CircTHBS1 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR-136-3p/IGF2R axis.

The precise molecular mechanism behind fetal growth restriction (FGR) is still unclear, although there is a strong connection between placental dysfunction, inadequate trophoblast invasion, and its etiology and pathogenesis. As a new type of non-coding RNA, circRNA has been shown to play a crucial role in the development of FGR. This investigation identified the downregulation of hsa_circ_0034533 (circTHBS1) in FGR placentas through high-sequencing analysis and confirmed this finding in 25 clinical placenta samples using qRT-PCR. Subsequent in vitro functional assays demonstrated that silencing circTHBS1 inhibited trophoblast proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) progression and promoted apoptosis. Furthermore, when circTHBS1 was overexpressed, cell function experiments showed the opposite result. Analysis using fluorescence in situ hybridization revealed that circTHBS1 was primarily found in the cytoplasmic region. Through bioinformatics analysis, we anticipated the involvement of miR-136-3p and IGF2R in downstream processes, which was subsequently validated through qRT-PCR and dual-luciferase assays. Moreover, the inhibition of miR-136-3p or the overexpression of IGF2R partially reinstated proliferation, migration, and invasion abilities following the silencing of circTHBS1. In summary, the circTHBS1/miR-136-3p/IGF2R axis plays a crucial role in the progression and development of FGR, offering potential avenues for the exploration of biological indicators and treatment targets.

miR-1293 suppresses osteosarcoma progression by modulating drug sensitivity in response to cisplatin treatment.

Chemotherapy is considered the primary treatment for osteosarcoma. however, its effectiveness is limited due to drug resistance and toxicity. Thus, identifying novel therapeutic targets to enhance the efficacy of chemotherapy is urgently needed. Here, we identified a novel cisplatin-sensitivity enhancing mechanism via up-regulation of the tumour suppressor gene, miR-1293. Meanwhile, higher levels of miR-1293 observed in prechemotherapy patients were associated with a more favorable prognosis. The mechanism underlying cisplatin upregulated miR-1293 expression involves hypomethylation of the miR-1293 promoter, which blocks the binding of the transcription repressor TFAP2A to the promoter. Furthermore, miR-1293 inhibits osteosarcoma progression by targeting TIMP1 to inactivate the Notch1/Hes1 and TGFBR1/Smad2/3 pathways, thereby promoting tumour cell death. The findings presented herein unveil a novel mechanism for enhancing cisplatin sensitivity and proposed a potential therapeutic strategy for osteosarcoma through pre-chemotherapy supplementation of miR-1293.

A large deletion in TSC2 causes tuberous sclerosis complex by dysregulating PI3K/AKT/mTOR signaling pathway.

BACKGROUND/AIM: Tuberous sclerosis complex (TSC) is a multi-system syndrome caused by loss-of-function mutation in TSC1 or TSC2. Most TSC patients present with cardiac rhabdomyoma or cortical tubers during fetal life, and the symptoms are not uniform as their age. The gene products of TSC1/2 are components of the TSC protein complex and are important role in the PI3K/AKT/mTOR (PAM) signaling pathway. Based on three members of a family with variable expressivity, the purpose of this study was to clarify the clinical features of TSC in different age groups and to analyze the genetic characteristics of TSC2 gene. METHODS: Clinical exome sequencing and co-segregation were used to identify a three-generation family with four affected individuals. HEK-293T cell model was constructed for subsequent experiments. Quantitative RT-PCR, western blotting, and subcellular localization were used to analyze the expression effect of TSC2 mutation. CCK-8 assay, wound healing assay, and cell cycle analysis were used to analyze the function effect of TSC2 mutation. RESULT: We identified a TSC family with heterozygous deletion of exon 4 in TSC2 by clinical exon sequencing. Sanger sequencing indicated that the affected individuals have 2541-bp deletion that encompassed exon 4 and adjacent introns. Deletion of exon 4 decreased the TSC2 mRNA and protein levels in HEK-293T cells, and activated the PI3K/AKT/mTOR pathway, thereby altering the cell cycle and promoting cell proliferation and migration. CONCLUSION: We confirmed the pathogenicity of the large deletion in TSC2 in a three- generations family.. Deletion of exon 4 of TSC2 affected cell proliferation, migration, and cell cycle via abnormal activation of the PAM pathway. This study evaluated the pathogenic effect of deletion of exon 4 of TSC2 and investigated the underlying mechanism.

Five-year outcomes of surgical aortic valve replacement with a novel bovine pericardial bioprosthesis.

OBJECTIVES: The short-term performance of the Cingular bovine pericardial aortic valve was proven. This study evaluated its 5-year safety and haemodynamic outcomes. METHODS: It enrolled 148 patients who underwent surgical aortic valve replacement with the Cingular bovine pericardial aortic valve between March 2016 and October 2017 in 5 clinical centres in China. Safety and haemodynamic outcomes were followed up to 5 years. The incidence of all-cause mortality, structural valve deterioration and reintervention was estimated by Kaplan-Meier analysis. RESULTS: The mean age of patients was 67.7 [standard deviation (SD) 5.1] years, and 36.5% of patients were female. The mean follow-up was 5.3 (SD 1.2) years. Five-year freedom from all-cause mortality, structural valve deterioration and all-cause reintervention were 91.2%, 100% and 99.3%, respectively. At 5 years, the mean gradient and effective orifice area of all sizes combined were 14.0 (SD 5.5) mmHg and 1.9 (SD 0.3) cm2, respectively. For 19- and 21-mm sizes of aortic prostheses, the mean gradients and effective orifice area at 5 years were 17.5 (SD 7.0) mmHg and 1.6 (SD 0.2) cm2 and 13.7 (SD 6.7) mmHg and 1.8 (SD 0.3) cm2, respectively. The incidence of moderate or severe patient-prosthesis mismatch was 4.1% and 0.0% patients at 5 years, respectively. CONCLUSIONS: The 5-year safety and haemodynamic outcomes of Cingular bovine pericardial aortic valve are encouraging. Longer-term follow-up is warranted to assess its true durability.

Genome-Wide Analysis of Cation/Proton Antiporter Family in Soybean (Glycine max) and Functional Analysis of GmCHX20a on Salt Response.

Monovalent cation proton antiporters (CPAs) play crucial roles in ion and pH homeostasis, which is essential for plant development and environmental adaptation, including salt tolerance. Here, 68 CPA genes were identified in soybean, phylogenetically dividing into 11 Na+/H+ exchangers (NHXs), 12 K+ efflux antiporters (KEAs), and 45 cation/H+ exchangers (CHXs). The GmCPA genes are unevenly distributed across the 20 chromosomes and might expand largely due to segmental duplication in soybean. The GmCPA family underwent purifying selection rather than neutral or positive selections. The cis-element analysis and the publicly available transcriptome data indicated that GmCPAs are involved in development and various environmental adaptations, especially for salt tolerance. Based on the RNA-seq data, twelve of the chosen GmCPA genes were confirmed for their differentially expression under salt or osmotic stresses using qRT-PCR. Among them, GmCHX20a was selected due to its high induction under salt stress for the exploration of its biological function on salt responses by ectopic expressing in Arabidopsis. The results suggest that the overexpression of GmCHX20a increases the sensitivity to salt stress by altering the redox system. Overall, this study provides comprehensive insights into the CPA family in soybean and has the potential to supply new candidate genes to develop salt-tolerant soybean varieties.

Low-Profile Broadband Dual-Polarized Dipole Antenna for Base Station Applications.

A low-profile broadband dual-polarized antenna is investigated for base station applications. It consists of two orthogonal dipoles, fork-shaped feeding lines, an artificial magnetic conductor (AMC), and parasitic strips. By utilizing the Brillouin dispersion diagram, the AMC is designed as the antenna reflector. It has a wide in-phase reflection bandwidth of 54.7% (1.54-2.70 GHz) and a surface-wave bound range of 0-2.65 GHz. This design effectively reduces the antenna profile by over 50% compared to traditional antennas without an AMC. For demonstration, a prototype is fabricated for 2G/3G/LTE base station applications. Good agreement between the simulations and measurements is observed. The measured -10-dB impedance bandwidth of our antenna is 55.4% (1.58-2.79 GHz), with a stable gain of 9.5 dBi and a high isolation of more than 30 dB across the impedance passband. As a result, this antenna is an excellent candidate for miniaturized base station antenna applications.

Mechanical Compatibility between Mg3(Sb,Bi)2 and MgAgSb in Thermoelectric Modules.

Thermoelectric (TE) modules are exposed to temperature gradients and repeated thermal cycles during their operation; therefore, mechanically robust n- and p-type legs are required to ensure their structural integrity. The difference in the coefficients of thermal expansion (CTEs) of the two legs of a TE module can cause stress buildup and the deterioration of performance with frequent thermal cycles. Recently, n-type Mg3Sb2 and p-type MgAgSb have become two promising components of low-temperature TE modules because of to their high TE performance, nontoxicity, and abundance. However, the CTEs of n-Mg3Sb2 and p-MgAgSb differ by approximately 10%. Furthermore, the oxidation resistances of these materials at increased temperatures are unclear. This work manipulates the thermal expansion of Mg3Sb2 by alloying it with Mg3Bi2. The addition of Bi to Mg3Sb2 reduces the coefficient of linear thermal expansion from 22.6 × 10-6 to 21.2 × 10-6 K-1 for Mg3Sb1.5Bi0.5, which is in excellent agreement with that of MgAgSb (21 × 10-6 K-1). Furthermore, thermogravimetric data indicate that both Mg3Sb1.5Bi0.5 and MgAgSb are stable in air and Ar at temperatures below ∼570 K. The results suggest the compatibility and robustness of Mg3Sb1.5Bi0.5 and MgAgSb as a pair of thermoelectric legs for low-temperature TE modules.

Rapid deep-learning-assisted design method for 2-bit coding metasurfaces.

This paper proposes a deep-learning-assisted design method for 2-bit coding metasurfaces. This method uses a skip connection module and the idea of an attention mechanism in squeeze-and-excitation networks based on a fully connected network and a convolutional neural network. The accuracy limit of the basic model is further improved. The convergence ability of the model increased nearly 10 times, and the mean-square error loss function converges to 0.000168. The forward prediction accuracy of the deep-learning-assisted model is 98%, and the accuracy of inverse design results is 97%. This approach offers the advantages of an automatic design process, high efficiency, and low computational cost. It can serve users who lack metasurface design experience.

ATPase family AAA domain-containing protein 2 (ATAD2): From an epigenetic modulator to cancer therapeutic target.

ATPase family AAA domain-containing protein 2 (ATAD2) has been widely reported to be a new emerging oncogene that is closely associated with epigenetic modifications in human cancers. As a coactivator of transcription factors, ATAD2 can participate in epigenetic modifications and regulate the expression of downstream oncogenes or tumor suppressors, which may be supported by the enhancer of zeste homologue 2. Moreover, the dominant structure (AAA + ATPase and bromine domains) can make ATAD2 a potential therapeutic target in cancer, and some relevant small-molecule inhibitors, such as GSK8814 and AZ13824374, have also been discovered. Thus, in this review, we focus on summarizing the structural features and biological functions of ATAD2 from an epigenetic modulator to a cancer therapeutic target, and further discuss the existing small-molecule inhibitors targeting ATAD2 to improve potential cancer therapy. Together, these inspiring findings would shed new light on ATAD2 as a promising druggable target in cancer and provide a clue on the development of candidate anticancer drugs.

MRI-Based Artificial Intelligence in Rectal Cancer.

Rectal cancer (RC) accounts for approximately one-third of colorectal cancer (CRC), with death rates increasing in patients younger than 50 years old. Magnetic resonance imaging (MRI) is routinely performed for tumor evaluation. However, the semantic features from images alone remain insufficient to guide treatment decisions. Functional MRIs are useful for revealing microstructural and functional abnormalities and nevertheless have low or modest repeatability and reproducibility. Therefore, during the preoperative evaluation and follow-up treatment of patients with RC, novel noninvasive imaging markers are needed to describe tumor characteristics to guide treatment strategies and achieve individualized diagnosis and treatment. In recent years, the development of artificial intelligence (AI) has created new tools for RC evaluation based on MRI. In this review, we summarize the research progress of AI in the evaluation of staging, prediction of high-risk factors, genotyping, response to therapy, recurrence, metastasis, prognosis, and segmentation with RC. We further discuss the challenges of clinical application, including improvement in imaging, model performance, and the biological meaning of features, which may also be major development directions in the future. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 2.

Exploring the Association Between Resilience and Quality of Life Among Glaucoma Patients: Sleep Disturbance as a Mediating Factor.

Background: Patients with glaucoma may experience many symptoms such as blindness, which seriously affect their quality of life (QoL). Resilience is playing a vital role in enhancing the QoL and well-being of patients with chronic diseases. In addition, sleep disturbance is common in patients with glaucoma, leading to a decline in their QoL. However, there is a dearth of research on whether sleep disturbance plays a mediating role between resilience and QoL among glaucoma patients. Objective: The aim of this study is to explore the role of sleep disturbance in the relationship between resilience and QoL among glaucoma patients. Methods: From July to December 2019, a cross-sectional survey was conducted on 215 glaucoma patients in an ophthalmic hospital in Liaoning Province. Hierarchical multiple regression (HMR) analyses and structural equation modeling (SEM) were conducted to examine the factors related to QoL and to test the hypothesis that sleep disturbance mediates the relationship between resilience and QoL among glaucoma patients. Results: The average QoL score among glaucoma patients was 43.85 ± 14.97 as reported by the Glaucoma Quality of Life-15 (GQL-15) scale, where a higher scores indicating a poorer QoL. Resilience was found to be linked with a lower QoL score (P < 0.01), while sleep disturbance was associated with a higher QoL score (P < 0.01). When sleep disturbance was included in the model as partial mediator, the path coefficients for the association between resilience and QoL score was significantly decreased (a*b = -0.1, BCa95% CI: -0.154∼-0.045). Conclusion: Findings of this study reflected that QoL among glaucoma patients in China was poor. Resilience was found to be an important positive factor, which could result in the improvement of QoL. Furthermore, sleep disturbance mediated the relationship between resilience and QoL among patients with glaucoma, thereby reducing the positive impact of resilience on QoL in glaucoma patients. Efforts to improve QoL among glaucoma patients may benefit from interventions that enhance the levels of resilience and promote healthy sleep.

Follow-Up of Newborns with Hepatitis B Antigenemia.

INTRODUCTION: There is a need for data to evaluate hepatitis B antigenemia in newborns of mothers with hepatitis B virus (HBV) infection. This study aims to investigate this. METHODS: Newborns with positive serum hepatitis B surface antigen (HBsAg) and/or e antigen (HBeAg) were enrolled in the study. RESULTS: One hundred and one newborns from 98 HBV-infected mothers were included. Median maternal serum HBV DNA level was 23,200 IU/mL at delivery. Among the newborns, 48 were boys and 53 were girls. Mean birth weight was 3190.5 g. Twenty-one newborns had concurrent seropositive HBsAg and HBeAg, nine had seropositive HBsAg and seronegative HBeAg, and 71 had seronegative HBsAg and seropositive HBeAg. Eight newborns had detectable serum HBV DNA. In the follow-up, serum HBsAg and HBeAg in the newborns with undetectable HBV DNA became negative before 6 months of age. Two infants with detectable HBV DNA were diagnosed with immunoprophylaxis failure, one of whom developed active hepatitis at 3 months of age. Liver biopsy in this case showed significant interface hepatitis, fibrous septa formation, and expansion of portal areas with occasional bridging fibrosis. CONCLUSIONS: Concurrent HBV viremia and antigenemia in newborns of HBV-infected mothers requires attention, while antigenemia without viremia is often transient.

Design of a Variable Stiffness Gecko-Inspired Foot and Adhesion Performance Test on Flexible Surface.

Adhesion robots have broad application prospects in the field of spacecraft inspection, repair, and maintenance, but the stable adhesion and climbing on the flexible surface covering the spacecraft has not been achieved. The flexible surface is easily deformed when subjected to external force, which makes it difficult to ensure a sufficient contact area and then detach from it. To achieve stable attachment and easy detachment on the flexible surface under microgravity, an adhesion model is established based on the applied adhesive material, and the relationship between peeling force and the rigidity of the base material, peeling angle, and working surface stiffness is obtained. Combined with the characteristics of variable stiffness structure, the adhesion and detachment force of the foot is asymmetric. Inspired by the adhesion-detachment mechanism of the foot of the gecko, an active adhesion-detachment control compliant mechanism is designed to achieve the stable attachment and safe detachment of the foot on the flexible surface and to adapt to surfaces with different rigidity. The experimental results indicate that a maximum normal adhesion force of 7.66 N can be generated when fully extended, and the safe detachment is achieved without external force on a flexible surface. Finally, an air floating platform is used to build a microgravity environment, and the crawling experiment of a gecko-inspired robot on a flexible surface under microgravity is completed. The experimental results show that the gecko-inspired foot with variable stiffness can satisfy the requirements of stable crawling on flexible surfaces.

AMTDB: A comprehensive database of autophagic modulators for anti-tumor drug discovery.

Autophagy, originally described as a mechanism for intracellular waste disposal and recovery, has been becoming a crucial biological process closely related to many types of human tumors, including breast cancer, osteosarcoma, glioma, etc., suggesting that intervention of autophagy is a promising therapeutic strategy for cancer drug development. Therefore, a high-quality database is crucial for unraveling the complicated relationship between autophagy and human cancers, elucidating the crosstalk between the key autophagic pathways, and autophagic modulators with their remarkable antitumor activities. To achieve this goal, a comprehensive database of autophagic modulators (AMTDB) was developed. AMTDB focuses on 153 cancer types, 1,153 autophagic regulators, 860 targets, and 2,046 mechanisms/signaling pathways. In addition, a variety of classification methods, advanced retrieval, and target prediction functions are provided exclusively to cater to the different demands of users. Collectively, AMTDB is expected to serve as a powerful online resource to provide a new clue for the discovery of more candidate cancer drugs.

Short-Term Consumption of Hydrogen-Rich Water Enhances Power Performance and Heart Rate Recovery in Dragon Boat Athletes: Evidence from a Pilot Study.

(1) Background: Exercise that exceeds the body's accustomed load can lead to oxidative stress and increased fatigue during intense training or competition, resulting in decreased athletic performance and an increased risk of injury, and the new medicinal H2 may be beneficial as an antioxidant. Therefore, we explored the effect of short-term supplementation of hydrogen-rich water (HRW) on the work performance and fatigue recovery of dragon boat athletes after training. (2) Methods: Eighteen dragon boat athletes who trained for 4 h a day (2 h in the morning and 2 h in the afternoon) were divided into an HRW group (n = 9) and a placebo water (PW) group (n = 9), drinking HRW or PW for 7 days. Each participant completed 30 s rowing dynamometer tests, monitoring the heart rate at baseline (i.e., Day 1) and after the intervention (on Day 8). (3) Result: Drinking HRW increased the maximum power and average power of the 30 s rowing test and decreased the maximum heart rate during the period. After the rowing test, the HRW group's heart rate dropped significantly after 2 min of recovery, while the PW group's heart rate did not drop. There was no significant difference between the 30 s rowing distance and the predicted duration of rowing 500 m. (4) Conclusions: Drinking HRW in the short term can effectively improve the power performance of dragon boat athletes and is conducive to the recovery of the heart rate after exercise, indicating that HRW may be a suitable means of hydration for athletes.

Unraveling the Roles of Protein Kinases in Autophagy: An Update on Small-Molecule Compounds for Targeted Therapy.

Protein kinases, which catalyze the phosphorylation of proteins, are involved in several important cellular processes, such as autophagy. Of note, autophagy, originally described as a mechanism for intracellular waste disposal and recovery, has been becoming a crucial biological process closely related to many types of human diseases. More recently, the roles of protein kinases in autophagy have been gradually elucidated, and the design of small-molecule compounds to modulate targets to positively or negatively interfere with the cytoprotective autophagy or autophagy-associated cell death may provide a new clue on the current targeted therapy. Thus, in this Perspective, we focus on summarizing the different roles of protein kinases, including positive, negative, and bidirectional regulations of autophagy. Moreover, we discuss several small-molecule compounds targeting these protein kinases in human diseases, highlighting their pivotal roles in autophagy for targeted therapeutic purposes.

Panic, Psycho-Behavioral Responses, and Risk Perception in the Earliest Stage of the COVID-19 Pandemic in China.

Background: Coronavirus Disease-19 (COVID-19), a rising global pandemic, has triggered psychological crises among the public. Panic, a severe symptom of mental disorders, is increasing in the public in China and it is urgent to provide research for intervention development. Objectives: This study aimed to assess the prevalence of public panic in China during the earliest stage of the COVID-19 pandemic and to explore the associated psychological behavioral responses and public's risk perception of the pandemic. Methods: A cross-sectional study using a web-based survey with convenience sampling was conducted with 2,484 participants nationally from February 11 to February 24, 2020 in China. A self-developed questionnaire was applied to assess the prevalence of public panic and its associated factors. Multivariable logistic regression analysis was applied to assess the risk and protective factors of public panic. Results: There were 23.39% (581/2,484) of the participants who reported experiencing panic during the earliest stage of the COVID-19 pandemic. Taking temperature repeatedly, being nervous in a crowd, being suspicious of infection in the family, being worried about the future, and worries about high infectivity of the COVID-19, lack of effective therapies, and wide impact of the COVID-19 pandemic increased the odds of public panic. Whereas, avoiding gatherings during holidays was negatively associated with the odds of public panic. Conclusions: Psycho-behavioral responses were closely associated with public panic during the earliest stage of the COVID-19 pandemic in China. Defusing excessive health-related worries, the guidance of appropriate self-protective behaviors, strengthening of health education in communities, and available treatment for mental disorders should be adopted to monitor the psychological responses and to guide the behaviors of the public.

Designing strategies of small-molecule compounds for modulating non-coding RNAs in cancer therapy.

Non-coding RNAs (ncRNAs) have been defined as a class of RNA molecules transcribed from the genome but not encoding proteins, such as microRNAs, long non-coding RNAs, Circular RNAs, and Piwi-interacting RNAs. Accumulating evidence has recently been revealing that ncRNAs become potential druggable targets for regulation of several small-molecule compounds, based on their complex spatial structures and biological functions in cancer therapy. Thus, in this review, we focus on summarizing some new emerging designing strategies, such as high-throughput screening approach, small-molecule microarray approach, structure-based designing approach, phenotypic screening approach, fragment-based designing approach, and pharmacological validation approach. Based on the above-mentioned approaches, a series of representative small-molecule compounds, including Bisphenol-A, Mitoxantrone and Enoxacin have been demonstrated to modulate or selectively target ncRNAs in different types of human cancers. Collectively, these inspiring findings would provide a clue on developing more novel avenues for pharmacological modulations of ncRNAs with small-molecule drugs for future cancer therapeutics.

Molecular Mechanism of Cyanidin-3-O-Glucoside Disassembling Aß Fibril In Silico.

The deposition of ß-amyloid (Aß) in the brain leads to neurotoxic effects and subsequent Alzheimer's disease (AD). While AD is becoming more and more prevalent in modern society, therapeutic efforts targeting Aß could be a promising solution. Currently, two natural products are reported to disintegrate preformed Aß fibril in vitro. Meanwhile, the chemical driving force behind this phenomenon remains unknown. Taking cyanidin-3-O-glucoside (Cy-3G) as an example, here we studied its interaction with different Aß polymorphs in silico. Negative charges on different Aß polymorphs draw the interaction with the flavylium cation on Cy-3G. Our results show that Aß in a single peptide form in solution exposed more hydrophobic solvent accessible surface area than its fibril structure (per protomer), and Cy-3G interacts more intensively with the single peptide form than fibril as indicated by more hydrogen bonding formed and more amino acid residues involved in their hydrophobic interactions. Thus, the single Aß peptide aggregation into fibril and fibril dissociation into single peptide equilibrium could be disturbed by the preferential binding of Cy-3G to the monomeric Aß peptide, which leads to the disassembly of the pathogenic Aß fibril. This study offers a novel perspective of Cy-3G alleviated AD syndrome beyond its dogmatic antioxidant activity.

Two MicroRNAs, miR-34a and miR-125a, Are Implicated in Bicuspid Aortopathy by Modulating Metalloproteinase 2.

It has been recognized that wall shear stress plays an important role in the development of Bicuspid Aortopathy (BA), but the intrinsic mechanism is not well elucidated. This study aims to explore the underlying relationship between hemodynamical forces and pathological phenomenon. Total RNA was prepared from aortic wall tissues collected from 20 BA patients. RNA sequencing, bioinformatic analysis and quantitative reverse-transcription PCR validation identified nine miRNAs that were up-regulated in the aortic part exposed to high wall shear stress compared to the low wall shear stress control, and six miRNAs that were down-regulated. Among these candidates, miR-34a and miR-125a, both down-regulated in the high wall shear stress parts, were shown to be potential inhibitors of the metalloproteinase 2 gene. Luciferase reporter assays confirmed that both miRNAs could inhibit the expression of metalloproteinase 2 mRNA in CRL1999 by complementing with its 3' untranslated region. Conversely, immunofluorescence assays showed that inhibition of miR-34a or miR-125a could lead to increased metalloproteinase 2 protein level. On the other hand, both miR-34a and miR-125a were shown to alleviate stretch-induced stimulation of metalloproteinase 2 expression in CRL1999 cells. The results suggested that miR-34a and miR-125a might be implicated in wall shear stress induced aortic pathogenesis due to their apparent regulatory roles in metalloproteinase 2 expression and extracellular matrix remodeling, which are key events in the weakening of aortic walls among BA patients.