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Wilson disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive disorder characterized by disorganized copper metabolism caused by mutations in the ATP7B gene. Currently, the main treatment options for WD involve medications such as d-penicillamine, trientine hydrochloride, zinc acetate, and liver transplantation. However, there are challenges that encompass issues of poor compliance, adverse effects, and limited availability of liver sources that persist. Stem cell therapy for WD is currently a promising area of research. Due to the advancement in stem cell directed differentiation technology in vitro and the availability of sufficient stem cell donors, it is expected to be a potential treatment option for the permanent correction of abnormal copper metabolism. This article discusses the research progress of stem cell therapy for WD from various sources, as well as the challenges and future prospects of the clinical application of stem cell therapy for WD.

Abstract Cell therapy has emerged as a viable approach for treating damaged organs or tissues, particularly with advancements in stem cell research and regenerative medicine. The innovative technique of cell sheet engineering offers the potential to create a cell-dense lamellar structure that preserves the extracellular matrix (ECM) secreted by cells, along with the cell-matrix and intercellular junctions formed during in vitro cultivation. In recent years, significant progress has been made in developing cell sheet engineering technology. A variety of novel materials and methods were utilized for enzyme-free cell detachment during the cell sheet formation process. The complexity of cell sheet structures increased to meet advanced usage demands. This review aims to provide an overview of the preparation methods and types of cell sheets, thereby enhancing the understanding of this rapidly evolving technology and offering a fresh perspective on the development and future application of cell sheet engineering. Graphical Abstract

Abstract The time-dependent effects in steel-concrete composite beam bridges can intensify track irregularities, subsequently leading to amplified train-bridge coupling vibrations. This phenomenon may increase the stress amplitudes in the bridge steel, thereby impacting the fatigue performance of the composite structures. This paper employs multiple rigid body dynamics to construct a high-speed train model and utilizes the finite element method to develop a steel-concrete composite beam element model that accounts for time-dependent effects, interfacial slip, and shear hysteresis. This approach enables the computational analysis of the train-bridge coupling system, facilitating an investigation into the influence of concrete’s time-dependent effects on the fatigue performance of railway steel-concrete composite bridges. Focusing on a 40-m simply supported composite bridge, the train-bridge coupling dynamic responses were computed for each operational year within a decade of the completion of construction. Applying the P-M linear fatigue damage accumulation theory, statistical analysis of stress history data across various operational periods was conducted to quantify the fatigue damage induced by a single eight-car high-speed train on the lower flange of the mid-span steel beam and the beam-end studs. The findings reveal that the beam-end studs sustain greater damage than the mid-span steel beam. Moreover, the detrimental impact of time-dependent effects diminishes with the increase of operational years. Notably, compared to the initial year, the fatigue damage to the lower flange of the mid-span steel beam by an eight-car train in the tenth year has surged by 39.3%. Conversely, the damage to the beam-end studs has decreased by 47.5%.

The steel–concrete composite beam, as a structural form that combines the advantages of steel and concrete, has been applied in railway engineering. However, with the increase in railway operation time, the degradation pattern of the service performance of steel–concrete composite bridges remains unclear. This paper proposes a method for calculating the long-term service performance of railway steel–concrete composite beams, considering the cumulative fatigue damage of steel beams and studs, based on the vehicle–bridge coupling theory and Miner’s linear cumulative damage criterion. The proposed method is validated using measured data from an in-service steel–concrete composite railway bridge with spans of 40 + 50 + 40 m. The calculated mid-span vertical displacement and the first two natural frequencies of the composite beam deviated from the measured results by only 2.1%, 7.7%, and 9.5%, respectively. The research results can provide a basis for extending the service life of composite beams and preventing the occurrence of safety accidents.

This study investigates the probabilistic seismic damage characteristics of a five-span RC simply supported girder bridge with double-column piers designed for a high-speed railway (HSR). The objective is to assess the bridge’s fragility by developing a refined nonlinear numerical model using the OpenSEES (Version 3.3.0) platform. Incremental dynamic analysis (IDA) was conducted with peak ground accelerations (PGA) ranging from 0.05 g to 0.5 g, and fragility curves for pier columns, tie beams, and bearings were developed. Additionally, a series–parallel relationship and a hierarchically iterated pair copula model were established to evaluate system fragility. The results indicate that as PGA increases, the damage probability of all bridge components rises, with bearings being the most vulnerable, followed by pier columns, and tie beams exhibiting the least damage. The models accurately simulate the correlations between members and system fragility, offering valuable insights into the bridge’s performance under seismic conditions.

Abstract Food digestion requires the cooperation of different digestive organs. The differentiation of digestive organs is crucial for larvae to start feeding. Therefore, during digestive organogenesis, cell identity and the tissue morphogenesis must be tightly coordinated but how this is accomplished is poorly understood. Here, we demonstrate that WD repeat domain 5 (Wdr5)-mediated H3K4 tri-methylation (H3K4me3) coordinately regulates cell differentiation, proliferation and apoptosis in zebrafish organogenesis of three major digestive organs including intestine, liver, and exocrine pancreas. During zebrafish digestive organogenesis, some of cells in these organ primordia usually undergo differentiation without apoptotic activity and gradually reduce their proliferation capacity. In contrast, cells in the three digestive organs of wdr5 −/− mutant embryos retain progenitor-like status with high proliferation rates, and undergo apoptosis. Wdr5 is a core member of COMPASS complex to implement H3K4me3 and its expression is enriched in digestive organs from 2 days post-fertilization (dpf). Further analysis reveals that lack of differentiation gene expression is due to significant decreases of H3K4me3 around the transcriptional start sites of these genes; this histone modification also reduces the proliferation capacity in differentiated cells by increasing the expression of apc to promote the degradation of β-Catenin; in addition, H3K4me3 promotes the expression of anti-apoptotic genes such as xiap-like, which modulates p53 activity to guarantee differentiated cell survival. Thus, our findings have discovered a common molecular mechanism for cell fate determination in different digestive organs during organogenesis, and also provided insights to understand mechanistic basis of human diseases in these digestive organs.

For managers of road infrastructure, culvert deterioration is a major concern since culvert failures can cause serious risks to the traveling public. The efficiency of the cost- and labor-intensive culvert inspection and maintenance process can be improved by properly identifying the key impact factors on culvert condition deterioration. Although the use of machine learning (ML) techniques to predict culvert conditions has been proven to be a promising tool for enhancing culvert management and enabling proactive scheduling of maintenance tasks, the information provided by the developed ML models has been given little attention for further use and analysis. By utilizing the predictor importance results of an evaluated decision tree (DT) culvert condition prediction model and the Mann–Whitney U test, this study provided insights to the identification of the key variables influencing culvert deterioration. According to the findings, five impact factors, including culvert span, pH, age, rise, and cover height, often have significant impact on the condition ratings of culverts made of various materials. In addition, such a statistical test-assisted factor identification process offered a way of identifying and enhancing the input variable selection for predictive ML model development.

Summary: As the principal effector cell population of the innate immune system, natural killer (NK) cells may make critical contributions to natural, immune-mediated control of HIV-1 replication. Using genome-wide assessments of activating and inhibitory chromatin features, we demonstrate here that cytotoxic NK (cNK) cells from elite controllers (ECs) display elevated activating histone modifications at the interleukin 2 (IL-2)/IL-15 receptor β chain and the BCL2 gene loci. These histone changes translate into increased responsiveness of cNK cells to paracrine IL-15 secretion, which coincides with higher levels of IL-15 transcription by myeloid dendritic cells in ECs. The distinct immune crosstalk between these innate immune cell populations results in improved IL-15-dependent cNK cell survival and cytotoxicity, paired with a metabolic profile biased toward IL-15-mediated glycolytic activities. Together, these results suggest that cNK cells from ECs display a programmed IL-15 response signature and support the emerging role of innate immune pathways in natural, drug-free control of HIV-1.

Background: The persistence of HIV-1-infected cells during antiretroviral therapy is well documented but may be modulated by early initiation of antiretroviral therapy in infants. Methods: Here, we longitudinally analyzed the proviral landscape in nine infants with vertical HIV-1 infection from Mozambique over a median period of 24 months, using single-genome, near full-length, next-generation proviral sequencing. Results: We observed a rapid decline in the frequency of intact proviruses, leading to a disproportional under-representation of intact HIV-1 sequences within the total number of HIV-1 DNA sequences after 12-24 months of therapy. In addition, proviral integration site profiling in one infant demonstrated clonal expansion of infected cells harboring intact proviruses and indicated that viral rebound was associated with an integration site profile dominated by intact proviruses integrated into genic and accessible chromatin locations. Conclusion: Together, these results permit rare insight into the evolution of the HIV-1 reservoir in infants infected with HIV-1 and suggest that the rapid decline of intact proviruses, relative to defective proviruses, may be attributed to a higher vulnerability of genome-intact proviruses to antiviral immunity. Technologies to analyze combinations of intact proviral sequences and corresponding integration sites permit a high-resolution analysis of HIV-1 reservoir cells after early antiretroviral treatment initiation in infants.

Obesity affects the function of multiple organs/tissues including the exocrine organ salivary glands. However, the effects of obesity on transcriptomes and cell compositions in the salivary glands have yet been studied by bulk RNA-sequencing and single-cell RNA-sequencing. Besides, the cell types in the sublingual gland, one of the three major salivary glands, have yet been characterized by the approach of single-cell RNA-sequencing. In this report, we find that the histological structure of the three major salivary glands are not obviously affected in the obese mice. Bulk RNA-sequencing analysis shows that the most prominent changes observed in the three major salivary glands of the obese mice are the mobilization of transcriptomes related to the immune response and down-regulation of genes related to the secretory function of the salivary glands. Based on single-cell RNA-sequencing analysis, we identify and annotate 17 cell clusters in the sublingual gland for the first time, and find that obesity alters the relative compositions of immune cells and secretory cells in the major glands of obese mice. Integrative analysis of the bulk RNA-sequencing and single-cell RNA-sequencing data confirms the activation of immune response genes and compromise of secretory function in the three major salivary glands of obese mice. Consequently, the secretion of extracellular matrix proteins is significantly reduced in the three major salivary glands of obese mice. These results provide new molecular insights into understanding the effect of obesity on salivary glands.

HIV-1 reservoir cells that circulate in peripheral blood during suppressive antiretroviral therapy (ART) have been well characterized, but little is known about the dissemination of HIV-1-infected cells across multiple anatomical tissues, especially the CNS. Here, we performed single-genome, near full-length HIV-1 next-generation sequencing to evaluate the proviral landscape in distinct anatomical compartments, including multiple CNS tissues, from 3 ART-treated participants at autopsy. While lymph nodes and, to a lesser extent, gastrointestinal and genitourinary tissues represented tissue hotspots for the persistence of intact proviruses, we also observed intact proviruses in CNS tissue sections, particularly in the basal ganglia. Multi-compartment dissemination of clonal intact and defective proviral sequences occurred across multiple anatomical tissues, including the CNS, and evidence for the clonal proliferation of HIV-1-infected cells was found in the basal ganglia, in the frontal lobe, in the thalamus and in periventricular white matter. Deep analysis of HIV-1 reservoirs in distinct tissues will be informative for advancing HIV-1 cure strategies.

Referência do artigo comentado: Yang, Yue; Zhang, Ensi. Cultural thought and philosophical elements of singing and dancing in Indian films. Trans/Form/Ação: Unesp Journal of Philosophy, v. 46, n. 4”, p. 315-328, 2023.

Primary liver cancer is one of the most common malignant tumors in China. The vast majority of primary liver cancer are hepatocellular carcinoma. Due to its high incidence and mortality from HCC, HCC has always been a feared type of cancer. Liver transplantation, as one of the important means to treat advanced liver cancer, has brought new hope to patients. However, as patients have been in a state of immunosuppression after liver transplantation, these patients face new problems of HCC recurrence and metastasis. A increasing number of studies have proved that blocking the PD-1/PD-L1 signaling pathway and restoring the immune killing inhibition of T cells can produce better therapeutic effects on tumors and chronic infectious diseases. As a promising treatment in the field of tumor immunotherapy, PD-1/PD-L1 inhibitors have achieved important results in liver cancer patients, but their application in liver transplantation patients is still highly controversial. This paper will introduce the mechanism of action of PD-1/PD-L1 signaling pathway and the current basic and clinical studies of PD-1/PD-L1 signaling pathway associated with immune response in HCC transplantation.

Summary: Copper is an essential component in the mitochondrial respiratory chain complex IV (cytochrome c oxidases). However, whether any nucleolar factor(s) is(are) involved in regulating the mitochondrial copper homeostasis remains unclear. The nucleolar localized Def-Capn3 protein degradation pathway cleaves target proteins, including p53, in both zebrafish and human nucleoli. Here, we report that hepatic depletion of mDEF in mice causes an excessive copper accumulation in the mitochondria. We find that mDEF-depleted hepatocytes show an exclusion of CAPN3 from the nucleoli and accumulate p53 and NRF1 proteins in the nucleoli. Furthermore, we find that NRF1 is a CAPN3 substrate. Elevated p53 and NRF1 enhances the expression of Sco2 and Cox genes, respectively, to allow more copper acquirement in the mDefloxp/loxp, Alb:Cre mitochondria. Our findings reveal that the mDEF-CAPN3 pathway serves as a novel mechanism for regulating the mitochondrial copper homeostasis through targeting its substrates p53 and NRF1.

This paper presents an experimental study on the box girder of a low-tower cable-stayed railway bridge with a W-shaped section that consists of prestressed concrete diagonal braces. A 1:6 scale test model was designed and constructed for the experiment. The mechanical behavior of the test model was investigated under two loading conditions: a double-track train symmetrical load and a single-track train unsymmetrical load. The experimental results were validated against a finite element model. Furthermore, the torsional performance of the box girder section was analyzed and discussed.

Timely and effective pest detection is essential for agricultural production, facing challenges such as complex backgrounds and a vast number of parameters. Seeking solutions has become a pressing matter. This paper, based on the YOLOv5 algorithm, developed the PestLite model. The model surpasses previous spatial pooling methods with our uniquely designed Multi-Level Spatial Pyramid Pooling (MTSPPF). Using a lightweight unit, it integrates convolution, normalization, and activation operations. It excels in capturing multi-scale features, ensuring rich extraction of key information at various scales. Notably, MTSPPF not only enhances detection accuracy but also reduces the parameter size, making it ideal for lightweight pest detection models. Additionally, we introduced the Involution and Efficient Channel Attention (ECA) attention mechanisms to enhance contextual understanding. We also replaced traditional upsampling with Content-Aware ReAssembly of FEatures (CARAFE), which enable the model to achieve higher mean average precision in detection. Testing on a pest dataset showed improved accuracy while reducing parameter size. The mAP50 increased from 87.9% to 90.7%, and the parameter count decreased from 7.03 M to 6.09 M. We further validated the PestLite model using the IP102 dataset, and on the other hand, we conducted comparisons with mainstream models. Furthermore, we visualized the detection targets. The results indicate that the PestLite model provides an effective solution for real-time target detection in agricultural pests.

Due to its widespread occurrence and high mortality rate, hepatocellular carcinoma (HCC) is an abhorrent kind of cancer. Immunotherapy is a hot spot in the field of cancer treatment, represented by immune checkpoint inhibitors (ICIs), which aim to improve the immune system’s ability to recognize, target and eliminate cancer cells. The composition of the HCC immune microenvironment is the result of the interaction of immunosuppressive cells, immune effector cells, cytokine environment, and tumor cell intrinsic signaling pathway, and immunotherapy with strong anti-tumor immunity has received more and more research attention due to the limited responsiveness of HCC to ICI monotherapy. There is evidence of an organic combination of radiotherapy, chemotherapy, anti-angiogenic agents and ICI catering to the unmet medical needs of HCC. Moreover, immunotherapies such as adoptive cellular therapy (ACT), cancer vaccines and cytokines also show encouraging efficacy. It can significantly improve the ability of the immune system to eradicate tumor cells. This article reviews the role of immunotherapy in HCC, hoping to improve the effect of immunotherapy and develop personalized treatment regimens.

Abstract Colorectal carcinoma (CRC) is one of the most prevalent malignant tumors worldwide. Meanwhile, the majority of CRC related deaths results from liver metastasis. Gene expression profile of CRC patients with liver Metastasis was identified using 4 datasets. The data was analyzed using GEO2R tool. GO and KEGG pathway analysis were performed. PPI network of the DEGs between 1 and 2 gene sets was also constructed. The set 1 is named between primary CRC tissues and metastatic CRC tissues. The set 2 is named between primary CRC tissues and normal tissues. Finally, the prognostic value of hub genes was also analyzed. 35 DEGs (set 1) and 142 DEGs (set 2) were identified between CRC liver metastatic cancer patients. The PPI network was constructed using the top 10 set 1 hub genes which included AHSG, SERPINC1, FGA, F2, CP, ITIH2, APOA2, HPX, PLG, HRG and set 2 hub genes which included TIMP1, CXCL1, COL1A2, MMP1, AURKA, UBE2C, CXCL12, TOP2A, ALDH1A1 and PRKACB. Therefore, ITIH2 might represent the potential core gene for colon cancer liver metastasis. COL1A2 behaves as a key gene in colorectal carcinoma.

IntroductionSpontaneous control of HIV-1 replication in the absence of anti-retroviral therapy (ART) naturally occurs in a small proportion of HIV-1-infected individuals known as elite controllers (EC), likely as a result of improved innate and adaptive immune mechanisms. Previous studies suggest that enhanced cytosolic immune recognition of HIV-1 reverse transcripts in conventional dendritic cells (mDC) from EC enables effective induction of antiviral effector T cell responses. However, the specific molecular circuits responsible for such improved innate recognition of HIV-1 in mDC from these individuals remain unknown.Results and methodsHere, we identified a subpopulation of EC whose mDC displayed higher baseline abilities to respond to intracellular HIV-1 dsDNA stimulation. A computational analysis of transcriptional signatures from such high responder EC, combined with functional studies, suggested cytosolic recognition of HIV-1 dsDNA by cGAS, combined with sensing of viral mRNA by RIG-I after polymerase III-mediated HIV-1 DNA transcription.DiscussionTogether, our work identifies collaborative networks of innate sensing pathways that enhance cell-intrinsic abilities of mDC to induce antiviral innate responses against HIV-1; these observations might be useful for the therapeutic induction of effective antiviral immune responses.

Bridges have a special place in transportation infrastructures and road networks due to their direct relationship with other places. These structures have the purpose of maintaining the traffic loads of the highway, crossing any obstacle, and performing effective communication between two destinations. Costs associated with bridge maintenance continue to be expensive due to their widespread use and stringent inspection requirements. Many researchers have been working on methods to use machine-learning (ML) techniques to forecast specific situations rather than physically checking bridges as part of the maintenance process in recent years. The practical value of the models has, however, been severely constrained by issues such relatively poor model evaluation results, unstable model performances, and the ambiguous application of established models in real-world scenarios. This work showed a thorough method of bridge condition prediction model building from feature engineering to model evaluation, along with a clear procedure of applying the produced model to actual usage, using data from the United States National Bridge Inventory (NBI) and the Adaboost algorithm. Multiple ML model assessment metrics’ findings revealed that the given model outperformed the majority of earlier studies in terms of values and stability. The case study demonstrated that there is a 30% reduction in the number of bridges that need to be inspected. This study serves as a crucial resource for the practical application of ML approaches in the forecast of the status of civil infrastructure. Additionally, it shows that boosted ML models may be a superior option as modeling algorithms advance. To explore the main influencing aspects of bridge conditions, a predictor importance analysis is also offered.

SARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19. However, the effects of viremia on immune responses in blood cells remain unclear. The current study comprehensively examined transcriptional signatures of PBMCs involving T cells, B cells, NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) respectively, from three different groups including individuals with moderate (nM), or severe disease with (vS) or without (nS) detectable plasma viral load. Whole transcriptome analysis demonstrated that all seven immune cell subsets were associated with disease severity regardless of cell type. Supervised clustering analysis demonstrated that mDCs and pDCs gene signatures could distinguish disease severity. Notably, transcriptional signatures of the vS group were enriched in pathways related to DNA repair, E2F targets, and G2M checkpoints; in contrast, transcriptional signatures of the nM group were enriched in interferon responses. Moreover, we observed an impaired induction of interferon responses accompanied by imbalanced cell-intrinsic immune sensing and an excessive inflammatory response in patients with severe disease (nS and vS). In sum, our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in seven major immune cells in COVID-19 patients.

Numerous missense mutations have been reported in autosomal dominant polycystic kidney disease which is one of the most common renal genetic disorders. The underlying mechanism for cystogenesis is still elusive, partly due to the lack of suitable animal models. Currently, we tried to establish a porcine transgenic model overexpressing human PKD2-D511V (hPKD2-D511V), which is a dominant-negative mutation in the vertebrate in vitro models. A total of six cloned pigs were finally obtained using somatic cell nuclear transfer. However, five with functional hPKD2-D511V died shortly after birth, leaving only one with the dysfunctional transgenic event to survive. Compared with the WT pigs, the demised transgenic pigs had elevated levels of hPKD2 expression at the mRNA and protein levels. Additionally, no renal malformation was observed, indicating that hPKD2-D511V did not alter normal kidney development. RNA-seq analysis also revealed that several ADPKD-related pathways were disturbed when overexpressing hPKD2-D511V. Therefore, our study implies that hPKD2-D511V may be lethal due to the dominant-negative effect. Hence, to dissect how PKD2-D511V drives renal cystogenesis, it is better to choose in vitro or invertebrate models.

As a common malignant tumor of gastrointestinal tract, the incidence of colorectal cancer (CRC) has gradually increased in recent years. In western developed countries, it has even become the second largest malignant tumor next to lung cancer. Immunotherapy is a hot topic in the field of cancer therapy, including immune checkpoint blockade (ICB), adoptive cell therapy (ACT), cancer vaccines and cytokines, aiming to improve the ability of the immune system to recognize, target and eliminate cancer cells. However, cold CRC, which accounts for a high proportion of CRC, is not so reactive to it. The development of immunotherapy to prevent cancer cells from forming “immune escape” pathways to the immune system in cold CRC, has been under increasing study attention. There is proof that an organic combination of radiotherapy, chemotherapy, and several immunotherapies can considerably boost the immune system’s capacity to eradicate tumor cells. In this review, we summarized the role of immunotherapy in colorectal cancer. In addition, we propose a breakthrough and strategy to improve the role of immunotherapy in cold CRC based on its characteristics.

The selection of suitable subcontractors for large construction companies is crucially important for the overall success of their projects. As the construction industry advances, a growing number of criteria need to be considered in the subcontractor selection process than simply considering the biding prices. This paper proposed a hybrid multi-criteria structure entropy weight (SEW)—TOPSIS group decision-making model that considers 10 criteria. The proposed model was able to handle large amount of subcontractors’ performance data that were collected in different types. Additionally, the model can integrate experts’ judgments while accounting for their varying level of expertise and correcting for their biases. This paper also provided a case study to demonstrate the proposed model’s effectiveness and efficiency, as well as its applicability of large construction companies. While this study was applied to construction subcontractors’ selection, the proposed methodology can also be easily extended to various decision-making scenarios with similar requirements.

Object-space model optimization (OSMO) has been proven to be a simple and high-accuracy approach for additive manufacturing of tomographic reconstructions compared with other approaches. In this paper, an improved OSMO algorithm is proposed in the context of OSMO. In addition to the two model optimization steps in each iteration of OSMO, another two steps are introduced: one step enhances the target regions’ in-part edges of the intermediate model, and the other step weakens the target regions’ out-of-part edges of the intermediate model to further improve the reconstruction accuracy of the target boundary. Accordingly, a new quality metric for volumetric printing, named ‘Edge Error’, is defined. Finally, reconstructions on diverse exemplary geometries show that all the quality metrics, such as VER, PW, IPDR, and Edge Error, of the new algorithm are significantly improved; thus, this improved OSMO approach achieves better performance in convergence and accuracy compared with OSMO.

An analytical solution for vertical vibrations of a simply supported bridge under the action of moving loads is derived and validated. The effect of bridge frequency, span length and vehicle length on the amplification factor of mid-span displacement is discussed using theoretical formulas and numerical results. The study finds and validates that the maximum bridge amplification factor is function of the length ratio of the bridge-to-vehicle. When the speed of the vehicle is high enough to cause bridge resonance, the maximum amplification factor of the bridge is a certain value, which has no relation to bridge’s frequency. The frequency only affects the speed the maximum amplification factor appears. The changes in the amplification factor are analyzed with the bridge-to-vehicle length ratio, which provides a basis for the selection of bridge span length. A simplified, practical formula for calculating the amplification factor is given. The presented results will be particularly useful for railway bridge preliminary design for high-speed trains and assessment of the expected maximum vibration levels.

Abstract Liver is the largest internal organ that serves as the key site for various metabolic activities and maintenance of homeostasis. Liver diseases are great threats to human health. The capability of liver to regain its mass after partial hepatectomy has widely been applied in treating liver diseases either by removing the damaged part of a diseased liver in a patient or transplanting a part of healthy liver into a patient. Vast efforts have been made to study the biology of liver regeneration in different liver-damage models. Regarding the sources of hepatocytes during liver regeneration, convincing evidences have demonstrated that different liver-damage models mobilized different subtype hepatocytes in contributing to liver regeneration. Under extreme hepatocyte ablation, biliary epithelial cells can undergo dedifferentiation to liver progenitor cells (LPCs) and then LPCs differentiate to produce hepatocytes. Here we will focus on summarizing the progresses made in identifying cell types contributing to producing new hepatocytes during liver regeneration in mice and zebrafish.

The fusion quality of infrared and visible image is very important for subsequent human understanding of image information and target processing. The fusion quality of the existing infrared and visible image fusion methods still has room for improvement in terms of image contrast, sharpness and richness of detailed information. To obtain better fusion performance, an infrared and visible image fusion algorithm based on latent low-rank representation (LatLRR) nested with rolling guided image filtering (RGIF) is proposed that is a novel solution that integrates two-level decomposition and three-layer fusion. First, infrared and visible images are decomposed using LatLRR to obtain the low-rank sublayers, saliency sublayers, and sparse noise sublayers. Then, RGIF is used to perform further multiscale decomposition of the low-rank sublayers to extract multiple detail layers, which are fused using convolutional neural network (CNN)-based fusion rules to obtain the detail-enhanced layer. Next, an algorithm based on improved visual saliency mapping with weighted guided image filtering (IVSM-GIF) is used to fuse the low-rank sublayers, and an algorithm for adaptive weighting of regional energy features based on Laplacian pyramid decomposition is used to fuse the saliency sublayers. Finally, the fused low-rank sublayer, saliency sublayer, and detail-enhanced layer are used to reconstruct the final image. The experimental results show that the proposed method outperforms other state-of-the-art fusion methods in terms of visual quality and objective evaluation, achieving the highest average values in six objective evaluation metrics.

Although the traditional image fusion method can obtain rich image results, obvious artificial noise and artifacts are often present in the resulting image. Fusion algorithms based on neural networks can avoid the shortcomings of traditional methods, but they are more complex and less flexible. In this study, we proposed a fusion method using the deep residual neural network ResNet152, which can not only effectively suppress artificial noise but also preserve the edge details of the image and improve the efficiency of the neural network. The proposed method is characterized by a multiscale transformation of an infrared image and visible light image in the optimized nonsubsampled contourlet transformation domain, and the deep residual neural network ResNet152 is used to extract the deep features of the low-pass component to guide the fusion of the low-pass component. The bandpass component is fused by taking the modulus maximum. This method can fully retain the global features and structural information of the source image in the result image. Compared to existing fusion methods using public test image sets, the experimental results show that on a subjective level, the fusion method creates sharper depth edges and fewer noise artifacts than traditional fusion methods. From an objective perspective, the average value for the results of the evaluation function is greater than that of other fusion methods.

Abstract Recovery of liver mass to a healthy liver donor by compensatory regeneration after partial hepatectomy (PH) is a prerequisite for liver transplantation. Synchronized cell cycle reentry of the existing hepatocytes after PH is seemingly a hallmark of liver compensatory regeneration. Although the molecular control of the PH-triggered cell cycle reentry has been extensively studied, little is known about how the synchronization is achieved after PH. The nucleolus-localized protein cleavage complex formed by the nucleolar protein Digestive-organ expansion factor (Def) and cysteine proteinase Calpain 3 (Capn3) has been implicated to control wounding healing during liver regeneration through selectively cleaving the tumor suppressor p53 in the nucleolus. However, whether the Def-Capn3 complex participates in regulating the synchronization of cell cycle reentry after PH is unknown. In this report, we generated a zebrafish capn3b null mutant (capn3b ∆19∆14 ). The homozygous mutant was viable and fertile, but suffered from a delayed liver regeneration after PH. Delayed liver regeneration in capn3b ∆19∆14 was due to disruption of synchronized cell proliferation after PH. Mass spectrometry (MS) analysis of nuclear proteins revealed that a number of negative regulators of cell cycle are accumulated in the capn3b ∆19∆14 liver after PH. Moreover, we demonstrated that Check-point kinase 1 (Chk1) and Wee1, two key negative regulators of G2 to M transition, are substrates of Capn3. We also demonstrated that Chk1 and Wee1 were abnormally accumulated in the nucleoli of amputated capn3b ∆19∆14 liver. In conclusion, our findings suggest that the nucleolar-localized Def-Capn3 complex acts as a novel regulatory pathway for the synchronization of cell cycle reentry, at least partially, through inactivating Chk1 and Wee1 during liver regeneration after PH.

Zika virus (ZIKV) poses a significant public health threat, but the immune landscape changes following ZIKV infection is still unclear. Here, the authors show, using flow cytometry and transcriptomic data, that ZIKV induces a multitude of immune responses, with plasmacytoid dendritic cells poised centrally to interact with other immune cell types.

During the drastic changing process of the construction industry in China, construction program management has been given significant attention. Due to the complexity of construction programs, selecting competent managers is crucially important to its success. Therefore, based on a comprehensive literature review, this paper combines regret theory and the Fuzzy-DEMATEL method to develop a multi-attribute model for construction program manager selection. Firstly, six competence elements are extracted, then the manager selection and evaluation index system are constructed. Secondly, the regret theory is used to simulate the psychological characteristics of the decision makers, combined with Fuzzy-DEMATEL, the comprehensive weights for each element are calculated. Lastly, all alternatives for the selection are sorted and the competent ones are selected. A case study is provided to exam the effectiveness of the developed model. Results shows that the proposed model adopted multi-attribute evaluation and group decision making and took into account the psychological behavior of decision makers as well as influences from the relationships between different attributes. Such results indicate that the proposed model is able to provide more comprehensive and scientific construction program manager selections, which can further improve the management of construction programs.

The thickness of steel plates used in the structure has gradually increased to meet the load-bearing capacity requirements of long-span steel bridges. Thick steel plate welded by arc welding process will result in considerable welding residual stress with complex distribution. Large welding residual stress will significantly impact the performance of steel bridges. At present; residual welding stress of thick steel plates is not considered enough in bridge engineering; which could lead to potential dangers in safety. In this paper; a butt welded joint with a thickness of 80 mm was designed; the residual welding stress was measured by X-ray diffraction method; and the distribution of residual stress in the direction perpendicular to the weld seam and along the direction of the weld seam is analyzed; and the distribution pattern of welding residual stress in thick steel plate is systematically studied. It is found that in the area near the weld; the stress in the direction along the weld seam is more significant than that in the perpendicular direction; the peak stress in the direction perpendicular to the weld seam usually appears in the weld seam and the heat-affected zone; and the maximum value tends to appear close to the last weld bead on the surface; on the path perpendicular to the weld seam; the stress in the direction perpendicular to the weld seam is distributed in a “Π” shape; the stress in the direction along the weld seam is distributed in an “M” shape; and the stresses in the direction along and perpendicular to the weld seam are symmetrically distributed; however the axis of symmetry may appear anywhere in and around the weld seam. The results could serve as a reference for welding residual stress analysis and guide optimization design of steel bridges made of thick steel plates.

Zebrafish have been found to be a premier model organism in biological and regeneration research. However, the comprehensive cell compositions and molecular dynamics during tissue regeneration in zebrafish remain poorly understood. Here, we utilized Microwell-seq to analyze more than 250,000 single cells covering major zebrafish cell types and constructed a systematic zebrafish cell landscape. We revealed single-cell compositions for 18 zebrafish tissue types covering both embryo and adult stages. Single-cell mapping of caudal fin regeneration revealed a unique characteristic of blastema population and key genetic regulation involved in zebrafish tissue repair. Overall, our single-cell datasets demonstrate the utility of zebrafish cell landscape resources in various fields of biological research.

Aristolochic acid I (AAI) is a nephrotoxic chemical found in the plant genera, Aristolochia and Asarum. AAI can be reduced to positively charged aristolochyl actam-nitrogen ions in organisms: this intermediate product increases the oxidative stress due to AAI. Glutathione (GSH) acts synergistically with other amino acids in the liver for metabolizing toxic chemicals. Further, this small peptide containing an -SH group binds to AAI and reduces oxidative stress in A549 cells exposed to AAI. Surface-enhanced Raman scattering (SERS) was selected to explore the metabolites of the reaction between AAI and GSH. Ag@HSA was used as the basis for detecting metabolites based on its excellent biocompatibility. Moreover, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDX), and dynamic light scattering (DLS) were used to characterize the prepared SERS support substrate. A luminescence experiment was used to detect metabolites based on their chemical characteristics. In vivo tests in nude mice showed that AAI displays high toxicity. An injection of 200 μL AAI (10−4 M) into the abdominal cavity caused rapid death. CCK-8 assays showed that the viability of cells increased after adding GSH, indicating that GSH is involved in the detoxification metabolism of AAI.

As a result of accumulating methylglyoxal and advanced glycation end products in the brains of patients with Alzheimer’s disease, it is considered a protein precipitation disease. The ubiquitin proteasome system is one of the most important mechanisms for cells to degrade proteins, and thus is very important for maintaining normal physiological function of the nervous system. This study recruited 48 individuals with Alzheimer’s disease (20 males and 28 females aged 75 ± 6 years) and 50 healthy volunteers (21 males and 29 females aged 72 ± 7 years) from the Affiliated Hospital of Youjiang Medical University for Nationalities (Baise, China) between 2014 and 2017. Plasma levels of malondialdehyde and H2O2 were measured by colorimetry, while glyoxalase 1 activity was detected by spectrophotometry. In addition, 20S proteasome activity in erythrocytes was measured with a fluorescent substrate method. Ubiquitin and glyoxalase 1 protein expression in erythrocyte membranes was detected by western blot assay. The results demonstrated that compared with the control group, patients with Alzheimer’s disease exhibited increased plasma malondialdehyde and H2O2 levels, and decreased glyoxalase 1 activity; however, expression level of glyoxalase 1 protein remained unchanged. Moreover, activity of the 20S proteasome was decreased and expression of ubiquitin protein was increased in erythrocytes. These findings indicate that proteasomal and glyoxalase activities may be involved in the occurrence of Alzheimer’s disease, and erythrocytes may be a suitable tissue for Alzheimer’s disease studies. This study was approved by the Ethics Committee of Youjiang Medical University for Nationalities (approval No. YJ12017013) on May 3, 2017.

The zebrafish intestine and liver, as in other vertebrates, are derived from the endoderm. Great effort has been devoted to deciphering the molecular mechanisms controlling the specification and development of the zebrafish intestine and liver; however, genome-wide comparison of the transcriptomes between these two organs at the larval stage remains unexplored. There is a lack of extensive identification of feature genes marking specific cell types in the zebrafish intestine and liver at 5 days post-fertilization, when the larval fish starts food intake. In this report, through RNA sequencing and single-cell RNA sequencing of intestines and livers separately dissected from wild-type zebrafish larvae at 5 days post-fertilization, together with the experimental validation of 47 genes through RNA whole-mount in situ hybridization, we identified not only distinctive transcriptomes for the larval intestine and liver, but also a considerable number of feature genes for marking the intestinal bulb, mid-intestine and hindgut, and for marking hepatocytes and cholangiocytes. Meanwhile, we identified 135 intestine- and 97 liver-enriched transcription factor genes in zebrafish larvae at 5 days post-fertilization. Our findings provide rich molecular and cellular resources for studying cell patterning and specification during the early development of the zebrafish intestine and liver.

A dynamic computational program considering slip, shear-lag and time-dependent effects of composite box-girder bridge–train coupling system is firstly proposed based on the authors’ previous studies. In the program, the long-term vertical displacement of a composite bridge is firstly calculated. The calculated vertical displacement is then superimposed on the existing uneven track as the new excitation of the composite box-girder bridge–train coupling system to obtain the dynamic responses of the bridge–train coupling system. A 3 × 40 m simply supported steel–concrete composite box-girder bridge is selected to investigate the influence of its time-dependent behavior on its dynamic responses. The results showed that the time-dependent effect will amplify the dynamic characteristics of the composite box-girder bridge and the high-speed train. The maximum vertical displacement and acceleration of the composite bridge increase by 8.82% and 13.64%, and the maximum vertical acceleration of the train body increases by 144.78%. Additionally, the slip and shear-lag effects have an impact on the dynamic responses of the composite box-girder bridge–train coupling system at different operation times. The dynamic responses of the coupling system strengthen with the decrease in shear connection stiffness. The dynamic responses of the system may be underestimated when the shear-lag effect is not neglected. Therefore, these conclusions should be given sufficient attention in the design, construction and operation of high-speed railway composite bridges.

Summary: The induction of broadly neutralizing antibodies (bnAbs) is highly desired for an effective vaccine against HIV-1. Typically, bnAbs develop in patients with high viremia, but they can also evolve in some untreated HIV-1 controllers with low viral loads. Here, we identify a subgroup of neutralizer-controllers characterized by myeloid DCs (mDCs) with a distinct inflammatory signature and a superior ability to prime T follicular helper (Tfh)-like cells in an STAT4-dependent fashion. This distinct immune profile is associated with a higher frequency of Tfh-like cells in peripheral blood (pTfh) and an enrichment for Tfh-defining genes in circulating CD4+ T cells. Correspondingly, monocytes from this neutralizer controller subgroup upregulate genes encoding for chemotaxis and inflammation, and they secrete high levels of IL-12 in response to TLR stimulation. Our results suggest the existence of multi-compartment immune networks between mDCs, Tfh, and monocytes that may facilitate the development of bnAbs in a subgroup of HIV-1 controllers. : Martin-Gayo et al. identify a subgroup of HIV-1 controllers who mount potent neutralizing antibodies against the virus. The distinguishing features of this subset of individuals include a tightly regulated network of transcriptional and functional interactions between dendritic cells, T cells, and monocytes. Keywords: HIV, dendritic cell, systems biology, CD4 T cell, bnAb, controller, neutralizer, monocyte, B cell, RNAseq

Automatically predicting age group and gender from face images acquired in unconstrained conditions is an important and challenging task in many real-world applications. Nevertheless, the conventional methods with manually-designed features on in-the-wild benchmarks are unsatisfactory because of incompetency to tackle large variations in unconstrained images. This difficulty is alleviated to some degree through convolutional neural networks (CNN) for its powerful feature representation. In this paper, we propose a new CNN-based method for age group and gender estimation leveraging residual networks of residual networks (RoR), which exhibits better optimization ability for age group and gender classification than other CNN architectures. Moreover, two modest mechanisms based on observation of the characteristics of age group are presented to further improve the performance of age estimation. In order to further improve the performance and alleviate over-fitting problem, RoR model is pre-trained on ImageNet first, and then it is fune-tuned on the IMDB-WIKI-101 data set for further learning the features of face images, finally, it is used to fine-tune on Adience data set. Our experiments illustrate the effectiveness of RoR method for age and gender estimation in the wild, where it achieves better performance than other CNN methods. Finally, the RoR-152+IMDB-WIKI-101 with two mechanisms achieves new state-of-the-art results on Adience benchmark.

Target detection in hyperspectral imagery (HSI) aims at extracting target components of interest from hundreds of narrow contiguous spectral bands, where the prior target information plays a vital role. However, the limitation of the previous methods is that only single-layer detection is carried out, which is not sufficient to discriminate the target parts from complex background spectra accurately. In this paper, we introduce a hierarchical structure to the traditional algorithm matched filter (MF). Because of the advantages of MF in target separation performance, that is, the background components are suppressed while preserving the targets, the detection result of MF is used to further suppress the background components in a cyclic iterative manner. In each iteration, the average output of the previous iteration is used as a suppression criterion to distinguish these pixels judged as backgrounds in the current iteration. To better stand out the target spectra from the background clutter, HSI spectral input and the given target spectrum are whitened and then used to construct the MF in the current iteration. Finally, we provide the corresponding proofs for the convergence of the output and suppression criterion. Experimental results on three classical hyperspectral datasets confirm that the proposed method performs better than some traditional and recently proposed methods.

Digestive organ expansion factor (Def) is a nucleolar protein that plays dual functions: it serves as a component of the ribosomal small subunit processome for the biogenesis of ribosomes and also mediates p53 degradation through the cysteine proteinase calpain-3 (CAPN3). However, nothing is known about the exact relationship between Def and CAPN3 or the regulation of the Def function. In this report, we show that CAPN3 degrades p53 and its mutant proteins p53A138V, p53M237I, p53R248W, and p53R273P but not the p53R175H mutant protein. Importantly, we show that Def directly interacts with CAPN3 in the nucleoli and determines the nucleolar localisation of CAPN3, which is a prerequisite for the degradation of p53 in the nucleolus. Furthermore, we find that Def is modified by phosphorylation at five serine residues: S50, S58, S62, S87, and S92. We further show that simultaneous phosphorylations at S87 and S92 facilitate the nucleolar localisation of Capn3 that is not only essential for the degradation of p53 but is also important for regulating cell cycle progression. Hence, we propose that the Def-CAPN3 pathway serves as a nucleolar checkpoint for cell proliferation by selective inactivation of cell cycle-related substrates during organogenesis.

Metal additive manufacturing (MAM) technology has experienced rapid development in recent years. As both equipment and materials progress towards increased maturity and commercialization, material metallurgy technology based on high energy sources has become a key factor influencing the future development of MAM. The calculation of phase diagrams (CALPHAD) is an essential method and tool for constructing multi-component phase diagrams by employing experimental phase diagrams and Gibbs free energy models of simple systems. By combining with the element mobility data and non-equilibrium phase transition model, it has been widely used in the analysis of traditional metal materials. The development of CALPHAD application technology for MAM is focused on the compositional design of printable materials, the reduction of metallurgical imperfections, and the control of microstructural attributes. This endeavor carries considerable theoretical and practical significance. This paper summarizes the important achievements of CALPHAD in additive manufacturing (AM) technology in recent years, including material design, process parameter optimization, microstructure evolution simulation, and properties prediction. Finally, the limitations of applying CALPHAD technology to MAM technology are discussed, along with prospective research directions. [ABSTRACT FROM AUTHOR]