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Heparin-binding growth factor (HB-EGF) is a member of the epidermal growth factor (EGF) ligand family which has a crucial role in women's health. However, there is a lack of comprehensive review to summarize the significance of HB-EGF. Therefore, this work first described the expression patterns of HB-EGF in the endometrium and ovary of different species and gestational time. Then, the focus was on exploring how it promotes the successful implantation and regulates the process of decidualization and the function of ovarian granulosa cells as an intermediate molecule. Otherwise, we also focused on the clinical and prognostic significance of HB-EGF in female-related cancers (including ovarian cancer, cervical cancer, and endometrial cancer) and breast cancer. Lastly, the article also summarizes the current drugs targeting HB-EGF in the treatment of ovarian cancer and breast cancer. Overall, these studies found that the expression of HB-EGF in the endometrium is spatiotemporal and species-specific. And it mediates the dialogue between the blastocyst and endometrium, promoting synchronous development of the blastocyst and endometrium as an intermediate molecule. HB-EGF may serve as a potentially valuable prognostic clinical indicator in tumors. And the specific inhibitor of HB-EGF (CRM197) has a certain anti-tumor ability, which can exert synergistic anti-tumor effects with conventional chemotherapy drugs. However, it also suggests that more research is needed in the future to elucidate its specific mechanisms and to accommodate clinical studies with a larger sample size to clarify its clinical value. [ABSTRACT FROM AUTHOR]

Background and aims: The levels of reactive oxygen species (ROS) including superoxide anion radical (O2•−), hydrogen peroxide (H2O2) increase in plants under Zinc (Zn) deficiency stress. However, less is known about whether excessive levels of ROS mediate root development and growth under Zn deficient condition. Methods: Maize variety Zhengdan 958 was chosen to grow with nutrient solution culture with the treatments (DAT) of 0 and 1 μM Zn supply. Exogenous H2O2 and its scavenger (N, N-dimethylthiourea, DMTU), and a catalase inhibitor (Aminotriazole, AT) were added. The distribution of ROS in roots were detected by chemical staining and fluorescent probe technology. The differential expression of related genes and proteins in roots were analyzed through proteomics and transcriptomics approaches. Results: Zn deficiency stress caused high O2•−and H2O2 levels in roots and decreased crown root elongation. Exogenous addition of DMTU reduced the H2O2 content in roots and the inhibitory effect of Zn deficiency on root elongation. Under Zn supply, the addition of H2O2 and AT resulted in short crown roots. The down-regulation of several genes associated with cell wall extension, such as cellulose synthase, xyloglucan endtransglucosylase/hydrolase and beta expansin 8, were found in the transcriptome and proteome data of Zn-deficient root. Conclusion: It is suggested that H2O2 might be involve in the inhibition of crown root development in maize plants subjected to Zn deficiency stress, which may account for the down-regulation of genes related to cell wall extension through transcriptomic and proteomic analysis. [ABSTRACT FROM AUTHOR]

Background: Clinically, recurrent spontaneous abortion (RSA) is a pregnancy illness that is difficult to treat. Impaired decidualization is a documented cause of RSA, but the etiology and mechanism are still unknown. cAMP-responsive element binding protein 5 (CREB5) is a member of the ATF/CREB family. CREB5 has been reported to be related to pathological pregnancy, but there are few related studies on this topic in patients with RSA, and the underlying mechanism is unclear. Methods: We collected decidual tissues from RSA patients and healthy pregnant women to measure the expression level of CREB5, PRL, IGFBP1, ATG5, LC3B, and SQSTM/p62. Then, the changes in CREB5 expression and autophagy levels were measured in human endometrial stromal cells (hESCs) during decidualization. The expression levels of PRL and IGFBP1 were tested in sh-CREB5/ov-CREB5 hESCs after decidualization induction, and the autophagy level in sh-CREB5/ov-CREB5 hESCs was measured without decidualization induction. The decidualization ability of sh-CREB5 and ov-CREB5 hESCs treated with an autophagy inducer or inhibitor was measured. To investigate the effect of CREB5 in hESCs on the invasion and migration of HTR8/SVneo cells, we performed a coculture experiment. Finally, we examined the expression of CREB5 and autophagy key proteins in mouse decidual tissues by constructing an abortion mouse model. Results: In our study, we found that the expression of CREB5 was unusually elevated in the uterine decidua of RSA patients, but the expression of PRL, IGFBP1, and autophagy were decreased. During the decidualization of hESCs, the expression of CREB5 gradually decreases in a time-dependent manner with increasing autophagy. Moreover, by knocking down or overexpressing CREB5 in hESCs, it was found that CREB5 can impair decidualization and reduce autophagy in hESCs. Furthermore, the damage caused by CREB5 in terms of decidualization can be reversed by the addition of an autophagy inducer (rapamycin). In addition, CREB5 can increase the secretion of proteins (IL-1β and TGF-β1) in hESCs to inhibit trophoblast invasion and migration. Conclusions: Our data support the supposition that CREB5 disturbs the decidualization of endometrial stromal cells and interactions at the maternal–fetal interface by inhibiting autophagy and that its abnormal upregulation and dysfunction may lead to RSA. It may function as a diagnostic and therapeutic target for RSA. Similarly, we found that in the spontaneous abortion mouse model, the expression of CREB5 in the decidual tissue of the abortion group was significantly increased, and autophagy was decreased. [ABSTRACT FROM AUTHOR]

The tunneling process in water-rich silty fine sand stratum often faces challenges such as arch collapse due to the instability of the initial support arch foot. The present study focuses on the Taoshuping 3# inclined shaft section, modifies the two-side heading method (THM), and introduces the double-heading at bottom method (DBM). Field monitoring and numerical simulations are employed to investigate the formation pressure, deformation evolution, and the advantages of the construction scheme using the loosened zone and stress distribution features. The obtained results show that DBM exhibits a maximu m settlement during arch excavation, constituting approximately 36% of the total settlement, with a total value of 222.21 mm. Furthermore, the plastic zone induced by DBM ranges from 1.23 to 2 times the tunnel diameter, with vertical and horizontal surrounding soil pressures of 140.72 kPa and 46.25 kPa, respectively. DBM is markedly superior to THM. This approach reduces the formation of wedge-shaped shear bodies caused by excessive stress at the sidewalls in THM excavation. Even with tunnel excavation support, the surrounding soil maintains an arch effect, validated through calculations using Protodyakonovco theory and Terzaghi theory, verifying the efficiency of the support structure design. [ABSTRACT FROM AUTHOR]

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A scalable, reusable, and broad-coverage unified material knowledge representation shows its importance and will bring great benefits to data sharing among materials communities. A knowledge graph (KG) for materials terminology, which is a formal collection of term entities and relationships, is conceptually important to achieve this goal. In this work, we propose a KG for materials terminology, named Materials Genome Engineering Database Knowledge Graph (MGED-KG), which is automatically constructed from text corpus via natural language processing. MGED-KG is the most comprehensive KG for materials terminology in both Chinese and English languages, consisting of 8,660 terms and their explanations. It encompasses 11 principal categories, such as Metals, Composites, Nanomaterials, each with two or three levels of subcategories, resulting in a total of 235 distinct category labels. For further application, a knowledge web system based on MGED-KG is developed and shows its great power in improving data sharing efficiency from the aspects of query expansion, term, and data recommendation. [ABSTRACT FROM AUTHOR]

In recent years, the field of bionics has attracted the attention of numerous scholars. Some models combined with biological vision have achieved excellent performance in computer vision and image processing tasks. In this paper, we propose a new bio-inspired lightweight contour detection network (BLCDNet) by combining parallel processing mechanisms of bio-visual information with convolutional neural networks. The backbone network of BLCDNet simulates the parallel pathways of ganglion cell–lateral geniculate nucleus and primary visual cortex (V1) area, realizing parallel processing and step-by-step extraction of input information, effectively extracting local features and detailed features in images, and thus improving the overall performance of the model. In addition, we design a depth feature extraction module combining depth separable convolution and residual connection in the decoding network to integrate the output of the backbone network, which further improves the performance of the model. We conducted a large number of experiments on BSDS500 and NYUD datasets, and the experimental results show that the BLCDNet proposed in this paper achieves the best performance compared with traditional methods and previous biologically inspired contour detection methods. In addition, BLCDNet still outperforms some VGG-based contour detection methods without pre-training and with fewer parameters, and it is competitive among all of them. The research in this paper also provides a new idea for the combination of biological vision and convolutional neural networks. [ABSTRACT FROM AUTHOR]

Cuproptosis-related genes (CRGs) are important for tumor development. However, the functions of CRGs across cancers remain obscure. We performed a pan-cancer investigation to reveal the roles of CRGs across cancers. In an analysis of 26 cancers, 12 CRGs were differentially expressed, and those CRGs were found to have prognostic value across different cancer types. The expression of CRGs exhibited varied among tumors of 6 immune subtypes and were significantly correlated with the 16 sensitivities of drugs. The expression of CRGs were highly correlated with immunological subtype and tumor microenvironment (TME) of prostate cancer. We also established CRGs-related prognostic signatures that closely correlated with prognosis and drug sensitivity of prostate cancer patients. Single-cell RNA-seq revealed that several CRGs were enriched in the cancer cells. Finally, an in vitro experiment showed that elesclomol, a cuproptosis inducer, targets ferredoxin 1 and suppress cell viability in prostate cancer cells. In conclusion, we carried out a comprehensive investigation for determining CRGs in differential expression, prognosis, immunological subtype, TME, and cancer treatment sensitivity across 26 malignancies; and validated the results in prostate cancer. Our research improves pan-cancer knowledge of CRGs and identifies more effective immunotherapy strategies. [ABSTRACT FROM AUTHOR]

Objectives: To develop a radiomics model in contrast-enhanced cone-beam breast CT (CE-CBBCT) for preoperative prediction of axillary lymph node (ALN) status and metastatic burden of breast cancer. Methods: Two hundred and seventy-four patients who underwent CE-CBBCT examination with two scanners between 2012 and 2021 from two institutions were enrolled. The primary tumor was annotated in each patient image, from which 1781 radiomics features were extracted with PyRadiomics. After feature selection, support vector machine models were developed to predict ALN status and metastatic burden. To avoid overfitting on a specific patient subset, 100 randomly stratified splits were made to assign the patients to either training/fine-tuning or test set. Area under the receiver operating characteristic curve (AUC) of these radiomics models was compared to those obtained when training the models only with clinical features and combined clinical-radiomics descriptors. Ground truth was established by histopathology. Results: One hundred and eighteen patients had ALN metastasis (N + (≥ 1)). Of these, 74 had low burden (N + (1~2)) and 44 high burden (N + (≥ 3)). The remaining 156 patients had none (N0). AUC values across the 100 test repeats in predicting ALN status (N0/N + (≥ 1)) were 0.75 ± 0.05 (0.67~0.93, radiomics model), 0.68 ± 0.07 (0.53~0.85, clinical model), and 0.74 ± 0.05 (0.67~0.88, combined model). For metastatic burden prediction (N + (1~2)/N + (≥ 3)), AUC values were 0.65 ± 0.10 (0.50~0.88, radiomics model), 0.55 ± 0.10 (0.40~0.80, clinical model), and 0.64 ± 0.09 (0.50~0.90, combined model), with all the ranges spanning 0.5. In both cases, the radiomics model was significantly better than the clinical model (both p < 0.01) and comparable with the combined model (p = 0.56 and 0.64). Conclusions: Radiomics features of primary tumors could have potential in predicting ALN metastasis in CE-CBBCT imaging. Clinical relevance statement: The findings support potential clinical use of radiomics for predicting axillary lymph node metastasis in breast cancer patients and addressing the limited axilla coverage of cone-beam breast CT. Key Points: • Contrast-enhanced cone-beam breast CT-based radiomics could have potential to predict N0 vs. N + (≥ 1) and, to a limited extent, N + (1~2) vs. N + (≥ 3) from primary tumor, and this could help address the limited axilla coverage, pending future verifications on larger cohorts. • The average AUC of radiomics and combined models was significantly higher than that of clinical models but showed no significant difference between themselves. • Radiomics features descriptive of tumor texture were found informative on axillary lymph node status, highlighting a higher heterogeneity for tumor with positive axillary lymph node. [ABSTRACT FROM AUTHOR]

With the wide application of cantilever roadheader in urban subway tunnel construction, accurate prediction of excavation performance of cantilever roadheader in rock stratum has become a research hotspot. Accurate prediction of tunneling performance of cantilever roadheader in rock stratum is the key to its successful application in tunnel engineering. Based on Guiyang Rail Transit Line 1 and Line 3, this paper conducts field investigation and statistical analysis of data on the construction performance and tunneling characteristics of roadheader, and establishes a prediction database of tunneling performance of hard rock cantilever roadheader. The principal component analysis (PCA) was introduced into the deep belief network (DBN) to optimize the input parameters of the DBN model, and the PCA–DBN model for the performance prediction of hard rock cantilever roadheader was proposed. The new model is trained and predicted based on the data of Guiyang Rail Transit Line 1, and the rationality and feasibility of the model are verified through the field data test and analysis of Guiyang Rail Transit Line 3. The results show that the performance prediction model of hard rock cantilever roadheader based on PCA–DBN can realize real-time and continuous prediction of tunneling performance of ground roadheader in front of tunnel face according to engineering measured data. The comparative analysis with the DBN model shows that the accuracy of the PCA–DBN prediction model is better than that of the DBN model, which can better adapt to complex and changeable geological conditions. The new model provides a new method and possibility for accurately predicting the tunneling performance of cantilever roadheader in hard rock. Highlights: A prediction database of hard rock cantilever roadheader tunneling performance was established. The performance prediction model of hard rock cantilever roadheader based on PCA–DBN was established. The performance prediction model realizes real-time and continuous prediction of tunneling performance of ground roadheader. The prediction accuracy of PCA–DBN is higher than DBN in predicting the performance of cantilever roadheader. [ABSTRACT FROM AUTHOR]

Ras homology enriched in the brain (Rheb) is well established as a critical regulator of cell proliferation and differentiation in response to growth factors and nutrients. However, the role of Rheb1 in limb development remains unknown. Here, we found that Rheb1 was dynamically expressed during the proliferation and differentiation of chondrocytes in the growth plate. Given that Prrx1+ limb-bud-like mesenchymal cells are the source of limb chondrocytes and are essential for endochondral ossification, we conditionally deleted Rheb1 using Prrx1-Cre and found a limb dwarfism in Prrx1-Cre; Rheb1fl/fl mice. Normalized to growth plate height, the conditional knockout (cKO) mice exhibited a significant decrease in column count of proliferative zones which was increased in hypertrophic zones resulting in decreased growth plate size, indicating abnormal endochondral ossification. Interestingly, although Rheb1 deletion profoundly inhibited the transcription factor Sox9 in limb cartilage; levels of runx2 and collagen type 2 were both increased. These novel findings highlight the essential role of Rheb1 in limb growth and indicate a complex regulation of Rheb1 in chondrocyte proliferation and differentiation. [ABSTRACT FROM AUTHOR]

Objective: Here, we explored the phenotype and function of MAIT cells in the peripheral blood of patients with HSP. Methods: Blood samples from HSP patients and HDs were assessed by flow cytometry and single-cell RNA sequencing to analyze the proportion, phenotype, and function of MAIT cells. Th-cytokines in the serum of HSP patients were analyzed by CBA. IgA in cocultured supernatant was detected by CBA to analyze antibody production by B cells. Results: The percentage of MAIT cells in HSP patients was significantly reduced compared with that in HDs. Genes related to T cell activation and effector were up-regulated in HSP MAIT cells, indicating a more activated phenotype. In addition, HSP MAIT cells displayed a Th2-like profile with the capacity to produce more IL-4 and IL-5, and IL-4 was correlated with IgA levels in the serum of HSP patients. Furthermore, CD40L was up-regulated in HSP MAIT cells, and CD40L+ MAIT cells showed an increased ability to produce IL-4 and to enhance IgA production by B cells. Conclusion: Our data demonstrate that MAIT cells in HSP patients exhibit an activated phenotype. The enhanced IL-4 production and CD40L expression of MAIT cells in HSP patients could take part in the pathogenesis of HSP. [ABSTRACT FROM AUTHOR]

Structural batteries offer a new way to reduce device mass and increase the overall energy density of devices. An important feature of structural batteries is that they are designed to be subjected to external loads, which generally have a significant impact on electrochemical reactions in normal batteries. In the present work, a multi-field coupled model for a bilayer electrode was developed by considering the effects of external loads and concentration-dependent modulus. It was found that a positive external load, which bent the unlithiated electrode toward the active electrode side, accelerated the Li-ion diffusion process, whereas a negative external load, which was applied in the opposite direction to the positive external load, hindered the diffusion of Li ions. The curvature variation of the bilayer electrode was a result of the coupling effect of external loading, Li-ion concentration distribution, and the concentration-dependent modulus. The convex curvature of the bilayer electrode (bending toward the active electrode side) increased the Li-ion binding capacity of the active electrode, and an opposite effect was found for the concave curvature. During the lithiation process, positive external load exerts a greater influence on the stress distribution across the bilayer electrode compared to negative external load. The results of this work can provide theoretical guidance to design structural batteries under external loading. [ABSTRACT FROM AUTHOR]

Purpose: Cone-beam breast CT (CBBCT) has an inherent limitation that the axilla cannot be imaged in its entirety. We aimed to develop and validate a nomogram based on clinical factors and contrast-enhanced (CE) CBBCT radiomics features to predict axillary lymph node (ALN) metastasis and complement limited axilla coverage. Material and methods: This retrospective study included 312 patients with breast cancer from two hospitals who underwent CE-CBBCT examination in a clinical trial (NCT01792999) during 2012–2020. Patients from TCIH comprised training set (n = 176) and validation set (n = 43), and patients from SYSUCC comprised external test set (n = 93). 3D ROIs were delineated manually and radiomics features were extracted by 3D Slicer software. RadScore was calculated and radiomics model was constructed after feature selection. Clinical model was built on independent predictors. Nomogram was developed with independent clinical predictors and RadScore. Diagnostic performance was compared among three models by ROC curve, and decision curve analysis (DCA) was used to evaluate the clinical utility of nomogram. Results: A total of 139 patients were ALN positive and 173 patients were negative. Twelve radiomics features remained after feature selection. Location and focality were selected as independent predictors for ALN status. The AUC of nomogram in external test set was higher than that of clinical model (0.80 vs. 0.66, p = 0.012). DCA demonstrated that the nomogram had higher overall net benefit than that of clinical model. Conclusion: The nomogram combined CE-CBBCT-based radiomics features and clinical factors could have potential in distinguishing ALN positive from negative and addressing the limitation of axilla coverage in CBBCT. [ABSTRACT FROM AUTHOR]

Vaccination is the best way to build an immune barrier to control a new infectious disease. Considering the limited production capacity at the initial stage of vaccine production, the problem of multistage vaccine production and allocation is studied under the policy of free treatment for infected patients by the government. Given the population and infection rates of different regions and the vaccine production capacity of each stage, an integer programming model is established to minimize the sum of production-and-vaccination cost and treatment cost of infected patients, which is solved by the GUROBI solver. The correctness of the model is verified by simulation, and the necessity of considering the treatment cost of infected patients in the objective function is further analyzed, which confirmed the correctness of the free treatment policy for patients in China. A heuristic algorithm is designed to solve the large-scale problem and numerical experiments are conducted to verify the efficiency of this algorithm. Furthermore, based on the sensitivity analysis results of parameters, the optimal vaccine production and allocation strategy are proposed, which provide the decision basis for the government departments to make reasonable vaccine production and vaccination plan. [ABSTRACT FROM AUTHOR]

In this paper, we study the task of unsupervised 2D image-based 3D shape retrieval (UIBSR), which aims to retrieve unlabeled shapes (target domain) using labeled images (source domain). Previous works on UIBSR mainly focus on aligning the prototypes generated by the source labels and predicted target pseudo labels for reducing the cross-domain discrepancy. However, simply maintaining consistency between features may corrupt the original semantic information. Moreover, the existing methods usually ignore the diversity of the instances during the adaptation process, which results in reducing the discrimination of features. To solve these problems, we propose the prototype-based semantic consistency (PSC) learning method, exploring semantic knowledge in both prototype-prototype and prototype-instance relationships in the probability space rather than the embedding space to preserve the structure of semantic information. Besides, we propose a novel adversarial scheme between feature extractor and classifier to explore the characteristic of different instances, which can further enhance the model to learn more robust representations. Extensive experiments on two challenging datasets demonstrate the superiority of our proposed method. [ABSTRACT FROM AUTHOR]

While exposure to high levels of all-trans retinoic acid (atRA) during pregnancy is known to suppress murine embryonic palate mesenchymal (MEPM) cells proliferation and to result in cleft palate (CP) development, the underlying mechanisms are poorly understood. Accordingly, this study was designed with the goal of clarifying the etiological basis for atRA-induced CP. A murine model of CP was established via the oral administration of atRA to pregnant mice on gestational day (GD) 10.5, after which transcriptomic and metabolomic analyses were performed with the goal of clarifying the critical genes and metabolites associated with CP development through an integrated multi-omics approach. MEPM cells proliferation was altered by atRA exposure as expected, contributing to CP incidence. In total, 110 genes were differentially expressed in the atRA treatment groups, suggesting that atRA may influence key biological processes including stimulus, adhesion, and signaling-related activities. In addition, 133 differentially abundant metabolites were identified including molecules associated with ABC transporters, protein digestion and absorption, mTOR signaling pathway, and the TCA cycle, suggesting a link between these mechanisms and CP. Overall, combined analyses of these transcriptomic and metabolomic results suggested that the MAPK, calcium, PI3K-Akt, Wnt, and mTOR signaling pathways are particularly important pathways enriched in the palatal cleft under conditions of atRA exposure. Together, these integrated transcriptomic and metabolomic approaches provided new evidence with respect to the mechanisms underlying altered MEPM cells proliferation and signal transduction associated with atRA-induced CP, revealing a possible link between oxidative stress and these pathological changes. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is an extensively existing environmental pollutant that has neurotoxic effects. However, the molecular mechanism of Cd on neuronal maturation is unveiled. Single-cell RNA sequencing (scRNA-seq) has been widely used to uncover cellular heterogeneity and is a powerful tool to reconstruct the developmental trajectory of neurons. In this study, neural stem cells (NSCs) from subventricular zone (SVZ) of newborn mice were treated with CdCl2 for 24 h and differentiated for 7 days to obtain neuronal lineage cells. Then scRNA-seq analysis identified five cell stages with different maturity in neuronal lineage cells. Our findings revealed that Cd altered the trajectory of maturation of neuronal lineage cells by decreasing the number of cells in different stages and hindering their maturation. Cd induced differential transcriptome expression in different cell subpopulations in a stage-specific manner. Specifically, Cd induced oxidative damage and changed the proportion of cell cycle phases in the early stage of neuronal development. Furthermore, the autocrine and paracrine signals of Wnt5a were downregulated in the low mature neurons in response to Cd. Importantly, activation of Wnt5a effectively rescued the number of neurons and promoted their maturation. Taken together, the findings of this study provide new and comprehensive insights into the adverse effect of Cd on neuronal maturation. [ABSTRACT FROM AUTHOR]

It has been well documented that Machiavellianism has a positive effect on break-up distress. However, there are few research explored the internal mechanism. In this study, we investigated the mediating role of self-concealment and the moderating role of gender. Machiavellianism Personality Scale, Self-Concealment Scale and Break-up Distress Scale was distributed through an online questionnaire platform. A sample of 869 undergraduate students was received, and their age ranged from 16 to 25 years old (M = 19.48, SD = 1.15). As we predicted, the relationship between Machiavellianism and break-up distress was partially mediated by self-concealment. The direct effect of Machiavellianism on break-up distress and the mediating effect of self-concealment were moderated by gender. Specifically, compared with boys, the effect of Machiavellianism on self-concealment was stronger for girls, while the effect of Machiavellianism on break-up distress was stronger for boys. These findings confirm how Machiavellianism affects break-up distress and provide new intervention ideas for solving the psychological crisis of college students after the dissolution of romantic relationships. [ABSTRACT FROM AUTHOR]

Disk-like domain receptor 1 (DDR1) is a crucial regulator of pro-inflammatory mediators and matrix-degrading enzymes. Although mounting evidence supports a vital role for DDR1 in the tumorigenesis of some cancers, no pan-cancer analysis of DDR1 has been reported. Therefore, we aimed to explore the prognostic value of DDR1 in 33 cancer types and investigate its potential immune function. We used a range of bioinformatics approaches to explore the potential carcinogenic role of DDR1 in multiple cancers. We found that DDR1 was expressed at high levels in most cancers. DDR1 expression was positively or negatively associated with prognosis in different cancers. DDR1 expression was significantly associated with DNA methylation in 8 cancers, while there was a correlation between DDR1 expression and RNA methylation-related genes and mismatch repair gene in most cancers. Furthermore, DDR1 expression was significantly associated with microsatellite instability in 6 cancers and tumor mutation burden in 11 cancers. In addition, DDR1 expression was also significantly correlated with immune cell infiltration, tumor microenvironment, immune-related genes, and drug resistance in various cancers. In conclusion, DDR1 can serve as a potential therapeutic target and prognostic marker for various malignancies due to its vital role in tumorigenesis and tumor immunity. [ABSTRACT FROM AUTHOR]

Polyketides are a class of natural products with astonishing structural diversities, fascinating biological activities, and a versatile of applications. In polyketides biosynthesis, acyltransferases (ATs) are the 'gatekeeping' enzymes selecting the specific CoA-activated acyl groups as building blocks and transferring them onto the phosphopantetheine arm of acyl carrier proteins (ACPs) to enable the following condensation reactions to assemble the polyketide chain. Herein, the Art2 protein from aurantinins, a group of the antibacterial polyketides, is characterized in vitro as an AT that can load a CoA-activated succinyl unit onto the first ACP domain of Art17 (ACPArt17-1). In addition, another two proteins, GbnB and EtnB, involved in the biosynthesis of gladiolin and etnangien respectively, were traced by literature mining, homologous searching, and product structure analysis and then identified as functional succinyl-CoA ATs by the ACPArt17-1 assays. Taken together, by the assay method employing ACPArt17-1 as an acyl acceptor, we identified three ATs that can introduce a succinyl unit into the polyketide assembly line, which enriches the toolbox of polyketide biosynthetic enzymes and sets a stage for incorporating a succinyl unit into polyketide backbones in synthetic biological manners. Key points: • Three acyltransferases that are able to load ACP with a succinyl unit were characterized in vitro. • ACPArt17-1 can be used as an acceptor to assay succinyl-CoA AT from different polyketides. • The succinyl unit can be incorporated into polyketides assembly process. [ABSTRACT FROM AUTHOR]

Collapsibility and structural are two of the typical characteristics of natural undisturbed loess. It is of great significance to effectively simulate the collapsibility and structural of natural loess by preparing artificially loess. However, the existing methods of artificially preparing collapsible loess are complex, and the collapsibility of the prepared samples is difficult to control. In this paper, the collapsibility mechanism of loess was re-analyzed, and on this basis, a new method for preparing artificial collapsible loess using remolded loess, industrial salt, CaO particles and gypsum powder was proposed. The basic principle is: the CaO particles have structural strength and would transfer to Ca(OH)2 after soaking, this progress can simulate the disappearance of loess structural strength; The dissolution of industrial salt can simulate the collapse of loess internal pores, the collapsibility of artificial loess can be adjusted by adjusting the percentage of industrial salt; the gypsum powder can simulate the cementation of loess as a bonding material. The shear test, consolidation test and collapsibility test of artificially prepared loess and undisturbed loess were carried out. The test results of artificial loess were compared with undisturbed loess. The results show that: the plastic limit and liquid limit of the artificially prepared loess is smaller than that of the undisturbed loess; The optimal moisture content and maximum dry density are close to that of the undisturbed loess; The collapsibility coefficient of artificial prepared samples increases first and then decreases with the increase of load level, and gradually increases with the increase of industrial salt particle content; The structural parameters of artificially prepared loess samples first increase and then decrease with the shear process, but the structural parameters of artificial prepared loess and undisturbed loess are different under different confining pressure conditions. [ABSTRACT FROM AUTHOR]

Fault-tolerant control (FTC) of a non-affine system with uncertainties is one of critical issues in nonlinear control. In this paper, in the presence of unknown actuator failures, an event-trigger-based FTC scheme is proposed for such a nonlinear system with predefined performance. For actuator failures, a compensation mechanism is designed to alleviate their impacts. By utilizing a predefined performance function, higher tracking accuracy can be obtained. Meanwhile, an event-triggered mechanism with a time-varying threshold, depending on tracking error, reduces the number of communications for a controller-to-actuator channel. An adaptive event-triggered function is then proposed with the compensation mechanism to improve the self-adjusting ability of the triggered function. Also, extended state observers and tracking differentiators are utilized to reconstruct unknown dynamics of the system and to simplify high-order derivation of virtual control laws, respectively. The stability of the closed-loop system is analyzed by input-to-state practically stability. Finally, two simulation results are supplied to verify the effectiveness of the proposed control method. [ABSTRACT FROM AUTHOR]

A geothermal energy pile is a revolutionary piling technique that combines a pile foundation with a ground source heat pump system that not only supports the structure but also provides heating and cooling for buildings and bridges. The thermo-mechanical behavior of long energy piles in soft clay has rarely been investigated, despite their increasing utilization. A long floating energy pile with a length-to-diameter ratio of 66.7 was evaluated on its own and monitored in service of the supported structure in the city of Kunshan, China. With vertical mechanical loads, the experiment involved alternate cooling and heating cycles, allowing for careful analysis and assessment of the pile's temperature, stress, and displacement. Temperature-induced stress, axial force, and friction resistance of the pile shaft, as well as the change in displacement of the energy pile throughout building, were all studied. The field observations revealed without any surprise that a longer energy pile outperformed a shorter one in terms of heating exchange capacity with a more homogenous temperature distribution along the pile. Following a quasi-linear relationship with the temperature variation, the thermo-induced additional axial force soared with the larger length-diameter ratio of the pile and may even reach four times that of the pile under pure mechanical loads. Important additional settlements were also observed especially in cooling conditions. The shaft frictions along the long bored energy pile were found to have a complicated distribution, which requires further investigations. [ABSTRACT FROM AUTHOR]

Senile plaques composed of β-amyloid protein (Aβ) and neurofibrillary tangles (NFTs) composed of intracellular hyper-phosphorylated tau are major causes of cognitive impairment and neuronal damage in Alzheimer disease (AD). Astragalin (AST), a naturally-occurring flavonoid compound, was reported to have neuroprotective effects in the brain, but its effects in AD remain unknown. Herein, the learning and memory deficits were alleviated and neuronal damage in the hippocampus were inhibited after the senescence-accelerated mouse prone 8 (SAMP8) mouse were given AST (5 mg/kg or 10 mg/kg) daily by gavage for 2 months. Furthermore, AST reduced Aβ1−40 and Aβ1−42 deposition, decreased β-carboxyl-terminal fragment (β-CTF) protein level and tau hyper-phosphorylation, but increased α-CTF protein level and glycogen synthase kinase-3beta (GSK-3β) phosphorylation in hippocampus of SAMP8 mice. Meanwhile, the effects of AST on AD were also explored in vitro by treating primary neurons with amyloid-β1–42 oligomers (Aβ1−42O). Consistently, AST also alleviated amyloid-β1–42 oligomers (Aβ1−42O)-induced neuronal damage, amyloid plaques, and tau phosphorylation in vitro model. Of note, estrogen receptor (ER)α and ERβ expression in the hippocampus of SAMP8 mice and Aβ1−42O-treated neurons was significantly decreased but their levels were increased by AST. Moreover, in vivo and in vitro experiments revealed that ER antagonist, Fulvestrant, reversed the effects caused by AST. Altogether, our investigation indicates that AST may ameliorate cognitive deficits and AD-type pathologies in SAMP8 mice and Aβ1−42O-treated neurons through upregulating ERα and ERβ expression. Our findings indicate the value of AST as a potential reagent for AD treatment. [ABSTRACT FROM AUTHOR]

Purpose: Wearable devices in the scenario of connected home healthcare integrated with artificial intelligence have been an effective alternative to the conventional medical devices. Despite various benefits of wearable electrocardiogram (ECG) device, several deficiencies remain unsolved such as noise problem caused by user mobility. Therefore, an insensitive and robust classification model for cardiac arrhythmias detection system needs to be devised. Methods: A one-dimensional seven-layer convolutional neural network (CNN) classification model with dedicated design of structure and parameters is developed to perform automatic feature extraction and classification based on large volume of original noisy signals. Record-based ten-fold cross validation scheme is devised for evaluation to ensure the independence of the training set and test set, and further improve the robustness of our method. Results: The model can effectively detect cardiac arrhythmias, and can reduce the computational workload to a certain extent. Our experimental results outperform most recent literature on the cardiac arrhythmias classification with diagnostic accuracy of 0.9874, sensitivity of 0.9811, and specificity of 0.9905 for original signals; diagnostic accuracy of 0.9876, sensitivity of 0.9813, and specificity of 0.9907 for de-noised signals, respectively. Conclusion: The evaluation indicates that our proposed approach, which performs well on both original signals and de-noised signals, fits well with wearable ECG monitoring and applications. [ABSTRACT FROM AUTHOR]

Objectives: To compare the background parenchymal enhancement (BPE) levels on contrast-enhanced cone-beam breast CT (CE-CBBCT) and MRI, evaluate inter-reader reliability, and analyze the relationship between clinical factors and BPE level on CE-CBBCT. Methods: In this retrospective study, patients who underwent both CE-CBBCT and MRI were analyzed. BPE levels on CE-CBBCT and MRI were assessed by five specialists independently in random fashion, with a wash-out period of 4 weeks. Weighted kappa was used to analyze the agreement between CE-CBBCT and MRI, and intraclass correlation coefficient (ICC) was used to evaluate the inter-reader reliability for each modality. The association between BPE level on CE-CBBCT and clinical factors was evaluated by univariate and multivariate logistic regression. Results: A total of 221 patients from January 2017 to April 2021 were enrolled. CE-CBBCT showed substantial agreement (weighted kappa = 0.690) with MRI for BPE evaluation, with good degree of inter-reader reliability on both CE-CBBCT (ICC = 0.712) and MRI (ICC = 0.757). Based on majority reports, BPE levels on CE-CBBCT were lower than MRI (p < 0.001). BPE level on CE-CBBCT was significantly associated with menstrual status (odds ratio, OR = 0.125), breast density (OR = 2.308), and previously treated breast cancer (OR = 0.052) (all p < 0.05). BPE level for premenopausal patients was associated with menstrual cycle, with lower BPE level for the 2nd week of menstrual cycle (OR = 0.246). Conclusions: CE-CBBCT showed substantial agreement and comparable inter-reader reliability with MRI for BPE evaluation, indicating that the corresponding BI-RADS lexicons could be used to describe BPE level on CE-CBBCT. The 2nd week of menstrual cycle timing is suggested as the optimal examination period for CE-CBBCT. Key Points: • CE-CBBCT showed substantial agreement and comparable inter-reader reliability with MRI for BPE evaluation. • Menstrual status, breast density, and previously treated breast cancer were associated with the BPE level on CE-CBBCT images. • The 2ndweek of the menstrual cycle is suggested as the optimal examination period for CE-CBBCT. [ABSTRACT FROM AUTHOR]

The human gut microbiome encodes a large variety of antimicrobial peptides (AMPs), but the short lengths of AMPs pose a challenge for computational prediction. Here we combined multiple natural language processing neural network models, including LSTM, Attention and BERT, to form a unified pipeline for candidate AMP identification from human gut microbiome data. Of 2,349 sequences identified as candidate AMPs, 216 were chemically synthesized, with 181 showing antimicrobial activity (a positive rate of >83%). Most of these peptides have less than 40% sequence homology to AMPs in the training set. Further characterization of the 11 most potent AMPs showed high efficacy against antibiotic-resistant, Gram-negative pathogens and demonstrated significant efficacy in lowering bacterial load by more than tenfold against a mouse model of bacterial lung infection. Our study showcases the potential of machine learning approaches for mining functional peptides from metagenome data and accelerating the discovery of promising AMP candidate molecules for in-depth investigations. Antimicrobial peptides are identified from metagenomics data using deep learning. [ABSTRACT FROM AUTHOR]

The development of synthetic methodologies towards enhanced performance in biomass conversion is desirable due to the growing energy demand. Here we design two types of Ru impregnated MIL-100-Cr defect engineered metal-organic frameworks (Ru@DEMOFs) by incorporating defective ligands (DLs), aiming at highly efficient catalysts for biomass hydrogenation. Our results show that Ru@DEMOFs simultaneously exhibit boosted recyclability, selectivity and activity with the turnover frequency being about 10 times higher than the reported values of polymer supported Ru towards D-glucose hydrogenation. This work provides in-depth insights into (i) the evolution of various defects in the cationic framework upon DLs incorporation and Ru impregnation, (ii) the special effect of each type of defects on the electron density of Ru nanoparticles and activation of reactants, and (iii) the respective role of defects, confined Ru particles and metal single active sites in the catalytic performance of Ru@DEMOFs for D-glucose selective hydrogenation as well as their synergistic catalytic mechanism. The catalytic performance of metal‒organic frameworks can be tuned by introducing defects in their structure. Here, the authors introduce defects and impregnate ruthenium nanoparticles in cationic metal-organic frameworks, which enables enhanced recyclability and catalytic performance in D-glucose hydrogenation. [ABSTRACT FROM AUTHOR]

The polysaccharides of Salvia miltiorrhiza (SMP) were prepared through water-extraction and alcohol-precipitation method optimized by employing the response surface methodology. Furthermore, the structural characteristics and activities of SMP as well as its three derivatives (SMP-S, SMP-Fe and SMP-Se) were analyzed. SMP was composed of galacturonic acid, glucose, galactose and arabinose and the molecular weights were 3.79 × 106 Da, 3.17 × 104 Da and 693.68 Da. The sulfur content of SMP-S was 13.53%, the iron content of SMP-Fe was 26.12% and the content of selenium in SMP-Se was 0.984 mg/g. Their surface morphology, meso-structure and thermal stability were determined by scanning electron microscope, transmission electron microscope and thermogravimetric analyzer, respectively. Further, the antioxidant and immunomodulatory activities of SMPs were studied. The study found that three modified polysaccharides not only exhibited higher antioxidant activity, but also higher immunomodulatory activity compared to SMP. This lays a theoretical foundation for the development of Salvia miltiorrhiza polysaccharide-related foods. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Dedicated breast CT: state of the art" which appeared in the 03 September 2021 issue.

Dedicated breast CT is being increasingly used for breast imaging. This technique provides images with no compression, removal of tissue overlap, rapid acquisition, and available simultaneous assessment of microcalcifications and contrast enhancement. In this second installment in a 2-part review, the current status of clinical applications and ongoing efforts to develop new imaging systems are discussed, with particular emphasis on how to achieve optimized practice including lesion detection and characterization, response to therapy monitoring, density assessment, intervention, and implant evaluation. The potential for future screening with breast CT is also addressed. Key Points: • Dedicated breast CT is an emerging modality with enormous potential in the future of breast imaging by addressing numerous clinical needs from diagnosis to treatment. • Breast CT shows either noninferiority or superiority with mammography and numerical comparability to MRI after contrast administration in diagnostic statistics, demonstrates excellent performance in lesion characterization, density assessment, and intervention, and exhibits promise in implant evaluation, while potential application to breast cancer screening is still controversial. • New imaging modalities such as phase-contrast breast CT, spectral breast CT, and hybrid imaging are in the progress of R & D. [ABSTRACT FROM AUTHOR]

In this paper, a new model of undisturbed loess was presented based on the modified Cam-clay model with the structural and anisotropic parameters. The associated flow rule, combined with the consistency condition, was used to derive the incremental stress-strain relationship and establish a new model. The new model has a total of eight parameters, which can be obtained through routine labor tests. A triaxial test was conducted by selecting natural undisturbed loess. A comparison between the experimental results and calculated results shows that the new model is better than the modified Cam-clay model in simulating the stress-strain characteristics of natural undisturbed loess. [ABSTRACT FROM AUTHOR]

Dedicated breast CT is an emerging 3D isotropic imaging technology for breast, which overcomes the limitations of 2D compression mammography and limited angle tomosynthesis while providing some of the advantages of magnetic resonance imaging. This first installment in a 2-part review describes the evolution of dedicated breast CT beginning with a historical perspective and progressing to the present day. Moreover, it provides an overview of state-of-the-art technology. Particular emphasis is placed on technical limitations in scan protocol, radiation dose, breast coverage, patient comfort, and image artifact. Proposed methods of how to address these technical challenges are also discussed. Key Points: • Advantages of breast CT include no tissue overlap, improved patient comfort, rapid acquisition, and concurrent assessment of microcalcifications and contrast enhancement. • Current clinical and prototype dedicated breast CT systems differ in acquisition modes, imaging techniques, and detector types. • There are still details to be decided regarding breast CT techniques, such as scan protocol, radiation dose, breast coverage, patient comfort, and image artifact. [ABSTRACT FROM AUTHOR]

Background: Botulinum toxin (BoNT) injection is the most commonly performed procedure in cosmetic surgery. However, blind injection is unable to take individual anatomical variations into consideration, which is the main contributing factor to complications. Ultrasound (US) imaging was introduced to reduce complications and improve effects. This article will review uses of US in aesthetic BoNT injection. Method: A systematic electronic search was performed using the PubMed, MEDLINE, Web of science. Search terms were set to focus on aesthetic BoNT injection. Two independent reviewers subsequently reviewed the resultant articles based on strict inclusion and exclusion criteria. Selected manuscripts were analysed and grouped by procedure categories. Clinical cases were all performed by one plastic surgeon in our department. Results: The search finally retained 24 articles. Five procedural categories were identified, including masseter (n = 16), frontalis (n = 2), glabella complex (n = 2), trapezius (n=1), and gastrocnemius (n = 3). US imaging is practical and instructive for pre-operative assessments as in needle-type selection, injection point localization and depth setting, as well as post-operative follow-ups regarding injection feedback (for instance, the extent of muscle volume decreases). What's more, ultrasound-guided injection makes needle trajectory visualized so as for the needle to reach the target muscle in avoidance of potential damage to neurovascular bundle, gland or adjacent muscle. Conclusion: Muscles, such as masseter, frontalis, glabella complex, trapezius and gastrocnemius, and their adjacent structures can be well visualized using US, and as such, US can be a useful tool for a variety of pre-operative, intra-operative and post-operative procedures. Level of Evidence IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

At the early stage of public health emergencies, when the conventional medical reserves prepared are insufficient, and productivity could temporarily not meet the surge in demand, donations can be used to cover excess demand for medical supplies to a large extent. This paper explicitly considers the allocation problem of limited medical reserves during a public health emergency, incorporating uncertainty in demand and donated supplies and the priorities of health care centers. The problem is formulated as a two-stage stochastic program that regards the donated supplies as an efficient recourse action, aiming to minimize the total losses. The optimal allocation strategy of limited medical reserves and donations is obtained by solving the model using Gurobi solver. Finally, the effectiveness of the proposed approach is verified by a series of computational results, which show that the solutions of our method not only benefit the emergency demand fulfill rate but reduce the total losses as well. [ABSTRACT FROM AUTHOR]

Nanowires require surface passivation due to their inherent large surface to volume ratio. We investigate the effect of embedding InP nanowires in different oxides with respect to surface passivation by use of electron beam induced current measurements enabled by a nanoprobe based system inside a scanning electron microscope. The measurements reveal remote doping due to fixed charge carriers in the passivating POx/Al2O3 shell in contrast to results using SiOx. We used time-resolved photoluminescence to characterize the lifetime of charge carriers to evaluate the success of surface passivation. In addition, spatially resolved internal quantum efficiency simulations support and correlate the two applied techniques. We find that atomic-layer deposited POx/Al2O3 has the potential to passivate the surface of InP nanowires, but at the cost of inducing a field-effect on the nanowires, altering their electrostatic potential profile. The results show the importance of using complementary techniques to correctly evaluate and interpret processing related effects for optimization of nanowire-based optoelectronic devices. [ABSTRACT FROM AUTHOR]

To study the abnormal precursory information of rock before failure, uniaxial compression tests were carried out on sandstone specimens; meanwhile, the infrared thermal camera was utilized to monitor the infrared radiation temperature (IRT) variation of the specimen surface synchronously during failure process. The test results show that with the increases of strain, the average infrared radiation temperature (AIRT) decreased gradually; when strain raises to a certain degree, the AIRT increased abruptly; thereafter, the AIRT decreased gradually with increasing strain. Therefore, the mutation point of AIRT can be regarded as the abnormal precursory information of sandstone before failure. Through analysis, the average stress at the abnormal point was 79.93% of the uniaxial compression strength of the sandstone specimens tested in this paper, and the average strain at this point was 0.9%. In addition, due to the end effect, the IRT field distribution of the sandstone specimen surface presented a decreasing tendency from top to bottom at the initial loading stage. As strain increases, the IRT field distribution tended to be high in middle and low in two ends. Closing to failure, a Y-shaped high-temperature band caused by the shear failure of the specimen appeared in the infrared thermal image. After comparison, the position of the Y-sharped high-temperature band is basically corresponding to the actually failure position of the specimen. With the increases of strain, the IRT distribution ranges decreased and the IRT frequency distribution histogram form gradually approached to the normal distribution. [ABSTRACT FROM AUTHOR]

Bilateral deep foundation pit excavation would cause the stress redistribution and large deformation of the adjacent tunnel, and even induce the lining structure cracking. This paper aims to investigate the deformation and stress response of tunnel to bilateral foundation pit construction. The Zhengzhou East High-speed Railway Station (Zhengzhou East HRS) was taken as an example to conduct the analysis. First, the numerical calculation software Midas GTS/NX was used to simulate the foundation pit construction progress, the deformation and stress of tunnel structure were discussed. Then, some field work about tunnel deformation was conducted and the deformation characteristics was studied. The results show that under the repeated disturbance of the bilateral foundation pit construction, the tunnel deformation increased fluctuatingly, with the cumulative uplift and convergent deformation of about 26 mm and 16 mm, respectively. In addition, the cumulative change of the lining stress at DM16 section inside the foundation pit was 6.02% greater than that at DM30 section outside of the foundation pit, indicating the effectiveness of the reinforcement measures. [ABSTRACT FROM AUTHOR]

Aurantinins (ARTs) are antibacterial polyketides featuring a unique 6/7/8/5-fused tetracyclic ring system and a triene side chain with a carboxyl terminus. Here we identify the art gene cluster and dissect ART's C-methyl incorporation patterns to study its biosynthesis. During this process, an apparently redundant methyltransferase Art28 was characterized as a malonyl-acyl carrier protein O-methyltransferase, which represents an unusual on-line methyl esterification initiation strategy for polyketide biosynthesis. The methyl ester bond introduced by Art28 is kept until the last step of ART biosynthesis, in which it is hydrolyzed by Art9 to convert inactive ART 9B to active ART B. The cryptic reactions catalyzed by Art28 and Art9 represent a protecting group biosynthetic logic to render the ART carboxyl terminus inert to unwanted side reactions and to protect producing organisms from toxic ART intermediates. Further analyses revealed a wide distribution of this initiation strategy for polyketide biosynthesis in various bacteria. Aurantinins are polyketides with unusual connectivities and broad antibacterial activity. Here the authors show the biosynthesis of aurantinins, which proceeds via an on-line methyl esterification at the terminus that enables the iterative chain elongations prior to condensation and cyclization. [ABSTRACT FROM AUTHOR]

In the pursuit of heterogeneous catalysts with high reactivity, metal organic framework (MOF) nanomaterials have received tremendous attentions. However, many MOF catalysts especially Fe-based MOFs need to be utilized immediately after synthesis or being activated using high temperature, because of the easy loss of reactivity in humid environments resulting from the occupation of active Fe sites by water molecules. Here, we describe an inspiring strategy of growing MIL-101-Fe nanoparticles inside the three-dimensional confined space of graphene aerogel (GA), generating shapeable GA/MIL-101-Fe nanocomposite convenient for practical use. Compared to MIL-101-Fe, GA/MIL-101-Fe as catalyst demonstrates much higher reactivity in Fenton-like reaction, attributing to smaller MIL-101-Fe particle size, presence of active Fe(II) sites, and abundant defects in GA. Strikingly, the weakly hydrophobic nature of the composite greatly inhibits the loss of catalytic reactivity after being stored in humid air and accelerates the recovery of reactivity in mild temperature, by resisting the entrance of water molecules and helping to exclude water molecules. This work demonstrates that a delicate design of nanocomposite structure could not only improve the reactivity of the catalytic component, but also overcome its intrinsic drawback by taking advantage of the properties of host. We hope this functional nanoconfinement strategy could be extended to more scenarios in other fields. [ABSTRACT FROM AUTHOR]

Though Pb(II) adsorption onto HA has been extensively studied, its kinetic and thermodynamic features are not fully understood. This work investigated the kinetic processes and isotherms of Pb(II) adsorption onto a humic acid (HA) derived from leonardite in an aqueous solution. The basic properties of the HA were determined by standard methods, and Fourier transform infrared spectroscopic (FTIR) technique. Adsorption kinetic experiments were conducted at 120 mg Pb/L at 288, 298, 308, and 318 K. The adsorption data were best fitted into the pseudo-second-order model, suggesting the chemisorption nature of Pb(II) adsorption. Batch adsorption experiments were conducted at 0–200 mg Pb/L, and the data fit the Freundlich and Temkin models well. Pb(II) adsorption onto HA initially increased, then decreased, with rising temperature. Thermodynamic parameters showed that Pb(II) adsorption was exothermic and spontaneous. Though Cu(II), Zn(II), or Cd(II) could compete with Pb(II) for adsorption, the low cost and high adsorption capacity of leonardite-derived HA determined that it was an excellent adsorbent to remove Pb(II) from an aqueous solution. The optimized experimental conditions derived from the central composite design (CCD) were 20 mg HA, pH 5.0, 4-h react time, and 80 mg Pb/L. [ABSTRACT FROM AUTHOR]

Cohen syndrome (CS) is an autosomal recessive congenital disorder characterized by mutation in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. In the current study, a Chinese family has two young sibling cases having a developmental delay, physical obesity, high myopia, and a special face, which suspected to be CS. The purpose of the study was to identify variants and further analyze their pathogenicity for CS. Next-generation sequencing (NGS) revealed a compound heterozygous mutation in VPS13B gene in the proband, which comprises a frameshift mutation in NM_017890.4: c.10076_10077delCA (p.T3359fs*29) and a putative splice site mutation in c.6940 + 1G > T. Both Minigene assay in vitro and splicing assay in vivo confirmed that the splicing mutation in c.6940 + 1G > T generates a frameshift transcript with whole exon 38 skipping. Eventually, quantitative real-time PCR demonstrated that either of the two mutations can lead to degradation of the VPS13B gene at the transcriptional level. Functional studies of variants identified in CS patients are essential for their subsequent genetic counseling and prenatal diagnoses and could also be the start point for new therapeutic approaches, currently based only on symptomatic treatment. [ABSTRACT FROM AUTHOR]

Yarrowia lipolytica strain is a promising cell factory for the conversion of lignocellulose to biofuels and bioproducts. Despite the inherent robustness of this strain, further improvements to lignocellulose-derived inhibitors toxicity tolerance of Y. lipolytica are also required to achieve industrial application. Here, adaptive laboratory evolution was employed with increasing concentrations of ferulic acid. The adaptive laboratory evolution experiments led to evolve Y. lipolytica strain yl-XYL + *FA*4 with increased tolerance to ferulic acid as compared to the parental strain. Specifically, the evolved strain could tolerate 1.5 g/L ferulic acid, whereas 0.5 g/L ferulic acid could cause about 90% lethality of the parental strain. Transcriptome analysis of the evolved strain revealed several targets underlying toxicity tolerance enhancements. YALI0_E25201g, YALI0_F05984g, YALI0_B18854g, and YALI0_F16731g were among the highest upregulated genes, and the beneficial contributions of these genes were verified via reverse engineering. Recombinant strains with overexpressing each of these four genes obtained enhanced tolerance to ferulic acid as compared to the control strain. Fortunately, recombinant strains with overexpression of YALI0_E25201g, YALI0_B18854g, and YALI0_F16731g individually also obtained enhanced tolerance to vanillic acid. Overall, this work demonstrated a whole strain improvement cycle by "non-rational" metabolic engineering and presented new targets to modify Y. lipolytica for microbial lignocellulose valorization. Key points: • Adaptive evolution improved the ferulic acid tolerance of Yarrowia lipolytica • Transcriptome sequence was applied to analyze the ferulic acid tolerate strain • Three genes were demonstrated for both ferulic acid and vanillic acid tolerance [ABSTRACT FROM AUTHOR]

Karst geology is widely distributed in China; the great differences in natural conditions bring it an array of characteristics in different regions. There is a huge area of the buried karst in Wuhan, exhibiting a unique, but complicated engineering geological environment. This paper summarizes the geological conditions in Wuhan, with special focus on its karst geology. At present, a total of six karst belts have been detected, and they were divided into five structure types. For shield tunnelling in karst region, some problems such as water ingress or mud inrush, partial ground collapse, damage or failure of shield machine, and metro operation and management issues may be raised as a result of the activity of the karst geology. To prevent occurrence of possible hazards, a series of countermeasures suggested for hazard and risk mitigation were discussed in this paper. A case history, where the study section belongs to the Wuhan metro line 6, is referred to evaluate effectiveness of the adopted treatment measures. The feedbacks demonstrated that water ingress was successfully avoided, and ground deformation was effectively controlled in the study section throughout the construction phase. This study can provide significant reference information and experience for metro tunnel constructed in karst region. [ABSTRACT FROM AUTHOR]

Background and aim: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide, but its pathogenesis remains imprecisely understood and requires further clarification. Recently, the tumor suppressor p53 has received growing attention for its role in metabolic diseases. In this study, we performed in vivo and in vitro experiments to identify the contribution of p53–autophagy regulation to NAFLD. Methods: Livers from wild-type and p53 knockout mice as well as p53-functional HepG2 cells and p53-dysfunctional Huh7 cells were examined for autophagy status and HMGB1 translocation. In vivo and in vitro NAFLD models were established, and steatosis was detected. In the cell models, autophagy status and steatosis were examined by p53 and/or HMGB1 silencing. Results: First, the silencing of p53 could induce autophagy both in vivo and in vitro. In addition, p53 knockout attenuated high-fat diet-induced NAFLD in mice. Similarly, knockdown of p53 could alleviate palmitate-induced lipid accumulation in cell models. Furthermore, high mobility group box 1 (HMGB1) was proven to contribute to the effect of silencing p53 on alleviating NAFLD in vitro as an autophagy regulator. Conclusion: The anti-NAFLD effect of functional p53 silencing is associated with the HMGB1-mediated induction of autophagy. [ABSTRACT FROM AUTHOR]

The distribution and appearance of nuclei are essential markers for the diagnosis and study of cancer. Despite the importance of nuclear morphology, there is a lack of large scale, accurate, publicly accessible nucleus segmentation data. To address this, we developed an analysis pipeline that segments nuclei in whole slide tissue images from multiple cancer types with a quality control process. We have generated nucleus segmentation results in 5,060 Whole Slide Tissue images from 10 cancer types in The Cancer Genome Atlas. One key component of our work is that we carried out a multi-level quality control process (WSI-level and image patch-level), to evaluate the quality of our segmentation results. The image patch-level quality control used manual segmentation ground truth data from 1,356 sampled image patches. The datasets we publish in this work consist of roughly 5 billion quality controlled nuclei from more than 5,060 TCGA WSIs from 10 different TCGA cancer types and 1,356 manually segmented TCGA image patches from the same 10 cancer types plus additional 4 cancer types. Measurement(s) nucleus • segmented nucleus Technology Type(s) unsupervised machine learning • hematoxylin and eosin stain Factor Type(s) cancer type Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12377135 [ABSTRACT FROM AUTHOR]