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Abstract Background In this study, an automatic corneal contour extraction algorithm with a shared model is developed to extract contours from dynamic corneal videos containing noise, which improves the accuracy of corneal biomechanical evaluation and clinical diagnoses. The algorithm does not require manual labeling and completes the unsupervised semantic segmentation of each frame in corneal dynamic deformation videos based on a fully convolutional deep-learning network using corneal geometry and texture information. Results We included 1027 corneal videos at Tianjin Eye Hospital (Nankai University Affiliated Eye Hospital) from May 2020 to November 2021. The videos were obtained by the ultra-high-speed Scheimpflug camera, and then we used the shared model mechanism to accelerate the segmentation of corneal regions in videos, effectively resist noise, determine corneal regions based on shape factors, and finally achieve automatic and accurate extraction of corneal region contours. The Intersection over Union (IoU) of the extracted and real corneal contours using this algorithm reached 95%, and the average overlap error was 0.05, implying that the extracted corneal contour overlapped almost completely with the real contour. Conclusions Compared to other algorithms, the method introduced in this study does not require manual annotation of corneal contour data in advance and can still extract accurate corneal contours from noisy corneal videos with good repeatability.

The local inhomogeneity along the thickness direction of the extruded plate of spray-formed aluminum alloy 7055 were investigated. The thermal extrusion process was simulated by using DEFORM-3D software to understand its formation mechanism. In order to reduce the extrusion-induced inhomogeneity and improve the mechanical properties, the evolution of the secondary phase during different heat treatments and its influence on the peak aged hardness and tensile strength of the alloy were emphatically analyzed. The results show that the strain rate and temperature during the thermal extrusion process tend to decrease from the surface to the center, which leads to the local inhomogeneity of the microstructure and properties in the thickness direction. Such inhomogeneity can be reduced by heat treatments combining long-time or slow-heating solution treatments (F2 and F3) with peak ageing at 120 °C, due to similar content of S (Al2MgCu) phase after solution treatment and η′ phase (peak-ageing) in different regions of the alloy. The alloy solution treated with a slow heating rate (F3) and then peak aged shows highest hardness and tensile strength, because the slow heating process during the solution treatment promotes the precipitation of Al3Zr particles, and there are less S (Al2MgCu) phases after solution treatment which is conducive to the η′ phase precipitation during the subsequent aging process.

Summary: Pain is a multi-dimensional phenomenon that encompasses both physical pain experienced physiologically and social pain experienced emotionally. The interactions between them are thought to lead to increased pain load. However, the effect of social pain on physical pain perception during interactions remains unclear. Four experiments were conducted merging physical and social pains to examine the behavioral pattern and neural mechanism of the effect of social pain on physical pain perception. Seemingly paradoxical effects of social pain were observed, which both facilitated and inhibited physical pain perception under different attention orientations. Brain imaging revealed that the posterior insula encoded the facilitatory effect, whereas the frontal pole engaged in the inhibitory effect. At a higher level, the thalamus further modulated both processes, playing a switch-like role under different concern statuses of social pain. These results provide direct evidence for the dual-pathway mechanism of the effect of social pain on physical pain.

Spray forming is a manufacturing process that enables the production of high-performance metallic materials with exceptional properties. Due to its rapid solidification nature, spray forming can produce materials that exhibit fine, uniform, and equiaxed microstructures, with low micro-segregation, high solubility, and excellent workability. Al-Zn-Mg-Cu alloys have been widely used in the aerospace field due to their excellent properties, i.e., high strength, low density, and outstanding machinability. The alloy manufactured by spray forming has a combination of better impact properties and higher specific strength, due to its higher cooling rate, higher solute concentration, and lower segregation. In this manuscript, the recent development of spray-formed Al-Zn-Mg-Cu alloys is briefly reviewed. The influence of hot working, i.e., hot extrusion, hot forging, and hot rolling, as well as different heat treatments on the property and microstructure of spray-formed Al-Zn-Mg-Cu alloys is introduced. The second phases and their influence on the microstructure and mechanical properties are summarized. Finally, the potential in high-temperature applications and future prospects of spray-formed aluminum alloys are discussed.

Hypervirulent Klebsiella pneumoniae (hvKp) is a notorious clinical pathogen that is more likely to cause severe primary and metastatic abscesses. The dissemination of antimicrobial-resistant hvKp isolates has been reported worldwide, posing a great challenge and severe clinical threat. However, the mechanisms of antimicrobial-resistant hvKp isolates prevalent worldwide are not well precise. Outer membrane vesicles (OMVs) secreted from gram-negative bacteria are an important vehicle for delivering effector molecules inter- and intra-species. To explore whether OMVs as the vector of virulence genes horizontal transfer among Klebsiella pneumoniae and to explain the potential mechanism for the development of antimicrobial-resistant hvKp isolates, we isolated OMVs from hvKp and classical Klebsiella pneumoniae (cKp) by sequential differential centrifugation, respectively. Then, the characteristics and contents of hvKp-OMVs and cKp-OMVs were analyzed. These hvKp-OMVs contain virulence genes, which could be transferred from hvKp horizontally to extended-spectrum beta lactamase (ESBL)-producing cKp, leading to the production of antimicrobial-resistant hypervirulent transformants. Further experiments confirmed the transformants exhibited antimicrobial resistance and hypervirulent phenotypes in vitro and in vivo. In short, this work demonstrated that hvKp-OMVs facilitated virulence genes transfer, allowing an increase in the virulence level of ESBL-producing cKp and providing a new mechanism for the emergence of antimicrobial-resistant hvKp isolates.

PurposeTo implement two Artificial Intelligence (AI) methods, radiomics and deep learning, to build diagnostic models for patients presenting with architectural distortion on Digital Breast Tomosynthesis (DBT) images.Materials and MethodsA total of 298 patients were identified from a retrospective review, and all of them had confirmed pathological diagnoses, 175 malignant and 123 benign. The BI-RADS scores of DBT were obtained from the radiology reports, classified into 2, 3, 4A, 4B, 4C, and 5. The architectural distortion areas on craniocaudal (CC) and mediolateral oblique (MLO) views were manually outlined as the region of interest (ROI) for the radiomics analysis. Features were extracted using PyRadiomics, and then the support vector machine (SVM) was applied to select important features and build the classification model. Deep learning was performed using the ResNet50 algorithm, with the binary output of malignancy and benignity. The Gradient-weighted Class Activation Mapping (Grad-CAM) method was utilized to localize the suspicious areas. The predicted malignancy probability was used to construct the ROC curves, compared by the DeLong test. The binary diagnosis was made using the threshold of ≥ 0.5 as malignant.ResultsThe majority of malignant lesions had BI-RADS scores of 4B, 4C, and 5 (148/175 = 84.6%). In the benign group, a substantial number of patients also had high BI-RADS ≥ 4B (56/123 = 45.5%), and the majority had BI-RADS ≥ 4A (102/123 = 82.9%). The radiomics model built using the combined CC+MLO features yielded an area under curve (AUC) of 0.82, the sensitivity of 0.78, specificity of 0.68, and accuracy of 0.74. If only features from CC were used, the AUC was 0.77, and if only features from MLO were used, the AUC was 0.72. The deep-learning model yielded an AUC of 0.61, significantly lower than all radiomics models (p

Abstract Background Emergence of new pathogen strains of Magnaporthe oryzae is a major reason for recurrent failure of the resistance mediated by a single resistance gene (Pi) in rice. Stacking various Pi genes in the genome through marker-assisted selection is thus an effective strategy in rice breeding for achieving durable resistance against the pathogen. However, the effect of pyramiding of multiple Pi genes using transgenesis still remains largely unknown. Results Three Pi genes Pib, Pi25 and Pi54 were transferred together into two rice varieties, the indica variety Kasalath and the japonica variety Zhenghan 10. Transgenic plants of both Kasalath and Zhenghan 10 expressing the Pi transgenes showed imparted pathogen resistance. All the transgenic lines of both cultivars also exhibited shorter growth periods with flowering 2–4 days early, and shorter plant heights with smaller panicle. Thus, pyramiding of the Pi genes resulted in reduced grain yields in both rice cultivars. However, tiller numbers and grain weight were generally similar between the pyramided lines and corresponding parents. A global analysis of gene expression by RNA-Seq suggested that both enhancement and, to a lesser extent, inhibition of gene transcription occurred in the pyramided plants. A total of 264 and 544 differentially expressed genes (DEGs) were identified in Kasalath and Zhenghan 10, respectively. Analysis of the DEGs suggested that presence of the Pi transgenes did not alter gene expression only related to disease resistance, but also impacted many gene transcriptions in the pathways for plant growth and development, in which several were common for both Kasalath and Zhenghan 10. Conclusion Pyramiding of the Pi genes Pib, Pi25 and Pi54 via transgenesis is a potentially promising approach for improving rice resistance to the pathogen Magnaporthe oryzae. However, pleiotropic effects of the Pi genes could potentially result in yield loss. These findings support the idea that immunity is often associated with yield penalties. Rational combination of the Pi genes based on the genetic background may be important to balance yield and disease resistance.

Abstract The authors analyse a Bayesian framework for posing and solving inverse reinforcement learning (IRL) problems that arise in decision‐making and optimisation settings. The authors propose a non‐parametric Bayesian model using Gaussian process (GP) and preference graphs, which offer an effective and computationally efficient method for ill‐posed IRL problems in large or infinite state space. This approach only requires a finite number of demonstrations that is much less than the amount required for approximating the feature expectation or value functions in previous IRL methods. The proposed learning framework is expressive as it relies on a Bayesian structure in which assumptions are explicit and changeable. It is also robust in that it formalises on convex optimisation, which retains the promise of computationally manageable implementations for practical problems. To deal with more realistic IRL problems where the dynamics is also unknown, the GP model can be easily combined with the method to learn the dynamics at the same time. Experimental results prove the superiority of the authors method to current prevailing IRL algorithms with fewer numbers of demonstrations in both discrete and continuous state space.

Abstract Background Early and rapid identification of Pseudomonas aeruginosa (P. aeruginosa) in patients with suspected ventilator-associated pneumonia (VAP) provides theoretical clinical advantages in therapeutic optimization strategies. Methods The P. aeruginosa-multiple cross displacement amplification (PA-MCDA) assay was conducted at an isothermal temperature during the amplification stage, and products were visually detected by color changes. The entire process was completed within 1 h. A total of 77 strains, including P. aeruginosa species and various other species of non-P. aeruginosa, were used to evaluate PA-MCDA assays. Bronchoalveolar lavage fluid (BALF) of suspected VAP patients was examined by the MCDA assay. Results The MCDA assay exhibited a 100% analytical specificity in detecting PA from all 77 strains, and the limit of detection was as low as 100 fg DNA per reaction. A temperature of 65 °C was recommended as standard during the amplification stage. The agreement between PA-MCDA and bacteria culture was 91.18% (κ = 0.787; p = 0.000) in the identification of P. aeruginosa in BALF from suspected VAP. The PA-MCDA assay showed values of 92.31%, 90.78%, 77.41%, and 97.18% for sensitivity, specificity, positive predictive value, and negative predictive value, respectively. PA-MCDA had a higher detective rate of P. aeruginosa than bacteria culture in patients with antipseudomonal therapy. Conclusions The instrument-free platform of the MCDA assay makes it a simple, rapid, and applicable procedure for “on-site” diagnosis and point-of-care testing for the presence of P. aeruginosa without the need for specific bacterial culture.

Abstract Phloem systemicity is a desirable property for insecticides to control sucking insects. However, the development of phloem systemic insecticides is challenging. One possible strategy is to link existed insecticides with endogenous substances so that the resulting conjugates can be transported by specific transporters into the phloem. In this study, novel dipeptide promoieties were introduced into chlorantraniliprole, which is an efficient and broad-spectrum anthranilic diamide insecticide without phloem mobility. Twenty-two new dipeptide-chlorantraniliprole conjugates have been synthesized. Systemic tests showed that all conjugates exhibited phloem mobility in Ricinus communis. In particular, compound 4g with alanyl-alanine dipeptide fragment was able to accumulate in phloem sap (114.49 ± 11.10 μM) in the form of its hydrolysis product 5g. Results of bioassay showed that conjugates 4g and 5g were able to exhibit comparable insecticidal activity against Plutella xylostella L. and Spodoptera exigua compared to its parent compound chlorantraniliprole. This work demonstrated that the dipeptide structures were able to contribute to the improvement of the uptake and phloem mobility of chlorantraniliprole, and two phloem mobile conjugates with satisfactory in vivo insecticidal effect was obtained as new candidates for high-efficient insecticides.

BackgroundAllergen immunotherapy (AIT) can induce immune tolerance to allergens by activating multiple mechanisms, including promoting IgG4 synthesis and blunting IgE production. However, the longitudinal data of sIgE and sIgG4 to allergen components during AIT are limited.ObjectiveWe sought to investigate the persistence and evolution of sIgE and sIgG4 against house dust mite (HDM) components during AIT and explore their correlation with clinical responses.MethodsSixty allergic rhinitis (AR) with/without asthma patients receiving AIT for HDM were enrolled in AIT group. Thirty AR patients without receiving AIT served as control group. Blood samples were collected for sIgE, sIgG4 to HDM components (Derp 1, Derf 1, Derp 2, Derf 2, Derp 7, Derp 10, Derp 21 and Derp 23) assay at baseline, Month 6 and Month 18 of AIT. Combined symptom and medication scores (CSMS) were obtained accordingly.ResultsIn the AIT group, sIgG4 to the HDM components of Derp 1, Derf 1, Derp 2 and Derf 2, Derp 21 significantly increased at Month 18 compared to the baseline (36.2 UA/mL vs 158.8 UA/mL, 46.4 UA/mL vs 94.6 UA/mL, 80.5 UA/mL vs 152.3 UA/mL, 78.3 UA/mL vs 205.1 UA/mL, 42.3 UA/mL vs 59.3 UA/mL, all p0.05).The numbers of positive HDM component sIgE and sIgG4 increased from 4.5 to 5 and 0 to 1.5 respectively (both p0.05).ConclusionAIT can induce the production of sIgG4 to HDM components. However, the increased sIgG4 levels of HDM component do not correlate with the corresponding sIgE levels at baseline or with AIT response. sIgG4 to HDM components do not qualify as a biomarker to evaluate the efficacy of AIT.

Extracellular vesicles (EVs) loaded with proteins, nucleic acids, membrane lipids, and other virulence factors could participate in pathogenic processes in some fungi such as Cryptococcus neoformans and Candida albicans. However, the specific characteristics of EVs derived from Talaromyces marneffei (TM) still have not been figured out yet. In the present study, it has been observed that TM-derived EVs were a heterogeneous group of nanosized membrane vesicles (30–300 nm) under nanoparticle tracking analysis and transmission electron microscopy. The DiI-labeled EVs could be taken up by RAW 264.7 macrophage cells. Incubation of EVs with macrophages would result in increased expression levels of reactive oxygen species, nitric oxide, and some inflammatory factors including interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor. Furthermore, the expression of co-stimulatory molecules (CD80, CD86, and MHC-II) was also increased in macrophages stimulated with EVs. The level of inflammatory factors secreted by macrophages showed a significant decrease when EVs were hydrolyzed by protease, while that of DNA and RNA hydrolase treatment remained unchanged. Subsequently, some virulence factors in EVs including heat shock protein, mannoprotein 1, and peroxidase were determined by liquid chromatography–tandem mass spectrometry. Taken together, our results indicated that the TM-derived EVs could mediate inflammatory response and its protein would play a key role in regulating the function of RAW 264.7 macrophage cells.

Fusarium pseudograminearum causes crown rot in wheat. This study aimed to assess the effects of the bacterial strain QTH8 isolated from Cotinus coggygria rhizosphere soil against F. pseudograminearum. Bacterial strain QTH8 was identified as Bacillus halotolerans in accordance with the phenotypic traits and the phylogenetic analysis of 16S rDNA and gyrB gene sequence. Culture filtrates of bacterial strain QTH8 inhibited the mycelial growth of F. pseudograminearum and resulted in mycelial malformation such as tumor formation, protoplast condensation, and mycelial fracture. In addition, bacterial strain QTH8 also inhibited the mycelial growth of Hainesia lythri, Pestalotiopsis sp., Botrytis cinerea, Curvularia lunata, Phyllosticta theaefolia, Fusarium graminearum, Phytophthora nicotianae, and Sclerotinia sclerotiorum. The active compounds produced by bacterial strain QTH8 were resistant to pH, ultraviolet irradiation, and low temperature, and were relatively sensitive to high temperature. After 4 h exposure, culture filtrates of bacterial strain QTH8—when applied at 5%, 10%, 15%, 20%, 25%, and 30%—significantly reduced conidial germination of F. pseudograminearum. The coleoptile infection assay proved that bacterial strain QTH8 reduced the disease index of wheat crown rot. In vivo application of QTH8 to wheat seedlings decreased the disease index of wheat crown rot and increased root length, plant height, and fresh weight. Iturin, surfactin, and fengycin were detected in the culture extract of bacterial strain QTH8 by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Bacterial strain QTH8 was identified for the presence of the ituC, bacA, bmyB, spaS, srfAB, fend, and srfAA genes using the specific polymerase chain reaction primers. B. halotolerans QTH8 has a vital potential for the sustainable biocontrol of wheat crown rot.

I-motifs play key regulatory roles in biological processes, holding great potential as attractive therapeutic targets. In the present study, we developed a novel fluorescent probe G59 with strong and selective binding to the c-myc gene promoter i-motif. G59 had an i-motif-binding carbazole moiety conjugated with naphthalimide fluorescent groups. G59 could differentiate the c-myc i-motif from other DNA structures through selective activation of its fluorescence, with its apparent visualization in solution. The smart probe G59 showed excellent sensitivity, with a low fluorescent detection limit of 154 nM and effective stabilization to the c-myc i-motif. G59 could serve as a rapid and sensitive probe for label-free screening of selective c-myc i-motif binding ligands under neutral crowding conditions. To the best of our knowledge, G59 is the first fluorescent probe with high sensitivity for recognizing the i-motif structure and screening for selective binding ligands.

Abstract Background During ischemic stroke (IS), adenosine 5′-triphosphate (ATP) is released from damaged nerve cells of the infract core region to the extracellular space, invoking peri-infarct glial cellular P2 purinoceptors singling, and causing pro-inflammatory cytokine secretion, which is likely to initiate or aggravate motor and cognitive impairment. It has been proved that electroacupuncture (EA) is an effective and safe strategy used in anti-inflammation. However, EA for the role of purine receptors in the central nervous system has not yet been reported. Methods Ischemia-reperfusion injured rat model was induced by middle cerebral artery occlusion and reperfusion (MCAO/R). EA treatment at the DU 20 and DU 24 acupoints treatment were conducted to rats from the 12 h after MCAO/R injury for consecutive 7 days. The neurological outcomes, infarction volumes and the level of astroglial and microglial/macrophage hyperplasia, inflammatory cytokine and P2X7R and P2Y1R expression in the peri-infarct hippocampal CA1and sensorimotor cortex were investigated after IS to evaluate the MCAO/R model and therapeutic mechanism of EA treatment. Results EA effectively reduced the level of pro-inflammatory cytokine interleukin-1β (IL-1β) as evidenced by reduction in astroglial and microglial/macrophage hyperplasia and the levels of P2X7R and ED1, P2X7R and GFAP, P2Y1R and ED1, P2Y1R and GFAP co-expression in peri-infarct hippocampal CA1 and sensorimotor cortex compared with that of MCAO/R model and Non-EA treatment, accompanied by the improved neurological deficit and the motor and memory impairment outcomes. Therefore, our data support the hypothesis that EA could exert its anti-inflammatory effect via inhibiting the astroglial and microglial/macrophage P2 purinoceptors (P2X7R and P2Y1R)-mediated neuroinflammation after MCAO/R injury. Conclusion Astroglial and microglial/macrophage P2 purinoceptors-mediated neuroinflammation and hyperplasia in peri-infarct hippocampal CA1 and sensorimotor cortex were attenuated by EA treatment after ischemic stroke accompanied by the improved motor and memory behavior performance.

Biological nematicides have been widely used to lower the losses generated by phytoparasitic nematodes. The purpose of this study was to evaluate the nematicidal effects of Escherichia coli BL21(DE3) against Meloidogyne javanica and to identify nematicide-related genes. Culture filtrates of BL21(DE3) caused juvenile mortality and inhibited egg hatching in a dose-dependent manner. In the greenhouse, treatment of tomato seedlings with BL21(DE3) culture filtrates at 50 and 100% concentrations not only reduced the amount of M. javanica egg masses and galls, but improved plant root and shoot fresh weight. Culture filtrate analysis indicated that the nematicidal active ingredients of strain BL21(DE3) were non-proteinaceous, heat and cold resistant, sensitive to pH and volatile. To identify the genes associated with nematicidal activity, a BL21(DE3) library of 5000 mutants was produced using Tn5 transposase insertion. The culture filtrate of the MB12 mutant showed no nematicidal activity after 72 h of treatment and thermal asymmetrical interlaced PCR demonstrated that the carB gene was disrupted. Nematicidal activity was restored when the pH of the MB12 culture filtrate was adjusted to the original pH value (4.15) or following MB12 complementation with the carB gene, confirming a role for carB in mediating pH value and nematicidal activity. The outcomes of this pilot study indicate that BL21(DE3) is a potential microorganism for the continuable biological control of root-knot nematode in tomato and that carB affects the nematicidal activity of BL21(DE3) by modulating the pH environment.

Abstract Renal ischemia‒reperfusion injury (IRI) is one of the main causes of acute kidney injury (AKI), which is a potentially life-threatening condition with a high mortality rate. IRI is a complex process involving multiple underlying mechanisms and pathways of cell injury and dysfunction. Additionally, various types of cell death have been linked to IRI, including necroptosis, apoptosis, pyroptosis, and ferroptosis. These processes operate differently and to varying degrees in different patients, but each plays a role in the various pathological conditions of AKI. Advances in understanding the underlying pathophysiology will lead to the development of new therapeutic approaches that hold promise for improving outcomes for patients with AKI. This review provides an overview of the recent research on the molecular mechanisms and pathways underlying IRI-AKI, with a focus on regulated cell death (RCD) forms such as necroptosis, pyroptosis, and ferroptosis. Overall, targeting RCD shows promise as a potential approach to treating IRI-AKI.