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Background clutters pose challenges to defocus blur detection. Existing approaches often produce artifact predictions in background areas with clutter and relatively low confident predictions in boundary areas. In this work, we tackle the above issues from two perspectives. Firstly, inspired by the recent success of self-attention mechanism, we introduce channel-wise and spatial-wise attention modules to attentively aggregate features at different channels and spatial locations to obtain more discriminative features. Secondly, we propose a generative adversarial training strategy to suppress spurious and low reliable predictions. This is achieved by utilizing a discriminator to identify predicted defocus map from ground-truth ones. As such, the defocus network (generator) needs to produce 'realistic' defocus map to minimize discriminator loss. We further demonstrate that the generative adversarial training allows exploiting additional unlabeled data to improve performance, a.k.a. semi-supervised learning, and we provide the first benchmark on semi-supervised defocus detection. Finally, we demonstrate that the existing evaluation metrics for defocus detection generally fail to quantify the robustness with respect to thresholding. For a fair and practical evaluation, we introduce an effective yet efficient AUF

Background: Extreme environmental stress interactions with DNA methylation may produce episodic memory for environmental adaptation. Methods: In the present study, 64 volunteers born and living at an altitude of 4,700 m were recruited, including 32 volunteers who were repeatedly exposed to high altitudes (up to 8,848 m, up to 11 times). We explored the changes in the genes hosting 741,489 CpG loci as well as 39 physiological phenotypes under superposition extreme high-altitude exposure (SEH). Results: 13 CpG for 11 genes were identified with tightly linked networks to five phenotypes. Bayesian causal network analysis suggests network properties of 15 SEH-related phenotypic networks and MP-SSN, reflected in increased robustness with an increasing number of SEH exposures, suggesting environmental resistance. In addition, we explored the characteristics under SEH of the MP-SSN network nodes in populations with significant differences in SpO2 (n High-adaptability= 28; n Low-adaptability= 36) and found concomitant changes in five phenotypes and CpG methylation, while the changes occurred earlier in the high SpO2 population (Climbing age = 5 times). Conclusion: Considering evidence from the literature and database validation, we suggest that the promoter and enhancer regions of the LIPN and PLCH1 genes may be influenced by methylation memory generated by light environment exposure during SEH exposure. Methylation memory may have an effect on the phenotype by influencing the action of the pathway in which the gene is located, thus advancing the environmental adaptation status of SEH, such as SpO2 and SP.

Alkali metal potassium is conducive to structure promotion and electronic modulation in metal oxides. Here, K species was successfully introduced into α-MnO2 via in situ synthesis (Pre-K/MnO2) and hydrothermal impregnation method (Post-K/MnO2) with target to boost the low-temperature reactivity and deep destruction efficiency for toluene oxidation. Results reveal that Post-K/MnO2 possesses the highest catalytic activity with toluene (1000 ppm) totally mineralized at just 258 °C, achieving over 70 °C of temperature reduction than that of Pre-K/MnO2. K specie shows obvious charge transfer balance ability in MnO2, forming MnO6-K-MnO6 bridging bond and leading to more uniform energy of Mn-O bonds. High electron density of K+ can promote the activation of oxygen molecules, resulting in a better catalytic performance of toluene. Abundant Bronsted acid sites are beneficial for toluene adsorption and regeneration of hydroxyl on the surface, which promote the degradation of intermediates during toluene oxidation. Moreover, Post-K/MnO2 shows satisfied catalytic performance under different space velocities and initial concentrations and humid condition. Density functional theory (DFT) calculation revealed the situation of oxygen vacancy and toluene/oxygen adsorption energy in catalysts with different K doping locations. Results showed that the adsorption energy is stronger when K located in large tunnel (0.46 × 0.46 nm), and it is easier to form oxygen vacancy while K entered the small tunnel (0.33 × 0.33 nm). The present work paves new insights into the designing of efficient transition metal oxide catalyst for VOC deep purification.

Oxygen vacancy plays an important role in adsorption and activation of oxygen species and therefore promotes the catalytic performance of materials in heterogeneous oxidation reactions. Here, a series of K-doped ɑ-MnO2 materials with different K loadings were synthesized by a reproducible post processing process. Results show that the presence of K+ enhances the reducibility and oxygen vacancy concentration of ɑ-MnO2 due to the break of charge balance and the formation of low valence Mn species. 4-K/MnO2 material exhibits the highest toluene oxidation activity and satisfied long-term stability and water resistance owing to its superior reducibility and abundant surface absorbed oxygen (Oads). In situ DRIFTS demonstrate that Oads greatly accelerates toluene dehydrogenation rate and promotes benzoate formation, enhancing the activation and decomposition of toluene molecules. Moreover, the CC cleavage of benzene ring (forming maleic anhydride) is the rate-determining step of toluene oxidation, which can be easily occurred over 4-K/MnO2.

Objectives: Hyperuricemia has become a public health problem that needs to be solved urgently. As traditional Chinese medicine, Astragalus membranaceus has high research value. In recent years, how to improve the bioavailability of Astragalus has been the subject of growing interest in the academic. Microbial fermentation has brought hope and dawn to address the above problem. Methods: Eighty mice were randomly divided into 8 groups (n=10): the normal control group, the hyperuricemia group, the benzbromarone group, the Bacillus subtilis-fermenting Astragalus group (0.25, 0.5 and 1 g/kg Astragalus), the unfermented Astragalus group, and the Bacillus subtilis group. To explore the underlying mechanism, levels of XOD, inflammatory factors, p38 mitogen-activated protein kinase (p38 MAPK), and nuclear factor-κB (NF-κB) were investigated. Results: Fermented Astragalus inhibited liver uric acid synthesis and protected the function of the kidney via anti-inflammation inhibiting the p38 MAPK/NF-κB pathways. It was speculated that increased total flavonoids, formononetin, and astragaloside IV of fermented Astragalus would result in a better therapeutic effect than unfermented Astragalus. Conclusion: The work undertaken sheds light on the development of Astragalus and the prevention and treatment of hyperuricemia.

Background As a life-threatening respiratory syndrome, acute lung injury (ALI) is characterized by uncontrollable inflammatory activities. Semaglutide (SEM) has been identified as an effective anti-inflammatory drug in a variety of diseases. This study intended to explore the functional effect and potential mechanisms of SEM in ALI. Methods Lipopolysaccharide (LPS) was used to construct an in vivo ALI model based on Sprague-Dawley (SD) rats and an in vitro ALI model based on human pulmonary artery endothelial cells (HPAECs). Hematoxylin & eosin (H&E) staining and ELISA were applied to evaluate the histopathological changes in pulmonary tissues and detect TNF-α and IL-6 levels. RT-qPCR and Western blotting were used to measure gene and protein expressions in pulmonary tissues and cells. HPAEC viability and apoptosis were evaluated by CCK-8 method and flow cytometry methods. Results Semaglutide pretreatment significantly mitigated pulmonary injury, reduced TNF-α and IL-6 production, and led to a decrease in cleaved caspase-3 level and an increase in Bcl-2 level, suggesting SEM could ameliorate LPS-induced ALI in rats. In vitro, SEM increased the proliferative capability and mitigated inflammation and apoptosis in LPS-stimulated HPAECs. In addition, SEM inhibited HDAC5-mediated NF-κB signaling pathway in HPAECs. HDAC5 overexpression or NF-κB signaling activation could partly impair SEM-mediated protective effects against LPS-induced damage to HPAECs. Conclusion Semaglutide restrains LPS-induced ALI by inhibiting HDAC5/NF-κB signaling pathway.

The development of highly active single-atom catalysts (SACs) and identifying their intrinsic active sites in oxidizing industrial hazardous hydrocarbons are challenging prospects. Tuning the electronic metal-support interactions (EMSIs) is valid for modulating the catalytic performance of SACs. We propose that the modulation of the EMSIs in a Pt1−CuO SAC significantly promotes the activity of the catalyst in acetone oxidation. The EMSIs promote charge redistribution through the unified Pt−O−Cu moieties, which modulates the d-band structure of atomic Pt sites, and strengthens the adsorption and activation of reactants. The positively charged Pt atoms are superior for activating acetone at low temperatures, and the stretched Cu−O bonds facilitate the activation of lattice oxygen atoms to participate in subsequent oxidation. We believe that this work will guide researchers to engineer efficient SACs for application in hydrocarbon oxidation reactions.\ud \ud Open Research

The plant immune system is fundamental for plant survival in natural ecosystems and for productivity in crop fields. Substantial evidence supports the prevailing notion that plants possess a two-tiered innate immune system, called pattern-triggered immunity (PTI) and effector-triggered immunity (ETI). PTI is triggered by microbial patterns via cell surface-localized pattern-recognition receptors (PRRs), whereas ETI is activated by pathogen effector proteins via predominantly intracellularly localized receptors called nucleotide-binding, leucine-rich repeat receptors (NLRs)1–4. PTI and ETI are initiated by distinct activation mechanisms and involve different early signalling cascades5,6. Here we show that Arabidopsis PRR and PRR co-receptor mutants—fls2 efr cerk1 and bak1 bkk1 cerk1 triple mutants—are markedly impaired in ETI responses when challenged with incompatible Pseudomonas syrinage bacteria. We further show that the production of reactive oxygen species by the NADPH oxidase RBOHD is a critical early signalling event connecting PRR- and NLR-mediated immunity, and that the receptor-like cytoplasmic kinase BIK1 is necessary for full activation of RBOHD, gene expression and bacterial resistance during ETI. Moreover, NLR signalling rapidly augments the transcript and/or protein levels of key PTI components. Our study supports a revised model in which potentiation of PTI is an indispensable component of ETI during bacterial infection. This revised model conceptually unites two major immune signalling cascades in plants and mechanistically explains some of the long-observed similarities in downstream defence outputs between PTI and ETI. Bacteria elicit two distinct immune responses in Arabidopsis thaliana, mediated by diverse signalling receptors but working in a synergistic manner.

Background Lymph node (LN) metastasis status is the most important prognostic factor and determines treatment strategy. Methylation alteration is an optimal candidate to trace the signal from early stage tumors due to its early existence, multiple loci and stability in blood. We built a diagnostic tool to screen and identify a set of plasma methylation markers in early stage occult LN metastasis. Methods High-throughput targeted methylation sequencing was performed on tissue and matched plasma samples from a cohort of 119 non-small cell lung cancer (NSCLC) patients with a primary lesion of less than 3.0 cm in diameter. The methylation profiles were compared between patients with and without occult LN metastases. We carried out a set of machine-learning analyses on our discovery cohort to evaluate the utility of cell free DNA methylation profiles in early detection of LN metastasis. Two preliminary prognostic models predictive of LN metastasis were built by random forest with differentially methylated markers shared by plasma and tissue samples and markers present either in plasma or tissue samples respectively. The performance of these models was then evaluated using receiver operating characteristic (ROC) statistics derived from ten-fold cross validation repeated ten times. Results Within this cohort, 27 cases (27/119, 22.7%) were found to have occult LN metastases found by pathological examination. Compared with those without metastases, 878 and 52 genes were differentially methylated in terms of tissue (MTA3, MIR548H4, HIST3H2A, etc.) and plasma (CIRBP, CHGB, FCHO1, etc.) respectively. 19 of these genes (ICAM1, EPH4, COCH, etc.) were overlapped. We selected 22 pairs of cases with or without occult LN metastasis by matching gender, age, smoking history and tumor histology to build and test the plasma model. The AUC of the preliminary prediction model using markers shared by plasma and tissue samples and markers present either in plasma or tissue samples is 88.6% (95% CI, 87.8-89.4%) and 74.9% (95% CI, 72.2-77.6%) respectively. Conclusions We identified a set of specific plasma methylation markers for early occult LN metastasis of NSCLC and established a preliminary non-invasive blood diagnostic tool.

Additional file 1.. Fig. S1. Annotation rules for hemodynamic intervention. Table S1. Clinical variables used in HSI and plausibility filter for each variable. Table S2. Missing rate of clinical variables. Table S3. Baseline characteristics comparison between unstable and stable patients. Table S4. Performances of HSI model, shock index and systolic blood pressure in TPEVGH cohort. Table S5. Confusion matrix of HSI model under different threshold. Table S6. Subgroup performance of HSI model in TPEVGH. Table S7. Median comparison between the US cohort and TPEVGH cohort.

At present, uncovering how to preventandcontrol hyperuricemia has become an important public health issue. Fermented traditionalChinesemedicine has exhibited promising applications in the clinical management of hyperuricemia. In this study, we generated a hyperuricemic mouse model to explore the potent therapeutic ability of Bacillus subtilis-fermented Astragalus membranaceus (BFA) on this condition by multi-omics analysis. We found that the serum uric acid level was decreased in hyperuricemic mice after BFA treatment. BFA effectively attenuated renal inflammation and regulated the expression of urate transporters. Additionally, we found that BFA could increase the abundances of butyrate-producing bacteria, including Butyricimonas synergistica, Odoribacter splanchnicus, and Collinsella tanakaei, and probiotics, including Lactobacillus intestinalis and Bacillus mycoides, in hyperuricemic mice. Therefore, we believe that BFA has the potential to become a novel safe and valid functional food for addressing hyperuricemia.

Kiwifruit is one of the most popular fruits, and the area of its cultivation in China has grown rapidly over the last decade. However, kiwifruit vines are vulnerable to waterlogging, especially in the extensive areas of south China where it is grown. This has become an important factor limiting yields. Therefore, it is necessary to clarify the responses of kiwifruit to waterlogging. Here, we have selected Actinidia valvata Dunn which is able to withstand waterlogging conditions and the waterlogging-susceptible Actinidia deliciosa to perform the RNA-seq of roots under waterlogging stress. Seedling roots of Actinidia valvata Dunn and Actinidia deliciosa presented distinct root phenotypes after waterlogging treatments. Genome mapping showed a large genome difference between Actinidia valvata Dunn and Actinidia deliciosa. Transcription factors MYB, MYB-related, AP2-EREBP, bHLH, WRKY, and NAC were identified as the key genes involved in the response to waterlogging stress of kiwifruit. Meanwhile, the MAPK signaling pathway and the glycolysis/gluconeogenesis pathway were identified as the vital pathways involved in the response to waterlogging, and key genes were identified from these two pathways. These results will broaden our understanding of transcriptional response of waterlogging stress and will provide new insights into the molecular mechanisms associated with waterlogging stress. Furthermore, identification of the genes responsible will assist in the breeding of kiwifruit tolerant of waterlogging.

Realizing the simultaneous adsorption and activation of O

Though the highest CO

Pt/Eu2O3-CeO2 materials with different Eu concentrations were prepared and applied to toluene destruction, and the remarkable promotion impact of EuOx on Pt/CeO2 can be observed. The characterization results reveal that the presence of EuOx significantly enhances the redox property, lattice O concentration, and Ce3+ ratio of the Pt/CeO2 material, which facilitates the dispersion and activity of Pt active sites and thus accelerates the decomposition process of toluene. Among all catalysts, a sample with an Eu content of 2.5 at.% (Pt/EC-2.5) possesses the best catalytic activity with 0.09 vol% of toluene completely destructed at 200 °C under a relatively high GHSV of 50000 h−1. The possible reaction pathway and mechanism of toluene combustion over Pt/Eu2O3-CeO2 samples are presented according to in-situ DRIFTS, which confirms that the toluene oxidation process obeys the Mars-van Krevelen mechanism with aldehydes and ketones as primary organic intermediates.

Shape effects of nanocrystal catalysts in different reactions have attracted remarkable attention. In the present work, three types of α-Fe2O3 oxides with different micromorphologies were rationally synthesized via a facile solvothermal method and adopted in deep oxidation of ethane. The physicochemical properties of prepared materials were characterized by XRD, N2 sorption, FE-SEM, HR-TEM, FTIR, in situ DRIFTS, XPS, Mössbauer spectroscopy, in situ Raman, electron energy loss spectroscopy, and H2-TPR. Moreover, the formation energy of oxygen vacancy and surface electronic structure on various crystal faces of α-Fe2O3 were explored by DFT calculations. It is shown that nanosphere-like α-Fe2O3 exhibits much higher ethane destruction activity and reaction stability than nanocube-like α-Fe2O3 and nanorod-like α-Fe2O3 due to larger amounts of oxygen vacancies and lattice defects, which greatly enhance the concentration of reactive oxygen species, oxygen transfer speed, and material redox property. In addition to this, DFT results reveal that nanosphere-like α-Fe2O3 has the lowest formation energy of oxygen vacancy on the (110) facet (Evo (110) = 1.97 eV) and the strongest adsorption energy for ethane (−0.26 eV) and O2 (−1.58 eV), which can accelerate the ethane oxidation process. This study has deepened the understanding of the face-dependent activities of α-Fe2O3 in alkane destruction.

Background Current non-invasive tests have limited sensitivities and lack capabilities of pre-operative risk stratification for bladder cancer (BC) diagnosis. We aimed to develop and validate a urine-based DNA methylation assay as a clinically feasible test for improving BC detection and enabling pre-operative risk stratifications. Methods A urine-based DNA methylation assay was developed and validated by retrospective single-center studies in patients of suspected BC in Cohort 1 (n = 192) and Cohort 2 (n = 98), respectively. In addition, a prospective single-center study in hematuria patient group (Cohort 3, n = 174) was used as a second validation of the model. Results The assay with a dual-marker detection model showed 88.1% and 91.2% sensitivities, 89.7% and 85.7% specificities in validation Cohort 2 (patients of suspected BC) and Cohort 3 (patients of hematuria), respectively. Furthermore, this assay showed improved sensitivities over cytology and FISH on detecting low-grade tumor (66.7–77.8% vs. 0.0–22.2%, 0.0–22.2%), Ta tumor (83.3% vs. 22.2–41.2%, 44.4–52.9%) and non-muscle invasive BC (NMIBC) (80.0–89.7% vs. 51.5–52.0%, 59.4–72.0%) in both cohorts. The assay also had higher accuracies (88.9–95.8%) in diagnosing cases with concurrent genitourinary disorders as compared to cytology (55.6–70.8%) and FISH (72.2–77.8%). Meanwhile, the assay with a five-marker stratification model identified high-risk NMIBC and muscle invasive BC with 90.5% sensitivity and 86.8% specificity in Cohort 2. Conclusions The urine-based DNA methylation assay represents a highly sensitive and specific approach for BC early-stage detection and risk stratification. It has a potential to be used as a routine test to improve diagnosis and prognosis of BC in clinic.

BACKGROUND: Current clinical management of patients with pulmonary nodules involves either repeated low-dose CT (LDCT)/CT scans or invasive procedures, yet causes significant patient misclassification. An accurate noninvasive test is needed to identify malignant nodules and reduce unnecessary invasive tests. METHOD: We developed a diagnostic model based on targeted DNA methylation sequencing of 389 pulmonary nodule patients’ plasma samples and then validation in 140 plasma samples independently. We tested the model in different stages and subtypes of pulmonary nodules. RESULTS: A 100-feature model was developed and validated for pulmonary nodule diagnosis; the model achieved a receiver operating characteristic curve–AUC (ROC-AUC) of 0.843 on 140 independent validation samples, with an accuracy of 0.800. The performance was well maintained in (a) a 6 to 20 mm size subgroup (n = 100), with a sensitivity of 1.000 and adjusted negative predictive value (NPV) of 1.000 at 10% prevalence; (b) stage I malignancy (n = 90), with a sensitivity of 0.971; (c) different nodule types: solid nodules (n = 78) with a sensitivity of 1.000 and adjusted NPV of 1.000, part-solid nodules (n = 75) with a sensitivity of 0.947 and adjusted NPV of 0.983, and ground-glass nodules (n = 67) with a sensitivity of 0.964 and adjusted NPV of 0.989 at 10% prevalence. This methylation test, called PulmoSeek, outperformed PET-CT and 2 clinical prediction models (Mayo Clinic and Veterans Affairs) in discriminating malignant pulmonary nodules from benign ones. CONCLUSION: This study suggests that the blood-based DNA methylation model may provide a better test for classifying pulmonary nodules, which could help facilitate the accurate diagnosis of early stage lung cancer from pulmonary nodule patients and guide clinical decisions. FUNDING: The National Key Research and Development Program of China; Science and Technology Planning Project of Guangdong Province; The National Natural Science Foundation of China National.

Mammography is used to detect breast cancer (BC), but its sensitivity is limited, especially for dense breasts. Circulating cell-free DNA (cfDNA) methylation tests is expected to compensate for the deficiency of mammography. We derived a specific panel of markers based on computational analysis of the DNA methylation profiles from The Cancer Genome Atlas (TCGA). Through training (n = 160) and validation set (n = 69), we developed a diagnostic prediction model with 26 markers, which yielded a sensitivity of 89.37% and a specificity of 100% for differentiating malignant disease from normal lesions [AUROC = 0.9816 (95% CI: 96.09-100%), and AUPRC = 0.9704 (95% CI: 94.54–99.46%)]. A simplified 4-marker model including cg23035715, cg16304215, cg20072171, and cg21501525 had a similar diagnostic power [AUROC = 0.9796 (95% CI: 95.56–100%), and AUPRC = 0.9220 (95% CI: 91.02–94.37%)]. We found that a single cfDNA methylation marker, cg23035715, has a high diagnostic power [AUROC = 0.9395 (95% CI: 89.72–99.27%), and AUPRC = 0.9111 (95% CI: 88.45–93.76%)], with a sensitivity of 84.90% and a specificity of 93.88%. In an independent testing dataset (n = 104), the obtained diagnostic prediction model discriminated BC patients from normal controls with high accuracy [AUROC = 0.9449 (95% CI: 90.07–98.91%), and AUPRC = 0.8640 (95% CI: 82.82–89.98%)]. We compared the diagnostic power of cfDNA methylation and mammography. Our model yielded a sensitivity of 94.79% (95% CI: 78.72–97.87%) and a specificity of 98.70% (95% CI: 86.36–100%) for differentiating malignant disease from normal lesions [AUROC = 0.9815 (95% CI: 96.75–99.55%), and AUPRC = 0.9800 (95% CI: 96.6–99.4%)], with better diagnostic power and had better diagnostic power than that of using mammography [AUROC = 0.9315 (95% CI: 89.95–96.34%), and AUPRC = 0.9490 (95% CI: 91.7–98.1%)]. In addition, hypermethylation profiling provided insights into lymph node metastasis stratifications (p

Alkali metal potassium is conducive to structure promotion and electronic modulation in metal oxides. Here, K species was successfully introduced into α-MnO

Oxygen vacancy plays an important role in adsorption and activation of oxygen species and therefore promotes the catalytic performance of materials in heterogeneous oxidation reactions. Here, a series of K-doped ɑ-MnO