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SummaryGenomic rearrangements contribute to gene copy number alterations, disruption of protein-coding sequences and/or perturbation of cis-regulatory networks. SCRaMbLE, a Cre/loxP-based system implanted in synthetic yeast chromosomes, can effectively introduce genomic rearrangements, and is thus a potential tool to study genomic rearrangements. However, the potential of SCRaMbLE to study genomic rearrangements is currently hindered, because a strain containing all 16 synthetic chromosomes is not yet available. Here, we constructed a yeast strain, SparLox83, containing 83 loxPsym sites distributed across all 16 chromosomes, with at least two sites per chromosome. Inducing Cre recombinase expression in SparLox83 produced versatile genome-wide genomic rearrangements, including inter-chromosomal events. Moreover, SCRaMbLE of the hetero-diploid strains derived from crossing SparLox83 with strains possessing synthetic chromosome III (synIII) from the Sc2.0 project led to increased diversity of genomic rearrangements and relatively faster evolution of traits compared to a strain with only synIII. Analysis of these evolved strains demonstrates that genomic rearrangements can perturb the transcriptome and 3D genome structure and can consequently impact phenotypes. In summary, a genome with sparsely distributed loxPsym sites can serve as a powerful tool to study the consequence of genomic rearrangements and help accelerate strain engineering in Saccharomyces cerevisiae.

Identification of long non-coding RNAs (lncRNAs) associated with common diseases is crucial for patient self-diagnosis and monitoring of health conditions using artificial intelligence (AI) technology at home. LncRNAs have gained significant attention due to their crucial roles in the pathogenesis of complex human diseases and identifying their associations with diseases can aid in developing diagnostic biomarkers at the molecular level. Computational methods for predicting lncRNA-disease associations (LDAs) have become necessary due to the time-consuming and labor-intensive nature of wet biological experiments in hospitals, enabling patients to access LDAs through their AI terminal devices at any time. Here, we have developed a predictive tool, LDAGRL, for identifying potential LDAs using a bridge heterogeneous information network (BHnet) constructed via Structural Deep Network Embedding (SDNE). The BHnet consists of three types of molecules as bridge nodes to implicitly link the lncRNA with disease nodes and the SDNE is used to learn high-quality node representations and make LDA predictions in a unified graph space. To assess the feasibility and performance of LDAGRL, extensive experiments, including 5-fold cross-validation, comparison with state-of-the-art methods, comparison on different classifiers and comparison of different node feature combinations, were conducted, and the results showed that LDAGRL achieved satisfactory prediction performance, indicating its potential as an effective LDAs prediction tool for family medicine and primary care.

Background As an important source of genetic variation, copy number variation (CNV) can alter the dosage of DNA segments, which in turn may affect gene expression level and phenotype. However, our knowledge of CNV in apple is still limited. Here, we obtained high-confidence CNVs and investigated their functional impact based on genome resequencing data of two apple populations, cultivars and wild relatives. Results In this study, we identified 914,610 CNVs comprising 14,839 CNV regions (CNVRs) from 346 apple accessions, including 289 cultivars and 57 wild relatives. CNVRs summed to 71.19 Mb, accounting for 10.03% of the apple genome. Under the low linkage disequilibrium (LD) with nearby SNPs, they could also accurately reflect the population structure of apple independent of SNPs. Furthermore, A total of 3,621 genes were covered by CNVRs and functionally involved in biological processes such as defense response, reproduction and metabolic processes. In addition, the population differentiation index ($${V}_{st}$$ V st ) analysis between cultivars and wild relatives revealed 127 CN-differentiated genes, which may contribute to trait differences in these two populations. Conclusions This study was based on identification of CNVs from 346 diverse apple accessions, which to our knowledge was the largest dataset for CNV analysis in apple. Our work presented the first comprehensive CNV map and provided valuable resources for understanding genomic variations in apple.

Background Emerging evidences show that Piwi-interacting RNAs (piRNAs) play a pivotal role in numerous complex human diseases. Identifying potential piRNA-disease associations (PDAs) is crucial for understanding disease pathogenesis at molecular level. Compared to the biological wet experiments, the computational methods provide a cost-effective strategy. However, few computational methods have been developed so far. Results Here, we proposed an end-to-end model, referred to as PDA-PRGCN (PDA prediction using subgraph Projection and Residual scaling-based feature augmentation through Graph Convolutional Network). Specifically, starting with the known piRNA-disease associations represented as a graph, we applied subgraph projection to construct piRNA-piRNA and disease-disease subgraphs for the first time, followed by a residual scaling-based feature augmentation algorithm for node initial representation. Then, we adopted graph convolutional network (GCN) to learn and identify potential PDAs as a link prediction task on the constructed heterogeneous graph. Comprehensive experiments, including the performance comparison of individual components in PDA-PRGCN, indicated the significant improvement of integrating subgraph projection, node feature augmentation and dual-loss mechanism into GCN for PDA prediction. Compared with state-of-the-art approaches, PDA-PRGCN gave more accurate and robust predictions. Finally, the case studies further corroborated that PDA-PRGCN can reliably detect PDAs. Conclusion PDA-PRGCN provides a powerful method for PDA prediction, which can also serve as a screening tool for studies of complex diseases.

Background Osteoblast phenotypic transition in vascular smooth muscle cells (VSMCs) has been unveiled as a common cause of vascular calcification (VC). Krüppel-Associated Box (KRAB)-Associated Protein 1(KAP1) is a transcriptional corepressor that modulates various intracellular pathological processes from gene expression to DNA repair to signal transduction. However, the function and mechanism of KAP1 on the osteoblastic differentiation of VSMCs have not been evaluated yet. Methods and results We demonstrate that the expression of KAP1 in VSMCs is significantly enhanced in vivo and in vitro calcification models. Downregulating the expression of KAP1 suppresses the osteoblast phenotypic transition of VSMCs, which is indicated by a decrease in the expression of osteoblast marker collagenase type I (COL I) and an increase in the expression of VSMC marker α-smooth muscle actin (α-SMA). Conversely, exogenous overexpression of KAP1 could promote osteoblast phenotypic transition of VSMCs. Moreover, KAP1 upregulated the expression of RUNX family transcription factor 2 (Runx2), an inducer of osteoblast that positively regulates many osteoblast-related genes, such as COL I. Evaluation of the potential mechanism demonstrated that KAP1 promoted osteoblast phenotypic transition of VSMCs by activating the extracellular regulated protein kinases (ERK) signaling pathway, which could activate Runx2. In support of this finding, KAP1-induced cell osteoblast phenotypic transition is abolished by treatment with PD0325901, a specific ERK inhibitor. Conclusions The present study suggested that KAP1 participated in the osteoblast differentiation of VSMCs via the ERK/Runx2 cascade and served as a potential diagnostics and therapeutics target for vascular calcification.

In order to study the influences of confining pressure and strain rate on the mechanical properties of the Nitrate Ester Plasticized Polyether (NEPE) propellant, uniaxial tensile tests were conducted using the self-made confining pressure system and material testing machine. The stress-strain responses of the NEPE propellant under different confining pressure conditions and strain rates were obtained and analyzed. The results show that confining pressure and strain rate have a remarkably influence on the mechanical responses of the NEPE propellant. As confining pressure increases (from 0 to 5.4 MPa), the maximum tensile stress and ultimate strain increase gradually. With the coupled effects of confining pressure and strain rate, the value of the maximum tensile stress and ultimate strain at 5.4 MPa and 0.0667 s−1 is 2.03 times and 2.19 times of their values under 0 MPa and 0.00333 s−1, respectively. Afterwards, the influence mechanism of confining pressure on the NEPE propellant was analyzed. Finally, based on the viscoelastic theory and continuous damage theory, a nonlinear constitutive model considering confining pressure and strain rate was developed. The damage was considered to be rate-dependent and pressure-dependent. The constitutive model was validated by comparing experimental data with predictions of the constitutive model. The whole maximum stress errors of the model predictions are lower than 4% and the corresponding strain errors are lower than 7%. The results show that confining pressure can suppress the damage initiation and evolution of the NEPE propellant and the nonlinear constitutive model can describe the mechanical responses of the NEPE propellant under various confining pressure conditions and strain rates. This research can lay a theoretical foundation for analyzing the structural integrity of propellant grain accurately under working pressure loading.

Background: The purpose of this study was to observe the impact of an internet-based management system on the incidence of intradialytic hypotension (IDH) and muscle cramps in hemodialysis patients. Methods: The patients, who underwent maintenance hemodialysis in the center from January 2018 to June 2020, were recruited and divided into the pre-intervention group (before operation of the internet-based hemodialysis management system, from January 2018 to December 2018) and intervention group (after operation of the system, from June 2019 to June 2020). The clinical outcomes were compared between groups. Results: The compound endpoint of >1 IDH or muscle cramps happened in 182 patients (61.7%) in the pre-intervention group and 99 participants (30.8%) in the intervention group (relative risk [RR] = 0.50 [95% confidence interval [CI], 0.42; 0.60]). IDH occurred in 122 patients (1–5 episodes in 47 patients, 6–10 episodes in 25 patients, and >10 episodes in 50 patients) and 33 patients (30 patients had 1–5 episodes and 3 patients had 6–10 episodes) before and after execution of the internet-based management system, respectively (RR = 0.25 [95% CI, 0.18; 0.35]). The incidence of muscle cramps was significantly decreased (RR = 0.57 [95% CI, 0.45; 0.73]) after the implementation of the system, and the number of patients with 6–10 episodes dropped from 10 to 1. Multivariate analyses also showed significantly lower RRs in the intervention group: 0.29 ([95% CI, 0.20; 0.41]) for IDH and 0.58 ([95% CI, 0.45; 0.74]) for muscle cramps. Compared with the pre-intervention, participants in the intervention group had a large improvement in self-management (p < 0.001) and self-efficacy (p < 0.001). Conclusion: The study found that the internet-based hemodialysis management system was effective in reducing the IDH and muscle cramp events and improving self-management. It provided a significant implication for the development and application of internet-based programs in hemodialysis management.

Aims We aimed to assess whether the safety outcomes exerted by sodium-glucose cotransporter 2 (SGLT2) inhibitors were associated with different renal function at baseline. Data Synthesis We searched randomized controlled trials comparing SGLT2 inhibitors with placebo in participants simultaneously involving the entire range of estimated glomerular filtration rate (eGFR) levels at baseline in one study. According to eGFR, we divided the population into two subgroups with eGFR 0.05). For osmotic diuresis, SGLT2 inhibitors significantly increased the risk by 75% (p = 0.036), and subgroup analyses showed that this effect was completely attributed to the increase in patients with eGFR ≥60 ml/min/1.73 m2 (p-interaction Conclusion The indication of no risk of osmotic diuresis in patients with eGFR

In order to study the influence of the deformations of the nozzle’s flexible sections on its inner wall’s heat transfer, this research uses the two-dimensional axisymmetric model and the k − ω SST turbulence model to numerically analyze the tail flow field of the flexible-extendible nozzle under multiple working conditions. The flow field and the inner wall’s heat transfer of the flexible sections with and without deformations are simulated and analyzed. The simulation results show that when the flexible sections are deformed, new shock waves will be generated in the tail flow field of the nozzle; the temperature and the heat flux of the first half of each flexible section decrease, while those at the end of each flexible section increase, and the deformations’ effect on temperature and heat flux diminishes over time. The research shows that the deformations of the flexible sections will make the inner wall’s heat transfer of the flexible sections uneven, and the inner wall’s ablation at the end of each flexible section may be aggravated, while that of the front half may be alleviated.

Long-term exposure to particulate air pollutants can lead to an increase in mortality of hemodialysis patients, but evidence of mortality risk with short-term exposure to ambient particulate matter is lacking. This study aimed to estimate the association of short-term exposure to ambient particulate matter across a wide range of concentrations with hemodialysis patients mortality.We performed a time-stratified case-crossover study to estimate the association between short-term exposures to PMDuring the study period, there were 18,114 case days and 61,726 control days. Of all case and control days, average PMThis study confirms that short-term exposure to particulate matter leads to increased mortality in hemodialysis patients. Policy makers and public health practices have a clear and urgent opportunity to pass air quality control policies that care for hemodialysis populations and incorporate air quality into the daily medical management of hemodialysis patients.

SummaryBackground Programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) have dramatically improved cancer therapy for many patients. Adverse kidney effects have been found to be an important complication but have unclear mechanisms. Methods We searched Embase, PubMed, and the Cochrane Library to identify potential eligible studies. All included studies were randomized controlled trials (RCTs) examining patients with solid tumors treated with anti-PD-1/PD-L1 monoclonal antibodies (mAbs) and/or chemotherapy. The relative risk (RR) was used to assess the risk of nephrotoxic events. Results We included 27 clinical trials (15,063 patients). Compared with chemotherapy, the RR of all-grade nephritis was significantly increased with anti-PD-1/PD-L1 mAbs (RR = 2.77, 95% CI: 1.09–6.99, P = 0.03). Furthermore, anti-PD-1/PD-L1 mAbs plus chemotherapy can significantly increase the RR of all-grade nephritis (RR = 2.99, 95% CI: 1.07–8.35, P = 0.04). There was also a significant increase in the RRs of all-grade increased blood creatinine (RR = 1.88, 95% CI: 1.24–2.86, P = 0.003) and acute kidney injury (AKI) (RR =3.35, 95% CI: 1.48–7.60, P = 0.004). Conclusions Anti-PD-1/PD-L1 mAbs can significantly increase nephrotoxicity in patients with solid tumors, especially when combined with chemotherapy. During the application of these drugs, we should remain aware of nephrotoxicity for better efficacy. Trial registration number and date of registration Not applicable.

When anti-PD-1 drugs target healthy tissues, it may cause immune-related adverse events (irAEs). Hematological toxicities and renal immune-related adverse reactions were rare; these events recorded were often clinically severe and life-threatening. In this study, we first reported on an elderly esophageal cancer (ESC) case of cytokine release syndrome (CRS) and irAEs induced by radiotherapy following anti-PD-1 drug treatment. A 69-year-old male patient with ESC was hospitalized on December 2, 2019, after three cycles of chemotherapy with docetaxel and nedaplatin accompanied by the addition of PD-1 inhibitor (Sintilimab). The chemotherapy scheme was interrupted due to the absence of any response. Instead, three-dimensional conformal radiotherapy (60 Gy/30 times, 5 times/week) was locally applied to treat the esophageal lesion. Typical CRS and irAEs, including mild diarrhea, intermittent low fever, and leukopenia, occurred after 6 times of radiotherapy, which was alleviated by symptomatic treatment. Such radiotherapy, however, encountered an unexpected early ending after 10 times with patient platelet level being significantly decreased to 31×109/L and the serum creatinine of the patients sharply increased from 78.4 to 609.5 µmol/L. CT scan presented scattered inflammation in both lung. It also showed that mediastinal lymph nodes and esophageal lesions were significantly reduced, and the patients received symptomatic treatment of glucocorticoids and other immunomodulators. The patient get discharged from the hospital after the combination treatment improved the irAEs symptoms. This paper showed the possibility of CRS and multiple-organ injuries as potential irAEs during radiotherapy following the anti-PD-1 therapy strategy and discussed the management of these adverse events (AEs).

A/B compartments are observed in Hi-C data and coincide with eu/hetero-chromatin. However, many genomic regions are ambiguous under A/B compartment scheme. We develop MOSAIC (MOdularity and Singular vAlue decomposition-based Identification of Compartments), an accurate compartmental state detection scheme. MOSAIC reveals that those ambiguous regions segregate into two additional compartmental states, which typically correspond to short genomic regions flanked by long canonical A/B compartments with opposite activities. They are denoted as micro-compartments accordingly. In contrast to the canonical A/B compartments, micro-compartments cover ∼30% of the genome and are highly dynamic across cell types. More importantly, distinguishing the micro-compartments underpins accurate characterization of chromatin structure-function relationship. By applying MOSAIC to GM12878 and K562 cells, we identify CD86, ILDR1 and GATA2 which show concordance between gene expression and compartmental states beyond the scheme of A/B compartments. Taken together, MOSAIC uncovers fine-scale and dynamic compartmental states underlying transcriptional regulation and disease.

Precise dynamic parameters are of great significance to the model-based controller of industrial robots. The least square (LS) method is widely used to identify the dynamic parameters in reality, but it is sensitive to the measurement noise and may obtain a biased solution. Besides, the nonlinear dynamics are the key and difficult point of identification, such as the nonlinear friction and the coupling effect of adjacent joint, but they are seldom solved simply and effectively. To cope with the above issues, we propose a backpropagation learning (BPL) method for parameter identification. The mean square error between the measured torque and the calculated torque from the dynamic model is taken as the loss function. The gradient of the loss function with respect to the parameters is computed, and the parameters are updated in the negative gradient direction to minimize the loss function until finding the optimal parameters with the minimum loss function. The optimal parameters will not only fit the modeled torque but also compensate for the torque caused by the unmodeled factors, thus improving the parameter accuracy. The proposed method is essentially a supervised learning method, so the impact of measurement noise is reduced by continuous training with a large amount of valid data. The proposed method is verified in an industrial robot platform, and the experimental results show that the proposed method has smaller errors than the weighted least squares (WLS) method and achieves similar accuracy to the semiparametric model (SPM) but has a better generalization ability.

The immunotoxicity induced by heavy metals on herbivorous insects reflect the alterations of the susceptibility to entomopathogenic agents in herbivorous insects exposed to heavy metal. In the present study, the susceptibility of gypsy moth larvae to Bacillus thuringiensis under Cd treatment at low and high dosages was investigated, and the gut microbiome-hemolymph metabolome responses that affected larval disease susceptibility caused by Cd exposure were examined. Our results showed that mortality of gypsy moth larvae caused by B. thuringiensis was significantly higher in larvae pre-exposed to Cd stress, and there was a synergistic effect between Cd pre-exposure and bacterial infection. Exposure to Cd significantly decreased the abundance of several probiotics (e.g., Serratia for the low Cd dosage and Weissella, Aeroonas, and Serratia for the high Cd dosage) and increased the abundances of several pathogenic bacteria (e.g., Stenotrophomonas, Gardnerella, and Cutibacterium for the low Cd dosage and Pluralibacter and Tsukamurella for the high Cd dosage) compared to the controls. Moreover, metabolomics analysis indicated that amino acid biosynthesis and metabolism were significantly perturbed in larval hemolymph under Cd exposure at both the low and high dosages. Correlation analysis demonstrated that several altered metabolites in larval hemolymph were significantly correlated with changes in the gut microbial community. The results demonstrate that prior exposure to Cd increases the susceptibility of gypsy moth larvae to B. thuringiensis in a synergistic fashion due to gut microbiota dysbiosis and hemolymph metabolic disorder, and thus microbial-based biological control may be the best pest control strategy in heavy metal-polluted areas.

Background Estimates of cervical lymph node (LN) metastasis in patients with middle and lower thoracic esophageal squamous cell carcinoma (ESCC) are important. A nomogram is a useful tool for individualized prediction. Methods A total of 235 patients were enrolled in this study. Univariate and multivariate analyses were performed to screen for independent risk factors and construct a nomogram to predict the risk of cervical LN metastasis. The nomogram performance was assessed by discrimination, calibration, and clinical use. Results Totally, four independent predictors, including the maximum diameter of tumor, paraesophageal lymph node status, recurrent laryngeal nerve lymph node status, and the CT-reported cervical LN status, were enrolled in the nomogram. The AUC of the nomogram model in the training and validation dataset were 0.833 (95% CI 0.762–0.905), 0.808 (95% CI 0.696–0.920), respectively. The calibration curve demonstrated a strong consistency between nomogram and clinical findings in predicting cervical LN metastasis. Decision curve analysis demonstrated that the nomogram was clinically useful. Conclusion We developed a nomogram that could be conveniently used to predict the individualized risk of cervical LN metastasis in patients with middle and lower thoracic ESCC.

In this paper, rice husk ash (RHA) with different average pore diameters and specific surface areas was used to replace 10% slag in the preparation of alkali-activated slag (AAS) pastes. The effect of RHA addition on the shrinkage, hydration, and strength of AAS pastes was studied. The results show that RHA with a porous structure will pre-absorb part of the mixing water during paste preparation, resulting in a decrease in the fluidity of AAS pastes by 5–20 mm. RHA has a significant inhibitory effect on the shrinkage of AAS pastes. The autogenous shrinkage of AAS pastes decreases by 18–55% at 7 days, and the drying shrinkage decreases by 7–18% at 28 days. This shrinkage reduction effect weakens with the decrease in RHA particle size. RHA has no obvious effect on the type of hydration products of AAS pastes, whereas RHA after proper grinding treatment can significantly improve the hydration degree. Therefore, more hydration products are generated and fills the internal pores of the pastes, which significantly improves the mechanical properties of the AAS pastes. The 28 day compressive strength of sample R10M30 (the content of RHA is 10%, RHA milling time is 30 min) is 13 MPa higher than that of blank sample.

Heavy metal exposure-triggered growth retardation and physiology disorder in phytophagous insects have been widely understood, but only a few studies have investigated its immunomodulatory effects on herbivorous insects. Here, the innate immunity of gypsy moth (Lymantria dispar) larvae under Cd stress was evaluated by integrating cellular and humoral immunity, and the immunomodulation mechanism of Cd stress was further understood by the proteomics analysis of larval hemolymph. Our results showed that the total hemocyte count, as well as phagocytic, encapsulation and bacteriostatic activity, of hemolymph in gypsy moth larvae exposed to Cd stress was significantly lower than that in un-treated larvae. Further proteomic analysis revealed that Cd exposure may reduce the total hemocyte count in larval hemolymph by inducing endoplasmic reticulum pathway-mediated hemocyte apoptosis, thereby causing the collapse of cellular immunity in gypsy moth larvae. In addition, the transcriptional level of signal transduction genes (IMD, Toll, Relish, JAK and STAT) and antimicrobial peptide genes (cecropin and lebocin), as well as the protein abundance of pattern recognition receptors (PGRP and GNBP3) in the Toll, IMD and JAK/STAT signaling pathways was significantly decreased in Cd-treated larvae, clearly implying an immunosuppresive effect of Cd stress on pathogen recognition, signal transduction and effector synthesis of humoral immunity in gypsy moth larvae. Taken together, these results suggest that Cd exposure decreases both cellular immunity and humoral immunity of gypsy moth larvae, and provides a new entry point for systematically and comprehensively unraveling the heavy metal pollutants-caused immunotoxicity.

Chromosome conformation capture-based experiments have shown that eukaryotic chromosomes are partitioned into A and B compartments conventionally identified by the first eigenvector (EV1) of dimension reduction methods. However, many genomic regions show marginal EV1 values, indicating the ambiguity of A/B compartment scheme on these regions. We develop MOSAIC (MOdularity and Singular vAlue decomposition-based Identification of Compartments), an accurate compartmental state detection scheme. MOSAIC reveals that those ambiguous regions segregate into two additional compartmental states, which typically correspond to small genomic regions flanked by large canonical A/B compartments with opposite activities. They are denoted as micro-compartments accordingly. In contrast to the canonical A/B compartments, micro-compartments cover ~30% of the genome and are highly dynamic between cell types. More importantly, distinguishing the micro-compartments underpins accurate characterization of chromatin structure-function relationship. By applying MOSAIC to GM12878 and K562 cells, we identify CD86, ILDR1 and GATA2 which show concordance between gene expression and compartmental states beyond the scheme of A/B compartments. Taken together, MOSAIC uncovers fine-scale and dynamic structures underlying canonical A/B compartments. Our results suggest dynamic chromatin compartmentalization is underlying transcriptional regulation and disease.

In this work, for the first time to our knowledge, the spatial degrees of freedom are introduced to opto-electronic neural networks, and the few-mode fiber based multiplexing is numerically simulated to realize parallel synapses.\ud

Metal additives have positive effects on the flow field such as increasing the temperature and thrust, while this may decrease local gaseous velocity due to inter-phase drag forces on the other hand. An in-house computational solver was developed to study the typical multiphase flow with combustion. The solver relies on Eulerian–Lagrangian model and the two-way coupling approach. Numerical simulations were carried out on an afterburning chamber of a solid-fuel ramjet to study the impact of using aluminum particles as metal additive. For micron-scale aluminum particles, the injection area, initial temperature, diameter and mass flow rate are varied influence factors, while the afterburning chamber and inlet primary high-temperature gases are fixed for all the test cases. It was found that better particle dispersion can result in higher combustion efficiency due to increasing the gas-particle contact area as well as better heat transfer and diffusion. Injecting aluminum particles with higher initial temperature and smaller diameter tend to get ignited faster and then burn more easily, which means releasing more heat in the length-limited flow field. However, the aluminum particle massflow rate has much more complicated comprehensive influence than the changing rules of the adiabatic combustion temperature based on the NASA CEA code.

Panel flutter in the presence of oblique shock waves and the associated shock wave/boundary-layer interaction have been identified as one of typical phenomena in the design and optimization of air-breathing, high-speed flight vehicles. The current study investigates this phenomenon using a previously considered two-dimensional model where an elastic panel with both ends pinned is impinged at the mid-point by an oblique shock wave with specified strength. An in-house code was used to solve the Euler or the full viscous compressible Navier–Stokes equation and nonlinear structural dynamics of the panel, where the conventional serial staggered algorithm was adopted for the fluid–structure interaction. As compared with previous studies of this topic, we focus on the effect of surface velocity feedback (i.e., using boundary blowing and suction for flow control), as well as the effect of the upstream boundary layer thickness, on the panel’s dynamic behavior, surface pressure distribution, and boundary-layer separation. The results show that for inviscid flow, boundary control with feedback gain above one can suppress the panel vibration; however, this effect is not clear for viscous flow, where feedback gain below one has some effect on attenuation of vibration. Further study shows that the panel velocity based control introduces a phase shift for the pressure in the inviscid flow as a damping effect, but the effect is not as strong in the viscous flow. Finally, the boundary layer thickness has a non-monotonic effect on the panel flutter and flow separation. At intermediate thicknesses considered here, the panel flutter is reduced and separation becomes less oscillatory.

Ducted Rocket Engine (DRE) is an important air-breathing propulsion technology. Its characteristic configuration includes air inlets and afterburning chamber for higher combustion efficiency and better working performance. In this paper, experiments were performed using a fuel-rich metalized solid propellant with an on-ground direct-connect facility. Various sensors were adopted inside the dual-inlet DRE for measuring temperature, pressure and thrust at the air-fuel ratio of 15. Meanwhile, Coupled Multiphase Reacting Phenomena Simulator (CMRPS), an in-house computational solver was developed and validated using two-way coupled Computational Fluid Dynamics and Discrete Element Method (CFD-DEM). The multiphase reacting flow inside DRE was successfully simulated at the same experimental working condition. Numerical results of the temperature, pressure fields and thrusts have good agreements with the measured experimental data. Temperature contours inside DRE indicate strong coupling effects because of the motion and combustion of metal additives. The highest temperature exists symmetrically near the downwind areas of dual inlets because of the induced high oxygen concentration and the enhanced secondary combustion. Mass fraction contours of main reacting components reveal the chemical pathways. Initially, propellant decomposes and then various components are injected into the fluid domain. Ammonium Perchlorate (AP) and magnesium react the fastest near the burning surface, which leads to a steep temperature increase there from 1050 K to over 2200 K. Then C-H components react gradually with the left oxygen in the primary combustor, while aluminum particles need to absorb heat and have difficult ignition characteristics because of oxidation cap. Air is induced into DRE through dual inlets, which contributes to the secondary combustion of C-H components and aluminum particles in the afterburning chamber. Besides influencing the temperature field, metal particles have great effects on the velocity field because of inter-phase drag force. Therefore, the central velocity characteristics on nozzle exit have obvious decrease, while thrust is increased comparing to the primary single-phase result. Average combustion efficiency can be statistically calculated with numerous exhausted metal particles. Moreover, thermal protection is important for the use of fuel-rich metalized solid propellant. Much attention was paid to the ablation characteristics inside DRE, which is closely related with the distribution of burning particles. CMRPS is meaning to the understanding and designing of multiphase combustor for higher combustion efficiency, meanwhile novel materials and thermal protection strategies can be pertinently improved for better working performance.

Tm3+/Yb3+: Y2Ti2O7 phosphors with color-tunable upconversion (UC) luminescence and optical thermometric property were synthesized and characterized. The phosphors exhibit intense blue and red UC emission bands under 980 nm excitation. The blue to red emission intensity ratio shows an enhancement with increasing excitation power. Hence, the UC color can be tuned from almost white to blue by control of the excitation power density. The temperature sensing behaviors are studied based on fluorescence intensity ratio (FIR) technique at different excitation powers. FIR-1 from the thermally coupled levels (1G4(a) and 1G4(b)) is insensitive to the excitation power, which can obtain consistent measurement results at different excitation powers. Meanwhile, the utilization of FIR-2 from non-thermally coupled levels (3F2,3 and 1G4(b)) can achieve higher sensing sensitivities with the maximal value of ∼0.81%K−1 at 398 K. Hence, Tm3+/Yb3+:Y2Ti2O7 phosphor has promising application prospects in the fields of upconverter, optical thermometer and color tunable device.

Drag and heat reduction strategy in hypersonic vehicle design has already attracted worldwide attention. In this paper, a novel combinational spike and multi-jet strategy has been proposed for the drag and heat reduction in hypersonic flows. The flow field induced by this novel strategy has been numerically investigated by an in-house code. High-resolution upwind scheme (AUSMPW) and SST k - ω turbulence model are employed in the code. The fluid-thermal interaction is considered by using the conjugate heat transfer (CHT) approach. In addition, the thrust produced by the opposing jet is taken into account in computing the total drag. The influences of the spike length-to-diameter ratio, jet pressure ratio and lateral jet location on the flow field, drag reduction and heat properties are investigated thoroughly. The numerical results reveal that this novel strategy has better drag and heat reduction efficiency of unit mass flow rate, and the negative thrust induced by the opposing jet proved to be an important factor for the total drag. The spike length-to-diameter ratio has a great influence on the drag reduction, and the drag coefficient decreases significantly as the spike length-to-diameter ratio increases. However, the Stanton number is less affected by the spike length-to-diameter ratio variation. The jet pressure ratio, including the pressure ratios of opposing jet and lateral jet, are the key parameters for the drag reduction and thermal protection, and both the drag coefficient and the Stanton number decrease significantly as jet pressure ratio rises. For the lateral jet location effect, it influences the flow features, drag reduction and thermal protection significantly. The drag coefficient can be reduced by nearly 20% as the lateral jet location increases from 0.1 to 0.7, and the peak value of the Stanton number increases sharply by 49.36% when the lateral jet location varies from 0.9 to 0.1.

The heart and neural crest derivatives expressed 2 antisense RNA 1 (HAND2-AS1) is a novel long noncoding RNA aberrantly expressed in human malignancies. We aimed to analyze the available data to evaluate the clinical prognostic significance of HAND2-AS1 in tumors.In this meta-analysis, electronic databases, including PubMed Cochrane Library, EMBASE, Medline, Web of Science, CNKI, and Wanfang, were searched from their inception up to December 1, 2021. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the relationship of HAND2-AS1expression level with prognosis and clinicopathological features in cancer patients. The publication bias was identified by Begg's test, and the sensitivity analysis was also performed.A total of 10 articles with 615 patients were included in the present meta-analysis. The combined results revealed that low expression of HAND2-AS1 was associated with poor overall survival (OS) (HR = 0.48, 95% CI: 0.36-0.64, P .001) in a variety of cancers. In addition, the decrease in HAND2-AS1 expression was also correlated with poor differentiation (OR = 4.36, 95% CI: 2.15-8.87, P .001) and lymph node metastasis (OR = 0.26, 95% CI: 0.13-0.54, P .001). The cancer genome atlas (TCGA) dataset further demonstrated that low expression of HAND2-AS1 was associated with poor OS and disease-free survival.Our results of this meta-analysis indicated that HAND2-AS1 may be a prognostic marker and even a therapeutic target for human cancer.

Neurensin‑2 (NRSN2) has been reported to act as an oncogene in several types of human cancer. However, the molecular mechanism of NRSN2 in esophageal squamous cell carcinoma (ESCC) remains to be elucidated.The mRNA expression levels of NRSN2 in ESCC tissues and cell lines were evaluated by quantitative real-time PCR (qRT-PCR). The protein expression levels of NRSN2 in ESCC tissues were measured by Immunohistochemical (IHC) method. Luciferase reporter and chromatin immunoprecipitation assays were conducted to confirm the upstream transcription factor of NRSN2. Loss- and gain-function assays were conducted to evaluate the effects of NRSN2 on ESCC cells proliferation, migration, and invasion. The function of NRSN2 was validated in vivo using tumor xenografts. The relationship between NRSN2 and AKT/mTOR pathway were confirmed by western blot assay.The expression level of NRSN2 was increased in ESCC tissues and cell lines. High expression level of NRSN2 was correlated with depth of invasion, lymph node metastasis, TNM stage, and poor prognosis of ESCC patients. NRSN2 was transcribed by E2F1. Knockdown of NRSN2 significantly inhibited ESCC cells proliferation, migration, and invasion, whereas NRSN2 overexpression showed reverse phenotypes. Overexpression of NRSN2 also enhanced ESCC tumorigenicity in vivo. Furthermore, the E2F1/NRSN2 axis promoted proliferation, migration, and invasion of ESCC cells by activating the AKT/mTOR pathway.NRSN2 is a direct transcriptional target of E2F1 to promote tumor progression in ESCC. NRSN2 may be a diagnostic biomarker or treatment target for ESCC.

Objective In order to find new strategies for the prevention of vascular calcification in uremic individuals especially treated by dialysis and develop novel therapeutic targets in vascular calcification, we explore the role of KCa3.1 in alkalinization‐induced VSMCs calcification in vitro. Method Rat VSMCs calcification model was established by beta‐glycerophosphate (β‐GP, 10 mM) induction. The pH of Dulbecco's modified Eagle's medium (DMEM) was adjusted every 24 h with 10 mM HCl or 10 mM NaHCO3. The mineralization was measured by Alizarin Red staining and O‐cresolphthalein complex one method. mRNA and protein expression were detected by RT‐PCR and Western blot or immunofluorescence. Ca2+ influx was measured by Elisa. Result The results indicated that alkalization induced an increase in Ca2+ influx to enhance VSMCs calcification. Furthermore, the increase of calcification was associated with the expression of KCa3.1 via advanced expression of osteoblastic differentiation markers alkaline phosphatase (ALP) and Runt‐related transcription factor 2 (Runx2). Blocking KCa3.1 with TRAM‐34 or shRNA vector can significantly lowered the effects of calcification in the activity of ALP and Runx2 expression. Conclusion Together all, our studies suggested that alkalinization can promote vascular calcification by upregulating KCa3.1 channel and enhancing osteogenic/chondrogenic differentiation by upregulating Runx2. The specific inhibitor TRAM‐34 and KCa3.1‐shRNA ameliorated VSMCs calcification by downregulating KCa3.1., Vascular calcification is associated with an increased cardiovascular risk among patients with chronic kidney disease. Alkaline loading in hemodialysis patients and alkali supplements contribute to vascular calcification. KCa3.1 has been reported to be a potential molecular target for pharmacological intervention in a diverse array of clinical conditions. In order to find new strategies for the prevention of vascular calcification in uremic individuals especially treated by dialysis and develop novel therapeutic targets in vascular calcification, we explore the role of KCa3.1 in alkalinization‐induced VSMCs calcification in vitro. Rat VSMCs calcification model was established by beta‐glycerophosphate (β‐GP, 10 mM) induction. The pH of DMEM was adjusted every 24 h with 10 mM HCl or 10 mM NaHCO3. The mineralization was measured by Alizarin Red staining and O‐cresolphthalein complex one method. mRNA and protein expression were detected by RT‐PCR and Western blot or immunofluorescence. Ca2+ influx was measured by Elisa. The results indicated that alkalization induced an increase in Ca2+ influx to enhance VSMCs calcification. Furthermore, the increase of calcification was associated with the expression of KCa3.1 via advanced expression of osteoblastic differentiation markers alkaline phosphatase (ALP) and Runt‐related transcription factor 2 (Runx2). Blocking KCa3.1 with TRAM‐34 or shRNA vector can significantly lowered the effects of calcification in the activity of ALP and Runx2 expression. Together all, our studies suggested that alkalinization can promote vascular calcification by upregulating KCa3.1 channel and enhancing osteogenic/chondrogenic differentiation by upregulating Runx2. The specific inhibitor TRAM‐34 and KCa3.1‐shRNA ameliorated VSMCs calcification by downregulating KCa3.1.

According to the numerical simulation, the sympathetic detonation of fiber composite shelled propellant was analyzed. Comparing the effects of fragments and reaction products shows that the impacting effect of fiber composite shell fragments is limited and can not lead the sympathetic detonation. The reason for sympathetic detonation in the closer distance is mainly reaction products.

It is essential to understand the fracture characteristics of a cracked propellant grain in a solid rocket motor during the motor ignition. In this paper, a finite element model of a solid rocket motor is developed, including the gas impingement flow field and the structural field. A circumferential crack is prefabricated on a round-hole type propellant grain. The gas pressure inside the cracked grain is obtained as a function of time by calculating the flow field. Then applying this pressure to the structural field, and J-integral at the crack tip can be calculated. The J-integral can represent the fracture toughness of the propellant. The results show that the circumferential crack in the propellant grain opens up as the gas pressure gradually increases. The J-integral values at the crack tip show an oscillating trend and are not monotonically increasing. This paper predicts the moment of crack propagation in the rocket motor grain under gas impingement conditions by comparing the JIC of the propellant.

Although taste is an important aspect of fruit quality, an understanding of its genetic control remains elusive in apple and other fruit crops. In this study, we conducted genomic sequence analysis of 497 Malus accessions and revealed erosion of genetic diversity caused by apple breeding and possible independent domestication events of dessert and cider apples. Signatures of selection for fruit acidity and size, but not for fruit sugar content, were detected during the processes of both domestication and improvement. Furthermore, we found that single mutations in major genes affecting fruit taste, including Ma1, MdTDT, and MdSOT2, dramatically decrease malate, citrate, and sorbitol accumulation, respectively, and correspond to important domestication events. Interestingly, Ma1 was identified to have pleiotropic effects on both organic acid content and sugar:acid ratio, suggesting that it plays a vital role in determining fruit taste. Fruit taste is unlikely to have been negatively affected by linkage drag associated with selection for larger fruit that resulted from the pyramiding of multiple genes with minor effects on fruit size. Collectively, our study provides new insights into the genetic basis of fruit quality and its evolutionary roadmap during apple domestication, pinpointing several candidate genes for genetic manipulation of fruit taste in apple.