risks in both water and ice. This study preliminarily investigated the distribution characteristics of toxic substances and their potential effects on human health in lakes in cold and arid regions during the frozen period. It not only clarified the pollution characteristics of lakes in cold and arid regions during the frozen period, but also provided beneficial supplements for the ecological protection of lake basins. This study lays a foundation for further environmental science research in the region in the future.

The National Oceanic and Atmospheric Administration’s (NOAA) Center for Satellite Applications and Research (STAR) facilitates and enables societal benefits from satellite oceanography, supporting operational and experimental satellite missions, developing new and improved ocean observing capabilities, engaging users by developing and distributing fit-for-purpose data, applications, tools, and services, and curating, translating, and integrating diverse data products into information that supports informed decision making. STAR research, development, and application efforts span from passive visible, infrared, and microwave observations to active altimetry, scatterometry, and synthetic aperture radar (SAR) observations. These efforts directly support NOAA’s operational geostationary (GEO) and low Earth orbit (LEO) missions with calibration/validation and retrieval algorithm development, implementation, maintenance, and anomaly resolution, as well as leverage the broader international constellation of environmental satellites for NOAA’s benefit. STAR’s satellite data products and services enable research, assessments, applications, and, ultimately, decision making for understanding, predicting, managing, and protecting ocean and coastal resources, as well as assessing impacts of change on the environment, ecosystems, and climate. STAR leads the NOAA Coral Reef Watch and CoastWatch/OceanWatch/PolarWatch Programs, helping people access and utilize global and regional satellite data for ocean, coastal, and ecosystem applications.

Abstract. Background:. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world. The ubiquitin-specific peptidase 25 (USP25) protein has been reported to participate in the development of several cancers. However, few studies have reported its association with HCC. In this study, we aimed to investigate the function and mechanism of USP25 in the progression of HCC. Methods:. We analyzed USP25 protein expression in HCC based on The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database cohorts. Then, we constructed USP25-overexpressing and USP25-knockdown HepG2, MHCC97H, and L-O2 cells. We detected the biological function of USP25 by performing a series of assays, such as Cell Counting Kit-8 (CCK-8), colony formation, transwell, and wound healing assays. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) analyses were performed to detect the interaction between USP25 and the Wnt/β-catenin signaling pathway. The relationship between USP25 and tripartite motif-containing 21 (TRIM21) was assessed through mass spectrometry and co-immunoprecipitation (Co-IP) analysis. Finally, we constructed a mouse liver cancer model with the USP25 gene deletion to verify in vivo role of USP25. Results:. USP25 was highly expressed in HCC tissue and HCC cell lines. Importantly, high expression of USP25 in tissues was closely related to a poor prognosis. USP25 knockdown markedly reduced the proliferation, migration, and invasion of HepG2 and MHCC97H cells, whereas USP25 overexpression led to the opposite effects. In addition, we demonstrated that USP25 interacts with TRIM21 to regulate the expression of proteins related to epithelial-mesenchymal transition (EMT; E-cadherin, N-cadherin, and Snail) and the Wnt/β-catenin pathway (β-catenin, Adenomatous polyposis coli, Axin2 and Glycogen synthase kinase 3 beta) and those of their downstream proteins (C-myc and Cyclin D1). Finally, we verified that knocking out USP25 inhibited tumor growth and distant metastasis in vivo. Conclusions:. In summary, our data showed that USP25 was overexpressed in HCC. USP25 promoted the proliferation, migration, invasion, and EMT of HCC cells by interacting with TRIM21 to activate the β-catenin signaling pathway.

Since the surrounding rocks of underground tunnels are frequently suffered from the dynamic disturbance of mechanical percussion drilling and explosive blasting, it is significantly meaningful to investigate the mechanical properties and failure behaviors of rock material with a tunnel-shaped opening under dynamic loads. In this work, seven groups of prismatic samples, including the intact samples and the samples with a circular opening of three kinds of diameters, a square opening, a horseshoe-shaped opening and a D-shaped opening, were prepared for dynamic compressive loading. The results show that the prismatic specimens satisfy the stress uniformity condition in impact tests using SHPB testing system with a bar diameter of 50 mm. The weakening effects of the existed openings on the dynamic compressive strength, elastic modulus and peak strain of rocks are closely associated with the size and shape of opening and the loading direction. Based on the energy parameters of the samples, the dissipated energy density of each group of samples can be solved. The failure degree of the samples characterized by dissipated energy density and fractal dimension are in good agreement. Besides, the failure mode of the intact specimen belongs to splitting tensile failure, while that of the pre-holed specimens can be classified as shear-dominated failure due to the coalescence of the openings and the shear cracks occurring along the diagonals of the specimens. The test results provide some insights into the mechanical behavior of rock materials under dynamic loads and lay an important theoretical foundation for support design and rock disaster prevention of underground tunnel.

Abstract Global climate models account for sea ice thickness by summing thermodynamic processes that affect thickness through phase change and dynamic processes that affect thicknesses through relative motion. Comparison of these individual processes with observations is essential for model interpretation and development. We utilized observational estimates of basal thermodynamic growth, overall thickness changes and their residual difference (including dynamics) to evaluate these processes in the National Center for Atmospheric Research (NCAR) Community Earth System Model 2 (CESM2) submission to the World Climate Research Program (WCRP) Ocean Model Comparison Project Phase 2 (OMIP2) and Pan‐Arctic Ice–Ocean Modeling and Assimilation System (PIOMAS). Both models exhibit a similar pattern of higher basal thermodynamic growth and lower residual effects and wintertime thickness in the central Arctic than observational estimates for 2010–2018, and vice versa in the peripheral seas. Correcting residual effect biases would ameliorate the biases in both mean thickness and basal thermodynamic growth.

IntroductionAs a key indicator to evaluate biodiversity and eco-function, habitat quality shows the value of ecosystem services. The Qinghai–Tibet Plateau occupies the highest elevation in the global dimension, where the regional environment is greatly affected by multiple factors including the terrain comprehensively.MethodsIn the present study, the InVEST model was employed to assess the habitat quality across varying terrain gradients. The study observed the displacement of the center of gravity of habitat quality under different topographical factors over the past 20 years to learn the trend of changes. Additionally, the Geo-detector model was enhanced to explore the contribution rate of driving factors including biodiversity in different topographic positions and overall.ResultsThe results found the following: (1) The habitat quality of the Qinghai–Tibet Plateau was positively correlated with the terrain gradient, and the mean values of habitat quality increased with the gradual increase in terrain gradient. In the period between 2000 and 2020, mean habitat quality values within the study area exhibited a slight fluctuating trend with the spatial distribution characterized by higher values in the southeast and lower values in the northwest. (2) Among different terrain gradients, trends in the mean center’s shift of habitat quality were diverse. The mean center of gradient I went north but gradient V went west. The mean center of the habitat quality in gradients II–IV showed an uncertain trend. (3) The NDVI exerted the most vital influence on the quality of habitats irrespective of different terrain gradients. Annual mean temperature, soil type, and slope occupied two to four places in each terrain.DiscussionThe study indicates that in the last two decades, the habitat quality on the Qinghai–Tibet Plateau has gradually increased across different terrain locations. In terms of policies to protect habitats, terrain should be classified and targeted accordingly.

The activities of the phospholipase C gamma (PLCγ) 1 and 2 enzymes are essential for numerous cellular processes. Unsurprisingly, dysregulation of PLCγ1 or PLCγ2 activity is associated with multiple maladies including immune disorders, cancers, and neurodegenerative diseases. Therefore, the modulation of either of these two enzymes has been suggested as a therapeutic strategy to combat these diseases. To aid in the discovery of PLCγ family enzyme modulators that could be developed into therapeutic agents, we have synthesized a high-throughput screening-amenable micellular fluorogenic substrate called C16CF3-coumarin. Herein, the ability of PLCγ1 and PLCγ2 to enzymatically process C16CF3-coumarin was confirmed, the micellular assay conditions were optimized, and the kinetics of the reaction were determined. A proof-of-principle pilot screen of the Library of Pharmacologically Active Compounds 1280 (LOPAC1280) was performed. This new substrate allows for an additional screening methodology to identify modulators of the PLCγ family of enzymes.

Objective To construct a mouse model of footpad inoculation with Fonsecaea monophora (F.monophora) melanin, and to analyze the differences in the virulence of F.monophora melanin from different sources. Virulence of F.monophora melanin and its influencing factors were also assessed. Methods F.monophora melanin was extracted by chemical digestion and acid-base method, and a mouse model of footpad melanin inoculation was constructed. Mice were divided into PBS group, chemical digestion group, acid-base group, and synthetic melanin group. The severity of mouse footpad swelling was measured. HE staining was performed to observe inflammatory cell infiltration and semi-quantitative analysis was performed. Results F.monophora melanin was successfully extracted. The chemical digestion method preserved the spatial morphology of melanin in the cell wall. In comparison to acid-base method, melanin extracted with chemical digestion method induced stronger and long-lasting footpad swelling, and more intense inflammatory reaction. Aggregation of neutrophils and macrophages was observed one day after injection of melanin. Seven days after injection of melanin, infiltration of neutrophils, macrophages and lymphocytes was observed. However, synthetic melanin group did not cause significant footpad swelling nor infiltration of neutrophils and lymphocytes although a small number of macrophages were seen. Conclusions The extracted F.monophora melanin can induce dramatic, inflammatory responses in mouse footpads. The complex spatial structure of melanin is associated with virulence, and synthetic melanin cannot mimic the virulence effects of F.monophora. Melanin extracted with chemical digestion method has advantages for study of fungal melanin virulence.

A rare coding variant in PLCγ2 (P522R) expressed in microglia induces a mild activation of enzymatic activity when compared to wild-type. This mutation is reported to be protective against the cognitive decline associated with late-onset Alzheimer's disease (LOAD) and therefore, activation of wild-type PLCγ2 has been suggested as a potential therapeutic target for the prevention and treatment of LOAD. Additionally, PLCγ2 has been associated with other diseases such as cancer and some autoimmune disorders where mutations with much greater increases in PLCγ2 activity have been identified. Here, pharmacological inhibition may provide a therapeutic effect. In order to facilitate our investigation of the activity of PLCγ2, we developed an optimized fluorogenic substrate to monitor enzymatic activity in aqueous solution. This was accomplished by first exploring the spectral properties of various “turn-on” fluorophores. The most promising turn-on fluorophore was incorporated into a water-soluble PLCγ2 reporter substrate, which we named C8CF3-coumarin. The ability of PLCγ2 to enzymatically process C8CF3-coumarin was confirmed, and the kinetics of the reaction were determined. Reaction conditions were optimized to identify small molecule activators, and a pilot screen of the Library of Pharmacologically Active Compounds 1280 (LOPAC1280) was performed with the goal of identifying small molecule activators of PLCγ2. The optimized screening conditions allowed identification of potential PLCγ2 activators and inhibitors, thus demonstrating the feasibility of this approach for high-throughput screening.

The zero-shot image classification technique aims to explore the semantic information shared between seen and unseen classes through visual features and auxiliary information and, based on this semantic information, to complete the knowledge migration from seen to unseen classes in order to complete the classification of unseen class images. Previous zero-shot work has either not extracted enough features to express the relationship between the sample classes or has only used a single feature mapping method, which cannot fully explore the information contained in the features and the connection between the visual–semantic features. To address the above problems, this paper proposes an embedded zero-shot image classification model based on bidirectional feature mapping (BFM). It mainly contains a feature space mapping module, which is dominated by a bidirectional feature mapping network and supplemented with a mapping network from visual to category label semantic feature space. Attention mechanisms based on attribute guidance and visual guidance are further introduced to weight the features to reduce the difference between visual and semantic features to alleviate the modal difference problem, and then the category calibration loss is utilized to assign a larger weight to the unseen class to alleviate the seen class bias problem. The BFM model proposed in this paper has been experimented on three public datasets CUB, SUN, and AWA2, and has achieved 71.9%, 62.8%, and 69.3% and 61.6%, 33.2%, and 66.6% accuracies under traditional and generalized zero-sample image classification settings, respectively. The experimental results verify the superiority of the BFM model in the field of zero-shot image classification.

This study explored the dynamics of bacterial community composition, response to environmental factors, and co-occurrence network models across different habitats of Wuliangsuhai Lake during the glacial period. Water quality analysis and high-throughput sequencing were performed at 14 monitoring sites within the lake. Additionally, a co-occurrence network between the two bacterial operational taxonomic unit (OTU)-OTUs was established. The results indicated significant differences in water quality indices, namely total nitrogen (TN), chemical oxygen demand (COD), total dissolved solids (TDS), salinity (SAL), chlorophyll-a (Chl.a), and electrical conductivity (EC), between the ice bodies of Wuliangsuhai Lake and subglacial water. Although there were no significant differences in α diversity across various media, substantial differences were observed in β diversity. The VIF and RDA analyses revealed that lake water quality factors significantly affected the microbial community structure and COD and TDS had the highest explanation for the community composition change. Network analysis demonstrated that competition dominated the bacterial community in water bodies with higher complexity and stability and ice body bacteria exhibited more reciprocal relationships and weaker resistance to external environmental disturbances. The co-occurrence network demonstrated a modular structure in the external environment, with g_Flavobacterium, f_Arcobacteraceae, and g_Sphingobacteriaceae being the main keystone species. Investigating the habitat heterogeneity of lake bacterial communities and identifying major groups and key species using molecular ecological network models and their topological effects can provide a theoretical foundation for monitoring and assessing the structural stability of lake ecosystems in cold regions.

The fluvial-deltaic reservoirs of the Oligocene Huagang Formation in the Xihu sag of the East China Sea shelf basin reflect rapid lateral change in sedimentary facies and poor morphology of conventional slice attributes, which bring difficulties to the reservoir prediction for subsequent exploration and development of lithologic reservoirs. The traditional seismic sedimentology technology is optimized by applying the characteristic technologies such as frequency-boosting interpretation, inversion-conventional −90° phase shift joint construction of seismic lithologic bodies, nonlinear slices, paleogeomorphology restoration, and multi-attribute fusion, to obtain typical slice attributes, which are conducive to geological form description and sedimentary interpretation. The Huagang Formation developed three types of sedimentary bodies: braided river, meandering river and shallow water delta, and the vertical sedimentary evolution was controlled by the mid-term base-level cycle and paleogeomorphology. In the early–middle stage of the mid-term base-level ascending cycle, braided channel deposits were dominant, and vertical superimposed sand bodies were developed. In the late stage of the ascending half-cycle and the early stage of the descending half-cycle, meandering river deposits were dominant, and isolated sand bodies were developed. In the middle–late stage of the descending half-cycle, shallow-water delta deposits were dominant, and migratory medium–thick sand bodies were developed. Restricted paleogeomorphology controlled the sand body distribution, while non-restricted paleogeomorphology had little effect on the sand body distribution. Based on reservoir characterization, the fault sealing type and reservoir updip pinch-out type structural lithological traps are proposed as the main directions for future exploration and development in the Xihu sag.

Insulin secretion is a signal‐triggered process that requires membrane fusion between the secretory granules and plasma membrane in pancreatic β cells. The exocytosis of insulin is mediated by target‐soluble N‐ethylmaleimide sensitive factor attachment protein receptors (SNAREs) on the plasma membrane and vesicle‐SNAREs on the vesicles, which assemble into a quaternary trans‐SNARE complex to initiate the fusion. Expression of fusion proteins is reduced in the islets of patients with type II diabetes, indicating that SNARE‐mediated fusion defect is closely related to insulin‐based metabolic diseases. Previous studies have suggested that epigallocatechin gallate (EGCG) has an inhibitory effect on membrane fusion. In the present study, we performed in vitro reconstitution assays to unravel the molecular mechanisms of EGCG in SNARE‐mediated insulin secretory vesicle fusion. Our data show that EGCG efficiently inhibits insulin secretory SNARE‐mediated membrane fusion. Mechanistic studies indicated that EGCG blocks the formation of the trans‐SNARE complex. Furthermore, calcium/synaptotagmin‐7‐stimulated fusion kinetics were largely reduced by EGCG, confirming that it is a potential regulator of SNARE‐dependent insulin secretion. Our findings suggest that the trans‐SNARE complex might be a promising target for controlling SNARE‐dependent vesicle fusion.

BackgroundEndoplasmic reticulum stress (ERS) is a critical factor in the development of ulcerative colitis (UC); however, the underlying molecular mechanisms remain unclear. This study aims to identify pivotal molecular mechanisms related to ERS in UC pathogenesis and provide novel therapeutic targets for UC.MethodsColon tissue gene expression profiles and clinical information of UC patients and healthy controls were obtained from the Gene Expression Omnibus (GEO) database, and the ERS-related gene set was downloaded from GeneCards for analysis. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis were utilized to identify pivotal modules and genes associated with UC. A consensus clustering algorithm was used to classify UC patients. The CIBERSORT algorithm was employed to evaluate the immune cell infiltration. Gene Set Variation Analysis (GSVA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore potential biological mechanisms. The external sets were used to validate and identify the relationship of ERS-related genes with biologics. Small molecule compounds were predicted using the Connectivity Map (CMap) database. Molecular docking was performed to simulate the binding conformation of small molecule compounds and key targets.ResultsThe study identified 915 differentially expressed genes (DEGs) and 11 ERS-related genes (ERSRGs) from the colonic mucosa of UC patients and healthy controls, and these genes had good diagnostic value and were highly correlated. Five potential small-molecule drugs sharing tubulin inhibitors were identified, including albendazole, fenbendazole, flubendazole, griseofulvin, and noscapine, among which noscapine exhibited the highest correlation with a high binding affinity to the targets. Active UC and 10 ERSRGs were associated with a large number of immune cells, and ERS was also associated with colon mucosal invasion of active UC. Significant differences in gene expression patterns and immune cell infiltration abundance were observed among ERS-related subtypes.ConclusionThe results suggest that ERS plays a vital role in UC pathogenesis, and noscapine may be a promising therapeutic agent for UC by affecting ERS.

As a class of novel biomaterials manufactured by synthetic biology technologies, recombinant collagens are candidates for a variety of medical applications. In this article, a regulatory scientific perspective on recombinant collagens and their medical devices is presented with a focus on the definition, translation, classification and technical review. Recombinant collagens are categorized as recombinant human collagen, recombinant humanized collagen and recombinant collagen-like protein, as differentiated by specific compositions and structures. Based on their intended uses and associated risks, recombinant collagen-based medical devices are generally classified as Class Ⅱ or Ⅲ in China. The regulatory review of recombinant collagen-based medical devices aims to assess their safety and efficacy demonstrated by scientific evidences generated from preclinical and clinical evaluations. Taken together, opportunities as well as challenges for their future clinical translation of recombinant collagen-based medical devices abound, which highlights the essential role of regulatory science to provide new tools, standards, guidelines and methods to evaluate the safety and efficacy of medical products.

Animal studies play a vital role in validating the concept, feasibility, safety, performance and efficacy of biomaterials products during their bench-to-clinic translation. This article aims to share regulatory considerations for animal studies of biomaterial products. After briefly emphasizing the importance of animal studies, issues of animal studies during biomaterial products’ translation are discussed. Animal studies with unclear purposes, flawed design and poor reporting quality could significantly reduce the translation efficiency and create regulatory challenges. Regulatory perspectives on the purpose, principle, quality and regulatory science of animal studies are also presented. Animal studies should have clear purposes, follow principles of 3R+DQ (replacement, reduction, refinement, design and quality) and execute under an efficiently operating quality management system. With the advancement of regulatory science, National Medical Products Administration of China has been developing a series of standards and guidance documents on animal studies of medical devices. Case studies of making decisions on whether to conduct animal studies are provided in the end with drug-eluting stents as examples. In summary, animal studies of biomaterial products should pay close attention to the rationale, design and quality in order to achieve their purposes.

Bone morphogenetic proteins (BMPs) are secretory proteins belonging to the transforming growth factor-β (TGF-β) superfamily. These proteins play important roles in embryogenesis, bone morphogenesis, blood vessel remodeling and the development of various organs. In recent years, as research has progressed, BMPs have been found to be closely related to cardiovascular diseases, especially atherosclerosis, vascular calcification, cardiac remodeling, pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT). In this review, we summarized the potential roles and related mechanisms of the BMP family in the cardiovascular system and focused on atherosclerosis and PAH.

Radar system environment is complex, and excessively high range sidelobes will cause weak targets to be lost and false targets. To solve this problem, a novel orthogonal frequency-division multiplexing(OFDM) radar low sidelobe waveform design method based on genetic algorithm(GA) is proposed. First, the OFDM waveform based on cyclic prefix(CP) is constructed. All sub carriers are modulated with m-sequence codes. Then, the main lobe and sidelobe ratio after pulse compression is taken as the objective function, and the phase parameter is taken as the optimization object. The objective function is transformed into an unconstrained optimization problem. Last, by using genetic algorithm to solve the optimization problem, the radar range sidelobe suppression is achieved. Theoretical analysis and simulation results show that this method can effectively suppress the range sidelobes.

Objective: This study aimed to investigate the clinical characteristics of acute myeloid leukemia with myelodysplasia-related changes (AMLMRC) according to the 2016 World Health Organization classification and the preferred therapy for patients with AML-MRC aged 60-75 years. Materials and Methods: We retrospectively analyzed differences in clinical data among 190 patients with AML-MRC and 667 patients with AML not otherwise specified (AML-NOS). We also compared different therapeutic regimens among patients with AML-MRC aged 60-75 years. Results: Compared with AML-NOS, patients with AML-MRC had significantly different clinical characteristics as well as worse overall survival (OS) (9.2 vs. 13.6 months; p

Planetary gearboxes are widely used in mechanical transmission systems due to their large transmission ratio and high transmission efficiency. In a planetary gearbox， the sun gear is usually set to float to balance the sharing of loads among planet gears. However， this floating set will result in the variation of pressure angle， overlap ratio and meshing phase in the meshing progress. In the previous studies， these parameters were reduced to constant. To study the influence of the dynamic parameters on the vibration response of planetary gearboxes under different operating conditions， a new lumped parameter model containing the time-varying pressure angle， time-varying overlap ratio and time-varying meshing phase is established. Based on this model， the vibration response mechanism of the sun gear is analyzed. Moreover， the comparison with the previous model is made and the rule of phase modulation caused by these dynamic parameters is revealed. By comparing the dynamic responses under different loads and rotation speeds， the phase modulation is studied in detail.

The Lewy bodies and Lewy neurites are key pathological hallmarks of Parkinson’s disease (PD). Single-point mutations associated with familial PD cause α-synuclein (α-Syn) aggregation, leading to the formation of Lewy bodies and Lewy neurites. Recent studies suggest α-Syn nucleates through liquid–liquid phase separation (LLPS) to form amyloid aggregates in a condensate pathway. How PD-associated mutations affect α-Syn LLPS and its correlation with amyloid aggregation remains incompletely understood. Here, we examined the effects of five mutations identified in PD, A30P, E46K, H50Q, A53T, and A53E, on the phase separation of α-Syn. All other α-Syn mutants behave LLPS similarly to wild-type (WT) α-Syn, except that the E46K mutation substantially promotes the formation of α-Syn condensates. The mutant α-Syn droplets fuse to WT α-Syn droplets and recruit α-Syn monomers into their droplets. Our studies showed that α-Syn A30P, E46K, H50Q, and A53T mutations accelerated the formation of amyloid aggregates in the condensates. In contrast, the α-Syn A53E mutant retarded the aggregation during the liquid-to-solid phase transition. Finally, we observed that WT and mutant α-Syn formed condensates in the cells, whereas the E46K mutation apparently promoted the formation of condensates. These findings reveal that familial PD-associated mutations have divergent effects on α-Syn LLPS and amyloid aggregation in the phase-separated condensates, providing new insights into the pathogenesis of PD-associated α-Syn mutations.

With the national economic transition and rapid development of technology,enterprises need digital transition.How to accelerate transition through IT architecture upgrading has become a new research topic for enterprises.The definition,function and common types of middle platforms were stated.The strategy and architecture of different enterprises’ middle platforms which differ in service chain length were also compared and analyzed.The concept of planning middle platform was proposed on the basis of decoupling production from operation.Considering the current situation of operators,some suggestions were put forward on how to design the middle platform and which type to choose.

Chromoblastomycosis (CBM) is a chronic disease caused by several species of dematiaceous fungi. In this study, a regional collection of 45 CBM cases was conducted in Guangdong, China, a hyper-endemic area of CBM. Epidemiology findings indicated that the mean age of cases was 61.38 ± 11.20 years, long duration ranged from 3 months to 30 years, and the gender ratio of male to female was 4.6:1. Thirteen cases (29%) declared underlying diseases. Verrucous form was the most common clinical manifestation (n = 19, 42%). Forty-five corresponding clinical strains were isolated, and 28 of them (62%) were identified as F. monophora; the remaining 17 (38%) were identified as F. nubica through ITS rDNA sequence analysis. Antifungal susceptibility tests in vitro showed low MICs in azoles (PCZ 0.015–0.25 μg/ml, VCZ 0.015–0.5 μg/ml, and ITZ 0.03–0.5 μg/ml) and TRB (0.015–1 μg/ml). Itraconazole combined with terbinafine was the main therapeutic strategy used for 31 of 45 cases, and 68% (n = 21) of them improved or were cured. Cytokine profile assays indicated upregulation of IL-4, IL-7, IL-15, IL-11, and IL-17, while downregulation of IL-1RA, MIP-1β, IL-8, and IL-16 compared to healthy donors (p < 0.05). The abnormal cytokine profiles indicated impaired immune response to eliminate fungus in CBM cases, which probably contributed to the chronic duration of this disease. In conclusion, we investigated the molecular epidemiological, clinical, and laboratory characteristics of CBM in Guangdong, China, which may assist further clinical therapy, as well as fundamental pathogenesis studies of CBM.

Human activities and global climate change have greatly increased nitrogen (N) and phosphorus (P) inputs and altered precipitation patterns in alpine meadows. Functional genes are important indicators of microorganisms that drive the nitrogen cycling process; however, the functional gene responses of soil nitrogen cycling to soil N and P availability and drought remain unclear. Separate or combined treatments of nitrogen and phosphorus fertilization and drought were conducted on the Zoige Wetland in the Qinghai-Tibet Plateau, and the abundances of nitrification functional genes AOA amoA and AOB amoA and denitrification functional genes nirS, nirK, and nosZ were measured to explore the response of functional genes to these treatments. Seven treatments, including control (CK), N addition (N), P addition (P), 50% reduction in precipitation (D), N and P addition (NP), N addition with drought (ND), and NP addition with drought (NPD), were investigated. The results indicated that N application significantly increased AOB amoA abundance, while P application and drought had no significant effects on the abundance of functional genes. The combined treatment of N and P addition and drought increased AOB amoA abundance but did not significantly affect AOA amoA abundance, suggesting that AOB amoA was more responsive to soil N and P availability and moisture change than AOA amoA. However, the abundance of denitrification functional genes was not affected by these treatments. Denitrification functional genes were less sensitive to soil N and P availability and moisture change than nitrification functional genes. The integrated effects of N addition, P addition, and drought did not affect the abundance of the above N cycling functional genes. These results indicate that AOB amoA may play a more critical role in the process of ammonia oxidation than AOA amoA in alpine meadows, and the denitrification genes (nirK, nirS, and nosZ) were better than ammoxidation genes (AOA and AOB) at adapting to the soil environmental changes caused by increasing N and P deposition and drought in alpine meadows.

Increases in nitrogen (N) deposition affect the nitrification and denitrification processes that are regulated by microorganisms. With the aim of understanding what happened to the soil nitrification and denitrification rates under the N application gradients, we set a field experiment treated with N at 6 different rates (0, 2, 4, 8, 16, and 32 g N·m−2·yr−1) in 2014. We determined the physico-chemical properties, abundances and community structures of the nitrifiers and denitrifiers, the net nitrification rate (NNR) and the potential denitrification rate (PDR) of soil samples that were collected in 2020. We found that the abundances of ammonia-oxidizing bacteria amoA (AOB amoA), the sum of ammonia-oxidizing archaea amoA (AOA amoA) and AOB amoA increased with the increase in N application rate, but the abundances of nosZ decreased with that. The microorganisms that dominate the ammonia oxidation process could shift from AOA to AOB under high N application rates. Furthermore, the soil microorganisms respond to the N addition preferentially with the abundance changes rather than the community composition changes. Moreover, the NNR increased with the N input, while the decrease in the PDR was due to the decrease in the pH value caused by high N application. The results also showed that the amoA gene abundance explained most (46.3%) of the variation in the NNR. Moreover, the soil moisture and pH explained 44.0% and 27.1% of the variation in the PDR, respectively. The results demonstrated that the NNR and PDR were mainly explained by functional genes abundances and environmental factors, respectively, in alpine meadow soil under sustained N deposition.

A Carboniferous trench-arc-basin system related to oceanic slab subduction has been thoroughly imaged by various geophysical probing approaches and proposed for the formation of West Junggar, Northwest China, located in the southwest of the Central Asian Orogenic Belt. However, debate on the origin of West Junggar still continues. Here, we present an integrated aeronautic magnetic–gravity observation to further identify the trench-arc-basin system and constrain the subduction mode. By deploying an integrated aerial magnetic–gravity survey consisting of 66,000 survey-line kilometers from August 3, 2015 to April 22, 2016, we determine the magnetic and gravitational anomaly across the study region by using geophysical potential-field processing. Our results reveal curial crust-scale variations in magnetic and gravitational structures beneath West Junggar and that a prominent Bouguer gravity high is located between the Darbut and Karamay–Urho faults, likely corresponding to a trapped oceanic slab. Notably, the Tacheng Basin is characterized by high-frequency magnetic signal and gravity highs, as well as the Carboniferous rifting–related sedimentary cover, which could be reasonably interpreted to be a back-arc basin. Integrated with these comprehensive geological and geophysical observations across West Junggar, the previous model of West Junggar trench-arc-basin system related to a fossil intra-oceanic subduction during the Late Paleozoic is further renewed.

Background: To reduce the high incidence and mortality of gastric cancer (GC), we aimed to develop deep learning-based models to assist in predicting the diagnosis and overall survival (OS) of GC patients using pathological images. Methods: 2333 hematoxylin and eosin-stained pathological pictures of 1037 GC patients were collected from two cohorts to develop our algorithms, Renmin Hospital of Wuhan University (RHWU) and the Cancer Genome Atlas (TCGA). Additionally, we gained 175 digital pictures of 91 GC patients from National Human Genetic Resources Sharing Service Platform (NHGRP), served as the independent external validation set. Two models were developed using artificial intelligence (AI), one named GastroMIL for diagnosing GC, and the other named MIL-GC for predicting outcome of GC. Findings: The discriminatory power of GastroMIL achieved accuracy 0.920 in the external validation set, superior to that of the junior pathologist and comparable to that of expert pathologists. In the prognostic model, C-indices for survival prediction of internal and external validation sets were 0.671 and 0.657, respectively. Moreover, the risk score output by MIL-GC in the external validation set was proved to be a strong predictor of OS both in the univariate (HR = 2.414, P

Sea ice leads, or fractures account for a small proportion of the Arctic Ocean surface area, but play a critical role in the energy and moisture exchanges between the ocean and atmosphere. As the sea ice area and volume in the Arctic has declined over the past few decades, changes in sea ice leads have not been studied as extensively. A recently developed approach uses artificial intelligence (AI) and satellite thermal infrared window data to build a twenty-year archive of sea ice lead detects with Moderate Resolution Imaging Spectroradiometer (MODIS) and later, an archive from Visible Infrared Imaging Radiometer Suite (VIIRS). The results are now available and show significant improvement over previously published methods. The AI method results have higher detection rates and a high level detection agreement between MODIS and VIIRS. Analysis over the winter season from 2002–2003 through to the 2021–2022 archive reveals lead detections have a small decreasing trend in lead area that can be attributed to increasing cloud cover in the Arctic. This work reveals that leads are becoming increasingly difficult to detect rather than less likely to occur. Although the trend is small and on the same order of magnitude as the uncertainty, leads are likely increasing at a rate of 3700 km2 per year with a range of uncertainty of 3500 km2 after the impact of cloud cover changes are removed.