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Abstract Background Interleukin-4 inducible gene 1 (IL4I1) regulates tumor progression in numerous tumor types. However, its correlation with immune infiltration and prognosis of patients in a pan-cancer setting remains unclear. Methods Data from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), UALCAN, Clinical Proteomic Tumor Analysis Consortium (CPTAC), Gene Expression Omnibus (GEO), cBioPortal, Cancer Single-cell State Atlas (CancerSEA), and Tumor IMmune Estimation Resource(TIMER) databases were used to evaluate IL4I1 expression, clinical features and prognostic effects, gene set enrichment, and correlation with immune cell infiltration, as well as the relationship between IL4I1 methylation and expression and survival prognosis. Correlations with 192 anticancer drugs were also analyzed. Results IL4I1 was significantly overexpressed in the majority of tumors, and the imbalance of IL4I1 was significantly correlated with overall survival and pathological stage. Moreover, total IL4I1 protein was increased in cancer. Therefore, IL4I1 may be used as a prognostic biomarker or protective factor in numerous types of cancer. The methylation level of IL4I1 may also be used as a prognostic marker. The functional enrichment of IL4I1 was closely related to the immunomodulatory pathway. In addition, the level of tumor-associated macrophage infiltration was positively correlated with the expression of IL4I1 in pan-cancerous tissues. scRNA-seq analysis suggested that IL4I1 differ significantly among different cells in the tumor microenvironment and was most enriched in macrophages. Various immune checkpoint genes were positively correlated with IL4I1 expression in most tumors. In addition, patients with high IL4I1 expression may be resistant to BMS-754807 and docetaxel, but sensitive to temozolomide. Conclusion IL4I1 may play a role as promoter of cancer and prognostic indicator in patients. High expression of IL4I1 is associated with the state of tumor immunosuppression and may contribute to tumor-associated macrophage invasion. Therefore, IL4I1 may be a new therapeutic target for the treatment and prognosis of patients with cancer.

The past three decades have witnessed extensive studies on motion-planning and tracking-control for autonomous vehicles (AVs). There is, however, a lack of studies on effective design methods for AVs, which consist of the subsystems of the mechanical vehicle, tracking-control, motion-planning, etc. To tackle this problem, this paper proposes a design approach for AVs. The proposed method features a design framework with two layers: at the upper layer, a particle swarm optimization (PSO) algorithm serves as a solver to a multi-objective optimization problem for desired AV trajectory-tracking performance; at the lower layer, a coupled dynamic analysis is conducted among the three subsystems, i.e., a nonlinear model for the mechanical vehicle, a motion-planning module, and a controller based on nonlinear model predictive control (NLMPC) for direction control. The simulation results demonstrate that the proposed method can effectively determine the desired design variables for the NLMPC controller and the mechanical vehicle to achieve optimal trajectory-tracking performance. The research findings from this work provide guidelines for designing AVs.

Articulated heavy vehicles exhibit poor lateral stability, which may lead to unstable motion modes, e.g., trailer-sway and jackknifing, causing severe accidents. Varying relevant vehicle parameters improves the static stability but degrades the dynamic stability. The past studies focused either on the static or dynamic stability alone. However, little attention has been paid to exploring the trade-off between the static and dynamic stabilities. To gain design insights for active safety systems for AHVs, this article studies this trade-off systematically. To this end, a systematic method is proposed to conduct the linear stability and trade-off analysis. To implement and demonstrate the proposed method, a linear three-degrees-of-freedom yaw-plane model is generated to represent a tractor/semi-trailer. A trade-off analysis is conducted considering two tractor rear-axle configurations and three trailer payload arrangements. In each case, simulation is performed in both steady-state and transient testing maneuvers. To validate the linear stability analysis based on the linear yaw-plane model, two nonlinear TruckSim models are introduced, and the corresponding simulation is conducted. Insightful understanding of the trade-off is gained through analyzing the simulation results, and the linear stability analysis will provide valuable guidelines for the design and development of active safety systems for AHVs.

Autonomous vehicles face challenges in small-target detection and, in particular, in accurately identifying traffic lights under low visibility conditions, e.g., fog, rain, and blurred night-time lighting. To address these issues, this paper proposes an improved algorithm, namely KCS-YOLO (you only look once), to increase the accuracy of detecting and recognizing traffic lights under low visibility conditions. First, a comparison was made to assess different YOLO algorithms. The benchmark indicates that the YOLOv5n algorithm achieves the highest mean average precision (mAP) with fewer parameters. To enhance the capability for detecting small targets, the algorithm built upon YOLOv5n, namely KCS-YOLO, was developed using the K-means++ algorithm for clustering marked multi-dimensional target frames, embedding the convolutional block attention module (CBAM) attention mechanism, and constructing a small-target detection layer. Second, an image dataset of traffic lights was generated, which was preprocessed using the dark channel prior dehazing algorithm to enhance the proposed algorithm’s recognition capability and robustness. Finally, KCS-YOLO was evaluated through comparison and ablation experiments. The experimental results showed that the mAP of KCS-YOLO reaches 98.87%, an increase of 5.03% over its counterpart of YOLOv5n. This indicates that KCS-YOLO features high accuracy in object detection and recognition, thereby enhancing the capability of traffic light detection and recognition for autonomous vehicles in low visibility conditions.

Integrating lithium metal anodes with polymer electrolytes is a promising technology for the next generation high-energy-density rechargeable batteries. As the progress is often hindered by the dendrite growth upon cycling, quantifying three-dimensional (3D) microstructures of dendrites in polymer electrolytes is essential to better understanding of dendrite formation for the development of mitigation strategies. Techniques for 3D quantification and visualization of dendrites, especially those with low Li contents, are rather limited. This study reports quantitative measurements of the spatial distribution of Li dendrites grown in solid polymer electrolytes using 3D tomographic neutron depth profiling (NDP) with improved spatial resolution, compositional range, and data presentation. Data reveal heterogeneous distribution of Li over length scales from tens nanometers to centimeters. While most dendrites grow from the plating toward the stripping electrode with dwindling Li quantities, dendrites apparently grown from the Li-stripping electrode are also observed. The discovery is only possibly due to the unique combination of the high specificity and high sensitivity of the neutron activation analysis of Li isotope.

BackgroundDistal arthrogryposis type 5D (DA5D) represents a subtype of distal arthrogryposis (DA) characterized by congenital joint contractures in the distal extremities. DA5D is inherited in a rare autosomal recessive manner and is associated with the ECEL1 gene. In this report, we describe a case of an infant with bilateral knee contractures and ptosis, caused by a novel compound heterozygous mutation of ECEL1.Case presentationWe conducted DNA extraction, whole-exome sequencing analysis, and mutation analysis of ECEL1 to obtain genetic data on the patient. We subsequently analyzed the patient’s clinical and genetic data. The proband was a 6 months-old male infant who presented with significant bilateral knee contracture disorders and bilateral ptosis. MRI demonstrated cartilage degradation in knee joint. Whole-exome sequencing of the patient’s DNA revealed a compound heterozygous mutation of c.2152-15C>A and c.110_155del in ECEL1. Analysis with the MutationTaster application indicated that c.110_155del was pathogenic (probability = 1), causing frameshift mutations affecting 151 amino acids (p.F37Cfs*151). The truncated protein lost the substructure of a transmembranous site based on the predicted protein crystal structure AF-O95672-F1. The variant of c.2152-15C>A of ECEL1 was also predicted to be disease-causing (probability = 0.98) as it impaired the methylation of ECEL1 serving as an H3K27me3 modification site, which led to the dysfunction of the second topological domain. Therefore, we concluded that the compound heterozygous mutation caused the pathogenic phenotype of this proband.ConclusionThe present case highlights the usefulness of molecular genetic screening in diagnosing unexpected joint disorder. Identification of novel mutations in the ECEL1 gene broadens the mutation spectrum of this gene and adds to the genotype-phenotype map of DA5D. Furthermore, rapid whole-exome sequencing analysis enabled timely diagnosis of this rare disease, facilitating appropriate treatment and scheduled follow-up to improve clinical outcomes.

Abstract The cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signalling pathway has been a promising target for anticancer immunity, but rationally activating and enhancing this pathway in tumour cells is critical. Herein, a glutathione sensitive ZnFe2O4‐based nanosystem is developed to programmatically initiate and enhance the STING signalling pathway in tumour cells. The prepared ZnFe2O4 nanoparticles were coated with cancer cell membrane (CCM), which enabled the nanosystem target tumour cells. In tumour cells, ZnFe2O4 nanoparticles could be disintegrated by responding to high level glutathione, and the released Fe3+ generated reactive oxygen species to induce the DNA leakage into the cytoplasm to stimulate cGAS. Then Zn2+ promoted cGAS‐DNA phase separation to intensify the cGAS enzymatic activity. In addition, the low dose encapsulation of paclitaxel (PTX) acting as an antimitotic agent (ZnFe2O4‐PTX@CCM) ensured the sustained activation of cGAS/STING pathway. The in vitro and in vivo results confirmed that ZnFe2O4‐PTX@CCM elevated the cGAS/STING activity, promoted dendritic cell maturation, increased cytotoxic T lymphocyte and natural killer cells infiltration, eventually inhibiting the tumour progress and postoperative recurrence. This study provided feasible references on constructing STING activation nanosystem for tumour immunotherapy.

Abstract Background Greater trochanteric pain syndrome (GTPS) possesses a harmful influence on quality of life. Numerous conservative management modalities with varying success have been proposed for patients with GTPS. However, it is not clear which treatment is more effective for reducing pain. The purpose of this Bayesian analysis was to assess the current evidence for the effectiveness of conservative treatments on improving Visual Analog Scale (VAS) pain scoring of GTPS and to determine the most effective treatment protocol. Methods A comprehensive study search was performed from inception until July 18, 2022, via the electronic databases PubMed, the Cochrane Library, and Web of Science for potential research. The risk of bias assessment for the included studies was independently performed based on the Cochrane Collaboration Risk of Bias Tool. Bayesian analysis was conducted by using ADDIS software (v1.16.5). The DerSimonian-Laird random effects model was used to perform the traditional pairwise meta-analysis. Results Eight full-text articles with a total of 596 patients with GTPS were included in the analysis. In comparing ultrasound-guided platelet-rich plasma application (PRP-U) to ultrasound-guided corticosteroid injection (CSI-U), patients who received PRP therapy experienced reduced pain as the VAS decreased significantly (MD, -5.21; 95% CI, -6.24 to -3.64). VAS score in group of extracorporeal shockwave treatment (ESWT) was significant improved than that in exercise (EX) group (MD, -3.17; 95% CI, -4.13 to -2.15). There were no statistically significantly different VAS scores between the CSI-U group and the CSI under landmark (CSI-B) group. The treatment efficacy rankings of the different treatments on improving VAS scores showed that the most likely efficacious treatment was PRP-U (99%) followed by ESWT (81%), CIS-U (58%), usual care (48%), CIS-B (54%), and EX (84%). Conclusion Bayesian analysis revealed that PRP injection and ESWT are relatively safe and effective in the treatment of GTPS. More multicenter high-quality randomized clinical trials with large sample sizes are still needed in the future to provide further evidence.

Abstract Background Radioresistance inducing by hypoxic microenvironment of hepatocellular carcinoma is a major obstacle to clinical radiotherapy. Advanced nanomedicine provides an alternative to alleviate the hypoxia extent of solid tumor, even to achieve effective synergistic treatment when combined with chemotherapy or radiotherapy. Results Herein, we developed a self-assembled nanoparticle based on hemoglobin and curcumin for photoacoustic imaging and radiotherapy of hypoxic hepatocellular carcinoma. The fabricated nanoparticles inhibited hepatoma migration and vascular mimics, and enhanced the radiosensitivity of hypoxic hepatoma cells in vitro via repressing cell proliferation and DNA damage repair, as well as inducing apoptosis. Benefit from oxygen-carrying hemoglobin combined with polyphenolic curcumin, the nanoparticles also effectively enhanced the photoacoustic contrast and the efficacy of radiotherapy for hepatocellular carcinoma in vivo. Conclusions Together, the current study offered a radiosensitization platform for optimizing the efficacy of nanomedicines on hypoxic radioresistant tumor. Graphical Abstract

Online videos have become the most popular method to obtain information for the public in recent years, such as TikTok and YouTube, and regional sites like Bilibili and Douyin. Compared with its growing influence, the analysis of user behavior on video sites is still less investigated. Herein, we fetch the video data from Bilibili.com and analyze the video views, comments, and other behaviors on the website. We found that the description model based on the Hawkes process can accurately predict the video views, which suggests that on the Bilibili website, the self-incentive mechanism of information cascade diffusion plays a decisive role in online views. Meanwhile, we also found that the view increment of the videos during the same period of time conforms to the general power-law distribution.

Objective: The objective of this study is to explore the bacterial distribution characteristics of air and bed environment in patients with cerebrovascular diseases and to analyze the relationship between bacterial distribution and nosocomial infection in patients with cerebrovascular diseases. Methods: In this study, the inpatients with cerebrovascular diseases who suffer from nosocomial infection are taken as the research objects. The pathogenic characteristics of the air environment in the ward and the environment in the bed unit are monitored, and the samples of cerebrovascular patients are collected for identification and drug sensitivity detection. The changes of the number of pathogens in different seasons are statistically compared, and the drug sensitivity test results of various pathogens are analyzed. Results: In large wards, the number of pathogens in the air environment in winter is significantly higher than that in spring. In summer, the number of pathogens in pillow environment is significantly more than that in small wards. Gram-negative bacilli are the main pathogens in the four seasons, followed by Gram-positive cocci and less fungal infections. Among them, Staphylococcus aureus is the main Gram-positive coccus, which is sensitive to vancomycin and other therapeutic drugs, and resistant to erythromycin and other therapeutic drugs. Gram-negative bacteria are mainly Klebsiella pneumoniae and Pseudomonas aeruginosa. K. pneumoniae is sensitive to imipenem, tekacillin, meropenem and ceftitam, and resistant to ampicillin. P. aeruginosa is sensitive to cefuroxime ester, cefazolin and cefuroxime sodium. It is resistant to ampicillin, ceftitam, compound sinomine and ampicillin plus sulbactam. Candida albicans is the main fungus, which is sensitive to ketoconazole, fluconazole, amphotericin and nystatin. Conclusion: The number of pathogenic bacteria in the ward environment of patients with cerebrovascular disease is affected by the size of the room and season. The main pathogenic bacteria are Gram-negative bacilli, followed by Gram-positive cocci and less fungal infections. Keywords: Cerebrovascular disease, Hospital infection, Pathogenic characteristics, Air environment, Bed unit environment

Car–trailer combinations can experience unstable motion modes such as trailer-sway, jackknifing and rollover that can lead to fatal accidents. These unstable motions can be mitigated with the use of an active trailer steering (ATS) system. Prior studies in ATS have leveraged the linear quadratic regulator (LQR) as an ATS controller but for many of these designs it was assumed that the vehicle and operating parameters were constant. In reality, vehicle and operating parameters may vary and have an impact on the stability of a car–trailer combination. In this paper, the weighting matrices of the LQR controller are determined using the GDE3 evolutionary optimization algorithm with the objective of addressing the design trade off between minimizing the car–trailer’s path-following performance for low vehicle speeds and minimizing the rearward amplification for high vehicle speeds. The effectiveness of the approach is demonstrated using a numerical simulation car–trailer model developed in the CarSim simulator. Our results show that the multi-objective tuned gain scheduling controller outperforms a non-tuned gain scheduling controller in terms of improving the lateral stability and the path following performance of car–trailer combinations in driver in the loop single lane-change maneuvers at a constant vehicle forward speed.

Macrolide-resistant Streptococcus suis is highly prevalent worldwide. The acquisition of the erm(B) gene mediated by mobile genetic elements (MGEs) in particular integrative and conjugative elements (ICEs) is recognized as the main reason for the rapid spread of macrolide-resistant streptococcal strains. However, knowledge about different erm(B)-carrying elements responsible for the widespread of macrolide resistance and their transferability in S. suis remains poorly understood. In the present study, two erm(B)- and tet(O)-harboring putative ICEs, designated as ICESsuYSB17_rplL and ICESsuYSJ15_rplL, and a novel erm(B)- and aadE-spw-like-carrying genomic island (GI), named GISsuJHJ17_rpsI, were identified to be excised from the chromosome and transferred among S. suis strains with different serotypes. ICESsuYSB17_rplL and ICESsuYSJ15_rplL were integrated downstream the rplL gene, a conserve locus of the ICESa2603 family. GISsuJHJ17_rpsI, with no genes belonging to the conjugation module, was integrated into the site of rpsI. All transconjugants did not exhibit obvious fitness cost by growth curve and competition assays when compared with the recipient. The results demonstrate that different erm(B)-carrying elements were presented and highlight the role of these elements in the dissemination of macrolide resistance in S. suis.

Solvothermal reaction of 4,4’,4’-nitrilotribenzoic acid (H3TCA) with Ca(NO3)2·4H2O and Cd(NO3)2·4H2O successfully afforded a heterometallic compound, that is, [Cd2Ca(TCA)2(DMA)2(H2O)3]n·2n(DMA) (1, DMA = N,N’-dimethylacetamide). The structure of 1 was further characterized through EA, diffraction of single crystal X-ray, and thermogravimetric analysis (TGA) together with powder X-ray diffraction (PXRD). Moreover, complex 1’s luminescent performance in solid state was also discussed at environmental temperature. The applications on the ischemic cerebral infarction therapy were evaluated, and the specific mechanism was investigated at the same time. Firstly, the hypersensitivity C-reactive protein (hs-CRP) content in human brain microvascular endothelial cell (HBMEC) was measured with real-time reverse transcription-polymerase chain reaction (RT-PCR). Then, interleukin-18 and interleukin-1β content released through the HBMEC was detected with enzyme-linked immunosorbent assay (ELISA).

This article mainly considers the problem of trajectory tracking control problem of quad-rotor system with velocity constrain under the consideration of safety. A model-based nonlinear controller is proposed which can guarantee not only the asymptotical stability for control system but also the velocity under a safe range. Firstly, based on backstepping design, a position tracking controller with velocity constraint is proposed to ensure that the desired position can be tracked with velocity constrains. At the second step, considering attitude subsystem, an attitude controller is proposed to improve the attitude dynamic response performance. Finally, the validity and superiority of the design has been verified in simulation results.

Latent Epstein-Barr virus (EBV) infection is strongly associated with several malignancies, including B-cell lymphomas and epithelial tumors. EBNA1 is a key antigen expressed in all EBV-associated tumors during latency that is required for maintenance of the EBV episome DNA and the regulation of viral gene transcription. However, the mechanism utilized by EBV to maintain latent infection at the levels of posttranslational regulation remains largely unclear. Here, we report that EBNA1 contains two SUMO-interacting motifs (SIM2 and SIM3), and mutation of SIM2, but not SIM3, dramatically disrupts the EBNA1 dimerization, while SIM3 contributes to the polySUMO2 modification of EBNA1 at lysine 477 in vitro. Proteomic and immunoprecipitation analyses further reveal that the SIM3 motif is required for the EBNA1-mediated inhibitory effects on SUMO2-modified STUB1, SUMO2-mediated degradation of USP7, and SUMO1-modified KAP1. Deletion of the EBNASIM motif leads to functional loss of both EBNA1-mediated viral episome maintenance and lytic gene silencing. Importantly, hypoxic stress induces the SUMO2 modification of EBNA1, and in turn the dissociation of EBNA1 with STUB1, KAP1 and USP7 to increase the SUMO1 modification of both STUB1 and KAP1 for reactivation of lytic replication. Therefore, the EBNA1SIM motif plays an essential role in EBV latency and is a potential therapeutic target against EBV-associated cancers.

Abstract Background Cronobacter species are associated with severe foodborne infections in neonates and infants, with particular pathovars associated with specific clinical presentations. However, before 2008 the genus was regarded as a single species named Enterobacter sakazakii which was subdivided into 8 phenotypes. This study re-analyzed, using multi-locus sequence typing (MLST) and whole genome sequence with single nucleotide polymorphism analysis (WGS-SNP), 52 strains which had been identified as Enterobacter sakazakii as according to the convention at the time of isolation. These strains had been isolated from dairy product imports into China from 9 countries between 2005 and 6. Bioinformatic analysis was then used to analyze the relatedness and global dissemination of these strains. Result FusA allele sequencing revealed that 49/52 strains were Cronobacter sakazakii, while the remaining 3 strains were Escherichia coli, Enterobacter cloacae, and Franconibacter helveticus. The C. sakazakii strains comprised of 8 sequence types (STs) which included the neonatal pathovars ST1, ST4 and ST12. The predominant sequence type was ST13 (65.3%, 32/49) which had been isolated from dairy products imported from 6 countries. WGS-SNP analysis of the 32 C. sakazakii ST13 strains revealed 5 clusters and 5 unique strains which did not correlate with the country of product origin. Conclusion The mis-identification of E. coli, E. cloacae and F. helveticus as Cronobacter spp. reinforces the need to apply reliable methods to reduce the incidence of false positive and false negative results which may be of clinical significance. The WGS-SNP analysis demonstrated that indistinguishable Cronobacter strains within a sequence type can be unrelated, and may originate from multiple sources. The use of WGS-SNP analysis to distinguishing of strains within a sequence type has important relevance for tracing the source of outbreaks due to Cronobacter spp.

This paper presents a design synthesis method for robust controllers of active vehicle suspensions (AVSs). Various control techniques have been applied to the design of AVSs for enhancing ride comfort and handling performance of ground vehicles. However, most of these model-based controller designs show poor robustness when the vehicle models are not accurate and operating conditions vary. To address the poor robustness problem of AVSs, a new controller is designed using the H∞ loop-shaping control technique. The controller targets robustness issues on vehicle models with parametric uncertainties and unmodelled dynamics. To facilitate the robust controller design, a design synthesis method is proposed: the H∞ loop-shaping controller design is formulated as a multi-objective optimization problem, the weighting functions’ parameters of the controller are treated as design variables, the expensive computing loads are handled by a parallel computing technique, and the solution of the optimization problem is the desired robust AVS controller. Simulation results demonstrate the benefits of the proposed AVS design.

Half-Heusler alloys such as the (Zr,Hf)NiSn intermetallic compounds are important thermoelectric materials for converting waste heat into electricity. Reduced electrical resistivity at the hot interface between the half-Heusler material and a metal contact is critical for device performance; however, this is yet to be achieved in practice. Recent experimental work suggests that a coherent interface between half-Heusler and full-Heusler compounds can form due to diffusion of transition metal atoms into the vacant sublattice of the half-Heusler lattice. We study theoretically the structural and electronic properties of such an interface using a first-principles based approach that combines ab initio calculations with macroscopic modeling. We find that the prototypical interface HfNi2Sn/HfNiSn provides very low contact resistivity and almost ohmic behavior over a wide range of temperatures and doping levels. Given the potential of these interfaces to remain stable over a wide range of temperatures, our study suggests that full-Heuslers might provide nearly ideal electrical contacts to half-Heuslers that can be harnessed for efficient thermoelectric generator devices.

In this study, we describe an inter-laboratory collaborative ring trial validation of species-specific TaqMan real-time PCR assays for the detection of porcine- and chicken-derived materials in meat products. We comprehensively evaluated the performance of these assays in different environments and situations. This validation included the participation of thirteen laboratories across Europe and Asia. The results from the thirteen participating laboratories were analyzed to determine the specificity, accuracy, false positive rate, limit of detection (LOD), and probability of detection (POD) of the developed methods. These results indicated that the methods developed to detect porcine- and chicken-derived materials in meat products are robust and repeatable. The false positive and false negative rates were both 0%, and the LOD was determined to be five copies/reaction. The laboratory standard deviation (σL) was 0.30 for both detection methods, indicating that the developed methods are suitable for detection and identification of the porcine- and chicken-derived materials in meat products.

Meat products often consist of meat from multiple animal species, and inaccurate food product adulteration and mislabeling can negatively affect consumers. Therefore, a cost-effective and reliable method for identification and quantification of animal species in meat products is required. In this study, we developed a duplex droplet digital PCR (dddPCR) detection and quantification system to simultaneously identify and quantify the source of meat in samples containing a mixture of beef (Bos taurus) and pork (Sus scrofa) in a single digital PCR reaction tube. Mixed meat samples of known composition were used to test the accuracy and applicability of this method. The limit of detection (LOD) and the limit of quantification (LOQ) of this detection and quantification system were also identified. We conclude that our dddPCR detection and quantification system is suitable for quality control and routine analyses of meat products.