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Abstract Posttransplantation complications pose a major challenge to the long‐term survival and quality of life of organ transplant recipients. These complications encompass immune‐mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation. Here, we provide a comprehensive overview of the clinical features, risk factors, and molecular mechanisms of major posttransplantation complications. We systematically summarize the current understanding of the immunological basis of allograft rejection and graft‐versus‐host disease, the metabolic dysregulation associated with immunosuppressive agents, and the role of oncogenic viruses in posttransplantation malignancies. Furthermore, we discuss potential prevention and intervention strategies based on these mechanistic insights, highlighting the importance of optimizing immunosuppressive regimens, enhancing infection prophylaxis, and implementing targeted therapies. We also emphasize the need for future research to develop individualized complication control strategies under the guidance of precision medicine, ultimately improving the prognosis and quality of life of transplant recipients.

Multiple-input multiple-output (MIMO) technology is widely used in the field of radar imaging. Array sparse optimization reduces the hardware cost of MIMO radar, while virtual aperture and the equivalent phase center (EPC) principle simplify the radar signal model and reduce the computation and complexity of imaging algorithms. However, the application of sparse array structure and the EPC principle produces a non-negligible phase error, which affects the imaging quality. This paper simplifies the MIMO radar signal model based on the phase center approximation, analyzes the phase error generated by this method, and proposes an improved phase error correction method to solve the problem that the target cannot be well-focused at non-reference distance during imaging. In addition, this paper designs a sparse linear MIMO array with a periodic structure, which reduces the number of transmitting and receiving units, system complexity, and hardware costs. The proposed phase correction method was combined with the wavenumber domain algorithm to simulate and experiment on the designed antenna array, and good experimental results were obtained to verify the effectiveness of the proposed method.

Background: In recent years, the advancement of computational chemistry has offered new insights into the rational design of molecularly imprinted polymers (MIPs). From this aspect, our study tried to give quantitative parameters for evaluating imprinting efficiency and exploring the formation mechanism of MIPs by combining simulation and experiments. Methods: The pre-polymerization system of sulfadimethoxine (SDM) was investigated using a combination of quantum chemical (QC) calculations and molecular dynamics (MD) simulations. MIPs were prepared on the surface of silica gel by a surface-initiated supplemental activator and reducing agent atom transfer radical polymerization (SI-SARA ATRP). Results: The results of the QC calculations showed that carboxylic monomers exhibited higher bonding energies with template molecules than carboxylic ester monomers. MD simulations confirmed the hydrogen bonding sites predicted by QC calculations. Furthermore, it was observed that only two molecules of monomers could bind up to one molecule of SDM, even when the functional monomer ratio was up to 10. Two quantitative parameters, namely, the effective binding number (EBN) and the maximum hydrogen bond number (HBNMax), were defined. Higher values of EBN and HBNMax indicated a higher effective binding efficiency. Hydrogen bond occupancies and RDF analysis were performed to analyze the hydrogen bond formation between the template and the monomer from different perspectives. Furthermore, under the influence of the EBN and collision probability of the template and the monomers, the experimental results show that the optimal molar ratio of template to monomer is 1:3. Conclusions: The method of monomer screening presented in this study can be extended to future investigations of pre-polymerization systems involving different templates and monomers.

Summary: Kidney transplantation is essential for patients with end-stage renal disease; however, ischemia-reperfusion injury (IRI) during transplantation can lead to acute kidney damage and compromise survival. Recent studies have reported that antiferroptotic agents may be a potential therapeutic strategy, by reducing production of reactive oxygen species (ROS). Therefore, we constructed rutin-loaded polydopamine nanoparticles (PEG-PDA@rutin NPs, referred to as PPR NPs) to eliminate ROS resulting from IRI. Physicochemical characterization showed that the PPR NPs were ∼100 nm spherical particles with good ROS scavenging ability. Notably, PPR NPs could effectively enter lipopolysaccharide (LPS)-treated renal tubular cells, then polydopamine (PDA) released rutin to eliminate ROS, repair mitochondria, and suppress ferroptosis. Furthermore, in vivo imaging revealed that PPR NPs efficiently accumulated in the kidneys after IRI and effectively protected against IRI damage. In conclusion, PPR NPs demonstrated an excellent ability to eliminate ROS, suppress ferroptosis, and protect kidneys from IRI.

Background: Prediction of early recurrence (ER) of HCC after radical treatment is of great significance for follow-up and subsequent treatment, and there is a lot of unmet needs. Here, our goal is to develop and validate a radiomics nomogram that can predict ER after curative ablation. Objective: The aim of this study was to evaluate the efficacy and safety of regorafenib after disease progression with sorafenib in Chinese patients with advanced HCC through this retrospective analysis. Methods: 149 HCC patients treated between November 2008 and February 2018 were enrolled and randomly divided into training cohort (n = 105) and validation cohort (n = 44). The survival endpoint was recurrence-free survival (RFS). A total of 16908 radiomics features were extracted from the contrast-enhanced MR images of each patient. The minimum redundancy maximum relevance algorithm (mRMR) and random survival forest (RSF) were used for feature selection. Twelve kinds of support vector machine (SVM) models, a Cox regression model (Cox PH), a random survival forest (RSF) model and a gradient boosting model (GBoost) were used to build a radiomics signature. These models were trained after adjusting the model parameters using 5-fold cross-validation. The best models were selected according to the C-index. Results: Using the machine learning (ML) framework, 40 features were identified that demonstrated good prediction of HCC recurrence across all cohorts. The random survival forest (RSF) model showed higher prognostic value, with a C-index of 0.733–0.801 and an integrated Brier score of 0.147–0.165, compared with other SVM models, Cox regression models, etc. (all P

Fault diagnosis is one of the important applications of edge computing in the Industrial Internet of Things (IIoT). To address the issue that traditional fault diagnosis methods often struggle to effectively extract fault features, this paper proposes a novel rolling bearing fault diagnosis method that integrates Gramian Angular Field (GAF), Convolutional Neural Network (CNN), and Vision Transformer (ViT). First, GAF is used to convert one-dimensional vibration signals from sensors into two-dimensional images, effectively retaining the fault features of the vibration signal. Then, the CNN branch is used to extract the local features of the image, which are combined with the global features extracted by the ViT branch to diagnose the bearing fault. The effectiveness of this method is validated with two datasets. Experimental results show that the proposed method achieves average accuracies of 99.79% and 99.63% on the CWRU and XJTU-SY rolling bearing fault datasets, respectively. Compared with several widely used fault diagnosis methods, the proposed method achieves higher accuracy for different fault classifications, providing reliable technical support for performing complex fault diagnosis on edge devices.

Multilevel thresholding image segmentation is one of the widely used image segmentation methods, and it is also an important means of medical image preprocessing. Replacing the original costly exhaustive search approach, swarm intelligent optimization algorithms are recently used to determine the optimal thresholds for medical image, and medical images tend to have higher bit depth. Aiming at the drawbacks of premature convergence of existing optimization algorithms for high-bit depth image segmentation, this paper presents a pyramid particle swarm optimization based on complementary inertia weights (CIWP-PSO), and the Kapur entropy is employed as the optimization objective. Firstly, according to the fitness value, the particle swarm is divided into three-layer structure. To accommodate the larger search range caused by higher bit depth, the particles in the layer with the worst fitness value are employed random opposition learning strategy. Secondly, a pair of complementary inertia weights are introduced to balance the capability of exploitation and exploration. In the part of experiments, this paper used nine high-bit depth benchmark images to test the CIWP-PSO effectiveness. Then, a group of Brain Magnetic Resonance Imaging (MRI) images with 12-bit depth are utilized to validate the advantages of CIWP-PSO compared with other segmentation algorithms based on other optimization algorithms. According to the segmentation experimental results, thresholds optimized by CIWP-PSO could achieve higher Kapur entropy, and the multi-level thresholding segmentation algorithm based on CIWP-PSO outperforms the similar algorithms in high-bit depth image segmentation. Besides, we used image segmentation quality metrics to evaluate the impact of different segmentation algorithms on images, and the experimental results show that the MRI images segmented by the CIWP-PSO has achieved the best fitness value more times than images segmented by other comparison algorithm in terms of Structured Similarity Index and Feature Similarity Index, which explains that the images segmented by CIWP-PSO has higher image quality.

The effect of taurine (TAU) as a specific regulatory mediator on pancreatic function in obese rats induced by a high-fat-high-glucose (HFHG) diet was investigated. We fed male Sprague-Dawley rats under different conditions, namely the control, HFHG, TAU, and HFHG + TAU treatment groups for 4 months. Compared with the HFHG group, TAU supplementation significantly reduced malondialdehyde levels and increased superoxide dismutase, total antioxidant capacity, and glutathione levels in the rat pancreas. In addition, TAU significantly decreased the level of reactive oxygen species, and markedly increased the activity of heme oxygenase 1 (HO-1), Kelch-like ECH-associated protein 1 (KEAP-1), and nuclear factor erythrocyte-2-related factor 2 (Nrf2) in the rat pancreas. Notably, HFHG diet could induce pancreatic injury in the rats through the Nrf2/HO-1 signaling pathway and activate the mitochondrial channel-mediated apoptotic signaling pathway. The addition of TAU significantly improved the pancreatic tissue injury induced by the HFHG diet in the rats and reduced the protein expression of Caspase-3, Cleaved-caspase-3, Caspase-9 and Bcl-2 associated protein X (BAX), and increased the protein expression of B-cell lymphoma-2 (Bcl-2). In conclusion, this experiment confirmed that TAU could alleviate the oxidative stress and apoptosis induced by the HFHG diet in rat pancreatic β-cells.

Abstract Background Protein kinase C delta (PRKCD) and caspase recruitment domain family member 9 (CARD9) are genes involved in B and T cell activation, and cytokine production, which are vital mechanisms underlying autoimmune disease development. This study aimed to explore the association of the PRKCD and CARD9 genes with Vogt–Koyanagi–Harada disease (VKH) disease. The case–control study was performed to in 912 patients with VKH and 878 normal controls. MassARRAY system, SHEsis online platform, real-time PCR, and enzyme-linked immunosorbent assay were used to detect genotyping, haplotyping, mRNA expression, and cytokine levels, respectively. Results We found that rs74437127 C allele of PRKCD, rs3812555 CC genotype, and C allele of CARD9 were associated with increased susceptibility of VKH (Pc = 0.020, OR = 1.624; Pc = 2.04 × 10–5, OR = 1.810; Pc = 2.76 × 10–5, OR = 1.698, respectively). However, the rs74437127 T allele, and rs3812555 TC genotype and T allele were linked with decreased susceptibility to VKH (Pc = 0.020, OR = 0.616; Pc = 7.85 × 10–5, OR = 0.559; Pc = 2.76 × 10–5, OR = 0.589, respectively). PRKCD ATG and CARD9 GCTTA haplotypes decreased susceptibility to VKH (Pc = 3.11 × 10–3, OR = 0.594; Pc = 5.00 × 10–3, OR = 0.639, respectively). Functional studies on rs3812555 genotyped individuals revealed that CC carriers had significantly higher CARD9 mRNA expression and tumour necrosis factor-α production than TC/TT carriers (P = 1.00 × 10–4; P = 2.00 × 10–3, respectively). Conclusions We found an association between PRKCD rs74437127 and CARD9 rs3812555 polymorphisms and VKH susceptibility and revealed that the increased susceptibility of rs3812555 for VKH may be mediated by regulating CARD9 gene expression and the production of pro-inflammatory cytokines, such as TNF-α.

The brain network is an effective tool and has been widely used in the field of brain neurodegenerative disease analysis. Due to the high cost of accessing medical image data, efforts have been devoted to investigating data augmentation. However, the brain network containing topological characteristics of non-European space is different from the traditional image data, which makes it challenging to synthesize brain structural connectivity and limits the application of brain network analysis. In this paper, a Hemisphere-separated Cross-connectome Aggregating Learning (HCAL) model is proposed to synthesize realistic and diverse brain structural connectivities. Specifically, the latent representation is transformed from structural connectivity by the graph variational autoencoder (GVAE). To generate more diverse and high-quality structural connectivities, the hemisphere-separated generator with a cross-connectome aggregating mechanism is developed to first learn local topological patterns by splitting the whole brain into inter- and intra-hemispheres, then capture global topological characteristics among all the neighbors for each brain region. Also, the connectivity-aware discriminator is devised to make the adversarial training stable and enhance the disease diagnosis. Evaluations of the public Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset show that the proposed model generates brain structural networks with higher quality and more diversity than related methods. In addition, the classification performance using the augmented data achieved by our approach achieves an accuracy improvement of over 3% compared with the competing method. The proposed model provides an alternative way to synthesize brain networks for connectivity-based disease analysis.

Abstract Background Stem cell transplantation may improve visual acuity in patients with dry age-related macular degeneration. Herein, we aimed to summarise the evidence on the risks and benefits of stem cell transplantation for improving visual acuity, including the risk of adverse events. Methods Data were obtained from the PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials databases, and each database was interrogated from the date of inception until 19 March 2022. The rates of visual acuity outcomes and adverse events associated with stem cell transplantation were examined. All statistical analyses were conducted using Review Manager 5.4. The study was registered with PROSPERO (CRD 42022322902). Results The analysis examined 10 studies (102 patients), including one and three, randomised and non-randomised clinical trials, and one and five, multicentre prospective and prospective clinical trials, respectively. Meta-analysis showed changes in best-corrected visual acuity in the study eyes after stem cell transplantation (6 months: risk ratio [RR] = 17.00, 95% confidence interval [CI] 6.08–47.56, P

Abstract As the first rate-limiting enzyme in fatty acid oxidation (FAO), CPT1 plays a significant role in metabolic adaptation in cancer pathogenesis. FAO provides an alternative energy supply for cancer cells and is required for cancer cell survival. Given the high proliferation rate of cancer cells, nucleotide synthesis gains prominence in rapidly proliferating cells. In the present study, we found that CPT1A is a determining factor for the abnormal activation of FAO in nasopharyngeal carcinoma (NPC) cells. CPT1A is highly expressed in NPC cells and biopsies. CPT1A dramatically affects the malignant phenotypes in NPC, including proliferation, anchorage-independent growth, and tumor formation ability in nude mice. Moreover, an increased level of CPT1A promotes core metabolic pathways to generate ATP, inducing equivalents and the main precursors for nucleotide biosynthesis. Knockdown of CPT1A markedly lowers the fraction of 13C-palmitate-derived carbons into pyrimidine. Periodic activation of CPT1A increases the content of nucleoside metabolic intermediates promoting cell cycle progression in NPC cells. Targeting CPT1A-mediated FAO hinders the cell cycle G1/S transition. Our work verified that CPT1A links FAO to cell cycle progression in NPC cellular proliferation, which supplements additional experimental evidence for developing a therapeutic mechanism based on manipulating lipid metabolism.

Abstract Age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa and other retinal disorders are the main causes of visual impairment worldwide. In the past, these retinal diseases, especially dry age-related macular degeneration, proliferative diabetic retinopathy and retinitis pigmentosa, were treated with traditional surgery and drugs. However, the effect was moderate. In recent years, researchers have used embryonic stem cells, induced pluripotent stem cells, mesenchymal stem cells, olfactory ensheathing cells and other stem cells to conduct experiments and found that stem cells can inhibit inflammation, regulate immune response, secrete neurotrophic factors, and differentiate into retinal cells to replace and promote restoration of the damaged parts. These stem cells have the potential to treat retinal diseases. Whether it is in animal experiments or clinical trials, the increase in the number of retinal cells, maintenance of function and improvement of visual function all reflect the advanced of stem cells to treat retinal diseases, but its risk preserves the donor’s hidden pathogenic genes, immune rejection and tumorigenicity. With the development of exosomes study, researchers have discovered that exosomes come from a wide range of sources and can be secreted by almost all types of cells. Using exosomes with stem cell to treat retinal diseases is more effective than using stem cells alone. This review article summarizes the recent advances in the application of olfactory ensheathing cells and stem cells/exosomes in the treatment of retinal disorders.

Abstract Adenine nucleotide translocase‐1 (ANT1) is an ADP/ATP transporter protein located in the inner mitochondrial membrane. ANT1 is involved not only in the processes of ADP/ATP exchange but also in the composition of the mitochondrial membrane permeability transition pore (mPTP); and the function of ANT1 is closely related to its own conformational changes. Notably, various viral proteins can interact directly with ANT1 to influence mitochondrial membrane potential by regulating the opening of mPTP, thereby affecting tumor cell fate. The Epstein–Barr virus (EBV) encodes the key tumorigenic protein, latent membrane protein 1 (LMP1), which plays a pivotal role in promoting therapeutic resistance in related tumors. In our study, we identified a novel mechanism for EBV‐LMP1‐induced alteration of ANT1 conformation in cisplatin resistance in nasopharyngeal carcinoma. Here, we found that EBV‐LMP1 localizes to the inner mitochondrial membrane and inhibits the opening of mPTP by binding to ANT1, thereby favoring tumor cell survival and drug resistance. The ANT1 conformational inhibitor carboxyatractyloside (CATR) in combination with cisplatin improved the chemosensitivity of EBV‐LMP1‐positive cells. This finding confirms that ANT1 is a novel therapeutic target for overcoming cisplatin resistance in the future.

BackgroundThe studies on the association between sleep duration and myopia are limited, and the evidence is inconsistent. This study aimed to evaluate the association between sleep duration and myopia, cycloplegic spherical equivalent (SE) and axial length (AL) among Chinese children during the Corona Virus Disease 2019 (COVID-19) pandemic.MethodsThe study was a cross-sectional study on Chinese children aged 6–18 years. The comprehensive ophthalmic examinations for children included cycloplegic SE, AL, and standardized questionnaires. The questionnaire included sleep duration, parental myopia, outdoor time, and continuous near work duration without breaks. Myopia was defined as SE ≤-0.50 diopters (D).ResultsA total of 1,140 children were included in the analyses, with 84.7% of myopic children and 74.4% of children's daily sleep duration being more than 8 h/d. In univariate regression analysis, compared with sleep duration < 8 h/d, children with sleep duration of 8–9 and >9 h/d were less myopia (p < 0.01 for all), and had less myopic SE (p < 0.01 for all), and shorter AL (p < 0.01 for all). After adjusting for age, gender, parental myopia, outdoor time, and continuous near work duration without breaks, sleep duration was not associated with myopia, cycloplegic SE, and AL (p > 0.05 for all).ConclusionsThis study showed sleep duration was related to myopia, cycloplegic SE, and AL among Chinese children during the COVID-19 pandemic-related lifestyles, but no independent association.

BackgroundRenal transplantation is a very effective treatment for renal failure patients following kidney transplant. However, the clinical benefit is restricted by the high incidence of organ rejection. Therefore, there exists a wealth of literature regarding the mechanism of renal transplant rejection, including a large library of expression data. In recent years, research has shown the immune microenvironment to play an important role in renal transplant rejection. Nephrology web analysis tools currently exist to address chronic nephropathy, renal tumors and children’s kidneys, but no such tool exists that analyses the impact of immune microenvironment in renal transplantation rejection.MethodsTo fill this gap, we have developed a web page analysis tool called Comprehensive Analysis of Renal Allograft Rerejction in Immune Microenvironment (CARARIME).ResultsCARARIME analyzes the gene expression and immune microenvironment of published renal transplant rejection cohorts, including differential analysis (gene expression and immune cells), prognosis analysis (logistics regression, Univariable Cox Regression and Kaplan Meier), correlation analysis, enrichment analysis (GSEA and ssGSEA), and ROC analysis.ConclusionsUsing this tool, researchers can easily analyze the immune microenvironment in the context of renal transplant rejection by clicking on the available options, helping to further the development of approaches to renal transplant rejection in the immune microenvironment field. CARARIME can be found in http://www.cararime.com.

An efficient spectrum reconstruction algorithm based on the Tikhonov regularization for terahertz (THz) synthetic aperture radar (SAR) azimuth non-uniform sampling is proposed in this article. The high bandwidth, high azimuth resolution, and high frame rate characteristics of THz SAR contribute to its wide application prospects in both military and civilian remote sensing fields. However, the higher azimuth sampling rate also leads to the more severe non-uniform sampling issues of THz SAR. Traditional methods based on the hardware adjustment of pulse repetition frequency (PRF) and simple interpolation for azimuth resampling struggle to meet the higher imaging quality requirements. The back projection algorithm (BPA) can accurately focus non-uniformly sampled data but requires significant computational resources. The algorithm proposed in this paper, which can reconstruct the wavenumber spectrum of SAR azimuth non-uniformly sampled signals, transforms the spectrum reconstruction problem into a linear equation system and solves it using Tikhonov regularization, thereby exhibiting higher computational efficiency compared to BPA. Furthermore, the proposed algorithm is derived from precise theoretical formulations and controls the solution error by utilizing a regularization parameter, leading to a superior imaging quality compared to the azimuth resampling algorithm. In this paper, an accurate spectrum reconstruction formula of non-uniform sampling signals with a finite length is derived, the influence of noise error on the solution is analyzed, and the THz SAR azimuth non-uniform sampling signals are processed from the wavenumber domain. Finally, simulation and experimental results verify the effectiveness of the proposed algorithm.

A large-aperture radar composed of a multiple-input-multiple-output (MIMO) planar array can complete 3D through-wall imaging (TWI), but the simultaneous work of the multiple transceiver channels leads to difficulties in designing the hardware. In engineering, multiple transceiver channels are usually realized by time-division multiplexing (TDM) in MIMO radar, which is called TDM MIMO radar. A time delay will be introduced when the channels are switched, which will cause high sidelobes and position deviation in the 3D imaging of moving targets, also known as range migration. This paper proposes a motion compensation algorithm based on sparse array, designed to eliminate range migration in moving targets in 3D TWI scenes. In the proposed algorithm, the coincident array elements of the equivalent array are used as the compensation channels to calculate the position difference of the target, which can correct the remaining MIMO channels. The proposed algorithm is compared with no compensation, and the reference-channel-based motion compensation algorithm (RCMCA). According to the simulation and experimental results, the proposed motion compensation algorithm can effectively eliminate sidelobes, and keep the position deviation within 0.30 m in the 3D TWI of moving targets under the TDM MIMO radar, without increasing the system complexity.

Abstract p18 is a key negative regulator of cell cycle progression and mediates cell cycle arrest at the G1/S phase. Ubiquitination is the prime mechanism in regulating p18 protein abundance. However, so far no post- translational regulator, especially DUBs, has been identified to regulate the protein stability of p18. In this paper, we identified CYLD as a deubiquitinase of p18, which binds to and removes the K48-linked polyubiquitylation chains conjugated onto p18, thus stabilizing the p18 protein. Loss of CYLD causes the degradation of p18 and induces the G1/S transition. Epstein–Barr virus (EBV), is the human oncovirus etiologically linked to nasopharyngeal carcinoma (NPC). Here we found that EBV drives a replication passive environment by deregulating the CYLD-p18 axis. Functionally, CYLD inhibits cell proliferation and tumorigenesis through p18 in vivo. Restoring CYLD prevents EBV induced viral replication and tumor growth. Collectively, our results identify CYLD directly stabilizes p18 to regulate the cellular G1/S transition. The reconstitution of CYLD-p18 axis could be a promising approach for EBV-positive cancer therapy.

Abstract Epstein–Barr virus-associated diseases are important global health concerns. As a group I carcinogen, EBV accounts for 1.5% of human malignances, including both epithelial- and lymphatic-originated tumors. Moreover, EBV plays an etiological and pathogenic role in a number of non-neoplastic diseases, and is even involved in multiple autoimmune diseases (SADs). In this review, we summarize and discuss some recent exciting discoveries in EBV research area, which including DNA methylation alterations, metabolic reprogramming, the changes of mitochondria and ubiquitin-proteasome system (UPS), oxidative stress and EBV lytic reactivation, variations in non-coding RNA (ncRNA), radiochemotherapy and immunotherapy. Understanding and learning from this advancement will further confirm the far-reaching and future value of therapeutic strategies in EBV-associated diseases.

The formation of the Yellow River involved the draining of a series of ancestral local lakes along their course, substantially changing the regional, geomorphic, and paleoenvironmental evolution. However, the evolution of the Weihe-Sanmenxia Basin section of the Yellow River remains indistinct as previous studies regard the Weihe and Sanmenxia Basin as one integral basin of the Late Cenozoic. Here, we present the detrital zircon age spectra from the Pliocene-Pleistocene Sanmen Formation to clarify the drainage system evolution of the two basins since the Late Pliocene. The results reveal that these two basins belonged to different drainage systems in the Late Pliocene because no sediments from the marginal mountains of the Weihe Basin accumulated in the Sanmenxia Basin. At 2.8/2.6 Ma, the currents presented at the edge of the basins and transported the sediment of east Hua Mountain into the Sanmenxia Basin, where it was deposited. This integration likely leads to a mismatch between the deposition and regional paleoclimate in previous studies. At ∼1.0 Ma, the Sanmenxia Gorge was traversed and the Yellow River finally formed, depositing Jinshaan Gorge sediment into the Sanmenxia Basin and lower reaches of the Yellow River.

As a key equipment of manufacturing, the intelligence of CNC machine tools affects the development and progress of intelligent manufacturing. At the same time, the rapid development of various technologies in recent years, such as cloud computing and edge computing, has brought new methods to improve the intelligence of CNC machine tools. This article proposes a new architecture of intelligent machine tools based on edge-cloud collaboration (IMT-ECC). The hierarchical structure of IMT-ECC is introduced and consists of three layers, data acquisition, network communication and edge-cloud collaboration. Combining the real-time characteristic of edge computing and complex problem processing ability of cloud computing, the edge-cloud collaboration is designed to improve the intelligence of machine tools through data collaboration, information collaboration and knowledge collaboration. Finally, the feasibility of the new intelligent machine tool architecture based on edge-cloud collaboration is verified by experiments with gantry heavy-duty CNC machine tools.

ABSTRACT: Meat quality characteristics, including juiciness, flavor, and tenderness, can be mostly attributed to the total muscle fat content, intramuscular fat (IMF), and the composition of its fatty acids, which are regulated by the balance between lipid uptake, transport, synthesis, and subsequent metabolism, involving many genes and pathways. However, the detailed molecular mechanisms remain unclear. The purpose of this study was to identify the key signaling pathways related to chicken meat quality, and to provide help for improving chicken meat quality. The present study reports the RNA-sequencing analysis of pectorales and crureus of the Zhuanghe dagu chicken and the Arbor Acres Broiler chicken (AA chicken). We identified certain differentially expressed genes that affect IMF deposition, such as EHHADH, TECRL, NDUFAB1, PCCB, and HIBCH, which were upregulated in Zhuanghe dagu chicken , and GCDH, TPI1, ABHD13, PSMC1, MYST2, and FBXO11, which were upregulated in AA chickens. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes indicated that the extracellular matrix (ECM)–receptor interaction pathway is co-enriched in both tissues, and forms a sub-pathway of other enriched pathways. Intriguingly, the ECM–receptor interaction pathway genes are regulated differently in different gene pools. Collagens, which are main ECM constituents, and laminin and integrin β1 transmembrane receptors were significantly downregulated in both tissues of the AA chicken. The results showed that the ECM-receptor interaction pathway affect the quality of chicken meat by affecting the metabolism of intramuscular adipocytes. Further investigation of this signaling pathway will be helpful to the improvement of chicken meat quality.

Kidney transplantation is currently the first choice of treatment for various types of end-stage renal failure, but there are major limitations in the application of immunosuppressive protocols after kidney transplantation. When the dose of immunosuppressant is too low, graft rejection occurs easily, while a dose that is too high can lead to graft loss. Therefore, it is very important to explore the immune status of patients receiving immunosuppressive agents after kidney transplantation. To compare the immune status of the recipient’s whole peripheral blood before and after receipt of immunosuppressive agents, we used single-cell cytometry by time-of-flight (CyTOF) to detect the peripheral blood immune cells in five kidney transplant recipients (KTRs) from the Department of Organ Transplantation of Zhujiang Hospital of Southern Medical University before and after receiving immunosuppressive agents. Based on CyTOF analysis, we detected 363,342 live single immune cells. We found that the immune cell types of the KTRs before and after receipt of immunosuppressive agents were mainly divided into CD4+ T cells, CD8+ T cells, B cells, NK cells/γδ T cells, monocytes/macrophages, granulocytes, and dendritic cells (DCs). After further reclustering of the above cell types, it was found that the immune cell subclusters in the peripheral blood of patients underwent major changes after receipt of immunosuppressants. After receiving immunosuppressive therapy, the peripheral blood of KTRs had significantly increased levels of CD57+NK cells and significantly decreased levels of central memory CD4+ T cells, follicular helper CD4+ T cells, effector CD8+ T cells, effector memory CD8+ T cells and naive CD8+ T cells. This study used CyTOF to classify immune cells in the peripheral blood of KTRs before and after immunosuppressive treatment, further compared differences in the proportions of the main immune cell types and immune cell subgroups before and after receipt of immunosuppressants, and provided relatively accurate information for assessment and treatment strategies for KTRs.

Ca and P metabolic disorders during the egg-laying period can reduce egg production, impair eggshell quality, and even cause bone problems in hens; however, little is known regarding the capacity of duodenal and nephritic Ca and P absorption. Here, the levels of serum Ca and P metabolic indices and the expression of duodenal and renal Ca and P transporter genes were measured in hens at different egg-laying stages. The Ca, 25-(OH)-VD3, and 1,25-(OH)2-VD3 content increased during the peak (43 weeks of age) and late (72 weeks of age) egg-laying periods compared to that during the early (23 weeks of age) egg-laying period; however, there were no differences in Pi levels among the three egg-laying periods. Moreover, duodenal VDR and CaBP-D28k mRNA expression was markedly higher but NPt2b mRNA expression was markedly lower during the peak and late egg-laying periods than during the early egg-laying period. Furthermore, nephritic CaBP-D28k, PMCA1b, and FGFR1 mRNA expression was markedly higher but NPt2a and Cyp24a1 mRNA expression was markedly lower during the peak and late egg-laying periods than during the early egg-laying period. In conclusion, the present study indicated that the increased duodenal and nephritic Ca absorption during the peak and late egg-laying periods may be associated with the VD–VDR pathway, while the decreased P absorption despite relatively stable serum P levels in all three egg-laying stages may associated with osteolysis.

In order to study the pore structure characteristics of high-rank coals with different bedding, NMR experiments were carried out for high-rank coals with different bedding angles (0°, 30°, 45°, 60°, and 90°). The results show that the distribution of T2 map of high-rank coal with different bedding is similar to some extent, showing a double peak or triple peak distribution, and the first peak accounts for more than 97% of the total, indicating that small holes are developed in high-rank coal with different bedding, while macropores are not developed. The influence of bedding angle on the fracture proportion is less than 0.3%. Compared with the fracture proportion, the effect of bedding angle on the proportion of microhole, medium hole, and large hole is greater and presents a certain rule. There are certain differences in T2 cutoff value (T2C) of high-rank coal with different bedding. The relationship between bedding angle and T2C conforms to exponential function, and the correlation degree R2 is 0.839. The research results provide a theoretical basis for gas extraction and utilization and prevention of gas disaster in coal mines in China.

Objective: Epstein–Barr virus (EBV) is a well-recognized oncogenic virus that can induce host cell metabolic reprogramming and tumorigenesis by targeting vital metabolic enzymes or regulators. This study aims to explore the role of wild-type isocitrate dehydrogenase 2 (IDH2) in metabolic reprogramming and tumorigenesis induced by EBV-encoded latent membrane protein 1 (LMP1). Methods: Mechanistic dissection of wild-type IDH2 in EBV-LMP1-induced tumorigenesis was investigated using western blotting, real-time polymerase chain reaction (PCR), immunochemistry, chromatin immunoprecipitation (ChIP), and luciferase assay. The role of wild-type IDH2 was examined by cell viability assays/Sytox Green staining in vitro and xenograft assays in vivo. Results: IDH2 over-expression is a prognostic indicator of poorer disease-free survival for patients with head and neck squamous cell carcinoma (HNSCC). IDH2 expression is also upregulated in nasopharyngeal carcinoma (NPC, a subtype of HNSCC) tissues, which is positively correlated with EBV-LMP1 expression. EBV-LMP1 contributes to NPC cell viability and xenograft tumor growth mediated through wild-type IDH2. IDH2-dependent changes in intracellular α-ketoglutarate (α-KG) and 2-hydroxyglutarate (2-HG) contribute to EBV-LMP1-induced tumorigenesis in vitro and in vivo. Elevated serum 2-HG level is associated with high EBV DNA and viral capsid antigen-immunoglobulin A (VCA-IgA) levels in patients with NPC. A significantly positive correlation exists between serum 2-HG level and regional lymph node metastases of NPC. EBV-LMP1 enhances the binding of c-Myc with the IDH2 promoter and transcriptionally activates wild-type IDH2 through c-Myc. Targeting IDH2 decreased intracellular 2-HG levels and survival of EBV-LMP1-positive tumor cells in vitro and in vivo. Conclusions: Our results demonstrate that the EBV-LMP1/c-Myc/IDH2WT signaling axis is critical for EBV-dependent metabolic changes and tumorigenesis, which may provide new insights into EBV-related cancer diagnosis and therapy.

Abstract Background Kidneys from deceased donors are being used to meet the growing need for grafts. However, delayed graft function (DGF) and acute rejection incidences are high, leading to adverse effects on graft outcomes. Optimal induction intervention should include both renal structure injury repair and immune response suppression. Mesenchymal stem cells (MSCs) with potent anti-inflammatory, regenerative, and immune-modulatory properties are considered a candidate to prevent DGF and acute rejection in renal transplantation. Thus, this prospective multicenter paired study aimed to assess the clinical value of allogeneic MSCs as induction therapy to prevent both DGF and acute rejection in deceased donor renal transplantation. Methods Forty-two renal allograft recipients were recruited and divided into trial and control groups. The trial group (21 cases) received 2 × 106/kg human umbilical-cord-derived MSCs (UC-MSCs) via the peripheral vein before renal transplantation, and 5 × 106 cells via the renal artery during the surgical procedure. All recipients received standard induction therapy. Incidences of DGF and biopsy-proven acute rejection were recorded postoperatively and severe postoperative complications were assessed. Graft and recipient survivals were also evaluated. Results Treatment with UC-MSCs achieved comparable graft and recipient survivals with non-MSC treatment (P = 0.97 and 0.15, respectively). No increase in postoperative complications, including DGF and acute rejection, were observed (incidence of DGF: 9.5% in the MSC group versus 33.3% in the non-MSC group, P = 0.13; Incidence of acute rejection: 14.3% versus 4.8%, P = 0.61). Equal postoperative estimated glomerular filtration rates were found between the two groups (P = 0.88). All patients tolerated the MSCs infusion without adverse clinical effects. Additionally, a multiprobe fluorescence in situ hybridization assay revealed that UC-MSCs administered via the renal artery were absent from the recipient’s biopsy sample. Conclusions Umbilical-cord-derived MSCs can be used as clinically feasible and safe induction therapy. Adequate timing and frequency of UC-MSCs administration may have a significant effect on graft and recipient outcomes. Trial registration NCT02490020. Registered on June 29 2015

As one kind of significant manufacturing equipment, computer numerical control (CNC) machine tools have to be endowed with new functions to meet the requirements of processing devices in the era of “Industry 4.0.”Inter-connection and intelligence are the fundamental characteristics of CNC machine tools in this era. To make CNC machine tools be more accessible and promote them to a higher level of intelligence, this paper presents a new architecture of CNC machine tools based on a cyberphysical system and fog computing, named as a fog computing-based cyber-physical machine tool system (FC-CPMTS). The definition, functions, and hierarchical structure of the FC-CPMTS are described respectively. CNC machine tools, cyber space, and human beings are connected closely through sensing, computing, communicating, and controlling in the FC-CPMTS. The application of fog computing enhances autonomy and collaboration of CNC machine tools. It also reduces network traffic and calculation workload of the cloud platform in the FC-CPMTS. To demonstrate the rationality and feasibility of the FC-CPMTS, an FC-CPMTS for a heavy-duty CNC machine tool is taken as a case study. The result shows that autonomy, intelligence, interconnection, and interoperability of the CNC machine tool are improved.

Segmentation, propagation, and linkage of normal faults often occur in regions of active extension, and observations of the distribution and structural properties of segment boundaries can provide important insights for seismic hazard assessment. In this study, we carry out quantitative geomorphological analysis to evaluate the relative tectonic activity along the Langshan Piedmont Fault (LPF), which bounds the NW margin of the Hetao Graben, North China. On the basis of obtained morphometric indices (HI, BS, Smf, VF, SLK, and χ), tectonic knickpoint heights, footwall topography, and small unmanned aerial vehicles (sUAV)-based field observations, we demonstrate that: (i) The Langshan landscape is in a state of disequilibrium in response to active rock uplift and channel incision; (ii) The LPF consists of two major fault segments with lengths of 65 and 95 km, respectively, which likely have been linked with each other; (iii) Rupturing of the whole of one segment can generate an earthquake of M w ~7.3–7.5, and earthquake magnitude may reach M w ~7.8 if the entire fault trace of ~160 km is ruptured, posing a significant seismic risk in the western Hetao Graben. These findings would further our understanding of normal fault evolution through space and time in actively extending regions.

Abstract Ecological processes are generally scale-dependent and there is little consensus about the relative importance of deterministic versus stochastic processes in driving patterns of biological diversity. We investigated how the relationship between functional dispersion and environmental gradients changes with spatial scale in subtropical freshwater lakes. The functional alpha and beta dispersions of all the tested traits were significantly under-dispersed across spatial scales and along environmental gradients. Results showed more functional similarity within communities in leaf dry mass content and flowering duration but less functional turnover among communities in all the tested traits at regional scales (Yunnan-Guizhou plateau and the middle and low reaches of the Yangtze River). The strengths and directions of environmental effects on the functional alpha and beta dispersions depended on the selected traits, diversity metrics and spatial scales. Surprisingly, broad-scale factors - elevation and water transparency - decreased the functional turnover for most traits along the gradients, whereas fine-scale factors - water depth - produced the opposite patterns along the gradient, depending on the trait selected. Our study highlights the dominant role of deterministic assembly processes in structuring the local functional composition and governing the spatial functional turnover of macrophyte communities across multiple spatial scales.

The microscopic pore structure of coal affects the content of adsorbed gas. The microstructure of coal sample before and after loading is different, which will affect the adsorption and permeability of coal seam gas. In order to study this difference, the authors carried out mercury intrusion experiments on coal containing different coal samples and used nondestructive nuclear magnetic resonance (NMR) techniques, scanning electron microscopy, and transmission electron microscopy, to study the microstructure of coal samples before and after loading. The experimental results show that the pores of coal samples are mainly micropores and small pores, and the mesopores and macropores are relatively few. The T2 spectrum area of the coal sample is significantly increased after loading, and the parallel-layer coal samples’ T2 spectrum area is 46735, which is 9112 more than the vertical layer coal samples. The T2 spectrum of the vertical coalbed of saturated water samples shows a three-peak shape, the peak of the T2 spectrum is 12692, and the parallel bedding shows a bimodal morphology. The peak area of the T2 spectrum is 11277. The permeability of the parallel bedding coal sample is good, and the coal sample exhibits anisotropic properties. The pores and cracks of the coal samples increased after loading, and the localized area of the coal sample collapsed and formed a fracture zone, which was not conducive to the occurrence of coal seam gas. Further explanation of the changes in the permeability of the coal sample before and after loading will affect the gas storage and transportation.

The microscopic pore development of most coal seams in China leads to different permeability of coal seams and different gas drainage efficiency. Representative three coal rank coal samples were selected for saturation-centrifugation observation. The microscopic pore characteristics of coal samples were measured by nuclear magnetic resonance and liquid nitrogen adsorption methods. The experimental results showed that the coal samples were subjected to saturation-centrifugation and nuclear magnetic resonance (NMR) tests. It was found that the pores of the low-rank coal (XJ-1, XJ-2) were developed at various stages, and the connectivity between the pores was good and the permeability was also good. The adsorption pores of the intermediate coal (HB-1, HB-2) and high-rank coal (ZM-1, ZM-2) were relatively developed, and the connectivity between the pores was slightly poor. The parallel coal seam samples of coals of different ranks were better than the vertical bedding. The adsorption of liquid nitrogen showed that the low-order coal had more open pores and good gas permeability; the high-order coal had more openings at one end, more ink bottles, and narrow holes, and the gas permeability was not good. Studying the micropore structure and permeability of coals of different ranks has guiding significance for mastering the law of coal seam gas storage and transportation, extracting drilling arrangements, and increasing gas drainage and reducing greenhouse effect.

Soil microorganisms play an important role in the ecosystem, and have a certain relationship with the continuous cropping obstacles, which are common with sweet potato. However, there are few reports on the effects of continuous cropping of sweet potato on the microbial community structure in the rhizospheric soil. Here, we investigated the effects of continuous cropping of sweet potato on the fungal community structure in rhizospheric soil, in order to provide theoretical basis for prevention and control of continuous cropping obstacles. This study used X18 and Y138 varieties as experimental materials. Soil samples were collected during the early period of planting and harvest in two consecutive years, and fungi were analyzed using Illumina Miseq. Results showed that the fungi diversity and richness in rhizospheric soil of X18 and Y138 were significantly increased after continuous cropping; the most dominant fungi phylum was Ascomycota, which decreased significantly after continuous cropping. In addition, the content of beneficial fungi such as Chaetomium was reduced, while that of harmful fungi such as Verticillium, Fusarium, and Colletotrichum were increased. The composition of X18 and Y138 fungal community in the same sampling period after continuous cropping was similar, although that of the same sweet potato variety significantly differed with the sampling period. Overall, our results indicate that continuous cropping alters the fungal community structure of the sweet potato rhizospheric soil, such that the content of beneficial fungi decrease, while that of harmful fungi increase, thereby increasing soil-borne diseases and reducing the yield and quality of sweet potato. Furthermore, these effects are different for different sweet potato varieties. Thus, during actual production, attention should be paid to maintain the stability of sweet potato rhizospheric soil micro-ecology through rotation or application of microbial fertilizers and soil amendments to alleviate continuous cropping obstacles.

Having great impacts on machining precision, thermal error is one of the main error sources for heavy-duty computer numerical control machine tools. Thermal error compensation using prediction models with temperature field is an effective way to improve machining precision of computer numerical control machine tools. The accuracy and robustness of thermal error prediction models depend considerably on the selection of temperature measurement points. Too many temperature measurement points will increase the complexity of thermal error prediction models and incur over-fitting problems. To improve the complexity and performances of prediction models, a selection method of key temperature measurement points based on density peaks clustering is presented in this article. This method is able to cluster massive temperature measurement points quickly and select the key temperature measurement point which characterizes the common feature of each cluster automatically. It is verified on the ZK5540A heavy-duty computer numerical control gantry drilling machine tool. Six key temperature measurement points are selected from the total 222 temperature measurement points with this method. Then, the back propagation neural network optimized by genetic algorithm thermal error model with the six key temperature measurement points is built and the accuracy and robustness of the model are analyzed. The results show that the model has high prediction accuracy and strong robustness.

The tensile force on the hanger cables of a suspension bridge is an important indicator of the structural health of the bridge. Tensile force estimation methods based on the measured frequency of the hanger cable have been widely used. These methods empirically pre-determinate the corresponding model order of the measured frequency. However, because of the uncertain flexural rigidity, this empirical order determination method not only plays a limited role in high-order frequencies, but also hinders the online cable force estimation. Therefore, we propose a new method to automatically identify the corresponding model order of the measured frequency, which is based on a Markov chain Monte Carlo (MCMC)-based Bayesian approach. It solves the limitation of empirical determination in the case of large flexural rigidity. The tensile force and the flexural rigidity of cables can be calculated simultaneously using the proposed method. The feasibility of the proposed method is validated via a numerical study involving a finite element model that considers the flexural rigidity and via field application to a suspension bridge.

Analysis of the multiple factors affecting human identification ability based on pyroelectric infrared technology is a complex problem. First, we examine various sensed pyroelectric waveforms of the human body thermal infrared signal and reveal a mechanism for affecting human identification. Then, we find that the mechanism is decided by the distance, human target, pyroelectric infrared (PIR) sensor, the body type, human moving velocity, signal modulation mask, and Fresnel lens. The mapping relationship between the sensed waveform and multiple influencing factors is established, and a group of mathematical models are deduced which fuse the macro factors and micro factors. Finally, the experimental results show the macro-factors indirectly affect the recognition ability of human based on the pyroelectric technology. At the same time, the correctness and effectiveness of the mathematical models is also verified, which make it easier to obtain more pyroelectric infrared information about the human body for discriminating human targets.

The development of myopia is associated with scleral remodeling, but it is unclear which factors regulate this process. This study investigated bone morphogenetic protein-2 (BMP-2) expression in the sclera of guinea pigs with lens-induced myopia (LIM) and after recovery from myopia and evaluated the effect of BMP-2 on extracellular matrix (ECM) synthesis in human scleral fibroblasts (HSFs) cultured in vitro. Lens-induced myopia was brought about in two groups of guinea pigs (the lens-induced myopia and myopia recovery groups) by placing -4.00 D lenses on the right eye for three weeks. The left eye served as a contralateral control. In the recovery group, the lenses were removed after one week. The refractive power and axial length of the eyes were measured, and the BMP-2 expression levels in the sclera were measured. After three weeks, the lens-induced eyes acquired relative myopia in both groups of guinea pigs. Immunostaining of the eyeballs revealed significantly decreased BMP-2 expression in the posterior sclera of the myopic eyes compared to the contralateral eyes. One week after lens removal, BMP-2 expression recovered, and no differences were observed between the experimental and contralateral eyes in the recovery group. HSFs were cultured with BMP-2 or transforming growth factor-β1 (TGF-β1). Type I and type III collagen synthesis was significantly up-regulated following BMP-2 treatment in culture after one and two weeks, but the ratio of type III to type I collagen mRNA was not increased. Biosynthesis of glycosaminoglycan (GAG) and aggrecan was increased in HSFs treated with BMP-2. Some chondrogenesis-associated genes expression increased in HSFs treated with BMP-2. From this study, we concluded that BMP-2 is involved in scleral remodeling in the development and recovery of lens-induced myopia.