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Abstract Faced with the increasing number of flights, efficient and orderly operations have become a critical issue for busy airports. The closely spaced parallel runway paired approach technology has been proven to be an effective solution for increasing runway capacity and operational efficiency. This research focuses on determining the safety separation between paired aircraft, particularly the collision safety limit. This study refines the kinematic modeling process by constructing a three-dimensional kinematic model and advancing the starting point of paired approach, making the simulation process more aligned with reality. Subsequently, the Monte Carlo simulation method is applied, integrating the kinematic model and considering collision risks to simulate the entire paired approach process. Multiple scenarios are created, and simulation experiments are conducted to determine the safety separation between the two paired aircraft. Finally, by adjusting parameter settings and taking the example of the two closely spaced parallel runways at Chongqing Jiangbei International Airport, the correlation between various influencing factors and the safety separation is analyzed. Different scenarios are simulated 100,000 times each, and the results show that the speed difference between the two paired aircraft has the most significant impact on the safety separation, followed by the paired approach mode and runway centerline spacing. The wake turbulence category matching has a minimal effect on the safety separation. The results provide a theoretical basis for airports with closely spaced parallel runways to further reduce the separation between paired aircraft, thereby enhancing airport capacity and runway operational efficiency.

Abstract Flexible devices, such as soft bioelectronics and stretchable supercapacitors, have their practical performance limited by electrodes which are desired to have high conductivity and capacitance, outstanding mechanical flexibility and strength, great electrochemical stability, and good biocompatibility. Here, we report a simple and efficient method to synthesize a nanostructured conductive hydrogel to meet such criteria. Specifically, templated by a hyperconnective nanofibrous network from aramid hydrogels, the conducting polymer, polypyrrole, assembles conformally onto nanofibers through in-situ polymerization, generating continuous nanostructured conductive pathways. The resulting conductive hydrogel shows superior conductivity (72 S cm−1) and fracture strength (27.2 MPa). Supercapacitor electrodes utilizing this hydrogel exhibit high specific capacitance (240 F g−1) and cyclic stability. Furthermore, bioelectrodes of patterned hydrogels provide favorable bioelectronic interfaces, allowing high-quality electrophysiological recording and stimulation in physiological environments. These high-performance electrodes are readily scalable to applications of energy and power systems, healthcare and medical technologies, smart textiles, and so forth.

As the first study addressing family language policy (FLP) in d/Deaf-parented families in China, the current research explores language ideologies, practices and management held by different members within the families. Children of d/Deaf adults (Codas) form an unusual bimodal bilingual group, and the study concerning this group prompts us to rethink the notion of bilinguals as well as types of bilingual families within the FLP domain. The study is based on the data collected from online questionnaires, semi-structed interviews, and observations. Two versions of questionnaires were administered for both d/Deaf parents and Codas, which collected data from participants across Mainland China. Semi-structed interviews (with 10 d/Deaf parents and 4 Codas) and observations (in 4 families with underage Codas) were conducted in Shanghai. The analyses of the data suggest that language practices in d/Deaf parented families with hearing children can be viewed as miniatures of social language ecology and these families serve as micro-realisations of language socialisation, during which process both social factors on the macro level and family factors on the micro level make active contributions. Emphasised impacts are also attributed to the critical agentic roles of individuals within the families and the support given by communities and schools, whose different attitudes and practices can lead to various outcomes of the Codas' linguistic development. The study also offers new insights into the notion of successful FLP in these bimodal bilingual families.

Abstract Background Cardiometabolic multimorbidity (CM) is emerging as a global health challenge. This study investigated the potential impact of muscle strength on the risk of CM in middle-aged and older Chinese adults. Methods In total, 7610 participants were identified from the China Health and Retirement Longitudinal Study (CHARLS). Muscle strength was measured by absolute, relative grip strength (normalized for body mass index) and chair-rising time which were classified into three categories according to tertiles stratified by gender. Cox proportional hazards models were adopted to evaluate the effect of muscle strength on CM. Results During follow-up, 235(3.76%) participants from none cardiometabolic diseases (CMD), 140 (19.23%) from diabetes, 119 (21.17%) from heart disease, and 22 (30.56%) from stroke progressed to CM. In participants who had low relative grip strength, CM was more likely to occur in individuals with heart disease at baseline (HR: 1.89, 95%CIs: 1.10 to 3.23). Those with high chair-rising time had a higher risk of CM than those with low chair-rising time in the individuals with diabetes (HR: 1.85, 95%CIs:1.20 to 2.86) and with heart disease (HR: 1.67, 95%CIs:1.04 to 2.70). However, we did not observe an association between muscle strength and CM in participants without CMD or with stroke at baseline. Conclusions In Chinese middle-aged and older adults, low relative grip strength was associated with a higher risk of CM in individuals with heart disease, while high chair-rising time was associated with a higher risk of CM in individuals with diabetes or heart disease.

Abstract To evaluate the influence distance and evolution law of the jet blast under the full thrust state of the aircraft engine, we constructed a refined single-engine nozzle model in this study. Using a specific B737-800 engine as an illustrative example, this model takes into account both the internal combustion of the engine and the shearing effect of the tail cone on the airflow; based on a structured grid, the grid and far-field independence of the numerical solution were verified. The numerical simulation results obtained via the Fluent software were compared with the data outlined in the Boeing aircraft characteristics manual for a thorough analysis. Our results indicated that the calculated jet influence distance from the refined nozzle model aligns more closely with the data in the aircraft characteristics manual, albeit with superior accuracy compared to the simplified nozzle model employed in previous studies. The findings of this study can serve as a valuable reference for computing jet influence distances across various aircraft types and engine models, providing data support for the study of safety intervals for aircraft crossing the runway behind the takeoff point.

Abstract Background & Aims Glucose-lowering drug is associated with various cancers, but the causality with gastrointestinal cancer risk is rarely reported. We aimed to explore the causality between them in this Mendelian randomization (MR) study. Methods Two-sample MR, summary-data-based (SMR), mediation MR, and colocalization analyses was employed. Ten glucose-lowering drug targets (PPARG, DPP4, GLP1R, INSR, SLC5A2, ABCC8, KCNJ11, ETFDH, GPD2, PRKAB1) and seven types of gastrointestinal cancer (anal carcinoma, cardia cancer, gastric cancer, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), pancreatic cancer, rectum cancer) were included. Patients with gastrointestinal cancers from six different large GWAS databases, including the UK Biobank and Finnish cohorts were incorporated, for discovery and external validation. Meta-analysis was employed to integrate the results from both discovery and validation cohorts, thereby ensuring the reliability of findings. Results ABCC8/KCNJ11 were associated with pancreatic cancer risk in both two-sample MR (odds ratio (OR): 15.058, per standard deviation unit (SD) change of glucose-lowering durg target perturbation equivalent to 1 SD unit of HbA1c lowering; 95% confidence interval (95% CI): 3.824–59.295; P-value = 0.0001) and SMR (OR: 1.142; 95% CI: 1.013–1.287; P-value = 0.030) analyses. The mediation effect of body mass index (OR: 0.938; 95% CI: 0.884–0.995; proportion of mediation effect: 3.001%; P-value = 0.033) on ABCC8/KCNJ11 and pancreatic cancer was uncovered. Strong connections of DPP4 with anal carcinoma (OR: 0.123; 95% CI: 0.020–0.745; P-value = 0.023) and ICC (OR: 7.733; 95% CI: 1.743–34.310; P-value = 0.007) were detected. PPARG was associated with anal carcinoma (OR: 12.909; 95% CI: 3.217–51.795; P-value = 0.0003), HCC (OR: 36.507; 95% CI: 8.929-149.259; P-value

The evolution of inclusions in molten steel in tundish before and after vacuum treatment during the production of GCr15 bearing steel in a steel plant is analyzed， the results showed that total oxygen content in molten steel increased greatly in tundish. Magnesium aluminum Spinel inclusions increased in RH soft blowing and tundish to varying degrees， and the number increased significantly in tundish. The MgO aggregate particles in the working layer of the tundish coating are greatly reduced， and some MgO particles are dissolved in the molten steel， resulting in the increase of oxygen content in the molten steel.The effect of different SiO2 content on the phase of tundish coating was discussed by thermodynamic simulation analysis. It was proposed that the control of SiO2 content at range 4%~6% and the strengthening of tundish masonry management can reduce the formation of high temperature low melting phase in tundish coating and effectively improve the flaw detection eligibility rate of bearing steel GCr15 head slab.

Abstract Background and Aims Sex determining region Y related high-mobility group box protein 9 (Sox9) is expressed in a subset of hepatocytes, and it is important for chronic liver injury. However, the roles of Sox9+ hepatocytes in response to the acute liver injury and repair are poorly understood. Methods In this study, we developed the mature hepatocyte-specific Sox9 knockout mouse line and applied three acute liver injury models including PHx, CCl4 and hepatic ischemia reperfusion (IR). Huh-7 cells were subjected to treatment with hydrogen peroxide (H2O2) in order to induce cellular damage in an in vitro setting. Results We found the positive effect of Sox9 deletion on acute liver injury repair. Small heterodimer partner (SHP) expression was highly suppressed in hepatocyte-specific Sox9 deletion mouse liver, accompanied by less cell death and more cell proliferation. However, in mice with hepatocyte-specific Sox9 deletion and SHP overexpression, we observed an opposite phenotype. In addition, the overexpression of SOX9 in H2O2-treated Huh-7 cells resulted in an increase in cytoplasmic SHP accumulation, accompanied by a reduction of SHP in the nucleus. This led to impaired mitochondrial function and subsequent cell death. Notably, both the mitochondrial dysfunction and cell damage were reversed when SHP siRNA was employed, indicating the crucial role of SHP in mediating these effects. Furthermore, we found that Sox9, as a vital transcription factor, directly bound to SHP promoter to regulate SHP transcription. Conclusions Overall, our findings unravel the mechanism by which hepatocyte-specific Sox9 knockout ameliorates acute liver injury via suppressing SHP signaling and improving mitochondrial function. This study may provide a new treatment strategy for acute liver injury in future. Graphical Abstract

The path planning of unmanned aerial vehicles (UAVs) is crucial in UAV search and rescue operations to ensure efficient and safe search activities. However, most existing path planning algorithms are not suitable for post-disaster mountain rescue mission scenarios. Therefore, this paper proposes the IGWO-IAPF algorithm based on the fusion of the improved grey wolf optimizer (GWO) and the improved artificial potential field (APF) algorithm. This algorithm builds upon the grey wolf optimizer and introduces several improvements. Firstly, a nonlinear adjustment strategy for control parameters is proposed to balance the global and local search capabilities of the algorithm. Secondly, an optimized individual position update strategy is employed to coordinate the algorithm’s search ability and reduce the probability of falling into local optima. Additionally, a waypoint attraction force is incorporated into the traditional artificial potential field algorithm based on the force field to fulfill the requirements of three-dimensional path planning and further reduce the probability of falling into local optima. The IGWO is used to generate an initial path, where each point is assigned an attraction force, and then the IAPF is utilized for subsequent path planning. The simulation results demonstrate that the improved IGWO exhibits approximately a 60% improvement in convergence compared to the conventional GWO. Furthermore, the integrated IGWO-IAPF algorithm shows an approximately 10% improvement in path planning effectiveness compared to other traditional algorithms. It possesses characteristics such as shorter flight distance and higher safety, making it suitable for meeting the requirements of post-disaster rescue missions.

Earthquakes pose significant risks to national stability, endangering lives and causing substantial economic damage. This study tackles the urgent need for efficient post-earthquake relief in search and rescue (SAR) scenarios by proposing a multi-UAV cooperative rescue task allocation model. With consideration the unique requirements of post-earthquake rescue missions, the model aims to minimize the number of UAVs deployed, reduce rescue costs, and shorten the duration of rescue operations. We propose an innovative hybrid algorithm combining particle swarm optimization (PSO) and grey wolf optimizer (GWO), called the PSOGWO algorithm, to achieve the objectives of the model. This algorithm is enhanced by various strategies, including interval transformation, nonlinear convergence factor, individual update strategy, and dynamic weighting rules. A practical case study illustrates the use of our model and algorithm in reality and validates its effectiveness by comparing it to PSO and GWO. Moreover, a sensitivity analysis on UAV capacity highlights its impact on the overall rescue time and cost. The research results contribute to the advancement of vehicle-routing problem (VRP) models and algorithms for post-earthquake relief in SAR. Furthermore, it provides optimized relief distribution strategies for rescue decision-makers, thereby improving the efficiency and effectiveness of SAR operations.

Abstract The maturation of regional brain volumes from birth to preadolescence is a critical developmental process that underlies emerging brain structural connectivity and function. Regulated by genes and environment, the coordinated growth of different brain regions plays an important role in cognitive development. Current knowledge about structural network evolution is limited, partly due to the sparse and irregular nature of most longitudinal neuroimaging data. In particular, it is unknown how factors such as mother’s education or sex of the child impact the structural network evolution. To address this issue, we propose a method to construct evolving structural networks and study how the evolving connections among brain regions as reflected at the network level are related to maternal education and biological sex of the child and also how they are associated with cognitive development. Our methodology is based on applying local Fréchet regression to longitudinal neuroimaging data acquired from the RESONANCE cohort, a cohort of healthy children (245 females and 309 males) ranging in age from 9 weeks to 10 years. Our findings reveal that sustained highly coordinated volume growth across brain regions is associated with lower maternal education and lower cognitive development. This suggests that higher neurocognitive performance levels in children are associated with increased variability of regional growth patterns as children age.

Background: Artificial intelligence (AI) technology has been used for finding lesions via gastrointestinal endoscopy. However, there were few AI-associated studies that discuss bronchoscopy. Objectives: To use convolutional neural network (CNN) to recognize the observed anatomical positions of the airway under bronchoscopy. Design: We designed the study by comparing the imaging data of patients undergoing bronchoscopy from March 2022 to October 2022 by using EfficientNet (one of the CNNs) and U-Net. Methods: Based on the inclusion and exclusion criteria, 1527 clear images of normal anatomical positions of the airways from 200 patients were used for training, and 475 clear images from 72 patients were utilized for validation. Further, 20 bronchoscopic videos of examination procedures in another 20 patients with normal airway structures were used to extract the bronchoscopic images of normal anatomical positions to evaluate the accuracy for the model. Finally, 21 respiratory doctors were enrolled for the test of recognizing corrected anatomical positions using the validating datasets. Results: In all, 1527 bronchoscopic images of 200 patients with nine anatomical positions of the airway, including carina, right main bronchus, right upper lobe bronchus, right intermediate bronchus, right middle lobe bronchus, right lower lobe bronchus, left main bronchus, left upper lobe bronchus, and left lower lobe bronchus, were used for supervised machine learning and training, and 475 clear bronchoscopic images of 72 patients were used for validation. The mean accuracy of recognizing these 9 positions was 91% (carina: 98%, right main bronchus: 98%, right intermediate bronchus: 90%, right upper lobe bronchus: 91%, right middle lobe bronchus 92%, right lower lobe bronchus: 83%, left main bronchus: 89%, left upper bronchus: 91%, left lower bronchus: 76%). The area under the curves for these nine positions were >0.98. In addition, the accuracy of extracting the images via the video by the trained model was 94.7%. We also conducted a deep learning study to segment 10 segment bronchi in right lung, and 8 segment bronchi in Left lung. Because of the problem of radial depth, only segment bronchi distributions below right upper bronchus and right middle bronchus could be correctly recognized. The accuracy of recognizing was 84.33 ± 7.52% by doctors receiving interventional pulmonology education in our hospital over 6 months. Conclusion: Our study proved that AI technology can be used to distinguish the normal anatomical positions of the airway, and the model we trained could extract the corrected images via the video to help standardize data collection and control quality.

BackgroundThe gut microbiome is closely related to gastrointestinal (GI) cancer, but the causality of gut microbiome with GI cancer has yet to be fully established. We conducted this two-sample Mendelian randomization (MR) study to reveal the potential causal effect of gut microbiota on GI cancer.Materials and methodsSummary-level genetic data of gut microbiome were derived from the MiBioGen consortium and the Dutch Microbiome Project. Summary statistics of six GI cancers were drawn from United Kingdom Biobank. Inverse-variance-weighted (IVW), MR-robust adjusted profile score (MR-RAPS), and weighted-median (WM) methods were used to evaluate the potential causal link between gut microbiota and GI cancer. In addition, we performed sensitivity analyses and reverse MR analyses.ResultsWe identified potential causal associations between 21 bacterial taxa and GI cancers (values of p

BackgroundFood parenting practices are associated with child weight. Such associations may reflect the effects of parents' practices on children's food intake and weight. However, longitudinal, qualitative, and behavioral genetic evidence suggests these associations could, in some cases, reflect parents' response to children's genetic risk for obesity, an instance of gene–environment correlation. We tested for gene–environment correlations across multiple domains of food parenting practices and explored the role of parent-reported child appetite in these relationships.Materials and methodsData on relevant variables were available for N = 197 parent–child dyads (7.54 ± 2.67 years; 44.4% girls) participating in RESONANCE, an ongoing pediatric cohort study. Children's body mass index (BMI) polygenic risk score (PRS) were derived based on adult GWAS data. Parents reported on their feeding practices (Comprehensive Feeding Practices Questionnaire) and their child's eating behavior (Child Eating Behavior Questionnaire). Moderation effects of child eating behaviors on associations between child BMI PRS and parental feeding practices were examined, adjusting for relevant covariates.ResultsOf the 12 parental feeding practices, 2 were associated with child BMI PRS, namely, restriction for weight control (β = 0.182, p = 0.011) and teaching about nutrition (β = −0.217, p = 0.003). Moderation analyses demonstrated that when children had high genetic obesity risk and showed moderate/high (vs. low) food responsiveness, parents were more likely to restrict food intake to control weight.ConclusionOur results indicate that parents may adjust their feeding practices in response to a child's genetic propensity toward higher or lower bodyweight, and the adoption of food restriction to control weight may depend on parental perceptions of the child's appetite. Research using prospective data on child weight and appetite and food parenting from infancy is needed to further investigate how gene–environment relationships evolve through development.

Abstract Adhesion underwater is a major challenge. Mussel‐inspired complex coacervates functionalized with L‐3,4‐dihydroxyphenylalanine (L‐DOPA) are proposed for underwater adhesives through versatile chemistry of DOPA, however, simple, efficient, controllable, and nontoxic procedures to harness them are still under investigation. In this study, inspired from the mussel byssus formation process, coacervate adhesives are formed underwater by simple injection of an acidic proto‐coacervate of DOPA functionalized polyelectrolytes on underwater surfaces. The proto‐coacervate is initially an acidic liquid, it increased in pH due to water diffusion, resulting in coacervation driven by electrostatic interaction, without the requirement for pH adjustment or organic solvents. Additionally, the pH of liquid–liquid phase separation is tuned by substituting polyelectrolytes with different pKa, which satisfied different pH requirement in real life. The coacervate‐based adhesives on glass substrates exhibit strengths comparable to commercial glues when dry and to mussel glue when wet, showing high biocompatibility in human epidermis in vitro.

We report the synthesis of cellulose membranes from balsa wood with an exceptionally high responsivity to humidity change by chemical processing and mechanical compression. By varying the ambient humidity, the produced cellulose membranes can provide a variety of predetermined deformations, such as curve, s-like deformation and curl. The high humidity responsivity is originated from a self-maintained moisture gradient induced by an asymmetrical design of membrane surfaces, aided by the hygroscopic swelling of the cellulose. The moisture-driven actuators are then demonstrated as a three-finger gripper that can grab, hold and release objects 40 times the weight of its own. The combination of natural wood and stimuli-responsive behavior open a way to designing smart structures, actuators and soft robots with environmentally friendly, recyclable and biocompatible materials.

Abstract Objective To evaluate the efficacy and safety of PLD in treating of in patients who experience epithelial ovarian, fallopian tubal, and peritoneal cancer progression within 12 months after the first-line platinum-based therapy. Methods This was an open-label, single-arm and multicenter clinical trial. The ORR was the interim primary objective, and the DCR, AEs and QOL were the secondary objectives. The impact of factors on efficacy outcomes, the change trend of CA125 and the artificial platinum-free interval were exploratory endpoints. Results Totally, 115 patients were enrolled in this study and included in the ITT population. Moreover, 101 patients were included in the safety population. The median follow-up time was 4 months (IQR 2–6). In the ITT population, the confirmed ORR was 37.4% (95% CI, 28.4–46.4%), and the DCR was 65.2% (95% CI, 56.4–74.1%). The previous response status to platinum-based chemotherapy and baseline CA125 levels were significantly correlated with the ORR. The ORR was significantly higher in patients with a CA125 decrease after the first cycle than in the patients with a CA125 increase. The most common grade 3 or higher AE was hand-foot syndrome (3 [3.0%] of 101 patients). No statistically significant differences existed between the baseline and the postbaseline questionnaires. Conclusions For patients who experience platinum-resistant and platinum-refractory relapse, the use of PLD may be acceptable because of the associated satisfactory efficacy, low frequency of AEs and high patient QOL. Moreover, a low CA125 level at baseline and a reduction in CA125 after the first cycle are predictive factors for satisfactory efficacy.

Abstract Heavy metal (HM) pollutants can cause serious phytotoxicity or oxidative stress in plants. Buddleja L., commonly known as “butterfly bushes”, are frequently found growing on HM-contaminated land. However, to date, few studies have focused on the physiological and biochemical responses of Buddleja species to HM stress. In this study, potted seedlings of B. asiatica Lour. and B. macrostachya Wall. ex Benth. were subjected to various cadmium (Cd) concentrations (0, 25, 50, 100, and 200 mg kg−1) for 90 days. Both studied Buddleja species showed restricted Cd translocation capacity. Exposure to Cd, non-significant differences (p > 0.05) were observed, including quantum yield of photosystem II (PSII), effective quantum yield of PSII, photochemical quenching and non-photochemical quenching in both species between all studied Cd concentrations. Moreover, levels of cellular reactive oxygen species (ROS) significantly declined (p

Abstract Background Lepidoptera is one group of the largest plant-feeding insects and Spodoptera litura (Lepidoptera: Noctuidae) is one of the most serious agricultural pests in Asia countries. An interesting and unique phenomenon for gonad development of Lepidoptera is the testicular fusion. Two separated testes fused into a single one during the larva-to-pupa metamorphosis, which is believed to contribute to sperm production and the prevalence in field. To study the molecular mechanism of the testicular fusion, RNA sequencing (RNA-seq) experiments of the testes from 4-day-old sixth instar larvae (L6D4) (before fusion), 6-day-old sixth instar larvae (L6D6, prepupae) (on fusing) and 4-day-old pupae (P4D) (after fusion) of S. litura were performed. Results RNA-seq data of the testes showed that totally 12,339 transcripts were expressed at L6D4, L6D6 and P4D stages. A large number of differentially expressed genes (DEGs) were up-regulated from L6D4 to L6D6, and then more genes were down-regulated from L6D6 to P4D. The DEGs mainly belongs to the genes related to the 20E signal transduction pathway, transcription factors, chitin metabolism related enzymes, the families of cytoskeleton proteins, extracellular matrix (ECM) components, ECM-related protein, its receptor integrins and ECM-remodeling enzymes. The expression levels of these genes that were up-regulated significantly during the testicular fusion were verified by qRT-PCR. The matrix metalloproteinases (MMPs) were found to be the main enzymes related to the ECM degradation and contribute to the testicular fusion. The testis was not able to fuse if MMPs inhibitor GM6001 was injected into the 5th abdomen region at L6D6 early stage. Conclusions The transcriptome and DEGs analysis of the testes at L6D4, L6D6 and P4D stages provided genes expression information related to the testicular fusion in S. litura. These results indicated that cytoskeleton proteins, ECM-integrin interaction genes and ECM-related proteins were involved in cell migration, adhesion and fusion during the testicular fusion. The ECM degradation enzymes MMPs probably play a critical role in the fusion of testis.

Insect gut microbiota plays important roles in acquiring nutrition, preventing pathogens infection, modulating immune responses, and communicating with environment. Gut microbiota can be affected by external factors such as foods and antibiotics. Spodoptera frugiperda (Lepidoptera: Noctuidae) is an important destructive pest of grain crops worldwide. The function of gut microbiota in S. frugiperda remains to be investigated. In this study, we fed S. frugiperda larvae with artificial diet with antibiotic mixture (penicillin, gentamicin, rifampicin, and streptomycin) to perturb gut microbiota, and then examined the effect of gut microbiota dysbiosis on S. frugiperda gene expression by RNA sequencing. Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria were the most dominant phyla in S. frugiperda. We found that the composition and diversity of gut bacterial community were changed in S. frugiperda after antibiotics treatment. Firmicutes was decreased, and abundance of Enterococcus and Weissella genera was dramatically reduced. Transcriptome analysis showed that 1,394 differentially expressed transcripts (DETs) were found between the control and antibiotics-treated group. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) results showed that antibiotics-induced dysbiosis affected many biological processes, such as energy production, metabolism, and the autophagy–lysosome signal pathway. Our results indicated that dysbiosis of gut microbiota by antibiotics exposure affects energy and metabolic homeostasis in S. frugiperda, which help better understand the role of gut microbiota in insects.

Early childhood is a period marked by rapid brain growth accompanied by cognitive and motor development. However, it remains unclear how early developmental skills relate to neuroanatomical growth across time with no growth quantile trajectories of typical brain development currently available to place and compare individual neuroanatomical development. Even though longitudinal neuroimaging data have become more common, they are often sparse, making dynamic analyses at subject level a challenging task. Using the Principal Analysis through Conditional Expectation (PACE) approach geared towards sparse longitudinal data, we investigate the evolution of gray matter, white matter and cerebrospinal fluid volumes in a cohort of 446 children between the ages of 1 and 120 months. For each child, we calculate their dynamic age-varying association between the growing brain and scores that assess cognitive functioning, applying the functional varying coefficient model. Using local Fréchet regression, we construct age-varying growth percentiles to reveal the evolution of brain development across the population. To further demonstrate its utility, we apply PACE to predict individual trajectories of brain development.

The colonization of the human gut microbiome begins at birth, and over time, these microbial communities become increasingly complex. Most of what we currently know about the human microbiome, especially in early stages of development, was described using culture-independent sequencing methods that allow us to identify the taxonomic composition of microbial communities using genomic techniques, such as amplicon or shotgun metagenomic sequencing. Each method has distinct tradeoffs, but there has not been a direct comparison of the utility of these methods in stool samples from very young children, which have different features than those of adults. We compared the effects of profiling the human infant gut microbiome with 16S rRNA amplicon vs. shotgun metagenomic sequencing techniques in 338 fecal samples; younger than 15, 15–30, and older than 30 months of age. We demonstrate that observed changes in alpha-diversity and beta-diversity with age occur to similar extents using both profiling methods. We also show that 16S rRNA profiling identified a larger number of genera and we find several genera that are missed or underrepresented by each profiling method. We present the link between alpha diversity and shotgun metagenomic sequencing depth for children of different ages. These findings provide a guide for selecting an appropriate method and sequencing depth for the three studied age groups.

In this paper, we propose a tree-like topology networking scheme based on round-trip three-wavelength optical compensation technique over fiber-optic link. This scheme simplifies the system complexity of the local site, improves the scalability of the frequency dissemination network, and reduces the influence of Rayleigh backscattering on the local and remote sites. The feasibility of the scheme is verified by a set of fiber-optic frequency dissemination network, with a transmission frequency of 1 GHz. The network consists of two remote sites with distances of 20 and 55 km far from the local site, and the frequency compensation system is optimized. The experimental results show that the fractional frequency stability of the 20 and 55 km fiber links can reach 8.6 × 10-15@1s, 7.6 × 10-18@104s, and 1.3 × 10-14@1s, and 8.1 × 10-18@104s. The limitations of electrical amplifiers, WDM, and group velocity dispersion on long-term stability and network capacity are discussed. Our system demonstrates that the stable sharing of frequency signals from ultra-stable frequency sources at any site within a large metropolitan area is achievable.

The frequency transmission over free-space link can effectively overcome the dependence of existing optical fiber time-frequency transmission technology on optical fiber network. In this paper, we demonstrate a passive phase correction technique over a 124 m long indoor atmospheric radio frequency (RF) dissemination. This scheme simplifies the system, and suppresses the effects of Rayleigh backscattering. We verify the feasibility of the scheme by transmitting 1 GHz RF signals over the atmospheric link. After timing fluctuation compensation, the relative frequency stability can reach 6.8 × 10-15 for 1 s and 3.2 × 10-17 for 103 s, the RMS timing fluctuation is 186 fs in 5000 s. It can be proved that the scheme is very effective in eliminating phase noise caused by atmospheric link.

In order to relieve the stress caused by the surge of flight flow, Closely Spaced Parallel Runways (CSPRs) have been built in many hub airports, and a paired approach mode has been applied to CSPRs in some countries. This paper proposes a method for optimizing the wake separation between aircrafts which utilizes a paired approach, aiming at reducing longitudinal separation by using computational fluid dynamics technology. Firstly, the model of the wake vortex field of the paired lead aircraft is constructed. Secondly, the numerical simulation preparation for the characteristics of the wake vortex field is completed through the computational pretreatment of the model. Thirdly, a calculation model of wake safety interval based on paired approach operation is established. Finally, the proposed method shows its superiority comparing with other methods. This method realized visual analysis of wake vortex through optimization modeling based on computational fluid dynamics, contributing to increasing the capacity of the runway and improving the operation efficiency of an aerodrome.

Mechanistic target of rapamycin (mTOR) signaling pathway mediates the function of oncogenic receptor tyrosine kinases (RTKs). We aimed to elucidate new role of mTOR in EGFR-mutant (EGFR-mut) non-small cell lung cancer (NSCLC) and glioblastoma (GBM) with a focus on tumor microenvironments. Here, we report a novel regulatory link between mTOR complexes (mTORCs) and tissue factor (TF), an initiator of tumor-derived thrombosis. TF is elevated in EGFR-mut NSCLC/GBM cell lines and tumors from patients with poor prognosis. Application of mTORC1/2 inhibitors (AZD8055, WYE-125132, MTI-31, and rapamycin) or genetic mTORC-depletion all reduced TF expression, which appeared to be differentially mediated depending on cellular context. In U87MG and HCC827 cells, mTORC1 exerted a dominant role via promoting TF mRNA transcription. In EGFR-TKI-resistant H1975 and PC9 cells, it was mTORC2 that played a major role in specific repression of lysosomal-targeted TF protein degradation. Successful inhibition of TF expression was demonstrated in AZD8055- or MTI-31-treated H1975 and U87MG tumors in mice, while a TF-targeted antibody antagonized TF activity without reducing TF protein. Both the mTOR- and TF-targeted therapy induced a multifaceted remodeling of tumor microenvironment reflecting not only a diminished hypercoagulopathy state (fibrin level) but also a reduced stromal fibrosis (collagen distribution), compromised vessel density and/or maturity (CD31 and/or α-SMA) as well as a substantially decreased infiltration of immune-suppressive M2-type tumor-associated macrophages (CD206/F4/80 ratio). Thus, our results have identified TF as a functional biomarker of mTOR. Downregulation of mTOR-TF axis activity likely contributes to the therapeutic mechanism of mTORC1/2- and TF-targeted agents in EGFR-mut advanced NSCLC and GBM.

Semaphorin 3A (SEMA3A) is a member of the Semaphorins family, a class of membrane-associated protein that participates in the construction of nerve networks. SEMA3A has been reported to affect vascular permeability previously, but its influence in traumatic brain injury (TBI) is still unknown. To investigate the effects of SEMA3A, we used a mouse TBI model with a controlled cortical impact (CCI) device and a blood–brain barrier (BBB) injury model in vitro with oxygen-glucose deprivation (OGD). We tested post-TBI changes in SEMA3A, and its related receptors (Nrp-1 and plexin-A1) expression and distribution through western blotting and double-immunofluorescence staining, respectively. Neurological outcomes were evaluated by modified neurological severity scores (mNSSs) and beam-walking test. We examined BBB damage through Evans Blue dye extravasation, brain water content, and western blotting for VE-cadherin and p-VE-cadherin in vivo, and we examined the endothelial cell barrier through hopping probe ion conductance microscopy (HPICM), transwell leakage, and western blotting for VE-cadherin and p-VE-cadherin in vitro. Changes in miR-30b-5p were assessed by RT-PCR. Finally, the neuroprotective function of miR-30b-5p is measured by brain water content, mNSSs and beam-walking test. SEMA3A expression varied following TBI and peaked on the third day which expressed approximate fourfold increase compared with sham group, with the protein concentrated at the lesion boundary. SEMA3A contributed to neurological function deficits and secondary BBB damage in vivo. Our results demonstrated that SEMA3A level following OGD injury almost doubled than control group, and the negative effects of OGD injury can be improved by blocking SEMA3A expression. Furthermore, the expression of miR-30b-5p decreased approximate 40% at the third day and 60% at the seventh day post-CCI. OGD injury also exhibited an effect to approximately decrease 50% of miR-30b-5p expression. Additionally, the expression of SEMA3A post-TBI is regulated by miR-30b-5p, and miR-30b-5p could improve neurological outcomes post-TBI efficiently. Our results demonstrate that SEMA3A is a significant factor in secondary BBB damage after TBI and can be abolished by miR-30b-5p, which represents a potential therapeutic target.

Genetic risk score (GRS) based on disease risk-associated single nucleotide polymorphisms (SNPs) is an informative tool that can be used to provide inherited information for specific diseases in addition to family history. However, it is still unknown whether only SNPs that are implicated in a specific racial group should be used when calculating GRSs. The objective of this study is to compare the performance of race-specific GRS and nonrace-specific GRS for predicting prostate cancer (PCa) among 1338 patients underwent prostate biopsy in Shanghai, China. A race-specific GRS was calculated with seven PCa risk-associated SNPs implicated in East Asians (GRS7), and a nonrace-specific GRS was calculated based on 76 PCa risk-associated SNPs implicated in at least one racial group (GRS76). The means of GRS7 and GRS76 were 1.19 and 1.85, respectively, in the study population. Higher GRS7 and GRS76 were independent predictors for PCa and high-grade PCa in univariate and multivariate analyses. GRS7 had a better area under the receiver-operating curve (AUC) than GRS76 for discriminating PCa (0.602 vs 0.573) and high-grade PCa (0.603 vs 0.575) but did not reach statistical significance. GRS7 had a better (up to 13% at different cutoffs) positive predictive value (PPV) than GRS76. In conclusion, a race-specific GRS is more robust and has a better performance when predicting PCa in East Asian men than a GRS calculated using SNPs that are not shown to be associated with East Asians.

The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). PSMA-targeting polypeptide CQKHHNYLC was conjugated to SPIONs to form PSMA-targeting molecular MRI contrast agents. In vitro studies demonstrated specific uptake of polypeptide-SPIONs by PSMA expressing cells. In vivo MRI studies found that MRI signals in PSMA-expressing tumors could be specifically enhanced with polypeptide-SPION, and further Prussian blue staining showed heterogeneous deposition of SPIONs in the tumor tissues. Taken altogether, we have developed PSMA-targeting polypeptide-SPIONs that could specifically enhance MRI signal in tumor-bearing mice, which might provide a new strategy for the molecular imaging of PCa.