Is axillary artery cannulation necessary in type II hybrid aortic arch repair for acute type A aortic dissection?

INTRODUCTION: Axillary artery cannulation (AAC) has been widely employed in total arch replacement surgeries using the frozen elephant trunk (FET) technique for acute type A aortic dissection (ATAAD), showing better clinical results than femoral artery cannulation (FAC). Nevertheless, in type II hybrid arch repair (HAR), FAC is crucial for lower body perfusion. Hence, it is unclear whether AAC remains necessary or if AAC represents a more advantageous method for initiating cardiopulmonary bypass. METHODS: We conducted a study involving patients diagnosed with ATAAD who underwent type II HAR from August 2021 to December 2022. Demographic baseline and intraoperative data were collected, and the postoperative outcomes of patients receiving FAC only were compared with those receiving AAC. RESULTS: There were no significant differences in baseline demographics between patients who underwent FAC alone (n = 46) and those who underwent AAC (n = 39). Patients who underwent AAC showed a lower incidence of transient neurological dysfunction (TND) post-surgery compared to those who underwent FAC (12.8% vs 32.6%, p = .032). There were no significant differences between the groups in terms of postoperative mortality within 30 days, permanent neurological dysfunction (PND), length of stay in the intensive care unit (ICU) and postoperative ward, duration of mechanical ventilation, and other complications. CONCLUSIONS: Axillary artery cannulation may decrease the incidence of postoperative transient neurological dysfunction (TND) in type II HAR for ATAAD. Nonetheless, studies with larger sample sizes are necessary.

Mitophagy Regulates the Circadian Rhythms by Degrading NR1D1 in Simulated Microgravity and Isolation Environments.

Long-term spaceflight is known to induce disruptions in circadian rhythms, which are driven by a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus, but the underlying molecular mechanisms remain unclear. Here, we developed a rat model that simulated microgravity and isolation environments through tail suspension and isolation (TSI). We found that the TSI environment imposed circadian disruptions to the core body temperature, heart rate, and locomotor-activity rhythms of rats, especially in the amplitude of these rhythms. In TSI model rats' SCNs, the core circadian gene NR1D1 showed higher protein but not mRNA levels along with decreased BMAL1 levels, which indicated that NR1D1 could be regulated through post-translational regulation. The autophagosome marker LC3 could directly bind to NR1D1 via the LC3-interacting region (LIR) motifs and induce the degradation of NR1D1 in a mitophagy-dependent manner. Defects in mitophagy led to the reversal of NR1D1 degradation, thereby suppressing the expression of BMAL1. Mitophagy deficiency and subsequent mitochondrial dysfunction were observed in the SCN of TSI models. Urolithin A (UA), a mitophagy activator, demonstrated an ability to enhance the amplitude of core body temperature, heart rate, and locomotor-activity rhythms by prompting mitophagy induction to degrade NR1D1. Cumulatively, our results demonstrate that mitophagy exerts circadian control by regulating NR1D1 degradation, revealing mitophagy as a potential target for long-term spaceflight as well as diseases with SCN circadian disruption.

Research on Fiber-Optic Optical Coherence Ranging System Based on Laser Frequency Scanning Interferometry.

In this paper, a system for absolute distance measurement is proposed based on laser frequency scanning interferometry (FSI). The system utilizes a digitally tunable laser as the light source and employs synchronized pulses to drive an analog-to-digital converter (ADC) for interference signal acquisition. The frequency domain demodulation for absolute distance measurement is achieved through a three-spectrum line interpolation method based on the Hanning window. The system takes advantage of the spatial filtering characteristics of a single-mode optical fiber and the diffuse reflection properties of light to achieve a high integration of the prism system that forms the interference optical path. The resulting integrated fiber-optic probe is capable of measuring the distance to a non-cooperative target even when oriented at a certain angle with the target. We designed and fabricated a portable prototype. Experimental validation demonstrated that the maximum measurement distance of the system is 73.51 mm with a standard deviation of less than 0.19 µm for optimal measurement results. Even when there is an offset angle, the system maintains good measurement repeatability.

Research on the Algorithm of Position Correction for High-Speed Moving Express Packages Based on Traditional Vision and AI Vision.

The rapid development of the logistics industry poses significant challenges to the sorting work within this sector. The fast and precise identification of moving express parcels holds immense significance for the performance of logistics sorting systems. This paper proposes a motion express parcel positioning algorithm that combines traditional vision and AI-based vision. In the traditional vision aspect, we employ a brightness-based traditional visual parcel detection algorithm. In the AI vision aspect, we introduce a Convolutional Block Attention Module (CBAM) and Focal-EIoU to enhance YOLOv5, improving the model's recall rate and robustness. Additionally, we adopt an Optimal Transport Assignment (OTA) label assignment strategy to provide a training dataset based on global optimality for the model training phase. Our experimental results demonstrate that our modified AI model surpasses traditional algorithms in both parcel recognition accuracy and inference speed. The combined approach of traditional vision and AI vision in the motion express parcel positioning algorithm proves applicable for practical logistics sorting systems.

Urban energy performance improvement policy selection in China based on policy effect prediction: An analysis from the dimensions of economy, environment and well-being.

The environmental pollution and social well-being issue caused by the huge energy consumption in cities reflect the urgency of improving urban energy performance from multiple dimensions of economy, environment, and well-being. As a result, various countries and cities have promulgated a series of policies. However, the complexity of the policies makes the categories and utilities need to be further clarified, and the diseconomy caused by the lag of policy effect evaluation makes the focus of policy implementation need to be clear in advance. Therefore, based on public choice theory, this research follows the idea of "prior analysis" and takes Chinese cities as the research object. Firstly, the collected energy performance improvement policies of Chinese cities were analyzed and classified by the content analysis method, and the main utilities of all policies and the specific utilities of each category were summarized. Based on the multiple dimensions of urban energy performance research (namely, economy, environment and well-being dimensions), this research summarized the policy utilities that help to improve the urban energy performance of each dimension, and also preset the policy utility values. Secondly, the effect prediction model for urban energy performance improvement policies in each dimension was constructed by Back-propagation (BP) neural network. Thirdly, the energy performance of Chinese cities in 2020 measured by Data Envelopment Analysis method was taken as the benchmark value, and the energy performance of Chinese cities in 2025 measured by the policy effect prediction model was taken as the comparison value. According to the results of performance improvement, the energy performance improvement policies of Chinese cities were selected respectively from the dimensions of economy, environment and well-being. This research shows that: the energy performance improvement policies of Chinese cities mainly include six categories, namely energy conservation and emission reduction policies, energy development policies, ecological environmental policies, fiscal and tax policies, industrial policies and economic and social policies. It is needed to focus on ecological environmental policies, fiscal and tax policies and industrial policies to improve urban energy performance from the economic dimension. For the environmental dimension, the key and priority policies are ecological environmental policies. Compared with the economic dimension, the focus of implementing policies adds economic and social policies in the well-being dimension. In the implementation of policies, the differences of energy performance among cities can be reduced through multi-feature analysis of cities or regions, appropriate adjustment of specific measures and targets, and improvement of digital information management of urban energy performance. This research can effectively help cities clarify which policies require higher implementation intensity and attention before and during policy implementation, thereby maximizing multi-dimensional urban energy performance.

C4d as a Screening Tool and an Independent Predictor of Clinical Outcomes in Lupus Nephritis and IgA Nephropathy.

BACKGROUND: As an indispensable marker of complement cascades activation, C4d was confirmed of its crucial role in the pathogenesis of both lupus nephritis (LN) and IgA nephropathy (IgAN). While the studies directly comparing the diagnostic value, and outcomes predicting function of C4d between LN and IgAN are still absent. METHODS: A cohort of 120 LN patients, 120 IgAN patients who were diagnosed by renal biopsy between January 2015 and December 2017 and 24 healthy age matched controls were prospectively analyzed. The patients were followed till December 2020. The outcomes were adverse disease treatment response (disease relapse) and kidney disease progression event (decline of estimated glomerular filtration rate by more than 20% or end-stage kidney disease). The renal C4d deposition proportion and pattern were compared between IgAN and LN patients. In addition, the relationship between renal C4d deposition and disease subtypes, disease relapse as well as disease progression for LN and IgAN patients were also analyzed. RESULTS: The LN, IgAN patients and healthy controls were well matched in ages. The follow-up period was 38.5 (30.3-60.8) months for LN patients and 45.0 (30.5-57.0) months for IgAN patients. 78 patients (65.0%) with LN had renal C4d deposition, compared with only 39 IgAN patients (32.5%) with C4d deposition in renal tissues (P < 0.001). The LN patients shared different renal C4d distribution patterns with IgAN patients. Compared with IgAN patients, the C4d deposition in LN patients was significantly more in renal glomerulus (P < 0.001) and less in renal tubules (P = 0.003). For disease subtypes, renal C4d deposition was especially strong in class V membranous LN and IgAN with tubulointerstitial fibrosis (T1/T2) lesions. Renal C4d deposition was independently correlated with the disease relapse of LN patients (HR = 1.007, P = 0.040), and acted as an independent predictor of disease progression during the follow-up period for IgAN patients (HR = 1.821, P = 0.040). CONCLUSIONS: Renal C4d distribution proportion and pattern differed between LN and IgAN patients. The presence of C4d in renal tissue acted as an independent predictor of relapse for LN patients and disease progression for IgAN patients.

Efficacy of a novel percutaneous pedicle screw fixation and vertebral reconstruction versus the traditional open pedicle screw fixation in the treatment of single-level thoracolumbar fracture without neurologic deficit.

Objective: The aim of this study was to compare the efficacy and safety of a novel percutaneous pedicle screw fixation and vertebral reconstruction (PPSR) vs. that of open pedicle screw fixation (OPSF) in the treatment of thoracolumbar fractures. Methods: This retrospective study enrolled 153 patients who underwent PPSR and 176 patients who received OPSF. Periprocedural characteristics, radiographic parameters, and clinical outcomes were compared between the two groups. Results: The operation duration was 93.843 ± 20.611 in PPSR group and 109.432 ± 11.903 in OPSF group; blood loss was 131.118 ± 23.673 in PPSR group and 442.163 ± 149.701 in OPSF group, incision length was 7.280 ± 1.289 in PPSR group and 14.527 ± 2.893 in OPSF group, postoperative stay was 8.732 ± 1.864 in PPSR group and 15.102 ± 2.117 in OPSF group, and total hospitalization costs were 59027.196 ± 8687.447 in PPSR group and 73144.432 ± 11747.567 in OPSF group. These results indicated that these parameters were significantly lower in PPSR compared with those in OPSF group. No significant difference was observed in the incidence of complications between the two groups. The radiographic parameters including height of the anterior vertebra, Cobb angle, and vertebral wedge angle were better in PPSR group than in OPSF group. Recovery rate of AVH was 0.449 ± 0.079 in PPSR group and 0.279 ± 0.088 in OPSF group. Analysis of clinical results revealed that during postoperative period, the VAS and ODI scores in PPSR group were lower than those in OPSF group. Conclusions: Collectively, these results indicated that PPSR more effectively restored the height of anterior vertebra and alleviated local kyphosis compared with OPSF. Moreover, the VAS and ODI scores in PPSR group were better than those of OPSF group.

The predictive value of urinary kidney injury molecular-1 for long-term graft function in kidney transplant patients: a prospective study.

BACKGROUND: Monitoring allograft function during the early stages is crucial, and therefore requires biomarkers more sensitive than serum creatinine (Scr). Kidney injury molecular-1 (KIM-1) is a potent biomarker; however, disparities exist in the literature concerning its predictive value in allograft function. Therefore, this study aimed to evaluate its predictive value for the long-term prognosis of kidney transplantation patients. METHODS: A prospective study with a cohort comprising 160 patients scheduled for kidney transplantation was conducted to evaluate the predictive power of urinary KIM-1 (uKIM-1) and other renal ischemia-reperfusion biomarkers including urinary L-type fatty acid binding protein (uL-FABP), urinary N-acetyl-ß-D glucosaminidase (uNAG), and urinary neutrophil gelatinase-related lipoprotein (uNGAL) for allograft prognosis. RESULTS: One hundred and forty kidney recipients who were admitted to our hospital between September 2014 and December 2017 with a median follow-up of 30.3 months were included. Thirty-seven recipients had functional delayed graft function (fDGF) in the first week post transplantation, and 42 recipients had progressed to allograft dysfunction [estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2] by the end of the study, while nine recipients deteriorated into allograft loss (defined by the initiation of dialysis). The levels of uKIM-1 in the fDGF group were higher than those in the immediate graft function (IGF) recipients (P<0.05) at 0 hour post transplantation [5.885 (4.420-7.913) vs. 4.605 (3.417-5.653) ng/mmol], and on the first day post transplantation [5.569 (4.181-6.722) vs. 4.002 (3.222-6.488) ng/mmol]. The levels of uL-FABP in the fDGF group were also higher than those in the IGF group at 0 hour post transplantation (89.818±39.332 vs. 69.187±37.926 µg/mmol) and on the third day post transplantation [77.835 (60.368-100.678) vs. 66.841 (28.815-89.783) µg/mmol]. Multivariate Cox regression analysis demonstrated that recipients with higher uKIM-1 levels on the first day post transplantation had a 23.5% increase in the risk of developing fDGF and a 27.3% increase in the risk of prolonged renal allograft dysfunction. CONCLUSIONS: uKIM-1 on the first day post transplantation can predict short-term graft function and is a potent biomarker for the long-term prognosis of graft function.

Improving Prognostic and Chronicity Evaluation of Chronic Kidney Disease with Contrast-Enhanced Ultrasound Index-Derived Peak Intensity.

The capability of contrast-enhanced ultrasound (CEUS) to assess the prognosis and chronicity of chronic kidney disease (CKD) was evaluated in patients diagnosed with CKD in 2014 at Ren Ji Hospital, Shanghai, China. Time-intensity curves and quantitative indexes were created using QLab quantification software. Kidney biopsies were analyzed with α-smooth muscle actin immunohistochemistry. According to the renal chronicity score, patients were divided into four groups: minimal (n = 14), mild (n = 73), moderate (n = 49) and severe (n = 31). Multivariate logistic regression analysis revealed that the derived peak intensity (DPI) was independently associated with the renal chronicity score. Of 167 CKD patients (median follow-up: 30.4 ± 18.7 mo), 31 (18.6%) exhibited CKD progression, with a decline in the glomerular filtration rate of more than 25% or end-stage renal disease. Multivariate Cox regression analysis revealed that a lower DPI was independently associated with CKD progression. This study indicates that DPI is a reliable CEUS parameter for evaluating chronic renal changes and an independent prognostic factor of CKD.

Physiological Acclimatization of the Liver to 180-Day Isolation and the Mars Solar Day.

Physiological changes in humans are evident under environmental conditions similar to those on a Mars mission involving both a space factor (long-term isolation) and a time factor (the Mars solar day). However, very few studies have investigated the response of the liver to those conditions. Serum protein levels, bilirubin levels, aminotransferase activities, blood alkaline phosphatase, gamma-glutamyltransferase, lipid levels, and serum cytokines interleukin-6 and interferon-γ levels were analyzed 30 days before the mock mission; on days 2, 30, 60, 75, 90, 105, 120, 150, and 175 of the mission; and 30 days after the mission, in four subjects in 4-person 180-day Controlled Ecological Life Support System Experiment. Serum protein levels (total protein and globulin) decreased and bilirubin increased under the isolation environment from day 2 and exhibited chronic acclimatization from days 30 to 175. Effects of the Mars solar day were evident on day 75. Blood lipid levels were somewhat affected. No obvious peak in any enzyme level was detected during the mission. The change tendency of these results indicated that future studies should explore whether protein parameters especially globulin could serve as indicators of immunological function exposure to the stress of a Mars mission.

Personalized Epigenome Remodeling Under Biochemical and Psychological Changes During Long-Term Isolation Environment.

It has been reported that several aspects of human health could be disturbed during a long-term isolated environment (for instance, the Mars-500 mission), including psychiatric disorders, circadian disruption, temporal dynamics of gut microbiota, immune responses, and physical-activity-related neuromuscular performance. Nevertheless, the mechanisms underlying these disturbances and the interactions among different aspects of human adaptation to extreme environments remain to be elucidated. Epigenetic features, like DNA methylation, might be a linking mechanism that explains the involvement of environmental factors between the human genome and the outcome of health. We conducted an exploration of personalized longitudinal DNA methylation patterns of the peripheral whole blood cells, profiling six subjects across six sampling points in the Mars-500 mission. Specifically, we developed a Personalized Epigenetic-Phenotype Synchronization Analysis (PeSa) algorithm to explore glucose- and mood-state-synchronized DNA methylation sites, focusing on finding the dynamic associations between epigenetic patterns and phenotypes in each individual, and exploring the underling epigenetic connections between glucose and mood-state disturbance. Results showed that DMPs (differentially methylated-probes) were significantly enriched in pathways related to glucose metabolism (Type II diabetes mellitus pathway), mood state (Long-term depression) and circadian rhythm (Circadian entrainment pathway) during the mission. Furthermore, our data revealed individualized glucose-synchronized and mood-state-synchronized DNA methylation sites, and PTPRN2 was found to be associated with both glucose and mood state disturbances across all six subjects. Our findings suggest that personalized phenotype-synchronized epigenetic features could reflect the effects on the human body, including the disturbances of glucose and mood-states. The association analysis of DNA methylation and phenotypes, like the PeSa analysis, could provide new possibilities in understanding the intrinsic relationship between phenotypic changes of the human body adapting to long-term isolation environmental factors.

Effects of pretransplant peritoneal vs hemodialysis modality on outcome of first kidney transplantation from donors after cardiac death.

BACKGROUND: The effect of pretransplant peritoneal dialysis (PD) or hemodialysis (HD) modality on outcomes of kidney transplantation (KT) for end-stage renal disease (ESRD) is debatable. We evaluated the outcomes these modalities in KT from donor after cardiac death (DCD). METHODS: A cohort of 251 patients on HD, PD or pre-emptive who underwent first KT from DCD between January 2014 and December 2016 were prospectively analyzed to compare for outcomes on recovery of renal function, complications as well as patient and graft survival. The patients were followed till August 2017. Data on 104 HD and 98 PD were available for final comparative outcome analysis, 5 pre-emptive were analyzed as the control group. RESULTS: Both HD and PD group patients were well matched for demographic and baseline characteristics. The follow-up period was 12.5 (3.0, 22.0) months in HD and 12.0 (6.0, 20.0) months in PD patients. Post-transplant renal functions between the two groups showed no differences. Among PD patients, 16 (16.3%) suffered delayed graft function, versus 19 (18.3%) in HD, with no statistical differences (p = 0.715). Complications of acute rejection, infections were comparable between the groups. The patient survival, graft survival and death-censored graft survival were similar for HD and PD after adjusting for other multiple risk factors. CONCLUSIONS: Our results indicate that outcome of first KT from DCD is not affected by pretransplant dialysis modality of PD or HD in aspects of recovery of renal function, complications as well as patient and graft survival.

Target induced aggregation of Ce(III)-based coordination polymer nanoparticles for fluorimetric detection of As(III).

As(III) is the most harmful substance of all over 20 kinds of arsenic compounds. In addition, the trivalent oxidation state of arsenic is not stable, which can be oxidized to pentavalent arsenic. Thus, it is attractive and challenging to sensitively and selectively monitor As(III) concentration, rather than As(V) concentration, in water. However, most of detection techniques suffer from the inability to distinguish As(III) and As(V), or even need specialized personnel and additional equipment. Herein, novel luminescent Ce(III)-based coordination polymer nanoparticles (Ce-CPNs) have been proposed for selective detection of As(III). The Ce-CPNs are dispersive and show a fluorescence peak at 353 nm under excitation at 280 nm. With the presence of As(III), aggregation of Ce-CPNs occurs, resulting in quenching of the fluorescent Ce-CPNs due to the aggregation-caused π-π stacked layers of Ce-CPNs. Under optimal conditions, the detection limit for As(III) is down to 0.7 ppb. In addition, the Ce-CPNs are selective for As(III) over other ions and has been successfully applied for fluorescence sensing of As(III) in environmental water samples.

Luminescence determination of microRNAs based on the use of terbium(III) sensitized with an enzyme-activated guanine-rich nucleotide.

A method is reported for the fluorometric quantitation of microRNA. It is making use of a luminescent probe deribed from terbium(III) ion whose fluorescence is sensitized with a guanine-rich (G-rich) nucleotide. The probe has a large Stokes' shift and strong and sharp emission bands. The assay relies on the wide substrate specificity of terminal deoxynucleotidyl transferase (TdTase), which catalyzes the formation of long G-rich nucleotides when using microRNA primer as a trigger to start the polymerization. The addition of Tb(III) induces the formation of a G-quadruplex from the G-rich nucleotide, and this strongly enhances the green fluorescence of Tb(III) (peaking at 545 nm upon photoexcitation at 290 nm). Specifically, microRNA-21 was chosen as the analyte. The fluorescence intensity of Tb(III) increases linearly in the 1 pM to 1 nM microRNA concentration range, and the detection limit is as low as 0.11 pM. The method can distinguish between family members of microRNA and performs excellently even when applied to extracts of cancer cells. Graphical abstract A fluorometric technique is reported for the determination of microRNA. It is based on signal enhancement based on the sensitization of terbium(III) via a guanine-rich nucleotide sequence. Klenow Fragment exo- (KFexo-) generates DNA sequence at the 3'-OH of microRNA, and terminal deoxynucleotidyl transferase (TdTase) catalyzes the formation of long G-rich nucleotides.

Electrochemical sensor for arsenite detection using graphene oxide assisted generation of prussian blue nanoparticles as enhanced signal label.

An electrochemical sensor was fabricated for arsenite detection using graphene oxide-assisted generation of prussian blue nanoparticles as enhanced redox signal label. The 5'-thiolate-labeled (GT)21-ssDNA was first self-assembled on a gold electrode surface via Au-S bond. Graphene oxide can interact with ssDNA through π-π stacking interaction and facilitate the generation of prussian blue nanoparticles on its surface as an electrochemically active indicator. In the absence of arsenite, plenty of graphene oxide/prussian blue nanoparticles can be adsorbed on the electrode surface to produce a stronger redox signal of prussian blue nanoparticles. While in the presence of arsenite, (GT)21-ssDNA can recognize and combine with arsenite via hydrogen bonds to form (GT)21-ssDNA/arsenite complex with a frizzy structure. The conformational change of (GT)21-ssDNA led to less adsorption of graphene oxide/prussian blue nanoparticles on the electrode surface, resulting in a reduced redox response. The arsenite-induced (GT)21-ssDNA structure switching can be used for sensitive detection of arsenite with a linear range from 0.2 to 500 ppb and a detection limit down to 0.058 ppb. Benefiting from (GT)21-ssDNA containing arsenite recognition sequence, the proposed sensor exhibited excellent specificity against other heavy metal ions. The applicability of the electrochemical biosensor for arsenite assay in real water samples demonstrated the great potential of this strategy for trace arsenite detection in environment.

Ratiometric electrochemical assay for sensitive detecting microRNA based on dual-amplification mechanism of duplex-specific nuclease and hybridization chain reaction.

We propose a ratiometric electrochemical assay for detecting microRNA (miRNA) on the basis of dual-amplification mechanism by using distinguishable electrochemical signals from thionine (Thi) and ferrocene (Fc). The thiol-modified and ferrocene-labeled hairpin capture probes (CP) are first immobilized on an Au electrode via Au-S reaction. The target miRNA hybridizes with CP and unfolding the hairpin structure of CP to form miRNA-DNA duplexes. Then, kamchatka crab duplex specific nuclease (DSN) specifically cleaves the DNA in miRNA-DNA duplexes, leading to the release of miRNA and another cleaves cycle, meanwhile, numerous Fc leaves away from the electrode surface and leads to the signal-off of Fc. The residual fragment on electrode surface acts as a HCR primer to form dsDNA polymers through in situ HCR with the presence of the primer and two probes (HDNA and HDNA'), resulting in the capture of numerous DNA/Au NPs/Thi and the signal-on of Thi. The dual-amplification mechanism significantly amplifies the decrease of Fc signal and the increase of Thi signal for ratiometric readout (IThi/IFc), thus providing a sensitive method for the selective detection of miR-141 with a detection limit down to 11aM. The dual-signal ratiometric outputs have an intrinsic self-calibration to the effects from system, which is promising to be applied in biosensing and clinical diagnosis.

Association of variant in the ADIPOQ gene and functional study for its role in atherosclerosis.

The burden of atherosclerosis is heritable and associated with elevated risk of developing CVDs. Here, we evaluated genetic variants of adiponectin (ADIPOQ) gene, which has important role in anti- atherosclerosis, with risk of atherosclerosis among a large Chinese population. Our results show that rs74577862 was significantly associated with risk of atherosclerosis (OR=2.08; 95%CI=1.48-2.91; P=2.2×10-5). When stratified by atherosclerosis site, rs74577862 was associated with increased risk of both carotid atherosclerosis (OR=2.03; 95%CI=1.35-3.06; P=6.3×10-4) and coronary atherosclerosis (OR=2.11; 95%CI=1.44-3.09; P=1.1×10-4). In addition, we also carried out site-directed mutagenesis and dual-luciferase reporter assay to confirm the positive finding, which presents a significant decrease in luciferase expression for the reconstructed plasmid with rs74577862 A allele in comparison to the one with G allele (P<0.001). Real-time PCR also confirmed the findings above. These results strongly suggest that the functional SNP, ADIPOQ rs74577862 might contribute to atherosclerosis susceptibility.

Post-Translational Modification of Adiponectin Affects Lipid Accumulation, Proliferation and Migration of Vascular Smooth Muscle Cells.

BACKGROUND/AIMS: Adiponectin (Apn) is a multifunctional adipokine that circulates as several oligomeric complexes in the blood stream. Previous reports showed that several conserved lysine residues within the N-terminal collagenous domain of Apn are modified by hydroxylation and glycosylation. Here, we investigated the potential roles of post-translational modifications of Apn on the function of human vascular smooth muscle cells (VSMCs). METHODS: Blood samples of 92 coronary artery disease (CAD) patients and 20 healthy volunteers were collected and total and high molecular weight (HMW) Apn concentration and glycosylation were analyzed. RESULTS: The results revealed that total and HMW Apn derived from blood samples of CAD patients with severe stenosis significantly increased, however the glycosylation of HMW Apn significantly decreased. Functional studies of human VSMCs revealed that glycosylated Apn significantly inhibited the oxidized LDL-induced lipid accumulation, proliferation and migration of VSMCs, whereas non-glycosylated Apn had no inhibitory effects. CONCLUSION: Taken together, these data suggest that glycosylation of Apn is critically involved in regulating function against atherosclerosis by inhibiting lipid accumulation and proliferation and migration of VSMCs.

Renoprotective mechanisms of Astragaloside IV in cisplatin-induced acute kidney injury.

Nephrotoxicity remains a serious adverse effect of cisplatin chemotherapy, limiting its clinical usage. Numerous studies show that oxidative stress and inflammation are closely associated with cisplatin-induced renal damage. Astragaloside IV (AS-IV) has been found to possess antioxidant and anti-inflammation functions. Therefore, we investigated the potential curative effects of AS-IV against cisplatin-induced renal injury and the possible cellular mechanism for activity, both in vitro and in vivo. We found that pretreatment of HK-2 cells with AS-IV could mitigate cisplatin-induced cell damage caused by oxygen-free radicals and the inflammatory response, as evidenced by reduced formation of reactive oxygen species (ROS) and inflammatory cytokines. AS-IV improved cisplatin-induced renal dysfunction and histopathological injury in mice. Additionally, AS-IV enhanced the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). It also inhibited cisplatin-induced overproduction of kidney injury molecule-1 (KIM-1), malondialdehyde (MDA), tumour necrosis factor-α (TNF - α), and interleukin-1ß (IL-1ß) in kidney tissues. We found that the protective effects of AS-IV occurred via activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins and inhibition of nuclear factor-κappaB (NF-κB) activation. Further, small interfering RNA (siRNA) knockdown of Nrf2 abrogated the protective effects of AS-IV against cisplatin-induced oxidative stress and blocked the inhibitory effects of AS-IV on cisplatin-induced NF-κB activation and inflammatory cytokine production. In conclusion, our data suggested that AS-IV attenuated cisplatin-mediated renal injury, and these protective effects might be due to inhibition of both oxidative damage and inflammatory response via activation of Nrf2 system and suppression of NF-κB activation.

Simultaneously electrochemical detection of microRNAs based on multifunctional magnetic nanoparticles probe coupling with hybridization chain reaction.

We report a sensor combining two distinguishable magnetic nanoprobes (DNA1/Fe3O4 NPs/Thi and DNA2/Fe3O4 NPs/Fc) with target-triggered hybridization chain reaction (HCR) strategy for the simultaneous detection of microRNA-141 (miR-141) and microRNA-21 (miR-21). In the presence of targets, the thiol-modified hairpin capture probes (HCP1 and HCP2) specifically hybridize with miR-141 and miR-21 on a gold electrode, leading to the conformation change of HCP1 and HCP2, respectively. The conformation change subsequently triggers HCR to generate plentiful bonding sequences of magnetic nanoprobes. Thus, numerous thionine (Thi) modified DNA1/Fe3O4 NPs/Thi and ferrocene carboxaldehyde (Fc-CHO) modified DNA2/Fe3O4 NPs/Fc are captured by the well-designed HCR, via DNA hybridization respectively, giving rise to the dual magnified response of currents. The increase in the electrochemical currents at different potentials of the two magnetic nanoprobes enables us to simultaneously and quantitatively detect miR-141 and miR-21. Target-triggered HCR increases the amount of captured nanoprobes due to the increasing number of bonding sequences, greatly amplifying the currents of the two magnetic nanoprobes in the presence of targets, and ultimately realizing the dual signal amplification with increased sensitivity. The sensor can be applied for detecting miRNAs in cell lysates, thus, promising to be a clinic diagnosis of cancers by means of simultaneous detection of a variety of miRNA biomarkers.