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Mitophagy, the selective degradation of mitochondria by autophagy, plays a crucial role in cancer progression and therapy response. This study aims to elucidate the role of mitophagy-related genes (MRGs) in cutaneous melanoma (CM) through single-cell RNA sequencing (scRNA-seq) and machine learning approaches, ultimately developing a predictive model for patient prognosis. The scRNA-seq data, bulk transcriptomic data, and clinical data of CM were obtained from publicly available databases. The single-sample gene set enrichment analysis (ssGSEA) and weighted gene co-expression network analysis (WGCNA) were used to identify gene modules associated with mitophagy phenotypes. A machine learning framework employing ten different algorithms was used to develop the prognostic model. Based on scRNA-seq data, we identified 16 distinct cell subpopulations in melanoma, and melanoma cells exhibited significantly higher mitophagy scores. The turquoise module identified via WGCNA showed the strongest correlation with mitophagy scores. A prognostic model incorporating seven genes was developed through machine learning algorithms, achieving an average C-index of 0.754 across training and validation cohorts. Functionally, low-risk patients were enriched in interferon-gamma response and inflammatory processes, whereas high-risk patients showed enrichment in glycolysis regulation and signaling pathways such as KRAS and Wnt/β-catenin. Notably, low-risk patients demonstrated enhanced immune infiltration and greater sensitivity to immunotherapy. RT-qPCR validated the expression level of 7 model genes in human melanoma cell lines and normal melanocyte cell lines. Our study provides a comprehensive understanding of MRGs in melanoma and presents a novel prognostic model. These findings enhance our understanding of the tumor microenvironment and may guide personalized treatment strategies for CM patients. [ABSTRACT FROM AUTHOR]

Radiation-induced skin toxicity, resulting from ionizing or nonionizing radiation, is a common skin disorder. However, the underlying relationship between skin microbiota and radiation-induced skin toxicity remains largely unexplored. Herein, we uncover the microbiota–skin interaction based on a genome-wide association study (GWAS) featuring 150 skin microbiota and three types of skin microenvironment. Summary datasets of human skin microbiota were extracted from the GWAS catalog database, and summary datasets of radiation-induced skin toxicity from the FinnGen biobank. Mendelian Randomization (MR) analysis was leveraged to sort out the causal link between skin microbiota and radiation-induced skin toxicity. We identified 33 causal connections between human skin microbiota and radiation-induced skin toxicity, including 19 positive and 14 negative causative directions. Among these potential associations, the genus Staphylococcus could serve as a common risk factor for radiation-induced skin toxicity, especially for radiodermatitis. And Streptococcus salivarius was identified as a potential protective factor against radiation-induced skin toxicity. Additional analysis indicated no pleiotropy, heterogeneity, or reverse causal relationship in the results. We comprehensively assessed potential associations of skin microbiota with radiation-induced skin toxicity and identified several suggestive links. Our results provide promising targets for the prevention and treatment of radiation-induced skin toxicity. [ABSTRACT FROM AUTHOR]

Oceanic mesoscale eddies (with scale 101–102 km) and their submesoscale fine structures (with scale 100–101 km) can effectively induce vertical motions and bring nutrients into the oceanic euphotic layer, which leaves abundant footprints on the ocean surface chlorophyll distributions and have the potential to promote primary productivity of oceanic ecosystem. In return, these surface chlorophyll footprints observed by ocean color satellites can serve as a useful tool to reveal the spatial structures of mesoscale eddies and their submesoscale fine structures. By combining artificial intelligence (AI) algorithms to develop a series of identification strategies for typical surface chlorophyll patterns around mesoscale eddies, we find that over 20% of mesoscale eddy observations exhibit identifiable typical chlorophyll patterns, which tends to regulate an increase of the surface chlorophyll concentration within the corresponding eddies, especially enhancing by about 30% in nutrient‐restricted subtropical regions compared with the background values. Based on their geometric features, typical chlorophyll patterns are primarily classified as Core, Spiral, Tail, Ring, Loop, and Eye respectively by clustering algorithm. Further spatial‐spectral analysis found that the typical patterns on eddies exhibit a much steeper wave‐number spectral slope about −3, compared to the non‐typical distributions on eddies and the non‐eddy background distribution (about −2.7–−2.2). This implies that the occurrence of different typical chlorophyll patterns may correspond to specific mesoscale and submesoscale dynamic processes. Plain Language Summary: Mesoscale eddies and their submesoscale fine structures collectively play non‐negligible roles in sustaining nutrient supply and promoting productivity in the oceanic euphotic layer. Although submesoscale processes are believed to result in ageostrophic motions and allow forward oceanic energy cascade, the resolutions of traditional in‐situ ocean measurements and satellite altimetry observations are typically too coarse to resolve them. In this paper, we elaborate on artificial intelligence (AI) techniques to develop a series of typical surface chlorophyll pattern identification strategies. The AI framework automatically identified six types of typical chlorophyll patterns of mesoscale eddy, in the context of the generally comparable geometric characteristics that are potentially reflected from their underlined oceanic dynamics. Over 20% mesoscale eddy observations tend to exhibit identifiable typical chlorophyll patterns, which leads to a remarkable increase of surface chlorophyll concentration. The wave‐number spectrum of eddy‐induced typical patterns exhibit a significantly steeper slope, in comparison of the non‐typical distributions on eddies and the non‐eddy background distribution. Our results may help to establish parameterizations for the submesoscale processes of mesoscale eddies, or provide an observational baseline to verify high‐resolution physical‐biogeochemical coupled oceanic numerical models, or even improve the model simulations of oceanic primary productivity and carbon fixation capacity. Key Points: Six types of typical chlorophyll patterns on mesoscale eddies and their submesoscale fine‐structures are identified globally by artificial intelligence (AI) methodThe typical patterns tend to substantially enhance chlorophyll concentration of the corresponding eddiesThe wave‐number spectral slope of the typical chlorophyll pattern is significantly different from the background value [ABSTRACT FROM AUTHOR]

Selenium (Se) is an essential trace element for maintaining human health, for example, plays a crucial role in preventing aging-related diseases. However, most studies on the health effects of Se among the community middle-aged and elderly have been observational or the health indices were single, and the related study among the Chinese population is limited. Additionally, China is recognized as among the countries facing a significant deficiency in Se, and Se contents in the human body may decrease with age. Therefore, a two-step study was conducted to explore the health effects of Se exposure and supplementation among such populations in China. Firstly, a retrospective cohort study was conducted to compare the health outcomes between such populations residing in Se-rich regions and non-Se-rich regions, involving a total of 102 subjects, with 51 residing in Se-rich regions and 51 in non-Se-rich regions. The hair-Se (H-Se) contents, serum-Se (S-Se) contents, and total cholesterol of subjects from Se-rich regions were significantly higher than their counterparts. Notably, significant positive associations were observed between S-Se and lipids. Secondly, a before-after self-control Se supplementation study among subjects residing in non-Se-rich regions was conducted. A total of 40 subjects administered Se tablets orally for 30 days, with Se of 120 μg/day. The results showed significant increases in H-Se and S-Se. Se supplementation also exhibited positive effects on alanine aminotransferase, homocysteine, and fasting glucose; however, high-density lipoprotein cholesterol significantly decreased. Overall, the community middle-aged and elderly residing in Se-rich regions or receiving quantitative Se supplementation could effectively improve Se contents in bodies and certain health indices, excluding lipids. These improvements encompass liver function, cardiovascular health, and glucose metabolism. These findings enhance our understanding of how Se impacts the health of the middle-aged and elderly, emphasizing the significance of targeted interventions for such populations in non-Se-rich regions. Trial registration: ChiCTR2000040987 (https://www.chictr.org.cn). [ABSTRACT FROM AUTHOR]

The bonding performance of carbon fiber–reinforced polymer (CFRP)–concrete interface is an important research area, with adhesives serving as mediators for the transfer of interface stresses. However, there is significant variation in the mechanical properties of adhesives available in the market, and currently there is limited research on the patterns of how adhesive mechanical properties affect interfaces. First, dynamic thermomechanical analysis was used to investigate the glass transition temperature of the adhesive, Tg. Following this, tensile tests were conducted to assess the mechanical properties of the adhesive at various temperatures. Finally, the effects of the adhesive on the interface bonding properties of CFRP-concrete were studied by single shear tests at different ambient temperatures. The test results indicated that when the ambient temperature is lower than the glass transition temperature (Tg), as the temperature increases, although the mechanical properties of the adhesive decreased, the effective bonded length of interface increased significantly, leading to a gradual increase in interface load-bearing capacity. Furthermore, the interface constitutive model was modified by finite-element model inversion. The modified parameters K and τmax exhibited a linear increase relationship with the elastic modulus of the adhesive, and the modified parameter Gf showed a negative exponential power function relationship with the elastic modulus of the adhesive. [ABSTRACT FROM AUTHOR]

Cucumber (Cucumis sativus L.) is a globally prevalent and extensively cultivated vegetable whose yield is significantly influenced by various abiotic stresses, including drought, heat, and salinity. Transcription factors, such as zinc finger-homeodomain proteins (ZHDs), a plant-specific subgroup of Homeobox, play a crucial regulatory role in stress resistance. In this study, we identified 13 CsZHDs distributed across all six cucumber chromosomes except chromosome 7. Phylogenetic analysis classified these genes into five clades (ZHDI-IV and MIF) with different gene structures but similar conserved motifs. Collinearity analysis revealed that members of clades ZHD III, IV, and MIF experienced amplification through segmental duplication events. Additionally, a closer evolutionary relationship was observed between the ZHDs in Cucumis sativus (C. sativus) and Arabidopsis thaliana (A. thaliana) compared to Oryza sativa (O. sativa). Quantitative real-time PCR (qRT-PCR) analysis demonstrated the general expression of CsZHD genes across all tissues, with notable expression in leaf and flower buds. Moreover, most of the CsZHDs, particularly CsZHD9-11, exhibited varying responses to drought, heat, and salt stresses. Virus-induced gene silencing (VIGS) experiments highlighted the potential functions of CsZHD9 and CsZHD10, suggesting their positive regulation of stomatal movement and responsiveness to drought stress. In summary, these findings provide a valuable resource for future analysis of potential mechanisms underlying CsZHD genes in response to stresses. [ABSTRACT FROM AUTHOR]

Microneedle array systems loaded with responsive nanoparticles have received increasing attention due to the advantages of good drug stability, targeting ability, controlled release of drugs, high bioavailability, painlessness, and good patient compliance. Compared with oral drug delivery, microneedle transdermal drug delivery eliminates the need to pass through the gastrointestinal tract and liver, reducing the metabolic consumption of drugs by first‐pass effect. While compared with intravenous drug delivery, microneedle transdermal drug delivery reduces patient discomfort and does not require professional administration. However, there are few review articles on microneedles loaded with responsive nanoparticles. Herein, the current researches on microneedles loaded with specific responsive nanoparticles such as glucose‐responsive, pH‐responsive, enzyme‐responsive, light‐responsive, magnetic‐responsive, ultrasound‐responsive, and multiresponsive, and the biomedical application of these microneedle array systems are summarized. In addition, the challenges and prospects of microneedle strategies loaded with responsive nanoparticles are briefly discussed, which will facilitate the development of such versatile drug‐delivery strategy. [ABSTRACT FROM AUTHOR]

Motivation Effective drug delivery systems are paramount in enhancing pharmaceutical outcomes, particularly through the use of cell-penetrating peptides (CPPs). These peptides are gaining prominence due to their ability to penetrate eukaryotic cells efficiently without inflicting significant damage to the cellular membrane, thereby ensuring optimal drug delivery. However, the identification and characterization of CPPs remain a challenge due to the laborious and time-consuming nature of conventional methods, despite advances in proteomics. Current computational models, however, are predominantly tailored for balanced datasets, an approach that falls short in real-world applications characterized by a scarcity of known positive CPP instances. Results To navigate this shortfall, we introduce PractiCPP, a novel deep-learning framework tailored for CPP prediction in highly imbalanced data scenarios. Uniquely designed with the integration of hard negative sampling and a sophisticated feature extraction and prediction module, PractiCPP facilitates an intricate understanding and learning from imbalanced data. Our extensive computational validations highlight PractiCPP's exceptional ability to outperform existing state-of-the-art methods, demonstrating remarkable accuracy, even in datasets with an extreme positive-to-negative ratio of 1:1000. Furthermore, through methodical embedding visualizations, we have established that models trained on balanced datasets are not conducive to practical, large-scale CPP identification, as they do not accurately reflect real-world complexities. In summary, PractiCPP potentially offers new perspectives in CPP prediction methodologies. Its design and validation, informed by real-world dataset constraints, suggest its utility as a valuable tool in supporting the acceleration of drug delivery advancements. Availability and implementation The source code of PractiCPP is available on Figshare at https://doi.org/10.6084/m9.figshare.25053878.v1. [ABSTRACT FROM AUTHOR]

This study aimed to explore the occurrence of necroptosis in skeletal muscle after eccentric exercise and investigate the role and possible mechanisms of ZBP1 and its related pathway proteins in the process, providing a theoretical basis for the study of exercise-induced skeletal muscle injury and recovery. Forty-eight male adult Sprague–Dawley rats were randomly divided into a control group (C, n = 8) and an exercise group (E, n = 40). The exercise group was further divided into 0 h (E0), 12 h (E12), 24 h (E24), 48 h (E48), and 72 h (E72) after exercise, with 8 rats in each subgroup. At each time point, gastrocnemius muscle was collected under general anesthesia. The expression levels of ZBP1 and its related pathway proteins were assessed using Western blot analysis. The colocalization of pathway proteins was examined using immunofluorescence staining. After 48 h of eccentric exercise, the expression of necroptosis marker protein MLKL reached its peak (P < 0.01), and the protein levels of ZBP1, RIPK3, and HMGB1 also peaked (P < 0.01). At 48 h post high-load eccentric exercise, there was a significant increase in colocalization of ZBP1/RIPK3 pathway proteins, reaching a peak (P < 0.01). (1) Eccentric exercise induced necroptosis in skeletal muscle, with MLKL, p-MLKLS358, and HMGB1 significantly elevated, especially at 48 h after exercise. (2) After eccentric exercise, the ZBP1/RIPK3-related pathway proteins ZBP1, RIPK3, and p-RIPK3S232 were significantly elevated, particularly at 48 h after exercise. (3) Following high-load eccentric exercise, there was a significant increase in the colocalization of ZBP1/RIPK3 pathway proteins, with a particularly pronounced elevation observed at 48 h post-exercise. [ABSTRACT FROM AUTHOR]

Glandular trichomes (GTs), specialized structures formed by the differentiation of plant epidermal cells, are known to play important roles in the resistance of plants to external biotic and abiotic stresses. These structures are capable of storing and secreting secondary metabolites, which often have important agricultural and medicinal values. In order to better understand the molecular developmental mechanisms of GTs, studies have been conducted in a variety of crops, including tomato (Solanum lycopersicum), sweetworm (Artemisia annua), and cotton (Gossypium hirsutum). The MYC transcription factor of the basic helix-loop-helix (bHLH) transcription factor family has been found to play an important role in GT development. In this study, a total of 13 cucumber MYC transcription factors were identified in the cucumber (Cucumis sativus L.) genome. After performing phylogenetic analyses and conserved motifs on the 13 CsMYCs in comparison to previously reported MYC transcription factors that regulate trichome development, seven candidate MYC transcription factors were selected. Through virus-induced gene silencing (VIGS), CsMYC2 is found to negatively regulate GT formation while CsMYC4, CsMYC5, CsMYC6, CsMYC7, and CsMYC8 are found to positively regulate GT formation. Furthermore, the two master effector genes, CsMYC2 and CsMYC7, are observed to have similar expression patterns indicating that they co-regulate the balance of GT development in an antagonistic way. [ABSTRACT FROM AUTHOR]

To observe whether downhill running can lead to DNA damage in skeletal muscle cells and changes in mitochondrial membrane permeability and to explore whether the DNA damage caused by downhill running can lead to changes in mitochondrial membrane permeability by regulating the components of the endoplasmic reticulum mitochondrial coupling structure (MAM). A total of 48 male adult Sprague–Dawley rats were randomly divided into a control group (C, n = 8) and a motor group (E, n = 40). Rats in Group E were further divided into 0 h (E0), 12 h (E12), 24 h (E24), 48 h (E48) and 72 h (E72) after prescribed exercise, with 8 rats in each group. At each time point, flounder muscle was collected under general anaesthesia. The DNA oxidative damage marker 8-hydroxydeoxyguanosine (8-OHdG) was detected by immunofluorescence. The expression levels of the DNA damage-related protein p53 in the nucleus and the EI24 protein and reep1 protein in whole cells were detected by Western blot. The colocalization coefficients of the endoplasmic reticulum protein EI24 and the mitochondrial protein Vdac2 were determined by immunofluorescence double staining, and the concentration of Ca2+ in skeletal muscle mitochondria was detected by a fluorescent probe. Finally, the opening of the mitochondrial membrane permeability transition pore (mPTP) was detected by immunofluorescence. Twelve hours after downhill running, the mitochondrial membrane permeability of the mPTP opened the most (P < 0.05), the content of 8-OHdG in skeletal muscle peaked (P < 0.05), and the levels of the regulatory protein p53, mitochondrial Ca2+, and the EI24 and reep1 proteins peaked (P < 0.01). Moreover, the colocalization coefficients of EI24 and Vdac2 and the Mandes coefficients of the two proteins increased first and then recovered 72 h after exercise (P < 0.05). (1) Downhill running can lead to DNA damage in skeletal muscle cells, overload of mitochondrial Ca2+ and large opening of membrane permeability transformation pores. (2) The DNA damage caused by downhill running may result in p53 promoting the transcriptional activation of reep1 and EI24, enhancing the interaction between EI24 and Vdac2, and then leading to an increase in Ca2+ in skeletal muscle mitochondria and the opening of membrane permeability transition pores. [ABSTRACT FROM AUTHOR]

Pleurotus citrinopileatus, a nutritious and palatable edible mushroom, can be used as an appropriate material to prepare high‐grade flavoring agents. Based on this, the current study aimed to investigate the feasibility of a productive protease system from Actinomucor elegans to prepare P. citrinopileatus hydrolysate (PCH). The Actinomucor elegans crude protease (AECP) was prepared from the solid‐state fermentation product of P. citrinopileatus by A. elegans. AECP and four commercial proteases (alcalase, neutrase, papain, and protamex) were applied to acquire five kinds of PCHs. The physical‐chemical properties of PCHs as well as its concentration and composition of nonvolatile compounds were comparatively analyzed. Sensory evaluation and electronic tongue analysis were utilized to evaluate sensory characteristics. AECP was found to be the most effective protease, with the highest hydrolysis degree (35.91%) and protein recovery (81.46%). The result of molecular weight distribution indicated that peptides below 500 Da were the main fraction of AECP hydrolysates, while AECP hydrolysates showed the highest content of monosodium glutamate‐like (20.23 ± 0.16 mg/g) and flavor 5′‐nucleotide (4.30 ± 0.07 mg/g) peptides. In summary, the AECP hydrolysate had superior sensory profiles compared with other hydrolysates. In addition, AECP hydrolysates exhibited favorable kokumi taste in which peptides below 500 Da showed the highest correlation with kokumi by the results of partial least‐squares regression. These results indicated the feasibility of applying PCHs as flavor additives or seasoning in the food industry. AECP might be used as an alternative enzyme choice because of its low cost and high hydrolysis efficiency. Practical Application: Pleurotus citrinopileatus served as a potential raw material for natural seasonings because of its high protein content and appropriate ratio of umami amino acids to total amino acids. Enzymatic hydrolysis was an efficient approach to improve the flavor of P. citrinopileatus, where the choice of enzyme was one of the most critical factors. The research indicated that P. citrinopileatus hydrolysate prepared by A. elegans crude protease (AECP) exhibited an acceptable flavor, which provided theoretical support for the high‐value utilization of P. citrinopileatus as food seasoning. AECP might be applied as an alternative enzyme resource because of its low cost and high hydrolysis efficiency. [ABSTRACT FROM AUTHOR]

In this study, yeast, lactic acid bacteria, and acetic acid bacteria were isolated from traditional Chinese sourdough to enhance the organoleptic quality of whole wheat steamed bread. The Saccharomyces cerevisiae, Lactobacillus johnsonii, and Acetobacter pasteurianum showed superior fermentability and acid production capacity when compared with other strains from sourdough, which were mixed to produce the compound starter. It was found that the volume of whole wheat steamed bread leavened with compound starter increased by 12.8% when compared with that of the whole wheat steamed bread made by commercial dry yeast (DY-WB). A total of 38 volatile flavors were detected in the whole wheat steamed bread fermented by the compound starter (CS-WB), and the type of volatile flavors increased by 14 species when compared to the bread fermented by the dry yeast. In addition, some unique volatile flavor substances were detected in CS-WB, such as acetoin, 3-hydroxy-butanal, butyraldehyde, cuparene, etc. Moreover, the hardness and the chewiness of CS-WB decreased by 31.1 and 33.7% when compared with DY-WB, respectively, while the springiness increased by 10.8%. Overall, the formulated compound starter showed a desirable improvement in the whole wheat steamed bread and could be exploited as a new ingredient for steamed bread. [ABSTRACT FROM AUTHOR]

Polyvinylpyrrolidone (PVP) and graphene (G)-modified iron oxides (Fe2O3-PVP-G) are prepared by a simple hydrothermal reaction. Their morphology and structure were examined and proved by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and ultraviolet–visible diffuse reflectance spectroscopy. P-nitrophenol (p-NP) is a usual organic pollutant, which is highly toxic and difficult to decompose. Electrochemical reduction of p-NP is a widely used treatment, but the reduction products are still toxic. In this work, the electrochemical catalytic oxidation of p-NP was achieved on Fe2O3-PVP-G modified electrodes. Compared to pure Fe2O3, Fe2O3-PVP-G shows better catalytic performance, with a current density 10.4 times larger than that from Fe2O3. Electrochemical results verify that the improvement comes from the promotion of its activity and the favorable enrichment of p-NP with the help of the doped PVP and G. pH experiments indicate that p-NP is oxidized to aliphatic acid, which is non-toxic and environmentally friendly. Due to the protection of organic molecules, Fe2O3-PVP-G exhibits long-term stabilities on electrochemical oxidation on p-NP with the retention of 88.5% for 15 days. Our results also provide another perspective for studying electrocatalytic performances. [ABSTRACT FROM AUTHOR]

An efficient and catalyst-free protocol for the synthesis of a series of indole substituted or spiroxindole-consisted dihydropyrido[2,3-d]pyrimidine derivatives by one-pot three-component reaction of 2,6-diaminopyrimidin-4-one, various aryl aldehydes or isatins, and 3-cyanoacetyl indoles under microwave irradiation was investigated. The advantages of this methodology include high yields of products, short reaction time, easy work-up procedure and broad substrate scope. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a common chronic systemic autoimmune disease. Although there are a variety of treatments for RA, the substantial clinical therapies are still limited to disease-modifying anti-rheumatic drugs (DMARD), which would induce obvious side-effect in patients after long-term administration. Herein, an uncomplicated drug-induced self-assembly strategy was proposed to fabricate enzyme-loaded albumin nanomedicine. The hydrophobic drug methotrexate (MTX) could induce self-assembly of superoxide dismutase (SOD) and human serum albumin (HSA) to form HSA-SOD-MTX nanoparticle. After intravenous injection, dual-modal imaging including fluorescence imaging or single-photon emission computed tomography (SPECT)/CT imaging exhibits high accumulation of cyanine 5.5 (Cy5.5) or 125I labeled HSA-SOD-MTX nanoparticles in the joints of collagen-induced arthritis (CIA) mice. Importantly, using the synergy therapy of SOD enzyme to scavenge the reactive oxygen species (ROS) and MTX to suppress inflammation, HSA-SOD-MTX nanoparticles exhibit excellent therapeutic efficiency of RA in CIA mice compared with the other groups. Micro-CT and clinical arthritis score of RA mice further demonstrate that RA symptoms of mice treated with HSA-SOD-MTX nanoparticles is significantly relived, which was further demonstrated by the histological analysis and the inflammatory factors measurement. The synergy therapy of inflammation by MTX and SOD enzyme based on HSA-SOD-MTX nanoparticles show excellent therapeutic effects of RA without inducing obvious side effects. Therefore, our strategy may further promote the highly efficient therapy of RA using SOD enzyme to scavenge the ROS and decreasing the side-effect of MTX, which may provide the reference for clinical RA treatment. [ABSTRACT FROM AUTHOR]

Objectives: Atypical benign epilepsy with centro-temporal spikes (BECTS) have less favorable outcomes than typical BECTS, and thus should be accurately identified for adequate treatment. We aimed to investigate the glucose metabolic differences between typical and atypical BECTS using 18F-fluorodeoxyglucose positron emission tomography ([18F]FDG PET) imaging, and explore whether these differences can help distinguish. Methods: Forty-six patients with typical BECTS, 31 patients with atypical BECTS and 23 controls who underwent [18F]FDG PET examination were retrospectively involved. Absolute asymmetry index (|AI|) was applied to evaluate the severity of metabolic abnormality. Glucose metabolic differences were investigated among typical BECTS, atypical BECTS, and controls by using statistical parametric mapping (SPM). Logistic regression analyses were performed based on clinical, PET, and hybrid features. Results: The |AI| was found significantly higher in atypical BECTS than in typical BECTS (p = 0.040). Atypical BECTS showed more hypo-metabolism regions than typical BECTS, mainly located in the fronto-temporo-parietal cortex. The PET model had significantly higher area under the curve (AUC) than the clinical model (0.91 vs. 0.70, p = 0.006). The hybrid model had the highest sensitivity (0.90), specificity (0.85), and accuracy (0.87) of all three models. Conclusions: Atypical BECTS showed more widespread and severe hypo-metabolism than typical BECTS, depending on which the two groups can be well distinguished. The combination of metabolic characteristics and clinical variables has the potential to be used clinically to distinguish between typical and atypical BECTS. Key Points: • Distinguishing between typical and atypical BECTS is very important for the formulation of treatment regimens in clinical practice. • Atypical BECTS showed more widespread and severe hypo-metabolism than typical BECTS, mainly located in the fronto-temporo-parietal cortex. • The logistic regression model based on PET outperformed that based on clinical characteristics in classification of typical and atypical BECTS, and the hybrid model achieved the best classification performance. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of the establishment of a Chest Pain Center (CPC) on the treatment delay of ST-elevation myocardial infarction (STEMI) patients and the influencing factors of treatment delay in a large hospital in China.Methods: The study subjects are 318 STEMI patients admitted between August 2016 and July 2019 to a large general hospital in Henan, China. Data were extracted from the electronic medical records after removing personal identifiable information. The interrupted time series regression was used to analyze the treatment delay of patients before and after the CPC establishment.Results: After the CPC establishment, the patients' pre-hospital and in-hospital treatment delays were significantly reduced. SO-to-FMC (Symptom Onset to First Medical Contact time) decreased by 49.237 min and D-to-B (Door to Balloon time) decreased by 21.931 min immediately after the CPC establishment. In addition, SO-to-FMC delay is significantly correlated with age, occupation, nocturnal onset, and the way to hospital. D-to-B delay is significantly associated with time from initial diagnosis to informed consent of percutaneous coronary intervention (PCI), catheterization lab activation time, and time for PCI informed consent.Conclusion: The CPC significantly reduced the treatment delay of STEMI patients undergoing PCI. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy is known to be important for intracellular quality control in the lens. GJA8 is a major gap junction protein in vertebrate lenses. Mutations in GJA8 cause cataracts in humans. The well-known cataractogenesis mechanism is that mutated GJA8 leads to abnormal assembly of gap junctions, resulting in defects in intercellular communication among lens cells. In this study, we observed that ablation of Gja8b (a homolog of mammalian GJA8) in zebrafish led to severe defects in organelle degradation, an important cause of cataractogenesis in developing lens. The role of autophagy in organelle degradation in lens remains disputable. Intriguingly, we also observed that ablation of Gja8b induced deficient autophagy in the lens. More importantly, in vivo treatment of zebrafish with rapamycin, an autophagy activator that inhibits MAPK/JNK and MTORC1 signaling, stimulated autophagy in the lens and relieved the defects in organelle degradation, resulting in the mitigation of cataracts in gja8b mutant zebrafish. Conversely, inhibition of autophagy by treatment with the chemical reagent 3-MA blocked these recovery effects, suggesting the important roles of autophagy in organelle degradation in the lens in gja8b mutant zebrafish. Further studies in HLE cells revealed that GJA8 interacted with ATG proteins. Overexpression of GJA8 stimulated autophagy in HLE cells. These data suggest an unrecognized cataractogenesis mechanism caused by ablation of Gja8b and a potential treatment for cataracts by stimulating autophagy in the lens. Abbreviations: 3-MA: 3-methyladenine; ATG: autophagy related; AV: autophagic vacuoles; Dpf: days post fertilization; GJA1: gap junction protein alpha 1; GJA3: gap junction protein alpha 3; GJA8: gap junction protein alpha 8; Hpf: hours post fertilization; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; PtdIns3K: class III phosphatidylinositol 3-kinase; WT: wild type. [ABSTRACT FROM AUTHOR]

In recent years, the incidence of thyroid nodules has shown an increasing trend year by year and has become one of the important diseases that endanger human health. Ultrasound medical images based on deep learning are widely used in clinical diagnosis due to their cheapness, no radiation, and low cost. The use of image processing technology to accurately segment the nodule area provides important auxiliary information for the doctor's diagnosis, which is of great value for guiding clinical treatment. The purpose of this article is to explore the application value of combined detection of abnormal sugar-chain glycoprotein (TAP) and carcinoembryonic antigen (CEA) in the risk estimation of thyroid cancer in patients with thyroid nodules of type IV and above based on deep learning medical images. In this paper, ultrasound thyroid images are used as the research content, and the active contour level set method is used as the segmentation basis, and a segmentation algorithm for thyroid nodules is proposed. This paper takes ultrasound thyroid images as the research content, uses the active contour level set method as the basis of segmentation, and proposes an image segmentation algorithm Fast-SegNet based on deep learning, which extends the network model that was mainly used for thyroid medical image segmentation to more scenarios of the segmentation task. From January 2019 to October 2020, 400 patients with thyroid nodules of type IV and above were selected for physical examination and screening at the Health Management Center of our hospital, and they were diagnosed as thyroid cancer by pathological examination of thyroid nodules under B-ultrasound positioning. The detection rates of thyroid cancer in patients with thyroid nodules of type IV and above are compared; serum TAP and CEA levels are detected; PT-PCR is used to detect TTF-1, PTEN, and NIS expression; the detection, missed diagnosis, misdiagnosis rate, and diagnostic efficiency of the three detection methods are compared. This article uses the thyroid nodule region segmented based on deep learning medical images and compares experiments with CV model, LBF model, and DRLSE model. The experimental results show that the segmentation overlap rate of this method is as high as 98.4%, indicating that the algorithm proposed in this paper can more accurately extract the thyroid nodule area. [ABSTRACT FROM AUTHOR]

During the hot strip tandem rolling (HSTR) process, the strip is compressed and elongated continuously, causing significant elastic deformation of rolls. At the same time, the strip temperature undergoes rapid increase and decrease, and distributes unevenly along the strip width direction. Elastic deformation of rolls and strip temperature variations have a significant effect on strip deformation, resulting in various strip shape. In this study, a novel three-dimensional (3D) coupled thermal-mechanical elastic-plastic finite element (FE) model for the HSTR is proposed based on the segmentation modeling strategy, where the finish mill is divided into several sub-models. The data transfer technology is developed to integrate the sub-models into a whole model via transferring the strip crown and temperature among the sub-models. Furthermore, the active and deactive element method, rigid pushing technology, and element remesh are also used to improve the calculation efficiency and accuracy of the model. Multi-objective parameters, such as strip temperature, strip crown, elastic deformation of roll stacks, and rolling force during the HSTR process are studied systematically using the developed FE model. The results show that the calculated strip temperature and strip crown after F7 agree well with the measured values, and the relative error between calculated and measured rolling force at each stand is less than 10%. This work offers a fresh perspective on the HSTR simulation. [ABSTRACT FROM AUTHOR]

Purpose: Epilepsy is one of the most disabling neurological disorders, which affects all age groups and often results in severe consequences. Since misdiagnoses are common, many pediatric patients fail to receive the correct treatment. Recently, 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging has been used for the evaluation of pediatric epilepsy. However, the epileptic focus is very difficult to be identified by visual assessment since it may present either hypo- or hyper-metabolic abnormality with unclear boundary. This study aimed to develop a novel symmetricity-driven deep learning framework of PET imaging for the identification of epileptic foci in pediatric patients with temporal lobe epilepsy (TLE). Methods: We retrospectively included 201 pediatric patients with TLE and 24 age-matched controls who underwent 18F-FDG PET-CT studies. 18F-FDG PET images were quantitatively investigated using 386 symmetricity features, and a pair-of-cube (PoC)-based Siamese convolutional neural network (CNN) was proposed for precise localization of epileptic focus, and then metabolic abnormality level of the predicted focus was calculated automatically by asymmetric index (AI). Performances of the proposed framework were compared with visual assessment, statistical parametric mapping (SPM) software, and Jensen-Shannon divergence-based logistic regression (JS-LR) analysis. Results: The proposed deep learning framework could detect the epileptic foci accurately with the dice coefficient of 0.51, which was significantly higher than that of SPM (0.24, P < 0.01) and significantly (or marginally) higher than that of visual assessment (0.31–0.44, P = 0.005–0.27). The area under the curve (AUC) of the PoC classification was higher than that of the JS-LR (0.93 vs. 0.72). The metabolic level detection accuracy of the proposed method was significantly higher than that of visual assessment blinded or unblinded to clinical information (90% vs. 56% or 68%, P < 0.01). Conclusion: The proposed deep learning framework for 18F-FDG PET imaging could identify epileptic foci accurately and efficiently, which might be applied as a computer-assisted approach for the future diagnosis of epilepsy patients. Trial registration: NCT04169581. Registered November 13, 2019 Public site: https://clinicaltrials.gov/ct2/show/NCT04169581 [ABSTRACT FROM AUTHOR]

In recent years, the incidence of thyroid nodules has shown an increasing trend year by year and has become one of the important diseases that endanger human health. Ultrasound medical images based on deep learning are widely used in clinical diagnosis due to their cheapness, no radiation, and low cost. The use of image processing technology to accurately segment the nodule area provides important auxiliary information for the doctor's diagnosis, which is of great value for guiding clinical treatment. The purpose of this article is to explore the application value of combined detection of abnormal sugar-chain glycoprotein (TAP) and carcinoembryonic antigen (CEA) in the risk estimation of thyroid cancer in patients with thyroid nodules of type IV and above based on deep learning medical images. In this paper, ultrasound thyroid images are used as the research content, and the active contour level set method is used as the segmentation basis, and a segmentation algorithm for thyroid nodules is proposed. This paper takes ultrasound thyroid images as the research content, uses the active contour level set method as the basis of segmentation, and proposes an image segmentation algorithm Fast-SegNet based on deep learning, which extends the network model that was mainly used for thyroid medical image segmentation to more scenarios of the segmentation task. From January 2019 to October 2020, 400 patients with thyroid nodules of type IV and above were selected for physical examination and screening at the Health Management Center of our hospital, and they were diagnosed as thyroid cancer by pathological examination of thyroid nodules under B-ultrasound positioning. The detection rates of thyroid cancer in patients with thyroid nodules of type IV and above are compared; serum TAP and CEA levels are detected; PT-PCR is used to detect TTF-1, PTEN, and NIS expression; the detection, missed diagnosis, misdiagnosis rate, and diagnostic efficiency of the three detection methods are compared. This article uses the thyroid nodule region segmented based on deep learning medical images and compares experiments with CV model, LBF model, and DRLSE model. The experimental results show that the segmentation overlap rate of this method is as high as 98.4%, indicating that the algorithm proposed in this paper can more accurately extract the thyroid nodule area. [ABSTRACT FROM AUTHOR]

The evaluation results of the plant landscape scenic beauty estimation of roof greening can provide theoretical basis for the future development planning and design of roof greening in Zhengzhou. Taking 26 roof greening places in Zhengzhou city of Henan Province as the research object, 26 plant landscape samples were selected, and the beauty value of each sample was calculated by the beauty evaluation method (SBE). Finally, the beauty evaluation model was constructed as follows: SBE = −1.932 + 0.176X2 − 0.456X4 + 0.590X6 + 0.595X9 − 0.329X10 + 0.271X11. The results showed that the characteristics of life style, plant growth, richness of plant layers, road pavement, density of branches and leaves, and richness of plant color all had certain effects on the beauty of roof greening plant landscape. According to the evaluation results, some suggestions are put forward for the development of roof greening in Zhengzhou. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a toxic non-essential element, while calcium (Ca) is an essential element with high chemical similarity to Cd. Dietary intake is the major Cd exposure pathway for non-smokers. A multi-concentration dietary intervention experiment was designed to explore the optimum concentration of Ca in diet with obvious protective effects against the toxicity of livers and kidneys induced by Cd in mice. The mice were divided into six groups with different concentrations of Cd and Ca in their food: control-group (no Cd or Ca), Ca-group (100 g/kg Ca, without Cd), Cd-group (2 mg/kg Cd, without Ca), CaL+Cd-group (2 mg/kg Cd, 2 g/kg Ca), CaM+Cd-group (2 mg/kg Cd, 20 g/kg Ca) and CaH+Cd-group (2 mg/kg Cd, 100 g/kg Ca). The organ indexes, oxidative stress biomarkers, lesions and Cd concentrations were detected after a 30-day exposure period. Results showed that serum Aspartate Aminotransferase (AST) level in CaH+Cd-group was significantly lower than that in Cd-group, while close to that in control-group. The contents of Serum Blood Urea Nitrogen (BUN) in different groups showed the same trend. Concentrations of all oxidative stress biomarkers (GSH-Px, SOD, CAT, GSH and MDA) in CaH+Cd-group were close to the normal levels of control-group while significantly different from those in Cd-group. The only exception was the Malondialdehyde (MDA) levels in kidneys. This study suggests that Ca plays a protective role in relieving the Cd-induced toxicity of livers and kidneys and a concentration of 100 g/kg for Ca in diet showed the best protective effects. These findings could provide a clue for further studies concerning human diet intervention for Cd control. [ABSTRACT FROM AUTHOR]

The effects of the purified recombinant anabaena lipoxygenase (ana‐rLOX) on the rheological characteristics of whole wheat dough and the quality of bread were investigated. The lightness of whole wheat dough supplemented with ana‐rLOX was improved, which is superior to that of dough treated with benzoyl peroxide. The effect of ana‐rLOX on the strength of dough was analyzed by farinograph, extensograph, and dynamic rheological tests. Compared with the control, the stability time of dough treated with 40 IU/g ana‐rLOX increased by 35.4% and the farinograph quality number increased by 27.4%. In addition, the resistance to extension, as well as the elastic and viscous modulus, was improved by ana‐rLOX in a dose‐dependent manner. The height and specific volume of bread treated with ana‐rLOX increased by 17.3 and 15.2%, respectively, compared with the control, and the lightless, whiteness, and other textural parameters, such as hardness, springiness, chewiness, resilience, and gumminess, were significantly improved. Overall, the results of this study suggest the promising application of ana‐rLOX in enhancing quality of whole wheat flour. [ABSTRACT FROM AUTHOR]

In this study, we investigated the lipid metabolism regulatory activity of a novel metformin derivative (MD568) and its potential mechanism of action in obese rats with type 2 diabetes mellitus (T2DM). Previous gene chip analysis of 3T3‐L1 cells have shown that MD568 regulates the transcription of genes involved in the peroxisome proliferator‐activated receptor (PPAR) signalling pathway, fatty acid metabolism, and glycerolipid metabolism. In this study, obese T2DM rats were treated with MD568 (200 mg/kg) for 8 weeks. Results showed that MD568 significantly reduced the body weight gain, plasma glucose, insulin, total cholesterol, triglyceride, and low‐density lipoprotein cholesterol levels. MD568 treatment also improved the insulin resistance of obese T2DM model rats. In particular, in white adipose tissue, MD568 inhibited the excessive volume increment of adipose cells by down‐regulating the protein levels of CCAAT/enhancer‐binding protein‐α (C/EBP‐α) and PPAR‐γ, as well as the transcription of their target lipid metabolism‐related genes. In the liver, MD568 inhibited hepatic fatty lesions and interfered with hepatic gluconeogenesis by regulating the expression of lipid metabolism‐related genes and glycogen‐related kinases. In conclusion, our results suggest that the newly synthesized MD568 affects the maintenance of lipid homeostasis in obese type 2 diabetic rats. [ABSTRACT FROM AUTHOR]

The rapid development of the vehicular ad-hoc network (VANET) promotes the development of vehicle electronics, networking, and intelligence. In addition, each vehicle can establish social relationships with others freely in vehicular social networks (VSNs). Multimedia also plays an important entity in vehicles' data sharing. However, VSNs are still in the early stage of development, and it may bring many security challenges in the process of sharing multimedia data. Both the users' and vehicles' privacy may be leaked, and users' communication habits are easy to be analyzed by adversaries. In addition, the shared multimedia data are more likely to be maliciously tampered with or forged. In this paper, we propose a privacy-preserving scheme based on blockchain for multimedia data sharing in VSNs. We use cryptographical primitives to hide the real identity of users, vehicles and RSUs. At the same time, we use blockchain to ensure reliable data sources and keep attackers from tampering or forging multimedia data. Finally, the feasibility of our scheme is proved by theoretical security analysis and comprehensive experimental evaluation. [ABSTRACT FROM AUTHOR]

Developing earth-abundant, efficient and durable electrocatalysts for the oxygen evolution reaction (OER) is of great significance for sustainable energy storage and conversion devices such as water splitting devices and metal air batteries. In this study, a MIL-88A/Ni(OH)2 heterostructure was directly grown on carbon cloth (denoted as MIL-88A/Ni(OH)2-CC) for the first time by using a generic two-step hydrothermal method. The results showed that using carbon cloth as a three-dimensional self-supporting electrode could improve the conductivity of the catalyst, while the edges of the Ni(OH)2 layer can provide abundant active sites to synergistically boost the OER performance with MIL-88A. Impressively, the as-prepared MIL-88A/Ni(OH)2-CC catalyst delivers a current density of 10 mA cm−2 at low overpotentials of 250 mV in 1 M KOH and 352 mV in 0.1 M KOH, exhibiting small Tafel slope values of 36.4 mV dec−1 in 1 M KOH and 46.1 mV dec−1 in 0.1 M KOH, respectively. The MIL-88A/Ni(OH)2-CC catalyst also demonstrates a long-lasting stability superior to that of the RuO2/CC catalyst for the OER. Such intriguing OER properties can be attributed to the unique heterostructure at the interface between MIL-88A and Ni(OH)2, while density functional theory calculations also confirm that OH− has a very low adsorption energy at the interface of the heterostructure. [ABSTRACT FROM AUTHOR]

In this study, molecularly imprinting technology and stir bar absorption technology were combined to develop a microextraction approach based on a molecularly imprinted polymeric stir bar. The molecularly imprinted polymer stir bar has a high performance, is specific, economical, and simple to prepare. The obtained naftopidil-imprinted polymer-coated bars could simultaneously agitate and adsorb naftopidil in the sample solution. The ratio of template/monomer/cross-linker and conditions of template removal were optimized to prepare a stir bar with highly efficient adsorption. Fourier transform infrared spectroscopy, scanning electron microscopy, selectivity, and extraction capacity experiments showed that the molecularly imprinted polymer stir bar was prepared successfully. To utilize the molecularly imprinted polymer stir bar for the determination of naftopidil in complex body fluid matrices, the extraction time, stirring speed, eluent, and elution time were optimized. The limits of detection of naftopidil in plasma and urine sample were 7.5 and 4.0 ng/mL, respectively, and the recoveries were in the range of 90-112%. The within-run precision and between-run precision were acceptable (relative standard deviation <7%). These data demonstrated that the molecularly imprinted polymeric stir bar based microextraction with high-performance liquid chromatography was a convenient, rapid, efficient, and specific method for the precise determination of trace naftopidil in clinical analysis. [ABSTRACT FROM AUTHOR]

Background: Cirrhosis, or liver fibrosis, which is mainly triggered by cirrhosis fat-storing cells (CFSCs) activation, has traditionally been considered an irreversible disease. However, recent observations indicate that even advanced fibrosis is still reversible by removing the causative agents. Anti-fibrotic effects of bone marrow-derived stromal cells (BMSCs) have been demonstrated by inhibiting CFSCs via cytokines secretion; however, the mechanisms are still unclear. Aims: The purpose of this study was to explore the underlying mechanisms by which BMSCs modulate the function of activated CFSCs. Methods: After the co-culture of CFSCs with BMSCs supernatants with or without the addition of recombinant rat adrenomedullin (AM)/AM-specific siRNA, western blot analysis was mainly used to detect the differences of relative protein expression on CFSCs. Results: BMSC-secreted adrenomedullin (AM) effectively inhibited the proliferation and activation of CFSCs by suppressing the expression of Ang II and its binding receptor, AT1, which resulted in a reduction of p47-phox formation. Conclusions: Our data suggested that BMSCs inhibited CFSC activation in vitro via the AM-Ang II-p47-phox signaling pathway, and since CFSC activation is an essential part of hepatic fibrosis process, this inhibition by BMSCs implies us new insights into the potential treatment of hepatic fibrosis via BMSCs. [ABSTRACT FROM AUTHOR]

Mitochondrial malfunction and autophagy defects are often concurrent phenomena associated with neurodegeneration. We show that Miga, a mitochondrial outer-membrane protein that regulates endoplasmic reticulum-mitochondrial contact sites (ERMCSs), is required for autophagy. Loss of Miga results in an accumulation of autophagy markers and substrates, whereas PI3P and Syx17 levels are reduced. Further experiments indicated that the fusion between autophagosomes and lysosomes is defective in Miga mutants. Miga binds to Atg14 and Uvrag; concordantly, Miga overexpression results in Atg14 and Uvrag recruitment to mitochondria. The heightened PI3K activity induced by Miga requires Uvrag, whereas Miga-mediated stabilization of Syx17 is dependent on Atg14. Miga-regulated ERMCSs are critical for PI3P formation but are not essential for the stabilization of Syx17. In summary, we identify a mitochondrial protein that regulates autophagy by recruiting two alternative components of the PI3K complex present at the ERMCSs. [Display omitted] • Mitochondrial protein Miga regulates fusion between autophagosomes and lysosomes • Miga interacts with Atg14 to stabilize Syx17 • Miga interacted with Uvrag to regulate PI3K activity • Miga-induced ERMCSs are required for PI3K activity but not for Syx17 stabilization Miga is a mitochondrial outer-membrane protein that regulates endoplasmic reticulum-mitochondrial contact sites. Xu et al. show that Miga regulates autophagy by recruiting Atg14 and Uvrag, two alternative components of the PI3K complex. [ABSTRACT FROM AUTHOR]