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Abstract Backgrounds Papillary thyroid cancer (PTC), which is often driven by acquired somatic mutations in BRAF genes, is the most common pathologic type of thyroid cancer. PTC has an excellent prognosis after treatment with conventional therapies such as surgical resection, thyroid hormone therapy and adjuvant radioactive iodine therapy. Unfortunately, about 20% of patients develop regional recurrence or distant metastasis, making targeted therapeutics an important treatment option. Current in vitro PTC models are limited in representing the cellular and mutational characteristics of parental tumors. A clinically relevant tool that predicts the efficacy of therapy for individuals is urgently needed. Methods Surgically removed PTC tissue samples were dissociated, plated into Matrigel, and cultured to generate organoids. PTC organoids were subsequently subjected to histological analysis, DNA sequencing, and drug sensitivity assays, respectively. Results We established 9 patient-derived PTC organoid models, 5 of which harbor BRAFV600E mutation. These organoids have been cultured stably for more than 3 months and closely recapitulated the histological architectures as well as mutational landscapes of the respective primary tumors. Drug sensitivity assays of PTC organoid cultures demonstrated the intra- and inter-patient specific drug responses. BRAFV600E inhibitors, vemurafenib and dabrafenib monotherapy was mildly effective in treating BRAFV600E-mutant PTC organoids. Nevertheless, BRAF inhibitors in combination with MEK inhibitors, RTK inhibitors, or chemotherapeutic agents demonstrated improved efficacy compared to BRAF inhibition alone. Conclusions These data indicate that patient-derived PTC organoids may be a powerful research tool to investigate tumor biology and drug responsiveness, thus being useful to validate or discover targeted drug combinations.

Various geostatistical models have been used in epidemiological research to evaluate ambient air pollutant exposures at a fine spatial scale. Few studies have investigated the performance of different exposure models on population-weighted exposure estimates and the resulting potential misclassification across various modeling approaches. This study developed spatial models for NO2 and PM2.5 and conducted exposure assessment in Beijing, China. It explored three spatial modeling approaches: variable dimension reduction, machine learning, and conventional linear regression. It compared their model performance by cross-validation (CV) and population-weighted exposure estimates. Specifically, partial least square (PLS) regression, random forests (RF), and supervised linear regression (SLR) models were developed based on an ordinary kriging (OK) framework for NO2 and PM2.5 in Beijing, China. The mean squared error-based R2 (R2mse) and root mean squared error (RMSE) in leave-one site-out cross-validation (LOOCV) were used to evaluate model performance. These models were used to predict the ambient exposure levels in the urban area and to estimate the misclassification of population-weighted exposure estimates in quartiles between them. The results showed that the PLS-OK models for NO2 and PM2.5, with the LOOCV R2mse of 0.82 and 0.81, respectively, outperformed the other models. The population-weighted exposure to NO2 estimated by the PLS-OK and RF-OK models exhibited the lowest misclassification in quartiles. For PM2.5, the estimates of potential misclassification were comparable across the three models. It indicated that the exposure misclassification made by choosing different modeling approaches should be carefully considered, and the resulting bias needs to be evaluated in epidemiological studies.

MiR399 plays an important role in plant growth and development. The objective of the present study was to elucidate the evolutionary characteristics of the MIR399 gene family in grapevine and investigate its role in stress response. To comprehensively investigate the functions of miR399 in grapevine, nine members of the Vvi-MIR399 family were identified based on the genome, using a miRBase database search, located on four chromosomes (Chr 2, Chr 10, Chr 15, and Chr 16). The lengths of the Vvi-miR399 precursor sequences ranged from 82 to 122 nt and they formed stable stem–loop structures, indicating that they could produce microRNAs (miRNAs). Furthermore, our results suggested that the 2 to 20 nt region of miR399 mature sequences were relatively conserved among family members. Phylogenetic analysis revealed that the Vvi-MIR399 members of dicots (Arabidopsis, tomato, and sweet orange) and monocots (rice and grapevine) could be divided into three clades, and most of the Vvi-MIR399s were closely related to sweet orange in dicots. Promoter analysis of Vvi-MIR399s showed that the majority of the predicted cis-elements were related to stress response. A total of 66.7% (6/9) of the Vvi-MIR399 promoters harbored drought, GA, and SA response elements, and 44.4% (4/9) of the Vvi-MIRR399 promoters also presented elements involved in ABA and MeJA response. The expression trend of Vvi-MIR399s was consistent in different tissues, with the lowest expression level in mature and young fruits and the highest expression level in stems and young leaves. However, nine Vvi-MIR399s and four target genes showed different expression patterns when exposed to low light, high light, heat, cold, drought, and salt stress. Interestingly, a putative target of Vvi-MIR399 targeted multiple genes; for example, seven Vvi-MIR399s simultaneously targeted VIT_213s0067g03280.1. Furthermore, overexpression of Vvi_MIR399e and Vvi_MIR399f in Arabidopsis enhanced tolerance to drought compared with wild-type (WT). In contrast, the survival rate of Vvi_MIR399d-overexpressed plants were zero after drought stress. In conclusion, Vvi-MIR399e and Vvi-MIR399f, which are related to drought tolerance in grapevine, provide candidate genes for future drought resistance breeding.

The hardness and wear resistance of the surface of TC4 titanium alloy, which is widely used in aerospace and other fields, need to be improved urgently. Considering the economy, environmental friendliness, and high efficiency, Si-reinforced Ti-based composite coatings were deposited on the TC4 surface by the high-speed wire-powder laser cladding method, which combines the paraxial feeding of TC4 wires with the coaxial feeding of Si powders. The microstructures and wear resistance of the coatings were analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM), Vickers hardness tester, and friction and wear tester. The results indicate that the primary composition of the coating consisted of α-Ti and Ti5Si3. The microstructure of the coating underwent a notable transformation process from dendritic to petal, bar, and block shapes as the powder feeding speed increased. The hardness of the composite coatings increased with the increasing Si powder feeding rate, and the average hardness of the composite coating was 909HV0.2 when the feeding rate reached 13.53 g/min. The enhancement of the microhardness of the coatings can be attributed primarily to the reinforcing effect of the second phase generated by Ti5Si3 in various forms within the coatings. As the powder feeding speed increased, the wear resistance initially improved before deteriorating. The optimal wear resistance of the coating was achieved at a powder feeding rate of 6.88 g/min (wear loss of 2.55 mg and friction coefficient of 0.12). The main wear mechanism for coatings was abrasive wear.

The incidence and mortality from malignant tumors continue to rise each year. Consequently, early diagnosis and intervention are vital for improving patient’ prognosis and survival. The traditional pathological tissue biopsy is currently considered the gold standard for cancer diagnosis. However, it suffers from several limitations including invasiveness, sometimes not repeatable or unsuitable, and the inability to capture the dynamic nature of tumors in terms of space and time. Consequently, these limit the application of tissue biopsies for the diagnosis of early-stage tumors and have redirected the research focus towards liquid biopsies. Blood-based liquid biopsies have thus emerged as a promising option for non-invasive assessment of tumor-specific biomarkers. These minimally invasive, easily accessible, and reproducible tests offer several advantages, such as being mostly complication-free and efficient at monitoring tumor progression and tracing drug resistance. Liquid biopsies show great potential for cancer prediction, diagnosis, and prognostic assessment. Circulating tumor-educated platelets (TEPs) possess the unique ability to absorb nucleic acids from the bloodstream and to modify transcripts derived from megakaryocytes in response to external signals. In addition, circulating free RNA (cfRNA) constitutes a significant portion of the biomolecules present in the bloodstream. This paper aims to provide a comprehensive overview of the current research status regarding TEP RNA and cfRNA in liquid biopsies from various tumor types. Our analysis includes cancers of the lung, liver, pancreas, breast, nasopharynx, ovary and colon, as well as multiple myeloma and sarcoma. By synthesizing this information, we intend to establish a solid theoretical foundation for exploring potential applications of circulating RNA as a reliable biomarker for tumor diagnosis and monitoring.

Purpose: The aim of this study was to apply the Six Sigma methodology and failure mode and effect analysis (FMEA) to mitigate errors in intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) treatment planning with the first clinical installation of RefleXion X1. Methods and Materials: The Six Sigma approach consisted of 5 phases: define, measure, analyze, improve, and control. The define, measure, and analyze phases consisted of process mapping and an FMEA of IMRT and SBRT treatment planning on the X1. The multidisciplinary team outlined the workflow process and identified and ranked the failure modes associated with the plan check items using the American Association of Physicists in Medicine Task Group 100 recommendations. Items with the highest average risk priority numbers (RPNs) and severity ≥7 were prioritized for automation using the Eclipse Scripting Application Programming Interface (ESAPI). The “improve” phase consisted of developing ESAPI scripts before the clinical launch of X1 to improve efficiency and safety. In the “control” phase, the FMEA ranking was re-evaluated 1 year after clinical launch. Results: Overall, 100 plan check items were identified in which the RPN values ranged from 10.2 to 429.0. Fifty of these items (50%) were suitable for automation within ESAPI. Of the 10 highest-risk items, 8 were suitable for automation. Based on the results of the FMEA, 2 scripts were developed: Planning Assistant, used by the planner during preparation for planning, and Automated Plan Check, used by the planner and the plan checker during plan preparation for treatment. After 12 months of clinical use of the X1 and developed scripts, only 3 errors were reported. The average prescript RPN was 138.0, compared with the average postscript RPN of 47.8 (P < .05), signifying a safer process. Conclusions: Implementing new technology in the clinic can be an error-prone process in which the likelihood of errors increases with increasing pressure to implement the technology quickly. To limit errors in clinical implementation of the novel RefleXion X1 system, the Six Sigma method was used to identify failure modes, establish quality control checks, and re-evaluate these checks 1 year after clinical implementation.

BackgroundApolipoprotein E (APOE) ε2 and APOE ε4 are the most distinct alleles among the three APOE alleles, both structurally and functionally. However, differences in cognition, brain function, and brain structure between the two alleles have not been comprehensively reported in the literature, especially in non-demented elderly individuals.MethodsA neuropsychological test battery was used to evaluate the differences in cognitive performance in five cognitive domains. Independent component analysis (ICA) and voxel-based morphometry (VBM) were used separately to analyze resting-state functional magnetic resonance imaging (rs-fMRI) data and the structure MRI data between the two groups. Finally, correlations between differential brain regions and neuropsychological tests were calculated.ResultsAPOE ε2 carriers had better cognitive performance in general cognitive, memory, attention, and executive function than APOE ε4 carriers (all p

Terahertz (THz) absorbers with high absorptivity across a wide frequency band have attracted considerable interest. In this paper, we present the design of an ultra-broadband THz metamaterial absorber with high absorptivity based on a single-layer square silicon array and a silicon film backed with metallic gold. It is numerically demonstrated that the absorption exceeds 90% covering the frequency range of 0.62–8.75 THz (with an effective absorption bandwidth of 8.13 THz) when the conductivity of semiconductor (undoped silicon) is 600 S/m. Diffraction and impedance-matched induce strong absorption and the corresponding broad bandwidth. The proposed ultra-broadband THz absorber is polarization-insensitive at normal incidence. It can operate over a rather wide range of incidence angle up to 60 degrees for transverse magnetic (TM) terahertz wave. This work provides a way to achieving ultra-broadband terahertz absorption, which is very useful in the development of terahertz imaging, high sensitivity sensors and detection.

Filling mining with solid waste resources as aggregates is an important development direction for cleaner production in mines. The hydration products have an important effect on the mechanical properties of superfine tailings cemented paste backfill (SCPB). This paper investigates the mechanism of hydration product formation and thermal decomposition properties of SCPB by a series of experiments combined with thermal decomposition kinetics. Also, to optimize the mechanical properties of SCPB, the effect of Nano SiO2 (NS) on the related properties of SCPB is investigated. The results show that there are two main stages of the thermal decomposition of SCPB, and the kinetic models of these two stages are both reaction order models. After adding NS, the kinetic model of the second stage of thermal decomposition of SCPB is changed to random nucleation and growth model. The substances that undergo thermal decomposition reactions in the first stage are mainly hydration products such as ettringite and C-S-H, while the substances that undergo thermal decomposition reactions in the second stage are carbonates. The activation energy E and pre-exponential factor A of the first stage of thermal decomposition of SCPB with NS added are significantly improved, which indicates a more stable structure of its hydration products. The microscopic test results show that NS can promote the hydrolysis of C3S and gypsum and increase the production of hydration products, which in turn improves the strength of SCPB. In addition, the addition of NS to SCPB decreases the Ca/Si and increases the average silica chain length of C-S-H gels, while the H2O/Si decreases and the silica group increases, resulting in the enhancement of the structure of C-S-H gels.

Directed energy deposition (DED) has a widely application prospect, but dendrite and component segregation are not easily controlled and predicted. In this study, the method of applying ultrasonic assisted rolling was introduced to the DED to eliminate above phenomenon. A multiple process microstructure evolution simulation (involved melting, solidification, dynamitic recrystallization and grain growth) was also carried out, which introduced ultrasonic effect in the form of energy. The influence of ultrasonic amplitude (A), distance between laser focus point and ultrasonic roller (d0) on microstructure of Pb-Sn alloy deposition layer were explored. There is a good consistency between experiment and simulation with relative error of 4.33%. The results show that the roundness of grains is improved significantly after rolling, and the grain are refined with the increase of A and d0. In all tests of this study, comprehensive effect of ultrasonic rolling achieves the best when d0 is taken as 24 mm and A is taken as 20 μm, the average grain diameter (D0) in grain size counted zone is 18.8 μm which is 23.23% lower than that without rolling. This study laid a foundation for the development of ultrasonic assisted rolling DED and provide a multiple process microstructure simulation method.

Abstract The Asian cultivated rice consists of two major subspecies: indica and japonica. There are already many reports about the existence of genetic introgression between the two subspecies. They propose some possible introgression-related genes from the comparison of population parameters. This study uses the genome-wide variation data of Asia cultivated rice to investigate their genetic introgression on the whole genome level. We detect a total of 13 significantly high introgression loci between the tropical japonica and indica populations. Two different methods are used to identify the genetic introgression regions. For most of the detected introgression regions, they generally get consistent results. Some previously known introgression genes are detected in the identified introgression loci, such as heat resistance gene TT1 and GLW7. The biological functions for these genetic introgression regions are annotated by the published QTL mapping results. We find that genetic introgression plays a vital role in the determination of both the phenotype and the domestication process of different groups. Our study also provides useful information and resources for the study of rice gene function and the domestication process.

Abstract Background Transcatheter arterial embolization (TAE) is one of the first-line treatments for advanced hepatocellular cancer. The pain caused by TAE is a stark complication, which remains to be prevented by biomedical engineering methods. Methods Herein, a commercial embolic agent CalliSpheres® bead (CB) was functionally modified with lidocaine (Lid) using an electrostatic self-assembly technique. The products were coded as CB/Lid-n (n = 0, 5, 10, corresponding to the relative content of Lid). The chemical compositions, morphology, drug-loading, and drug-releasing ability of CB/Lid-n were comprehensively investigated. The biocompatibility was determined by hemolysis assay, live/dead cell staining assay, CCK8 assay, immunofluorescence (IHC) staining assay and quantitative real-time PCR. The thermal withdrawal latency (TWL) and edema ratio (ER) were performed to evaluate the analgesia of CB/Lid-n using a plantar inflammation model. A series of histological staining, including immunohistochemistry (IL-6, IL-10, TGF-β and Navi1.7) and TUNEL were conducted to reveal the underlying mechanism of anti-tumor effect of CB/Lid-n on a VX2-tumor bearing model. Results Lid was successfully loaded onto the surface of CalliSpheres® bead, and the average diameter of CalliSpheres® bead increased along with the dosage of Lid. CB/Lid-n exhibited desirable drug-loading ratio, drug-embedding ratio, and sustained drug-release capability. CB/Lid-n had mild toxicity towards L929 cells, while triggered no obvious hemolysis. Furthermore, CB/Lid-n could improve the carrageenan-induced inflammation response micro-environment in vivo and in vitro. We found that CB/Lid-10 could selectively kill tumor by blocking blood supply, inhibiting cell proliferation, and promoting cell apoptosis. CB/Lid-10 could also release Lid to relieve post-operative pain, mainly by remodeling the harsh inflammation micro-environment (IME). Conclusions In summary, CB/Lid-10 has relatively good biocompatibility and bioactivity, and it can serve as a promising candidate for painless transcatheter arterial embolization.

Abstract Declining insect populations emphasize the importance of understanding the drivers underlying reductions in insect fitness. Here, we investigated viruses as a threat to social insect reproduction, using honey bees as a model species. We report that in two independent surveys (N = 93 and N = 54, respectively) of honey bee (Apis mellifera) queens taken from a total of ten beekeeping operations across British Columbia, high levels of natural viral infection are associated with decreased ovary mass. Failed (poor quality) queens displayed higher levels of viral infection, reduced sperm viability, smaller ovaries, and altered ovary protein composition compared to healthy queens. We experimentally infected queens with Israeli acute paralysis virus (IAPV) and found that the ovary masses of IAPV-injected queens were significantly smaller than control queens, demonstrating a causal relationship between viral infection and ovary size. Queens injected with IAPV also had significantly lower expression of vitellogenin, the main source of nutrition deposited into developing oocytes, and higher levels of heat-shock proteins, which are part of the honey bee’s antiviral response. This work together shows that viral infections occurring naturally in the field are compromising queen reproductive success.

Abstract Lead white is one of the most important pigments in human history, and its synthesis has promoted the development of art and cosmetics. The corrosion approach to synthesize lead white appeared in Greece during the fourth century BCE, and since then lead white has been produced on a large-scale and widely used in painting and cosmetics across Europe. However, when and how synthetic lead white appeared in east Eurasia and whether it was also involved with beauty remained unclear. Here, we investigate some white cosmetic residues from the Liangdaicun site during the eighth century BCE in northern China through FTIR, XRD, SEM-EDS, radioactive and stable carbon isotope analyses. The results show that these residues were the earliest synthesized lead white in the world to date, which was produced by the precipitation method in solution distinct from the corrosion method practiced in ancient Greece. Thus, the synthesis of lead white should have evolved independently in east and west Eurasia during the first millennium BCE. The mass production of synthetic lead white with lower cost promoted the widespread use of white makeup in China and the Mediterranean World, which triggered a cosmetic revolution and highlighted that the pursuit of beauty stimulated the development of chemistry in human history, especially the earliest wet chemistry practice in China.

Abstract Background To determine the association between dynamic neutrophil-to-lymphocyte ratio (NLR) during hospitalization and mortality 1 month after ischemia reperfusion in patients undergoing endovascular treatment (EVT) with successful revascularization for acute large vessel occlusion stroke. Methods This retrospective study included patients who had undergone successful EVT. Information was collected regarding patients’ clinical characteristics, imaging data, and mortality at 1 month. Univariate and multivariate logistic regression models were applied to assess the association between NLR and mortality. We used a generalized additive model and a generalized additive mixed model to compare trends in NLR over time between survivors and nonsurvivors. Results A total of 237 patients were included. During the 1-month follow-up, 42 of these patients (17.7%) died. The multivariate analysis demonstrated that NLR obtained within 12 to 24 hours (odds ratio [OR] = 1.18; 95% confidence interval [CI]: 1.04, 1.33; P = 0.008), 24 to 48 hours (OR = 1.16; 95% CI: 1.01, 1.35; P = 0.044), and 48 to 72 hours (OR = 1.23; 95% CI: 1.03, 1.47; P = 0.021) after EVT were independently associated with mortality at 1 month. In addition, there was a trend for NLR to decrease gradually over time for both survivors and nonsurvivors; however, NLR in survivors decreased by an average of 0.29 daily than in nonsurvivors. Conclusions Increased NLR in the early period after EVT was associated with an increased risk of mortality, and a continued trend toward higher NLR over time was also linked with a higher mortality risk.

BackgroundPatients receiving maintenance dialysis experience increased rates of hospitalization and mortality. Apathy is associated with reduced quality of life and increased hospitalization, institutionalization, and death. Whether apathy contributes to poor outcomes in population undergoing maintenance dialysis remain unknown.MethodsWe conducted a prospective cohort study of maintenance dialysis population who were consecutively recruited at the Dialysis Center of Shanghai General Hospital between July 2017 and August 2018 and were followed up for 3 year. Apathy status was measured by the Apathy Evaluation Scale. The study outcomes were the occurrence of death and first hospitalization.ResultsA total of 647 participants included in this study, 274 (42.3%) had a current apathy and 373 (57.7%) were not. During the follow-up period, 394 (60.9%) were hospitalized, and 169 (26.1%) died. Kaplan–Meier analysis showed that the risks of hospitalization and mortality were significantly higher in individuals with apathy than in those without apathy (both p

BackgroundAlthough endovascular treatment (EVT) has become the standard treatment for acute large vessel occlusion (LVO), its safety and efficacy in older adults have not been fully determined. The present study aimed to compare the safety and efficacy of EVT for acute LVO between younger ( 0.05). The rate of 90-day mRS 0–3 was found to be higher in young patients than in older adults (39.9% vs. 56.5%, odds ratio = 0.64, 95% confidence interval = 0.44–0.94, p = 0.022).ConclusionWe found that patients less than or greater than 80 years of age share similar clinical outcomes, without increasing the risk of ICH and mortality.

Abstract Background The role and mechanism of centromeric protein N (CENP‐N), which has been associated with the development of various cancer types, are yet unclear in stomach adenocarcinoma (STAD). Methods Data from the Cancer Genome Atlas and Genotype‐Tissue Expression were used to determine whether CENP‐N expression was altered in STAD tumors compared to normal tissues. Xiantao was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis on CENP‐N. The relationship between CENP‐N expression and immune cell infiltration was assessed using TCGA database. The expression of CENP‐N in STAD and surrounding tissues was confirmed using immunohistochemical staining and the correlation between CENP‐N expression and clinicopathological characteristics was examined. The effects of CENP‐N knockdown by siRNA on proliferation were measured by CCK‐8 and EdU assays in AGS cells. Following siRNA transfection, flow cytometry was performed to evaluate cell cycle and apoptotic alterations in AGS cells. The effect of CENP‐N knockdown on the expression level of related proteins was detected by Westren blot. Results CENP‐N was highly expressed in STAD tissues, which was confirmed by our immunohistochemistry results. The degree of invasion, TNM stage, and lymph node metastases were all strongly associated with CENP‐N expression. CENP‐N was essential for the cell cycle, DNA replication, chromosomal segregation, and nuclear division; there was a positive correlation between CENP‐N expression and infiltrating Th2 and NK CD56dim cells and a negative correlation between CENP‐N expression and mast, pDC, NK, and B cell infiltration. When CENP‐N expression in AGS cells was knocked down, cell proliferation dramatically reduced (p

C-type natriuretic peptide (CNP) is a peptide molecule naturally found in follicles and can be used to extend meiotic resumption and enhance the potential for oocytes to develop. However, the mechanism by which CNP improves goat oocyte quality remains unclear. In this study, cumulus–oocyte complexes (COCs) from goats were pre-treated with CNP prior to IVM, and the results showed that pre-treatment with CNP enhanced goat oocyte maturation. First, we discovered that CNP maintained communication between cumulus cells and oocytes by regulating the transzonal projections (TZPs). We then found that CNP treatment reduced abnormal spindle formation and increased the expression of genes associated with spindle assembly and the spindle assembly checkpoint. Moreover, further analysis showed that oocytes exhibited better antioxidant ability in the CNP treatment group, which mainly manifested in higher glutathione (GSH) and lower reactive oxygen species (ROS) concentrations. Enhanced mitochondrial activity was signified via the augmented expression of mitochondrial oxidative metabolism and fusion and fission-related genes, thus diminishing the apoptosis of the oocytes. Overall, these results provide novel insights into the potential mechanism by which CNP treatment before IVM can improve oocyte quality.

Toll-like receptor 3 (TLR3) is a prominent member of the Toll-like receptor (TLR) family and has the ability to recognize and bind intracellular double-stranded RNA (dsRNA). Once triggered by a viral infection or other pathological condition, TLR3 activates immune cells and induces the production of interferons and other immune response molecules. Additionally, TLR3 is considered an important immune modulator, as it can regulate cell apoptosis and promote anticancer immunity. The investigation and application of TLR3 agonists in digestive system tumors have attracted widespread attention and are regarded as a promising cancer treatment strategy with potential clinical applications. TLR3 expression levels are generally elevated in most digestive system tumors, and higher TLR3 expression is associated with a better prognosis. Therefore, TLR3 has emerged as a novel therapeutic target for digestive system tumors. It has been used in combination with chemotherapy, radiotherapy, and targeted therapy and demonstrated excellent efficacy and tolerability. This has provided new ideas and hopes for the treatment of digestive system tumors. This review discusses the mechanisms of TLR3 and its frontier research in digestive system tumors.

Inspired by material hybrid design, novel hybrid sandwich shells were developed by filling a corrugated cylindrical structure with aluminum foam to achieve higher energy absorption performance. The crushing behavior of the foam-filled corrugated sandwich cylindrical shells (FFCSCSs) was investigated using theoretical and numerical methods. Numerical results revealed a significant enhancement in the energy absorption of FFCSCSs under axial compression, showcasing a maximum specific energy absorption of 60 kJ/kg. The coupling strengthening effect is highly pronounced, with a maximum value of F¯c/F¯ reaching up to 40%. The mechanism underlying this phenomenon can be approached from two perspectives. Firstly, the intrusion of folds into the foam insertions allows for more effective foam compression, maximizing its energy absorption capacity. Secondly, foam causes the folds to bend upwards, intensifying the mutual compression between the folds. This coupling mechanism was further investigated with a focus on analyzing the influence of parameters such as the relative density of the foam, the wall thickness of the sandwich shell, and the material properties. Moreover, a theoretical model was developed to accurately predict the mean crushing force of the FFCSCSs. Based on this model, the influence of various variables on the crushing behavior of the structure was thoroughly investigated through parametric studies.

Abstract Inspired by biomechanical studies, the spring-loaded inverted pendulum model is an effective behavior model to describe the running movement of animals and legged robots in the sagittal plane. However, when confronted with external lateral disturbances, the model has to move out of the 2-D plane and be extended to 3-D locomotion. With the degree of freedom increasing, the computational complexity is higher and the real-time control is more and more difficult, especially when considering the complex legged model. Here, we construct a control strategy based on the classical Raibert controller for legged locomotion under lateral impact disturbances. This strategy, named 3D-HFC, is composed of three core modules: touchdown angle control, body attitude angle control and energy compensation. The energy loss in each step is taken into consideration, and the real-time measured energy loss of the current step is adopted to predict that of the next step. We demonstrate the efficiency of the proposed control strategy on a simulated 3D-SLIP lower order model and a simulated running quadruped, which are perturbed by different impact forces. Furthermore, a quadruped bionic prototype named MBBOT was set up, on which lateral impact experiments were designed and implemented. Both simulation and experimental results show that the proposed approach can realize the impact disturbance rejection.

Additive and subtractive hybrid manufacturing (ASHM) technology has attracted extensive attention in industry and academia because of its vast design freedom and surface accuracy. The powder bed fusion (PBF) process has high forming accuracy, the ASHM of PBF process is more suitable for integrated precision manufacturing of components with complex internal structures. However, existing process planning for ASHM are not suitable for the ASHM of PBF process because of the limitation by the powder bed. This research work focused on planning the process for the ASHM of the PBF process, while dividing it into three stages. Firstly, a model adaptive compensation algorithm is proposed to retain the finish machining allowance. Then, considering tool accessibility and constraint of the powder bed, the compensation model is decomposed into several sub-models and the hybrid manufacturing of sub-models in the sequence of construction. Finally, some unprocessed parts of the internal structure could be re-process after removing the parts from the powder bed. Combined with experiments and examples, this hybrid manufacturing process planning can provide technical support for the integrated precision manufacturing of components with a complex internal structure based on the ASHM of the PBF process.

ABSTRACT Uremic cardiomyopathy (UCM) correlates with chronic kidney disease (CKD)-induced morbidity and mortality. Gut microbiota has been involved in the pathogenesis of certain cardiovascular disease, but the role of gut microbiota in the pathogenesis of UCM remains unknown. Here, we performed a case-control study to compare the gut microbiota of patients with CKD and healthy controls by 16S rRNA (rRNA) gene sequencing. To test the causative relationship between gut microbiota and UCM, we performed fecal microbiota transplantation (FMT) in 5/6th nephrectomy model of CKD. We found that opportunistic pathogens, particularly Klebsiella pneumoniae (K. pneumoniae), are markedly enriched in patients with CKD. FMT from CKD patients aggravated diastolic dysfunction in the mouse model. The diastolic dysfunction was associated with microbiome-dependent increases in heart-infiltrating IFNγ+ CD4+ T cells. Monocolonization with K. pneumoniae increased cardiac IFNγ+ CD4+ T cells infiltration and promoted UCM development of the mouse model. A probiotic Bifidobacterium animalis decreased the relative abundance of K. pneumoniae, reduced levels of cardiac IFNγ+ CD4+ T cells and ameliorated the severity of diastolic dysfunction in the mice. Thus, the aberrant gut microbiota in CKD patients, especially K. pneumoniae, contributed to UCM pathogenesis through the induction of heart-infiltrating IFNγ+ CD4+ T cells expansion, proposing that a Gut Microbiota-Gut-Kidney-Heart axis could play a critical role in elucidating the etiology of UCM, and suggesting that modulation of the gut bacteria may serve as a promising target for the amelioration of UCM. IMPORTANCE Uremic cardiomyopathy (UCM) correlates tightly with increased mortality in patients with chronic kidney disease (CKD), yet the pathogenesis of UCM remains incompletely understood, limiting therapeutic approaches. Our study proposed that a Gut Microbiota-Gut-Kidney-Heart axis could play a critical role in understanding etiology of UCM. There is a major need in future clinical trials of patients with CKD to explore if modulation of gut microbiota by fecal microbiota transplantation (FMT), probiotics or antibiotics can alleviate cardiac dysfunction, reduce mortality, and improve life quality.

A schematic model of SGSM2 suppressing the progression of RASWT thyroid cancer.

This article reveals an adequate comprehension of basic defense, security challenges, and attack vectors in deploying multi-network slicing. Network slicing is a revolutionary concept of providing mobile network on-demand and expanding mobile networking business and services to a new era. The new business paradigm and service opportunities are encouraging vertical industries to join and develop their own mobile network capabilities for enhanced performances that are coherent with their applications. However, a number of security concerns are also raised in this new era. In this article, we focus on the deployment of multi-network slicing with multi-tenancy. We identify the security concerns and discuss the defense approaches such as network slice isolation and insulation in a multi-layer network slicing security model. Furthermore, we identify the importance to appropriately select the network slice isolation points and propose a generic framework to optimize the isolation policy regarding the implementation cost while guaranteeing the security and performance requirements.

Passive upper limb exoskeletons are often designed to relieve muscle fatigue of manufacturing workers. Existing exoskeletons often provide partial assistance, and their assistive torque is only affected by elastic elements and mechanisms, which, however, are not sufficient because of the changing load of the shoulder joint due to the motion of the elbow and the weight of various tools. To improve the assistive effect without affecting the free movement of the arm, a passive exoskeletal vest has been designed. This exoskeleton has two operating states which can be switched using a unique ratchet bar mechanism. The upper arm can be locked at any vertical position when engaged. The assistive torque is determined by the load. The arm also can move freely without any resistance when separated. Seven subjects participated in the evaluation experiment, who performed static tasks, precision tasks, and dynamic tasks. The experimental data demonstrate that (1) the exoskeleton can effectively reduce the activation level of related muscles at a variety of tasks. (2) The accuracy and stability of the arm during heavy work are not affected. (3) The exoskeleton has a minimal restriction on the range of motion of the arm. (4) the comfort and portability achieved a high score of 8 (1-10) from subjective measures. The experimental results further revealed that the designed exoskeletal vest could effectively relieve the shoulder burden, where it does not impede or restrain the arm’s movements.

Here, the authors report the functionalization of monolayer transition metal dichalcogenides with hydrogen-bonded 2D supramolecular networks of cyanuric acid and melamine, leading to a pronounced n-doping effect and enhancement of MoS2 catalytic activity for hydrogen evolution reactions.

The global roll-out phase of the fifth-generation of mobile communication systems is currently underway. The industry and academia have already begun research on potential sixth-generation (6G) communication systems. The 6G communication system is anticipated to provide network connectivity for an extensive range of use cases in a variety of emerging vertical industries. Consequently, a new set of challenging requirements and more stringent key performance indicators have to be considered, a novel architecture has to be designed, and unique enabling technologies shall be developed in order to fulfill the technical, regulatory, and business demands of the communication service customers. These requirements place enormous pressure on the players in the telecommunications industry, including network operators, service providers, hardware suppliers, standards development organizations (SDOs), and regulatory authorities aimed at developing, standardizing, and regulating an energy-efficient, cost-effective, performing, and sustainable 6G communication ecosystem. One area of focus for 6G communication systems is the digital twin (DT) technology, which is a well-defined set of tools designed to create virtual representations of physical objects that serve as their digital counterparts. This article explores the applicability of the DT technology in the context of 6G communication systems by viewing it as a promising tool to make research, development, operation, and optimization of the next-generation communication systems highly efficient. The major contribution of this article is fivefold. Firstly, we provide critical analysis of the state-of-the-art literature in the field of DT technology in order to capture its essence in several application areas since its inception. Secondly, we conduct a comprehensive survey of the research concerning the deployment of DT technology in 6G communication systems. Thirdly, we discuss potential use cases and key areas of applications (along with detailed examples) of 6G communication systems that can benefit from DT technology. Fourthly, we present an overview of the activities of several SDOs that are active in the field of DT technology. Finally, we identify several open research challenges and future directions that need to be addressed before the end-to-end deployment of DT technology in 6G communication systems.

Point feature-based visual simultaneous localization and mapping (SLAM) systems are prone to performance degradation in low-texture environments due to insufficient extraction of point features. In this paper, we propose a tightly-coupled stereo visual-inertial SLAM system with point and line features (PLI-SLAM) to enhance the robustness and reliability of systems in low-texture environments. We improve Edge Drawing lines (EDlines) for line feature detection by introducing curvature detection and a new standard for minimum line segment length to improve the accuracy of the line features, while reducing the line feature detection time. We contribute also with an improved adapting factor based on experiment to adjust the error weight of line features, which further improves the localization accuracy of the system. Our system has been tested on the EuRoC dataset. Tests on public datasets and in real environments have shown that PLI-SLAM achieves high accuracy. Furthermore, PLI-SLAM could still operate robustly even in some challenging environments. The processing time of our method is reduced by 28%, compared to the ORB-LINE-SLAM based on point and line, when using Line Segment Detector (LSD).

Quantum-well intermixing (QWI) technology is commonly considered as an effective methodology to tune the post-growth bandgap energy of semiconductor composites for electronic applications in diode lasers and photonic integrated devices. However, the specific influencing mechanism of the interfacial strain introduced by the dielectric-layer-modulated multiple quantum well (MQW) structures on the photoluminescence (PL) property and interfacial quality still remains unclear. Therefore, in the present study, different thicknesses of SiO2-layer samples were coated and then annealed under high temperature to introduce interfacial strain and enhance atomic interdiffusion at the barrier–well interfaces. Based on the optical and microstructural experimental test results, it was found that the SiO2 capping thickness played a positive role in driving the blueshift of the PL peak, leading to a widely tunable PL emission for post-growth MQWs. After annealing, the blueshift in the InGaAs/AlGaAs MQW structures was found to increase with increased thickness of the SiO2 layer, and the largest blueshift of 30 eV was obtained in the sample covered with a 600 nm thick SiO2 layer that was annealed at 850 °C for 180 s. Additionally, significant well-width fluctuations were observed at the MQW interface after intermixing, due to the interfacial strain introduced by the thermal mismatch between SiO2 and GaAs, which enhanced the inhomogeneous diffusion rate of interfacial atoms. Thus, it can be demonstrated that the introduction of appropriate interfacial strain in the QWI process is of great significance for the regulation of MQW band structure as well as the control of interfacial quality.

Cell transplantation has been proved the promising therapeutic effects on intervertebral disc degeneration (IVDD). However, the increased levels of reactive oxygen species (ROS) in the degenerated region will impede the efficiency of human adipose-derived stem cells (human ADSCs) transplantation therapy. It inhibits human ADSCs proliferation, and increases human ADSCs apoptosis. Herein, we firstly devised a novel amphiphilic copolymer PEG-PAPO, which could self-assemble into a nanosized micelle and load lipophilic kartogenin (KGN), as a single complex (PAKM). It was an injectable esterase-responsive micelle, and showed controlled release ability of KGN and apocynin (APO). Oxidative stimulation promoted the esterase activity in human ADSCs, which accelerate degradation of esterase-responsive micelle. Compared its monomer, the PAKM micelle possessed better bioactivities, which were attributed to their synergistic effect. It enhanced the viability, autophagic activation (P62, LC3 II), ECM-related transcription factor (SOX9), and ECM (Collagen II, Aggrecan) maintenance in human ADSCs. Furthermore, it is demonstrated that the injection of PAKM with human ADSCs yielded higher disc height and water content in rats. Therefore, PAKM micelles perform promoting cell survival and differentiation effects, and may be a potential therapeutic agent for IVDD.

ObjectiveThe purpose of this study was to investigate the target dose discrepancy caused by intrafraction variation during stereotactic body radiotherapy (SBRT) for lung cancer.MethodsIntensity-modulated radiation therapy (IMRT) plans were designed based on average computed tomography (AVG CT) utilizing the planning target volume (PTV) surrounding the 65% and 85% prescription isodoses in both phantom and patient cases. Variation was simulated by shifting the nominal plan isocenter along six directions from 0.5 mm to 4.5 mm with a 1-mm step size to produce a series of perturbed plans. The dose discrepancy between the initial plan and the perturbed plans was calculated as the percentage of the initial plan. Dose indices, including ΔD99 for internal target volume (ITV) and gross tumor volume (GTV), were adopted as endpoint samples. The mean dose discrepancy was calculated under the 3-dimensional space distribution.ResultsWe found that motion can lead to serious dose degradation of the target and ITV in lung SBRT, especially during SBRT with PTV surrounding the lower isodose line. Lower isodose line may lead to larger dose discrepancy, while make steeper dose fall-off gradient. This phenomenon was compromised when 3-dimensional space distribution was considered.DiscussionThis result may provide a prospective reference for target dose degradation due to motion during lung SBRT treatment.

Reproduction involves the investment of resources into offspring. Although variation in reproductive effort often affects the number of offspring, adjustments of propagule size are also found in numerous species, including the Western honey bee, Apis mellifera. However, the proximate causes of these adjustments are insufficiently understood, especially in oviparous species with complex social organization in which adaptive evolution is shaped by kin selection. Here, we show in a series of experiments that queens predictably and reversibly increase egg size in small colonies and decrease egg size in large colonies, while their ovary size changes in the opposite direction. Additional results suggest that these effects cannot be solely explained by egg-laying rate and are due to the queens’ perception of colony size. Egg-size plasticity is associated with quantitative changes of 290 ovarian proteins, most of which relate to energy metabolism, protein transport, and cytoskeleton. Based on functional and network analyses, we further study the small GTPase Rho1 as a candidate regulator of egg size. Spatio-temporal expression analysis via RNAscope and qPCR supports an important role of Rho1 in egg-size determination, and subsequent RNAi-mediated gene knockdown confirmed that Rho1 has a major effect on egg size in honey bees. These results elucidate how the social environment of the honey bee colony may be translated into a specific cellular process to adjust maternal investment into eggs. It remains to be studied how widespread this mechanism is and whether it has consequences for population dynamics and epigenetic influences on offspring phenotype in honey bees and other species.

Abstract Background Honey bees are not only essential for pollination services, but are also economically important as a source of hive products (e.g., honey, royal jelly, pollen, wax, and propolis) that are used as foods, cosmetics, and alternative medicines. Royal jelly is a popular honey bee product with multiple potential medicinal properties. To boost royal jelly production, a long-term genetic selection program of Italian honey bees (ITBs) in China has been performed, resulting in honey bee stocks (here referred to as RJBs) that produce an order of magnitude more royal jelly than ITBs. Although multiple studies have investigated the molecular basis of increased royal jelly yields, one factor that has not been considered is the role of honey bee-associated gut microbes. Results Based on the behavioral, morphological, physiological, and neurological differences between RJBs and ITBs, we predicted that the gut microbiome composition of RJBs bees would differ from ITBs. To test this hypothesis, we investigated the bacterial composition of RJB and ITB workers from an urban location and RJBs from a rural location in China. Based on 16S rRNA gene profiling, we did not find any evidence that RJBs possess a unique bacterial gut community when compared to ITBs. However, we observed differences between honey bees from the urban versus rural sites. Conclusions Our results suggest that the environmental factors rather than stock differences are more important in shaping the bacterial composition in honey bee guts. Further studies are needed to investigate if the observed differences in relative abundance of taxa between the urban and rural bees correspond to distinct functional capabilities that impact honey bee health. Because the lifestyle, diet, and other environmental variables are different in rural and urban areas, controlled studies are needed to determine which of these factors are responsible for the observed differences in gut bacterial composition between urban and rural honeybees.

Dual-phase metallic glasses (DP-MGs), a special member of the MGs family, often reveal unusual strength and ductility, yet, their corrosion behaviors are not understood. Here, we developed a nanostructured Mg57Zn36Ca7 (at.%) DP-MG and uncovered its corrosion mechanism in simulated body fluid (SBF) at the near-atomic scale utilizing transmission electron microscope (TEM) and atom probe tomography (APT). The 10-nm-wide Ca-rich amorphous phases allow oxygen propagation into the DP-MG, resulting in a micrometer thick hydroxides/oxides layer. This dense corrosion layer protects the DP-MG from further corrosion, enabling a corrosion rate that is 77% lower than that of Mg (99.99% purity).

Abstract Korean hand papermaking is a renowned cultural tradition in the Korean peninsula. It is still practiced while scientific analysis of paper itself from a large data set is rare. In this study, a set of more than three hundred Korean handmade papers, collected in a reference collection book Hanji: Korean handmade paper, were chemically investigated, and their property data such as colour, pH, grammage, thickness, tensile strength, folding endurance were statistically analysed in order to determine general features for Korean papers. The influence of different paper sheet formation methods (Heullimtteugi vs Gadumtteugi) were revealed by multivariate data analysis and the chemical profiles of raw materials were studied by pyrolysis–gas chromatography/mass spectrometry (Py-GC/MS). The Korean handmade paper samples display colour gamut in the colour space L* (69.9–95.9), a* [(−3)-3], b* (0–20), most have neutral/alkaline pH values. Paper density, fiber orientation and physical properties are influenced by the sheet formation techniques. For instance, Gadumtteugi tends to produce papers with strong fiber orientation while Heullimtteugi produces papers with more evenly distribution of fibers. In addition, Py-GC/MS analysis results show that paper mulberry fibers contain less intensity lignin monomers and more terpenic compounds in comparison with gampi and mitsumata fibers. This study provides paper analysis from large sample set, statistics reveal that the material preparing and making craft determined the paper structure which reflected in their physical properties. These properties influenced paper performance and applications in art creations as well as relics conservation and restoration. The characterized paper sample database could be used for handmade paper studies in East Asian region. Consequently, this study contributes to a better understanding of contemporary Hanji properties as well as improves knowledge on handmade papers from the Korean peninsula.

Ultrasonic guided wave (UGW) technology based on piezoelectric sensors is considered a very promising technology for aircraft structural damage detection. Traditional piezoelectric sensors are made of lead zirconate titanate (PZT) ceramics, but their brittleness and hardness make them difficult to apply to curved structure surfaces. In this study, a novel 0–3 flexible piezoelectric composite was fabricated by dispersing PZT particles in silicone resin, and its performance for potential applications in UGW sensors was studied. The effects of polarization conditions, PZT volume fraction, and PZT powder size on the performance of the composite were investigated. The influence of ambient temperature on composite performance was discussed, and temperature adaptability experiments were conducted. The results show that the optimal poling process of 0–3 PZT/silicone resin piezoelectric composite has a poling time of 25 min, a poling electric field of 4 kV/mm, and a poling temperature of 100°C. When the sensor is required to meet the test strain range of 8,000 με, the composite should be fabricated with a PZT volume fraction of 50% and a powder size of 170∼212 μm to obtain optimal sensing sensitivity. At an ambient temperature range of -55–75°C, the fabricated piezoelectric composite sensor has good flexibility and sensitivity in detecting the guide wave signals. These research results provide a new flexible piezoelectric sensing technology for aircraft structural damage detection.

BackgroundThis study aimed to conduct a comparative analysis of the survival rates after segmentectomy, wedge resection, or lobectomy in patients with cStage IA lung squamous cell carcinoma (SCC).MethodsWe enrolled 4,316 patients who had cStage IA lung SCC from the Surveillance, Epidemiology, and End Results (SEER) database. The Cox proportional hazards model was conducted to recognize the potential risk factors for overall survival (OS) and lung cancer-specific survival (LCSS). To eliminate potential biases of included patients, the propensity score matching (PSM) method was used. OS and LCSS rates were compared among three groups stratified according to tumor size.ResultsKaplan–Meier analyses revealed no statistical differences in the rates of OS and LCSS between wedge resection (WR) and segmentectomy (SG) groups for patients who had cStage IA cancers. In patients with tumors ≤ 1 cm, LCSS favored lobectomy (Lob) compared to segmentectomy (SG), but a similar survival rate was obtained for wedge resection (WR) and lobectomy (Lob). For patients with tumors sized 1.1 to 2 cm, lobectomy had improved OS and LCSS rates compared to the segmentectomy or wedge resection groups, with the exception of a similar OS rate for lobectomy and segmentectomy. For tumors sized 2.1 to 3 cm, lobectomy had a higher rate of OS or LCSS than wedge resection or segmentectomy, except that lobectomy conferred a similar LCSS rate compared to segmentectomy. Multivariable analyses showed that patients aged ≥75 and tumor sizes of >2 to ≤3 cm were potential risk factors for OS and LCSS, while lobectomy and first malignant primary indicator were considered protective factors. The Cox proportional analysis also confirmed that male patients aged ≥65 to 1 to ≤3 cm, lobectomy showed better survival outcomes than sublobar resection. Our findings require further validation by randomized controlled trial (RCT) or other evidence.

ObjectiveAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective method for the treatment of refractory and relapsed acute leukemia, and the preconditioning methods before transplantationis one of the important factors affecting the survival of patients. Radiotherapy combined with chemotherapy is the most commonly used preconditioning method before transplantation. This study evaluated the safety and efficacy of total bone marrow combined with total lymphatic irradiation as a preconditioning method before hematopoietic stem cell transplantation.MethodsSeventeen patients with acute leukemia who were admitted to our center from 2016 to 2020 were selected. The median age was 17 years (8-35). The target area for TMLI includes the total bone marrow and total lymphatic space, and the organs at risk include the lens, lungs, kidneys, intestine, heart, and liver. The patients received a total bone marrow and lymphatic irradiation preconditioning regimen, the related acute adverse reactions were graded, and the prognosis of the patients after transplantation was observed.ResultsDuring patient preconditioning, only grade 1-2 toxicity was observed, and grade 3-4 toxicity did not occur. Except for one patient whose platelets were not engrafted, all the other patients were successfully transplanted. The median time of neutrophil implantation was 14 d (9-15 d), and the median time of platelet implantation was 14 d (13-21 d). With a median follow-up of 9 months (2-48), 4 relapses occurred, 3 died, and 10 leukemia patients survived and were disease-free. One-year overall survival was 69.8%, cumulative recurrence was 19.5%, disease-free-survival was 54.2%.ConclusionThe Allo-HSCT pretreatment regimen of total bone marrow combined with total lymphatic irradiation is safe and effective in the treatment of malignant hematological diseases. Total bone marrow combined with total lymphatic irradiation may completely replace total body irradiation, and the clinically observed incidence of acute toxicity is not high.

Malignant hyperthermia (MH) is a rare life-threatening response that is triggered by exposure to specific anesthetics commonly used during surgical interventions. Dantrolene is a well-known drug used as the first-line therapy for MH. A 14-year-old Chinese boy with a mutation in type 1 Ryanodine receptor (RyR1) whose muscle biopsy diagnosis was central core disease (CCD) had an occurrence of MH after a cervical spine surgery, during which he was placed under general anesthesia without volatile anesthetics or succinylcholine. The MH crisis treatment workflow was started and intravenous dantrolene was used, which was soon combined with sequent continuous veno-venous hemofiltration (CVVH) and plasma exchange (PE) therapy. We explored the pharmacokinetic profile of dantrolene during PE treatment. It showed that a one-compartment model with first-order kinetics was sufficient to characterize dantrolene pharmacokinetics (PK). The renal clearance estimate for dantrolene was 0.33 mL/(min*kg) and the volume of distribution was 0.51 L/kg. Though a 4-h PE elevated about 27% off-clearance for dantrolene, it eliminated extra dantrolene by a mere 4% of the area under the curve (AUC). We made no recommendation with respect to adjusting dantrolene dosing for MH adolescents with a 4-h PE.

Cemented paste backfill (CPB) is wildly used in mines production practices around the world. The strength of CPB is the core of research which is affected by factors such as slurry concentration and cement content. In this paper, a research on the UCS is conducted by means of a combination of laboratory experiments and machine learning. BPNN, RBFNN, GRNN and LSTM are trained and used for UCS prediction based on 180 sets of experimental UCS data. The simulation results show that LSTM is the neural network with the optimal prediction performance (The total rank is 11). The trial-and-error, PSO, GWO and SSA are used to optimize the learning rate and the hidden layer nodes for LSTM. The comparison results show that GWO-LSTM is the optimal model which can effectively express the non-linear relationship between underflow productivity, slurry concentration, cement content and UCS in experiments (R=0.9915, RMSE = 0.0204, VAF = 98.2847 and T = 16.37 s). The correction coefficient (k) is defined to adjust the error between predicted UCS in laboratory (UCSM) and predicted UCS in actual engineering (UCSA) based on extensive engineering and experimental experience. Using GWO-LSTM combined with k, the strength of the filling body is successfully predicted for 153 different filled stopes with different stowing gradient at different curing times. This study provides both effective guidance and a new intelligent method for the support of safety mining.

Lung cancer is the leading cause of cancer-related death worldwide. Therapies for lung cancer have relatively poor outcomes and need to be improved. Lung cancer immune cell infiltration associated RNA (LCIIAR) is a long noncoding RNA (lncRNA), which is overexpressed in human cancers. However, the clinical significance and functional role of LCIIAR in Lung Adenocarcinoma remain unclear. Here, we identified a novel long non-coding RNA (ENSG00000256802), termed LCIIAR (lung cancer immune cell infiltration associated lncRNA), up-regulated in lung cancer tissue and cell lines. We show that increase LCIIAR expression correlated with poor clinical stage and adverse clinical outcomes and that could also serve as an independent unfavorable prognostic factor in patients with Lung Adenocarcinima. GSEA analysis demonstrated that LCIIAR is mainly involved in the regulation of the immune response. We uncovered that elevate LCIIAR expression positively correlated with immune infiltration and immune modulator in Lung Adenocarcinoma. More importantly, we confirmed that silencing of LCIIAR expression significantly inhibits the proliferation, and migration abilities of these tumour cells. We also demonstrated that the LCIIAR/hsa-miR184/SLC16A3/CDCP1 network regulates SLC16A3/CDCP1 overexpression in and is associated with poor prognosis in this tumour. Therefore our findings revealed the critical role of LCIIAR in Lung Adenocarcinoma progression, which may also serve as a prognostic biomarker and novel therapeutic target.

Background and PurposeSpinal cord stimulation (SCS) has been reported to be a promising neuromodulation method for patients with disorders of consciousness (DOC). Our previous studies found that clinical characteristics of patients and SCS stimulation parameters could affect the therapeutic effects of SCS, while surgical-related factors remain unknown. Through the improvement of surgical procedures, most of the SCS electrodes are implanted in the middle, while a small number of electrodes have still deviated.MethodsA total of 137 patients received SCS treatment in our institutions from 1 January 2010 to 31 December 2020. Among them, 27 patients were found with electrode deviation and met the inclusion criteria. Patients were grouped according to whether the electrode deviation angle (EDA) is >30°, respectively. Clinical characteristics of patients and SCS stimulation parameters were compared. Potential related factors and outcomes were evaluated by Chi-square test or two-way repeated measures analysis.ResultsTwenty seven patients receiving cervical SCS treatment were found to have electrode deviation postoperatively. Among them, 12 patients were classified into the more deviation group. No significant difference was found among age, sex, pathogeny, course of DOC, C2–C5 distance, spinal cord to spinal canal ratio at C2 level, and preoperative JFK Coma Recovery Scale-Revised (CRS-R) scores. We found that the electrode direction significantly deviated to the contralateral side in the lateral decubitus position (P = 0.025). The maximum tolerant stimulation intensity in the less deviation group (1.70 ± 0.41) was significantly higher than that in the more deviation group (1.25 ± 0.34) (P = 0.006). Under the strongest stimulation, less unilateral limb tremor (P = 0.049) and paroxysmal sympathetic hyperactivity (PSH) episodes (P = 0.030) were found. EDA had a significant effect on postoperative CRS-R in patients, and patients in the less deviation group had significantly higher postoperative CRS-R (P < 0.01). There was also an interaction effect between EDA and postoperative time. With the prolonged postoperative time, the CRS-R improvement rate of patients with different EDA was different, and the CRS-R improved faster in patients with less EDA (P < 0.05).ConclusionsElectrode deviation will affect the outcome of patients receiving cervical SCS treatment. The intraoperative surgical position is associated with postoperative electrode deviation direction. The reduction of EDA under 30° can increase maximum tolerant stimulation intensity, reduce complications, and further improve patients' outcomes.

To achieve river channel detection in SAR (synthetic aperture radar) images, we developed a level-set-based model (LSBM) guided by a designed data-fitting energy which is called the SoDEF (sum of dual exponential functions)-fitting energy. Firstly, we designed a function by computing the sum of dual exponential functions to substitute for the quadratic function, and used it to construct the data-fitting energy. Secondly, the adaptive area-fitting centers (AFCs) were computed based on two kinds of grayscale characteristics, which are more accurate and more stable. Thirdly, the Dirac function in gradient descent flow was displaced by an edge indicator function to help the evolving level sets stop at the target edges. Moreover, some regularized terms were incorporated into the objective function to guarantee the model’s stability. The river channel detection experiments conducted with real SAR images indicated that the developed model is superior to the related state-of-the-art methods in its detection accuracy and efficiency.

This study aimed to evaluate the performance of sandwich panels with graded foam cores of layered densities against combined blast and fragment impact loading, and to ascertain the optimal gradient of core configuration that would maximize the performance of sandwich panels against combined loading. First, based on a recently developed composite projectile, impact tests of the sandwich panels against simulated combined loading were conducted to provide a benchmark for the computational model. Second, a computational model, based on three-dimensional finite element simulation, was constructed and verified by means of a comparison of the numerically calculated and experimentally measured peak deflections of the back facesheet and the residual velocity of the penetrated fragment. Third, the structural response and energy absorption characteristics were examined, based on numerical simulations. Finally, the optimal gradient of core configuration was explored and numerically examined. The results indicated that the sandwich panel responded in a combined manner involving global deflection, local perforation and perforation hole enlargement. As the impact velocity increased, both the peak deflection of the back facesheet and the residual velocity of the penetrated fragment increased. The front facesheet was found to be the most important sandwich component in consuming the kinetic energy of the combined loading. Thus, the compaction of the foam core would be facilitated by placing the low-density foam at the front side. This would further provide a larger deflecting space for the front facesheet, thus reducing the deflection of the back facesheet. The gradient of core configuration was found to have limited influence on the anti-perforation ability of the sandwich panel. Parametric study indicated that the optimal gradient of foam core configuration was not sensitive to time delay between blast loading and fragment impact loading, but was sensitive to the asymmetrical facesheet of the sandwich panel.

The utilization of solid waste for filling mining presents substantial economic and environmental advantages, making it the primary focus of current filling mining technology development. To enhance the mechanical properties of superfine tailings cemented paste backfill (SCPB), this study conducted response surface methodology experiments to investigate the impact of various factors on the strength of SCPB, including the composite cementitious material, consisting of cement and slag powder, and the tailings’ grain size. Additionally, various microanalysis techniques were used to investigate the microstructure of SCPB and the development mechanisms of its hydration products. Furthermore, machine learning was utilized to predict the strength of SCPB under multi-factor effects. The findings reveal that the combined effect of slag powder dosage and slurry mass fraction has the most significant influence on strength, while the coupling effect of slurry mass fraction and underflow productivity has the lowest impact on strength. Moreover, SCPB with 20% slag powder has the highest amount of hydration products and the most complete structure. When compared to other commonly used prediction models, the long-short term memory neural network (LSTM) constructed in this study had the highest prediction accuracy for SCPB strength under multi-factor conditions, with root mean square error (RMSE), correlation coefficient (R), and variance account for (VAF) reaching 0.1396, 0.9131, and 81.8747, respectively. By optimizing the LSTM using the sparrow search algorithm (SSA), the RMSE, R, and VAF improved by 88.6%, 9.4%, and 21.9%, respectively. The research results can provide guidance for the efficient filling of superfine tailings.

Thin structural elements such as large-scale covering plates of aerospace protection structures and vertical stabilizers of aircraft are strongly influenced by gravity (and/or acceleration); thus, exploring how the mechanical behaviors of such structures are affected by gravitational field is necessary. Built upon a zigzag displacement model, this study establishes a three-dimensional vibration theory for ultralight cellular-cored sandwich plates subjected to linearly varying in-plane distributed loads (due to, e.g., hyper gravity or acceleration), with the cross-section rotation angle induced by face sheet shearing accounted for. For selected boundary conditions, the theory enables quantifying the influence of core type (e.g., close-celled metal foams, triangular corrugated metal plates, and metal hexagonal honeycombs) on fundamental frequencies of the sandwich plates. For validation, three-dimensional finite element simulations are carried out, with good agreement achieved between theoretical predictions and simulation results. The validated theory is subsequently employed to evaluate how the geometric parameters of metal sandwich core and the mixture of metal cores and composite face sheets influence the fundamental frequencies. Triangular corrugated sandwich plate possesses the highest fundamental frequency, irrespective of boundary conditions. For each type of sandwich plate considered, the presence of in-plane distributed loads significantly affects its fundamental frequencies and modal shapes.

Foodborne prevention and treatment of hyperuricemia (HUA) has received widespread attention. Lactic acid bacteria (LAB) can improve intestinal function, while traditional medicine dandelion has the functions of detoxification and detumescence. Whether LAB fermented dandelion has any effects on HUA and the underlying mechanism is not clear. To address these questions, Lactobacillus acidophilus was selected or maximal xanthine oxidase activity. The effect of Lactobacillus acidophilus fermented dandelion (LAFD) on uric acid metabolism was evaluated by the HUA mouse model. Expression levels of UA, BUN, CRE, XOD, and inflammatory factors in serum were detected. Paraffin sections and staining were used to observe the kidney and small intestine, and mRNA expression of GLUT9, URAT1, OAT1, and ABCG2 related to uric acid metabolism were investigated. Furthermore, the intestinal flora was studied by contents of the cecum and high throughput 16S rRNA sequencing. The results showed that LAFD had a significant inhibitory effect on XOD in vitro (p < 0.01). LAFD could reduce the levels of UA, BUN, CRE, XOD, IL-1 β, IL-6, and TNF- α in serum (p < 0.05), thus inhibiting inflammatory reaction, and reducing UA by decreasing the mRNA expression of GLUT9, URAT1 in kidney and increasing the mRNA expression of OAT1 and ABCG2 in kidney and small intestine (p < 0.05). In addition, the 16S rRNA gene sequencing analysis demonstrated that LAFD treatment can help restore the imbalance of the intestinal microbial ecosystem and reverse the changes in Bacterodietes/Firmicutes, Muribaculaceae, Lachnospiraceae in mice with HUA. It is suggested that the mechanism of LAFD in treating HUA may be related to the regulation of the mRNA expressions of GLUT9, URAT1, OAT1, and ABCG2 in the kidney and small intestine, as well as the regulation of intestinal flora, which provides the experimental basis for the development of new plant fermented products.

In this study, open-cell copper foam with completely interconnected sphere pores was prepared by a modified sintering–dissolution process using a preformed calcium chloride template skeleton as space holder. Compared with the traditional foaming process method, the open-cell copper foam prepared by this method has fewer impurities and better surface morphology. In addition, the pore distribution can be controlled by adjusting the distribution of calcium chloride particles in the skeleton. The compression performance, airflow resistance, and filtration performance of the prepared open-cell copper foam were studied. The results show that with the increase in porosity, the bearing capacity of open-cell copper foam decreases, but the width of the stress platform increases. The prepared open-cell copper foam exhibits excellent energy absorption efficiency, reaching nearly 90% at a porosity of 85%. When the porosity is 85%, the static airflow resistance of the structure is as high as 9 KPa·s·m−2. Moreover, the structure has a filtration efficiency of more than 90% as the filtration thickness exceeds 20 mm, which demonstrates the excellent filtration ability. Such open-cell copper foam shows multi-functional potential as an impact damper, sound absorber, and impurity filter.