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Abstract Background Overconsumption of retinoic acid (RA) or its analogues/derivatives has been linked to severe craniomaxillofacial malformations, such as cleft palate and midface hypoplasia. It has been noted that RA disturbed the proliferation and migration of embryonic palatal mesenchymal (EPM) cells in these malformations, yet the exact mechanisms underlying these disruptions remained unclear. Methods A model of retinoic acid (RA)-induced cleft palate in fetal mice was successfully established. Histological alterations in the palate were evaluated using Hematoxylin and Eosin (H&E) staining and RNA in situ hybridization (RNAscope). Cellular proliferation levels were quantified via the Cell Counting Kit-8 (CCK-8) assay and EdU incorporation assay, while cell migration capabilities were investigated using wound healing and Transwell assays. Mitochondrial functions were assessed through Mito-Tracker fluorescence, mitochondrial reactive oxygen species (ROS) measurement, ATP level quantification, and mitochondrial DNA (mtDNA) copy number analysis. Differential gene expression and associated signaling pathways were identified through bioinformatics analysis. Alterations in the transcriptional and translational levels of Lhx6 and genes associated with mitophagy were quantified using quantitative PCR (qPCR) and Western blot analysis, respectively. Mitochondrial morphology and the mitochondrial autophagosomes within cells were examined through transmission electron microscopy (TEM). Results Abnormal palatal development in mice, along with impaired proliferation and migration of human embryonic palatal mesenchymal (HEPM) cells, was associated with RA affecting mitochondrial function and concomitant downregulation of Lhx6. Knockdown of Lhx6 in HEPM cells resulted in altered cell proliferation, migration, and mitochondrial function. Conversely, the aberrant mitochondrial function, proliferation, and migration observed in RA-induced HEPM cells were ameliorated by overexpression of Lhx6. Subsequent research demonstrated that Lhx6 ameliorated RA-induced dysfunction in HEPM cells by modulating PINK1/Parkin-mediated mitophagy, thereby activating the MAPK signaling pathways. Conclusion Lhx6 is essential for mitochondrial homeostasis via tuning PINK1/Parkin-mediated mitophagy and MAPK signaling pathways. Downregulation of Lhx6 by RA transcriptionally disturbs the mitochondrial homeostasis, which in turn leads to the proliferation and migration defect in HEPM cells, ultimately causing the cleft palate. Graphical abstract

Abstract DT systems, characterized by real-time capabilities, high precision, and high integration, have become essential in various domains. In the context of cultural heritage, a DT system encompasses comprehensive information about heritage sites, contextual data, and expert knowledge, forming a complex dynamic system. The substantial volume of information and diverse sources significantly increases the cognitive load for management personnel in understanding on-site situations. This study, from the perspective of situational awareness, introduces X-reality technologies (VR and AR) into DT systems for cultural heritage risk management. The aim is to evaluate the effectiveness of different X-reality technologies in cultural heritage risk perception and their impact mechanisms. A total of 184 participants were divided into two groups and experienced three different applications (2D desktop, VR, and AR). Using situational awareness rating techniques, participants' responses were measured across three dimensions: attention resource demand, attention resource supply, and understanding of the situation. SEM was employed to estimate the stability of the scale data. The results indicate that, compared to traditional 2D desktops, both VR and AR demonstrate advantages in enhancing heritage risk situational awareness. However, in AR mode, no significant advantages were found in the dimensions of attention resource demand and attention resource supply compared to traditional 2D desktop applications. Furthermore, a significant difference in immersion between VR and AR was found to affect the attention resource demand dimension. Although the results suggest differences in the interactivity of VR and AR in affecting the attention resource demand dimension, no significant differences were found. By comprehensively understanding the functional mechanisms of X-reality technologies in influencing cultural heritage risk situational awareness, this study provides design references for constructing DT systems for cultural heritage risk management. Additionally, it offers insights for heritage site managers, experts, and stakeholders to enhance risk perception efficiency, promoting more effective risk assessment, analysis, and strategic decision-making, thereby reducing damage to cultural heritage.

Abstract Historic timber structures face substantial fire loads and complex fire risks. Subsequent renovations and utilization may influence their fire safety performance. Therefore, accurately predicting indoor fire development in historic buildings and assessing their fire safety performance is crucial. Numerical fire simulation is currently at the forefront of analyzing and assessing fire risks in historic buildings. However, there is a shortage of globally accessible historic building fire data. This paper proposes a method to determine fire scenarios, peak heat release rates, and development curves of indoor fires in wooden historic buildings through a fire load investigation. Using the Guangzhou ancestral hall as an example, PyroSim fire dynamics simulation software is employed to calculate fire development and assess the available safe evacuation time. The simulation results are subsequently input into the Pathfinder evacuation simulation software to ascertain the required safe evacuation time for indoor occupants. A comparative assessment is conducted to evaluate the fire safety performance before and after the renovation of historic buildings. The research findings indicate that installing closed glass curtain walls in the courtyards of ancestral hall buildings in Guangzhou accelerates the infiltration of smoke during fires, leading to rapid fire spread and long-distance ignition, significantly reducing the time available for safe evacuation. Therefore, when renovating and utilizing the ancestral hall buildings in Guangzhou, the installation of ventilation and smoke extraction systems should be prioritized to slow down fire development. Additionally, controlling the number of indoor occupants is an effective management measure to mitigate fire damage in historic buildings.

Abstract Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that causes peripheral and autonomic nervous system dysfunction. Dysregulation of miRNAs plays a crucial role in DPN development. However, the role of miR-503-5p in DPN remains unknown. Herein, T2DM mice (db/db) were used as a DPN model in vivo, and astrocytes isolated from db/db mice were induced with high glucose levels as a DPN model in vitro. MiR-503-5p expression was analyzed using qRT-PCR. GFAP, MCP-1, and SEPT9 protein levels were analyzed using western blotting and immunofluorescence. Luciferase assays were performed to investigate the interaction between miR-503-5p and SEPT9. We found that miR-503-5p expression decreased in the spinal cord of DPN model mice and astrocytes treated with high glucose (HG). The db/db mice displayed higher body weight and blood glucose, lower mechanical withdrawal threshold and thermal withdrawal latency, and higher GFAP and MCP-1 protein levels than db/m mice. However, tail vein injection of agomiR-503-5p remarkably reversed these parameters, whereas antigomiR-503-5p enhanced them. HG markedly facilitated GFAP and MCP-1 protein expression in astrocytes, whereas miR-503-5p mimic or inhibitor transfection markedly blocked or elevated GFAP and MCP-1 protein expression, respectively, in astrocytes with HG. SEPT9 was a target of miR-503-5p. In addition, SEPT9 protein levels were found to be elevated in db/db mice and astrocytes treated with HG. Treatment with agomiR-503-5p and miR-503-5p mimic was able to reduce SEPT9 protein levels, whereas treatment with antigomiR-503-5p and miR-503-5p inhibitor led to inhibition of the protein. Furthermore, SEPT9 overexpression suppressed the depressing effect of miR-503-5p overexpression in astrocytes subjected to HG doses. In conclusion, miR-503-5p was found to alleviate peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 expression.

Abstract Aims/Introduction Mitochondrial damage caused by oxidative stress is a main driver of pancreatic β‐cell dysfunction in the pathogenesis of type 2 diabetes mellitus. Prohibitin2 (PHB2) is a vital inner mitochondrial membrane protein that participates in mitophagy to remove the damaged mitochondria. This study aimed to investigate the role and mechanisms of PHB2‐mediated mitophagy in oxidative stress‐induced pancreatic β‐cell dysfunction. Materials and Methods PHB2 and mitophagy‐related protein expression were analyzed by real‐time polymerase chain reaction and western blotting in RINm5F cells treated with H2O2 and islets of diabetic rats. Mitophagy was observed by mitochondrial and lysosome colocalization. RINm5F cells were transfected by phb2 siRNA or overexpression plasmid to explore the role of PHB2 in mitophagy of RINm5F cells. The mechanism of Nrf2 regulating PHB2 was explored by Nrf2 inhibitor and agonist. Results The expression of PHB2, mitophagy related protein PINK1, and Parkin were decreased in RINm5F cells incubated with H2O2 and in islets of diabetic rats. Overexpression of PHB2 protected β‐cells from oxidative stress by promoting mitophagy and inhibiting cell apoptosis, whereas transfection with PHB2 siRNA suppressed mitophagy. Furthermore, PHB2‐mediated mitophagy induced by oxidative stress was through the Nrf2/PHB2 pathway in β‐cells. Antioxidant NAC alleviated oxidative stress injury by promoting PHB2‐mediated mitophagy. Conclusion Our study suggested that PHB2‐mediated mitophagy can protect β‐cells from apoptosis via the Nrf2/PHB2 pathway under oxidative stress. Antioxidants may protect β‐cell from oxidative stress by prompting PHB2‐mediated mitophagy. PHB2‐mediated mitophagy as a potential mechanism takes part in the oxidative stress induced β‐cell injury.

Abstract Single-cell whole-genome sequencing methods have undergone great improvements over the past decade. However, allele dropout, which means the inability to detect both alleles simultaneously in an individual diploid cell, largely restricts the application of these methods particularly for medical applications. Here, we develop a new single-cell whole-genome sequencing method based on third-generation sequencing (TGS) platform named Refresh-seq (restriction fragment ligation-based genome amplification and TGS). It is based on restriction endonuclease cutting and ligation strategy in which two alleles in an individual cell can be cut into equal fragments and tend to be amplified simultaneously. As a new single-cell long-read genome sequencing method, Refresh-seq features much lower allele dropout rate compared with SMOOTH-seq. Furthermore, we apply Refresh-seq to 688 sperm cells and 272 female haploid cells (secondary polar bodies and parthenogenetic oocytes) from F1 hybrid mice. We acquire high-resolution genetic map of mouse meiosis recombination at low sequencing depth and reveal the sexual dimorphism in meiotic crossovers. We also phase the structure variations (deletions and insertions) in sperm cells and female haploid cells with high precision. Refresh-seq shows great performance in screening aneuploid sperm cells and oocytes due to the low allele dropout rate and has great potential for medical applications such as preimplantation genetic diagnosis.

AbstractPurpose To investigate the value of three-dimensional ultrasound fusion imaging (3DUS FI) technique for guiding needle placement in hepatocellular carcinoma (HCC) thermal ablation.Methods A total of 57 patients with 60 HCCs with 3DUS FI-guided thermal ablation were retrospectively included in the study. 3DUS volume data of liver were acquired preoperatively by freehand scanning with the tumor and predetermined 5 mm ablative margin automatically segmented. Plan of needle placement was made through a predetermined simulated ablation zone to ensure a 5 mm ablative margin with the coverage rate toward tumor and ablative margin. With real-time ultrasound and 3DUS fusion imaging, ablation needles were placed according to the plan. After ablation, the ablative margin was immediately evaluated by contrast-enhanced ultrasound and 3DUS fusion imaging. The rate of adequate ablative margin, complete response (CR), local tumor progression (LTP), disease-free survival (DFS), and overall survival (OS) was evaluated.Results According to postoperative contrast-enhanced CT or MR imaging, the complete response rate was 100% (60/60), and 83% of tumors (30/36) achieved adequate ablative margin (>5 mm) three-dimensionally. During the follow-up period of 6.0-42.6 months, LTP occurred in 5 lesions, with 1- and 2-year LTP rates being 7.0% and 9.4%. The 1- and 2-year DFS rates were 76.1% and 65.6%, and 1- and 2-year OS rates were 98.1% and 94.0%. No major complications or ablation-related deaths were observed in any patients.Conclusions Three-dimensional ultrasound fusion imaging technique may improve the needle placement of thermal ablation for HCC and reduce the rate of LTP.

IntroductionDesigning footwear for comfort is vital for preventing foot injuries and promoting foot health. This study explores the impact of auxetic structured shoe soles on plantar biomechanics and comfort, motivated by the integration of 3D printing in footwear production and the superior mechanical properties of auxetic designs. The shoe sole designs proposed in this study are based on a three-dimensional re-entrant auxetic lattice structure, orthogonally composed of re-entrant hexagonal honeycombs with internal angles less than 90 degrees. Materials fabricated using this lattice structure exhibit the characteristic of a negative Poisson's ratio, displaying lateral expansion under tension and densification under compression.MethodsThe study conducted a comparative experiment among three different lattice structured (auxetic 60°, auxetic 75° and non-auxetic 90°) thermoplastic polyurethane (TPU) shoe soles and conventional polyurethane (PU) shoe sole through pedobarographic measurements and comfort rating under walking and running conditions. The study obtained peak plantar pressures (PPPs) and contact area across seven plantar regions of each shoe sole and analyzed the correlation between these biomechanical parameters and subjective comfort.ResultsCompared to non-auxetic shoe soles, auxetic structured shoe soles reduced PPPs across various foot regions and increased contact area. The Auxetic 60°, which had the highest comfort ratings, significantly lowered peak pressures and increased contact area compared to PU shoe sole. Correlation analysis showed that peak pressures in specific foot regions (hallux, second metatarsal head, and hindfoot when walking; second metatarsal head, third to fifth metatarsal head, midfoot, and hindfoot when running) were related to comfort. Furthermore, the contact area in all foot regions was significantly associated with comfort, regardless of the motion states.ConclusionThe pressure-relief performance and conformability of the auxetic lattice structure in the shoe sole contribute to enhancing footwear comfort. The insights provided guide designers in developing footwear focused on foot health and comfort using auxetic structures.

Cooperative driving is crucial for improving traffic efficiency and safety for connected and automated vehicles (CAVs), especially in traffic bottlenecks. However, most of the state-of-the-art cooperative driving strategies neglect the issue of fairness. Fairness is essential to properly allocate road resources and improve the travel experience. In this paper, we focus on the fairness concerns in the on-ramp cooperative driving problem. First, we note that enhancing traffic efficiency usually leads to unfairness, but we propose solutions to balance both aspects. Using the fundamental relation in traffic flow theory, we illustrate the existence of the trade-off at congested on-ramps. We then make some modifications to the cooperative driving strategies to incorporate fairness considerations. Simulation results show that the modified strategies achieve trade-offs in agreement with the theoretical one, laying the foundation for implementing the trade-off in real-world scenarios. These findings are enlightening for the increasing research on fairness issues in cooperative driving, and contribute to the optimization of traffic management strategies.

Under the dual-carbon goals, enhancing the green development level of logistics industry and realizing its low-carbon transformation are important issues that need to be solved urgently. Amidst the continuous escalation in the total energy consumption of the national logistics industry, the Beijing-Tianjin-Hebei (BTH) region has exhibited a favorable descending trajectory in this respect. It is necessary to investigate the underlying reasons. Based on the panel data from 2012 to 2021, the DEA and Malmquist index are employed to analyze the low-carbon logistics efficiency of the BTH region from both static and dynamic perspectives. Furthermore, the inefficiency analysis is conducted to identify the deficiencies of low-carbon logistics industry in this region. Results show that (1) from the static perspective, the development of low-carbon logistics industry in the BTH region is relatively unbalanced. Compared to Tianjin and Hebei, Beijing's low-carbon logistics efficiency is significantly lower, becoming the focal area for attention; (2) from the dynamic perspective, technological progress is the main reason for the fluctuation of total factor productivity in the BTH region and a constraining factor for further improvements; (3) from the results of inefficiency analysis, the forthcoming emphasis on low-carbon logistics in Beijing should be on optimizing the number of logistics practitioners, transportation efficiency, and energy efficiency. Economic output and energy efficiency are relatively vulnerable aspects in Tianjin and Hebei, respectively, warranting due consideration. The research results of this paper have important practical implications for better developing low-carbon logistics in the BTH region and leveraging its leading role nationwide.

Coastal wetlands are characterized by high production and thus play an important role in global climate change. In past decades, the invasion of Spartina alterniflora has caused many problems of coastal wetlands in southeastern China, and the restoration of such areas was mainly conducted by replacing Spartina alterniflora with mangrove plants. This may impact the carbon storage dynamics in such areas. In this study, stable isotopes (δ13C and δ15N) and molecular analysis were used to reveal the impact of artificial restoration on the carbon storage of Quanzhou Bay Estuary Wetland Natural Reserve. The major results are as follows: (1) the change in dominant plants results in a changing major source of soil organic matter, from external sources to mangrove plants; (2) the decrease in soil organic matter following the removal of Spartina alterniflora may be primarily caused by the loss of external organic matter, while the production of mangroves may offset such loss and enhance the content and stability of carbon storage over the long term; (3) microbial CO2 assimilation may serve as an alternative source of bioavailable carbon and thus support the activity of benthic community. Our results revealed the long-term benefits of such restoration on the carbon storage function of wetlands invaded by Spartina alterniflora. Furthermore, the integrating of isotopic tracers and molecular technology may provide new insights in understanding the response of the carbon storage in coastal areas to human activity.

Strong winds or typhoon disasters pose significant risks to historical buildings in many countries and regions. Although numerous researchers have discussed the damage caused by natural wind disasters, little attention has been paid to the potential impact of renovation and adaptive reuse strategies on the wind resistance performance of historical buildings—an avoidable human-induced factor. This study selected the representative ancestral hall building in Guangzhou, namely Lujiang Academy, for on-site investigation and Computational Fluid Dynamics (CFD) simulation analysis. It examined two renovation approaches: installing glass curtain walls around the courtyard and enclosing the top of the courtyard with a glass canopy. This study also assessed the roof wind pressure distribution in its unaltered state to evaluate the impact of different renovation strategies on roof wind load distribution. The results showed that installing glass curtain walls can effectively reduce the upward suction effect on the main hall roof, thereby improving its wind resistance performance. Conversely, enclosing the courtyard with a glass canopy may increase negative pressure on areas such as the eaves and corridor roofs, raising the risk of roof damage. This study systematically evaluated the renovation strategies for historical buildings, detailing the specific impacts of different retrofit measures on the wind resistance performance of building roofs. The methods and findings are significant not only for the renovation of ancestral hall heritage buildings in Guangzhou but also for providing practical scientific methods and technical strategies for the conservation and renovation of similar historical structures. This research demonstrates an effective approach to enhancing wind resistance and preventive protection for historical buildings.

Seagrass is a group of flowering plants capable of completing their life cycle in a marine environment. It not only provides a refuge for biodiversity and essential fish spawning and nursery grounds, but also provides ecologically and socioeconomically important services for urban coasts. Seagrass is widely distributed along temperate and tropical coastlines globally. The biodiversity corresponds with differences in the relative importance of sexual (seed production) and asexual (clonal growth) life history strategies in the maintenance of seagrass populations. Sexual reproduction in predominantly clonal marine plants increases recombination favoring adaptation and enhancing species resilience to environmental change. Flowering induction is an important link in the transition from vegetative growth to reproductive growth of seagrasses. Recent studies on seagrasses suggest that flowering intensity and frequency are correlated with global climate change, and the response of seagrasses will be more complex, and potentially more resilient than previously imagined.Seagrass environments are characterized by physical conditions, such as temperature, salinity, currents, waves, turbulence, and light. Each of these parameters has the potential to affect vegetation from the smallest (molecular and physiological) to the largest (ecosystem as well as global) scale. Based on bibliometric methods, this study summarized the development trend of seagrass flowering formation research. The SCIE database of the Web of Science core collection of the Institute for Scientific Information (ISI) was chosen as the retrieval source, and select published international journals were chosen as the research object. With "seagrass flowering" as the search keyword, a total of 300 related publications were retrieved. In terms of the number of relevant publications each year, there was an overall increasing trend, indicating that this topic has gradually received more attention in recent years, which has great research potential.This review summarizes the research progress of flowering inducement in the sexual reproduction of seagrasses and discusses the influence of physical factors on the flowering induction of seagrasses. It was previously thought that the flowering pathway initiated by seagrasses in response to environmental factors and endogenous signals may focus on the photoperiod, vernalization, and spontaneous pathways. However, the sexual reproduction of different species is different, and studying the interaction between seagrasses and their physical environment may improve understanding of the processes that influence their biology. This review focuses on the following aspects: 1) Clarifying the period of concentrated flowering of the seagrass bed, which is conducive to studying the inducement of flowering of seagrass and protecting the seagrass seed bank. 2) Discussing whether more genotypes of seagrass should be introduced for planting in the process of seagrass bed repair to avoid large-scale clonal reproduction of a single genotype of seagrass. 3) How sexual reproduction of seagrasses under adverse environments can be used to indicate changes in the climate and environment. However, existing studies have paid little attention to the sexual reproduction of seagrass beds, and do not consider the sexual reproduction rate as a long-term monitoring indicator. It is suggested that the sexual reproduction rate should be combined with environmental factors in the future long-term monitoring and assessment of the health status of seagrass beds to jointly assess their pressure status.

ObjectiveThis study examined the potential of combining Doppler ultrasound (DUS) and CT angiography (CTA) for early detection and intervention of lower extremity arterial disease (LEAD) in diabetes.Concurrently, risk factors influencing LEAD progression were analyzed.Methods106 Type-2 diabetes patients with LEAD, having undergone DUS and CTA, were divided into four stages according to Fontaine stage. Results of DUS and CTA were compared across stages and potential risk factors were analyzed.ResultsPositive detection rates of LEAD differed between DUS and CTA for Fontaine stages I and II (P < 0.05), with no significant difference for stages III and IV (P > 0.05). CTA identified subgroups with mild to moderate stenosis and severe stenosis or occlusion, with positive rates on DUS of 17.95% and 89.9% respectively. Hypertension was found as an independent risk factor affecting LEAD progression.ConclusionCTA should be performed early for LEAD in diabetes patients at Fontaine stages I and II, regardless of DUS results. For diabetes patients with LEAD, stringent blood pressure control is crucial to delay disease progression.

Methyltransferase (MTase) enzymes catalyze the addition of a methyl group to a variety of biological substrates. MTase-like (METTL) proteins are Class I MTases whose enzymatic activities contribute to the epigenetic and epitranscriptomic regulation of multiple cellular processes. N6-adenosine methylation (m6A) is a common chemical modification of eukaryotic and viral RNA whose abundance is jointly regulated by MTases and METTLs, demethylases, and m6A binding proteins. m6A affects various cellular processes including RNA degradation, post-transcriptional processing, and antiviral immunity. Here, we used Nicotiana benthamiana and plum pox virus (PPV), an RNA virus of the Potyviridae family, to investigated the roles of MTases in plant–virus interaction. RNA sequencing analysis identified MTase transcripts that are differentially expressed during PPV infection; among these, accumulation of a METTL gene was significantly downregulated. Two N. benthamiana METTL transcripts (NbMETTL1 and NbMETTL2) were cloned and further characterized. Sequence and structural analyses of the two encoded proteins identified a conserved S-adenosyl methionine (SAM) binding domain, showing they are SAM-dependent MTases phylogenetically related to human METTL16 and Arabidopsis thaliana FIONA1. Overexpression of NbMETTL1 and NbMETTL2 caused a decrease of PPV accumulation. In sum, our results indicate that METTL homologues participate in plant antiviral responses.

ABSTRACTAgeing mechanism of PEEK powders at optimal powder bed temperature (Tb) and factors affecting their reusability remain unclear. This study investigated effects of gas type (air, nitrogen, and argon) and holding time (0–8 h) on physico-chemical properties of PEEK powders at optimal Tb. The hardness of sintered single-layers was measured to evaluate the quality of the parts. Results revealed that the flowability, morphology, and crystallinity of PEEK powders changed with holding time in different gases. Further, the ageing mechanism involved chain crosslinking within molecular chains in all gases but chain breakage in air. Further, laser power required for SLS decreased with the increase in holding time. However, the hardness of single-layers was stable for powders aged in argon for up to 8 h, but decreased by 7% for powders aged in nitrogen for 4 h. Severe degradation and blackening were observed for single-layers sintered in air using both virgin and aged powders.

Abstract Background Increasing evidence suggests that FBXW7 has a high frequency of mutations in esophageal squamous cell carcinoma (ESCC). However, the function of FBXW7, especially the mutations, is not clear. This study was designed to investigate the functional significance of FBXW7 loss of function and underlying mechanism in ESCC. Methods Immunofluorescence was applied to clarify the localization and main isoform of FBXW7 in ESCC cells. Sanger sequencing were performed to explore mutations of FBXW7 in ESCC tissues. Proliferation, colony, invasion and migration assays were performed to examine the functional roles of FBXW7 in ESCC cells in vitro and in vivo. Real-time RT-PCR, immunoblotting, GST-pulldown, LC–MS/MS and co-immunoprecipitation assay were used to explore the molecular mechanism underlying the actions of FBXW7 functional inactivation in ESCC cells. Immunohistochemical staining were used to explore the expression of FBXW7 and MAP4 in ESCC tissues. Results The main FBXW7 isoform in ESCC cells was the β transcript in the cytoplasm. Functional inactivation of FBXW7 led to activation of the MAPK signaling pathway and upregulation of the downstream MMP3 and VEGFA, which enhanced tumor proliferation cell invasion and migration. Among the five mutation forms screened, S327X (X means truncated mutation) had an effect similar to the FBXW7 deficiency and led to the inactivation of FBXW7 in ESCC cells. Three other point mutations, S382F, D400N and R425C, attenuated but did not eliminate FBXW7 function. The other truncating mutation, S598X, which was located outside of the WD40 domain, revealed a tiny attenuation of FBXW7 in ESCC cells. Notably, MAP4 was identified as a potential target of FBXW7. The threonine T521 of MAP4, which was phosphorylated by CHEK1, played a key role in the FBXW7-related degradation system. Immunohistochemical staining indicated that FBXW7 loss of function was associated with tumor stage and shorter survival of patients with ESCC. Univariate and multivariate Cox proportional hazards regression analyses showed that high FBXW7 and low MAP4 was an independent prognostic indicator and prospective longer survival. Moreover, a combination regimen that included MK-8353 to inhibit the phosphorylation of ERK and bevacizumab to inhibit VEGFA produced potent inhibitory effects on the growth of FBXW7 inactivation xenograft tumors in vivo. Conclusions This study provided evidence that FBXW7 loss of function promoted ESCC via MAP4 overexpression and ERK phosphorylation, and this novel FBXW7/MAP4/ERK axis may be an efficient target for ESCC treatment.

Abstract Fiber components form the standard not only in modern telecommunication but also for future quantum information technology. For high-performance single-photon detection, superconducting nanowire single-photon detectors (SPDs) are typically fabricated on a silicon chip and fiber-coupled for easy handling and usage. The fiber-to-chip interface hinders the SPD from being an all-fiber device for full utilization of its excellent performance. Here, we report a scheme of SPD that is directly fabricated on the fiber tip. A bury-and-planar fabrication technique is developed to improve the roughness of the substrate for all-fiber detectors’ performance for single-photon detection with amorphous molybdenum silicide (MoSi) nanowires. The low material selectivity and universal planar process enable fabrication and packaging on a large scale. Such a detector responds to a broad wavelength range from 405 nm to 1550 nm at a dark count rate of 100 cps. The relaxation time of the response pulse is ~ 15 ns, which is comparable to that of on-chip SPDs. Therefore, this device is free from fiber-to-chip coupling and easy packaging for all-fiber quantum information systems.

AbstractRecent regulations introduced by the Chinese government regarding big data technologies are welcome to those long concerned about the risks associated with their rapid deployment. However, these changes are not sufficient to safeguard privacy and data security. More importantly, these policies may not have fully accounted for the disruptive nature of these technologies. In this paper, we examine the need and the potential of new approaches in policy design regarding disruptive technologies by examining the case of facial recognition technology (FRT) in China. We argue that adaptive governance provides a useful framework for future policy design. Regulatory sandbox approach, policy mix and stakeholder engagement are among key policy measures to overcome regulatory challenges.

Purpose To investigate the value of three-dimensional ultrasound fusion imaging (3DUS-FI) in real-time guiding needle placement by phantom models and in vivo simulations.Materials and methods Two radiologists (beginner and expert) performed needle placement using two-dimensional ultrasound (2DUS) and 3DUS-FI, respectively. In the phantom study, single-needle placement was performed by puncturing the center point of each ball and assessed based on the specimen length. Multiple-needles placement was performed by placing three needles in each ball, and their locations were confirmed by computed tomography, and assessed based on the distance deviation between needles. In the in vivo simulation study, simulated-needle placement was performed by placing a virtual ablation needle in each liver tumor and assessed by the simulated ablative cover rate and margin.Results Specimen length was significantly longer with 3DUS-FI in the beginner, whereas no significant difference was observed in the expert (2DUS vs. 3DUS-FI: beginner, 14.60 ± 2.60 mm vs. 16.25 ± 1.38 mm, p = .017; expert, 16.78 ± 1.40 mm vs. 16.95 ± 1.15 mm, p = .668). Distance deviation between needles was significantly smaller with 3DUS-FI (2DUS vs. 3DUS-FI: beginner, 25.06 ± 16.07 mm vs. 3.72 ± 1.99 mm, p

Background: Sleep disturbances are associated with adverse perinatal outcomes. Thus, it is necessary to understand the continuous patterns of sleep during pregnancy and how moderators such as maternal age and pre-pregnancy body mass index impact sleep. Objective: This study aimed to examine the continuous changes in sleep parameters objectively (i.e. sleep stages, total sleep time, and awake time) in pregnant women and to describe the impact of maternal age and/or pre-pregnancy body mass index as moderators of these objective sleep parameters. Design: This was a longitudinal observational design. Methods: Seventeen women with a singleton pregnancy participated in this study. Mixed model repeated measures were used to describe weekly patterns, while aggregated changes describe these three pregnancy periods (10–19, 20–29, and 30–39 gestational weeks). Results: For the weekly patterns, we found significantly decreased deep (1.26 ± 0.18 min/week, p

The buildup dynamics from noise-seeded relaxation oscillation to harmonic mode-locking (HML) solitons generation have been well investigated in ultrafast fiber lasers. However, the transient multi-soliton dynamics in higher-order HML states are still attractive yet largely unexplored. We reveal here that, the experimental observation of the multi-soliton dynamics including soliton beating dynamics, soliton annihilation, transient bound state, two-soliton resonance state, soliton splitting, and multi-soliton repulsion dynamics are analyzed by the emerging time-stretched dispersive Fourier transform (TS-DFT) technique. Particularly, the excessive intracavity energy result in the double-pulse pulsating with transient bound states and three types of soliton molecules states can be observed in the earlier and middle part of the transition process. Numerical results further reveal that several similar multi-soliton dynamics operating at stable 2nd and 3rd states could be caused by a fine tuning of the pump power level in a hybrid mode-locked laser. Our results unveil a diverse set of ultrafast transient process in fiber lasers, and open up new ways into obtaining and controlling the generation of high-repetition-rate ultrashort pulses in fiber lasers.

Abstract Background Lung cancer, one of the most common malignant tumors, exhibits high inter- and intra-tumor heterogeneity which contributes significantly to treatment resistance and failure. Single-cell RNA sequencing (scRNA-seq) has been widely used to dissect the cellular composition and characterize the molecular properties of cancer cells and their tumor microenvironment in lung cancer. However, the transcriptomic heterogeneity among various cancer cells in non-small cell lung cancer (NSCLC) warrants further illustration. Methods To comprehensively analyze the molecular heterogeneity of NSCLC, we performed high-precision single-cell RNA-seq analyses on 7364 individual cells from tumor tissues and matched normal tissues from 19 primary lung cancer patients and 1 pulmonary chondroid hamartoma patient. Results In 6 of 16 patients sequenced, we identified a significant proportion of cancer cells simultaneously expressing classical marker genes for two or even three histologic subtypes of NSCLC—adenocarcinoma (ADC), squamous cell carcinoma (SCC), and neuroendocrine tumor (NET) in the same individual cell, which we defined as mixed-lineage tumor cells; this was verified by both co-immunostaining and RNA in situ hybridization. These data suggest that mixed-lineage tumor cells are highly plastic with mixed features of different types of NSCLC. Both copy number variation (CNV) patterns and mitochondrial mutations clearly showed that the mixed-lineage and single-lineage tumor cells from the same patient had common tumor ancestors rather than different origins. Moreover, we revealed that patients with high mixed-lineage features of different cancer subtypes had worse survival than patients with low mixed-lineage features, indicating that mixed-lineage tumor features were associated with poorer prognosis. In addition, gene signatures specific to mixed-lineage tumor cells were identified, including AKR1B1. Gene knockdown and small molecule inhibition of AKR1B1 can significantly decrease cell proliferation and promote cell apoptosis, suggesting that AKR1B1 plays an important role in tumorigenesis and can serve as a candidate target for tumor therapy of NSCLC patients with mixed-lineage tumor features. Conclusions In summary, our work provides novel insights into the tumor heterogeneity of NSCLC in terms of the identification of prevalent mixed-lineage subpopulations of cancer cells with combined signatures of SCC, ADC, and NET and offers clues for potential treatment strategies in these patients.

A new species, Belbolla mangrove sp. nov., isolated from the mangrove wetlands of Fujian and Zhejiang Provinces in China, is described and illustrated. Belbolla mangrove sp. nov. is characterized by a pharynx with four bulbs, a small gubernaculum with a short dorsocaudal apophysis, four weakly developed precloacal supplements, a conico-cylindrical tail with a terminal spinneret, and the absence of terminal setae. This new species differs from B. vietnamica by the absence of ocelli and the blunt and rounded proximal ends of the spicules. The 18S rDNA GenBank accession numbers of B. mangrove sp. nov. are provided.

Abstract The relationship between childhood socioeconomic status (SES) and type 2 diabetes (T2D) remains inconclusive, and the pathways and mechanisms driving this relationship have yet to be clarified. This study aimed to examine the pathways linking childhood SES to T2D prevalence in mid-late adulthood in a low- and middle-income country. The incidence of T2D diagnosed in mid-late Chinese adulthood was assessed using self-reports from the Health and Retirement Longitudinal Study (CHARLS). Childhood SES was assessed by the education, occupation, survivorship of the parents and the financial situation of the family, whereas adulthood SES was assessed by education and wage. This study performed structural equation modeling to clarify the direct and indirect pathways from childhood SES to T2D via childhood health, childhood food shortage, adulthood SES and physical activity. A total of 15,132 participants were included, and the prevalence of T2D was 5.24%. This study found that childhood SES was directly associated with T2D in mid-late adulthood, the probability of developing T2D increased by 9.20% of the standard deviation for each decrease in standard deviation in childhood SES. Childhood SES was indirectly associated with T2D via adulthood SES, physical activity, childhood health and food shortage. Adulthood SES and physical activity mainly mediated the indirect pathway from childhood SES and T2D. This study showed direct and indirect pathways from disadvantaged childhood SES to increased risk of T2D in mid-late Chinese adulthood. Childhood SES, adulthood SES, physical activity, childhood health and food shortage were identified as life-course interventional targets that should be considered in the development of effective strategies to reduce the burden of T2D and SES-related health inequities in childhood.

Continuous monitoring of perinatal women in a descriptive case study allowed us the opportunity to examine the time during which the COVID-19 infection led to physiological changes in two low-income pregnant women. An important component of this study was the use of a wearable sensor device, the Oura ring, to monitor and record vital physiological parameters during sleep. Two women in their second and third trimesters, respectively, were selected based on a positive COVID-19 diagnosis. Both women were tested using the polymerase chain reaction method to confirm the presence of the virus during which time we were able to collect these physiological data. In both cases, we observed 3–6 days of peak physiological changes in resting heart rate (HR), heart rate variability (HRV), and respiratory rate (RR), as well as sleep surrounding the onset of COVID-19 symptoms. The pregnant woman in her third trimester showed a significant increase in resting HR (p = 0.006) and RR (p = 0.048), and a significant decrease in HRV (p = 0.027) and deep sleep duration (p = 0.029). She reported experiencing moderate COVID-19 symptoms and did not require hospitalization. At 38 weeks of gestation, she had a normal delivery and gave birth to a healthy infant. The participant in her second trimester showed similar physiological changes during the 3-day peak period. Importantly, these changes appeared to return to the pre-peak levels. Common symptoms reported by both cases included loss of smell and nasal congestion, with one losing her sense of taste. Results suggest the potential to use the changes in cardiorespiratory responses and sleep for real-time monitoring of health and well-being during pregnancy.

There are generally two kinds of traffic control strategies to relieve traffic congestion in lane-drop bottlenecks: variable speed limits (VSL) control and lane-changing (LC) control. However, VSL has limited or even no effect due to many mandatory LC maneuvers near bottlenecks, while LC fails to reduce traffic congestion when traffic demand is high. Although a few control methods combine VSL and LC, they do not consider the interaction between VSL and LC, which rules out many potentially good alternatives. We instead propose an integrated VSL and LC control method under a connected and automated vehicle (CAV) environment, which can consider the interaction and simultaneously find the values of LC numbers and speed limits to maximize traffic efficiency. Our control is in the framework of the model predictive control (MPC), which consists of prediction, optimization, and implementation. We adopt an improved multi-class cell transmission model (CTM) for traffic state prediction, then use the genetic algorithm (GA) for optimization which optimizes traffic network performance, and implement our control method in the SUMO platform. Simulation results demonstrate that our control method greatly improves the capacity of the road and is robust to different traffic demands and scenarios. Our control outperforms no control and VSL-only control in travel time and exhaust emissions, which reduces total travel time by 23.86% to 44.62% and exhaust emissions by 10.29% to 48.19%.

BackgroundThe physical and emotional well-being of women is critical for healthy pregnancy and birth outcomes. The Two Happy Hearts intervention is a personalized mind-body program coached by community health workers that includes monitoring and reflecting on personal health, as well as practicing stress management strategies such as mindful breathing and movement. ObjectiveThe aims of this study are to (1) test the daily use of a wearable device to objectively measure physical and emotional well-being along with subjective assessments during pregnancy, and (2) explore the user’s engagement with the Two Happy Hearts intervention prototype, as well as understand their experiences with various intervention components. MethodsA case study with a mixed design was used. We recruited a 29-year-old woman at 33 weeks of gestation with a singleton pregnancy. She had no medical complications or physical restrictions, and she was enrolled in the Medi-Cal public health insurance plan. The participant engaged in the Two Happy Hearts intervention prototype from her third trimester until delivery. The Oura smart ring was used to continuously monitor objective physical and emotional states, such as resting heart rate, resting heart rate variability, sleep, and physical activity. In addition, the participant self-reported her physical and emotional health using the Two Happy Hearts mobile app–based 24-hour recall surveys (sleep quality and level of physical activity) and ecological momentary assessment (positive and negative emotions), as well as the Perceived Stress Scale, Center for Epidemiologic Studies Depression Scale, and State-Trait Anxiety Inventory. Engagement with the Two Happy Hearts intervention was recorded via both the smart ring and phone app, and user experiences were collected via Research Electronic Data Capture satisfaction surveys. Objective data from the Oura ring and subjective data on physical and emotional health were described. Regression plots and Pearson correlations between the objective and subjective data were presented, and content analysis was performed for the qualitative data. ResultsDecreased resting heart rate was significantly correlated with increased heart rate variability (r=–0.92, P

This study presents two new free-living marine nematodes, Haliplectus major sp. nov. and Haliplectus futianisus sp. nov., from a mangrove reservation in Shenzhen, China. Haliplectus major sp. nov. can be distinguished by its total body length of 1615–1998 µm; a cuticle annulated with eight rows of cuticle pores; amphidial fovea at 9–12 µm from the anterior end; a bipartite basal bulb with striated valve plates in both sexes; five to seven closely spaced precloacal supplements in males; a didelphic reproductive system in females, with the vulva at 49.64–52.37% of body length; and sexual dimorphism in tail shape, arcuate-conoid and 2.3–3.2 times anal body diameter long in males and elongate-conid and 3.5–4.2 times anal body diameter long in females. Haliplectus futianisus sp. nov. is characterized by a total body length of 574–655 µm; a cuticle annulated with eight rows of cuticle pores; amphidial fovea at 8–11 µm from the anterior end; a monopartite basal bulb with unstriated valve plates in both sexes; an absence of precloacal supplements in males; and a didelphic reproductive system in females, with the vulva at 42.33–45.63% of body length. The identification was confirmed by analyzing morphological characteristic and 18S rRNA gene sequences. The maximum likelihood (ML) topology was regarded as morphological evidence of H. major sp. nov. and H. futianisus sp. nov. being two distinct species.

Two new species belonging to the genus Anticyathus were discovered during an ecological investigation of mangrove sediment in China. Anticyathus shenzhensis sp. nov. and Anticyathus communis sp. nov. are both characterized by: annulated cuticles; ten cephalic setae in a circle; buccal cavity lined with six longitudinal reinforcements; amphids in broken circles or cryptic spirals, located at the very anterior of the head; pharynx with anterior cuticularized, gradually enlarging in posterior portion but without bulb; conical tail; arcuate spicules, the distal ends pointed, gradually broadening towards the proximal; gubernaculum has a dorsal–caudal apophysis; female with two opposed, outstretched ovaries. Anticyathus shenzhensis sp. nov. can be distinguished by ten cephalic setae of length about 2–4 µm; amphids diameter about 20–29% of corresponding body diameter; pharynx occupy 0.07–0.10 times of body length; cardia length about 25 µm; tail length 2.5–3.4 times of anal body diameter (abd) in males and 3.4–4.7 abd in females; spicules length 51–59 µm as arc and 0.71–1.04 abd; apophysis length 18–19 µm; female vulva at 52–56% of body length. Anticyathus communis sp. nov. is identified by ten cephalic setae length about 3–5 µm; amphids diameter about 20–32% of corresponding body diameter; cardia 17–27 µm long; tail length 3.6–4.5 abd in male, 5.3–5.5 abd in female; spicules proximal with distinctly cephalated, 0.74–0.96 abd; gubernaculum shape of “L”, consisting of sleeves around spicule and dorsal–caudal apophysis; five to seven pre-anal and seven to ten post-anal almost invisible papilla or papillae-like setae occur on each ventrally submedian line on the posterior body part of male; the tip of male tail with three slight elevation; female vulva at 52% of body length. A dichotomous key for the genus Anticyathus is given and 39 sequences of 18S rRNA gene from ten individuals of Anticyathus shenzhensis sp. nov. are provided in Genbank database.

The development of effective screening methods for Autism Spectrum Disorder (ASD) in early childhood remains a public health priority for communities around the world. Little is known regarding the concurrence between parent concerns about ASD and formal ASD diagnostic methods. This study aimed to examine the relationships among a priori parental ASD concern, ADOS classification, and a physician specialist's diagnosis. One hundred and thirty-four toddlers (74% male; mean age = 31.8 months, SD 4.4) received an evaluation at a university center specializing in ASD and neurodevelopmental disorders. Correspondence between a priori parental ASD suspicion and physician diagnosis of ASD was 61% (p = 0.028). Correspondence between a priori parental suspicion of ASD and ADOS ASD classification was 57% (p = 0.483). Correspondence between ADOS classification and physician diagnosis of ASD was 88% (p = 0.001). Our results have implications for evaluations in low resource regions of the world where access to physician specialists may be limited; the high correspondence between ADOS classification and a physician specialist's diagnosis supports the use of trained ADOS evaluators, such as field health workers or early childhood educators, in a tiered screening process designed to identify those most in need of a specialist's evaluation. Our results also have implications for public health efforts to provide parent education to enable parents to monitor their child's development and share concerns with their providers. Parent awareness and expression of concern coupled with timely responses from providers may lead toward earlier identification of ASD, and other neurodevelopmental disorders, and hence, generate opportunities for earlier and more personalized intervention approaches, which in turn may help improve long-term outcomes. Empowering parents and community members to screen for ASD may be especially important in regions of the world where access to formal diagnosis is limited.

Background: Vaccine hesitancy, associated with medical mistrust, confidence, complacency and knowledge of vaccines, presents an obstacle to the campaign against the coronavirus disease 2019 (COVID-19). The relationship between vaccine hesitancy and conspiracy beliefs may be a key determinant of the success of vaccination campaigns. This study provides a conceptual framework to explain the impact of pathways from conspiracy beliefs to COVID-19 vaccine hesitancy with regard to medical mistrust, confidence, complacency and knowledge of vaccines. Methods: A non-probability study was conducted with 1015 respondents between 17 April and 28 May 2021. Conspiracy beliefs were measured using the coronavirus conspiracy scale of Coronavirus Explanations, Attitudes, and Narratives Survey (OCEANS), and vaccine conspiracy beliefs scale. Medical mistrust was measured using the Oxford trust in doctors and developers questionnaire, and attitudes to doctors and medicine scale. Vaccine confidence and complacency were measured using the Oxford COVID-19 vaccine confidence and complacency scale. Knowledge of vaccines was measured using the vaccination knowledge scale. Vaccine hesitancy was measured using the Oxford COVID-19 vaccine hesitancy scale. Confirmatory factor analysis (CFA) was used to evaluate the measurement models for conspiracy beliefs, medical mistrust, confidence, complacency, and knowledge of vaccines and vaccine hesitancy. The structural equation modeling (SEM) approach was used to analyze the direct and indirect pathways from conspiracy beliefs to vaccine hesitancy. Results: Of the 894 (88.1%) respondents who were willing to take the COVID-19 vaccine without any hesitancy, the model fit with the CFA models for conspiracy beliefs, medical mistrust, confidence, complacency and knowledge of vaccines, and vaccine hesitancy was deemed acceptable. Conspiracy beliefs had significant direct (β = 0.294), indirect (β = 0.423) and total (β = 0.717) effects on vaccine hesitancy; 41.0% of the total effect was direct, and 59.0% was indirect. Conspiracy beliefs significantly predicted vaccine hesitancy by medical mistrust (β = 0.210), confidence and complacency (β = 0.095), knowledge (β = 0.079) of vaccines, explaining 29.3, 11.0, and 13.2% of the total effects, respectively. Conspiracy beliefs significantly predicted vaccine hesitancy through the sequential mediation of knowledge of vaccines and medical mistrust (β = 0.016), explaining 2.2% of the total effects. Conspiracy beliefs significantly predicted vaccine hesitancy through the sequential mediation of confidence and complacency, and knowledge of vaccines (β = 0.023), explaining 3.2% of the total effects. The SEM approach indicated an acceptable model fit (χ2/df = 2.464, RMSEA = 0.038, SRMR = 0.050, CFI = 0.930, IFI = 0.930). Conclusions: The sample in this study showed lower vaccine hesitancy, and this study identified pathways from conspiracy beliefs to COVID-19 vaccine hesitancy in China. Conspiracy beliefs had direct and indirect effects on vaccine hesitancy, and the indirect association was determined through medical mistrust, confidence, complacency, and knowledge of vaccines. In addition, both direct and indirect pathways from conspiracy beliefs to vaccine hesitancy were identified as intervention targets to reduce COVID–19 vaccine hesitancy.

Melamine-resin microspheres were synthesized at a pH of 4.0 for 20 min and used as silver nanoparticle (AgNP) carriers for surface enhanced resonant Raman scattering (SERRS) detection. An acetic acid–treatment reaction was introduced into the fabrication of the final substrate. The SERRS performance of the substrate was effectively optimized by regulating excess formaldehyde and experimental parameters, such as acidity, number of treatments and reaction temperature in the acid-treatment reaction. Based on the SERRS detection, it was declared that a trace amount of oligomers with a certain degree of polymerization is necessary for the construction of SERRS hotspots. In addition, it is important to remove excess oligomers with reference to the synthetic reaction of the polymer materials, given the special role of oligomers and the wide application of polymer materials in SERRS detection.

Background: Oral anticoagulation treatment (OAT) such as warfarin therapy is recommended for older adults with atrial fibrillation, heart failure, or who are at risk for venous thromboembolism. Despite its proven benefits, older adults report both dissatisfaction with OAT and reduced quality of life that can potentially lead to low adherence to OAT and decreased treatment efficacy. Objective: To test the feasibility of Mobile Applications for Seniors to enhance Safe anticoagulation therapy (MASS), a mobile-based health technology intervention designed to promote independence and self-care. Method s: This pilot study used a single-arm experimental pre–post design to test the feasibility of a 3-month intervention using MASS in 18 older adults (male: n = 14; White: n = 9; Hispanic: n = 7; Other: n = 2; M age = 67). MASS was available in English or Spanish. Participants completed surveys about their OAT knowledge, attitudes, quality of life with OAT, and adherence at baseline and at a 3-month follow-up. Satisfaction with the MASS intervention was also assessed at follow-up. Results: Anticoagulation knowledge significantly improved from baseline to follow-up ( M base = 12.5 ± 5.51, M follow-up = 14.78 ± 3.93, p = .007). Other outcomes were not different, pre- and post-tests. Participants reported they were generally satisfied with MASS, its ease of use and its usefulness. Conclusion: The results showed use of MASS improved older adults’ knowledge of OAT. Using mHealth apps may enhance self-care among older adults with chronic conditions who are also taking oral anticoagulants.

Influence of the excess monomer within the synthetic reaction solution of melamine resin microspheres (MFMSs) on the surface-enhanced Raman spectroscopy (SERS) enhancement from Rhodamine 6G (R6G) was investigated, where the R6G was adsorbed on the silver nanoparticles (AgNPs) that were loaded on the MFMSs. Surface characteristics of the MFMSs were modified by the excess monomer (i.e., the excessive melamine or formaldehyde) through its terminal overreaction, which can be simply controlled by some of the synthetic reaction conditions, thus further allowing us to optimize the assembly of the loaded AgNPs for the SERS detection. These SERS substrates incorporating the optimized MFMSs with the excess formaldehyde can also be used for tracing analyses of more environmental and food contaminants.

Functional genetic variations play important roles in shaping phenotypic differences among individuals through affecting gene expression, and thus, very likely to influence disease susceptibility, such as cancer susceptibility. One critical question in this era of post-genome wide association studies (GWAS) is how to assess the functional significance of the genetic variations identified from GWAS. In the current study, with lymphoblastoid cell lines (LCLs) from 74 non-related women with familial ovarian cancer and 47 unrelated controls matched on gender and race, we explored the associations between seven ovarian cancer risk variants identified from GWAS (rs3814113 on 9p22.2, rs2072590 on 2q31, rs2665390 on 3q25, rs10088218, rs1516982, rs10098821 on 8q24.21, and rs2363956 on 19p13) and whole genome mRNA expression profiles. We observed 95 significant trans-associations at a permutation level of 0.001. Compared to the other risk variants, rs10088218, rs1516982, and rs10098821 on 8q24.21 had the greatest number of significant associations (25, 16, and 38, respectively). Two possible cis-associations were observed between rs10098821 and c-Myc, and rs2072590 and HS.565379 (Permutated P = 0.0198 and 0.0399, respectively). Pathway enrichment analysis showed that several key biological pathways, such as cell cycle (P = 2.59×10(-06)), etc, were significantly overrepresented. Further characterization of significant associations between mRNAs and risk alleles might facilitate understanding the functions of GWAS discovered risk alleles in the genetic etiology of ovarian cancer.