4EBP2-regulated protein translation has a critical role in high-fat diet-induced insulin resistance in hepatocytes.

A high-fat diet (HFD) plays a critical role in hepatocyte insulin resistance. Numerous models and factors have been proposed to elucidate the mechanism of palmitic acid (PA)-induced insulin resistance. However, proteomic studies of insulin resistance by HFD stimulation are usually performed under insulin conditions, leading to an unclear understanding of how a HFD alone affects hepatocytes. Here, we mapped the phosphorylation rewiring events in PA-stimulated HepG2 cells and found PA decreased the phosphorylation level of the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2) at S65/T70. Further experiments identified 4EBP2 as a key node of insulin resistance in either HFD mice or PA-treated cells. Reduced 4EBP2 levels increased glucose uptake and insulin sensitivity, whereas the 4EBP2_S65A/T70A mutation exacerbated PA-induced insulin resistance. Additionally, the nascent proteome revealed many glycolysis-related proteins translationally regulated by 4EBP2 such as hexokinase-2, pyruvate kinase PKM, TBC1 domain family member 4, and glucose-6-phosphate 1-dehydrogenase. In summary, we report the critical role of 4EBP2 in regulating HFD-stimulated insulin resistance in hepatocytes.

Targeting estrogen receptor signaling for treating heart failure.

Heart failure (HF) is a significant public health problem worldwide. It has long been noted that premenopausal women, compared to postmenopausal women and men, have lower rates for developing this disease, as well as subsequent morbidity and mortality. This difference has been attributed to estrogen playing a cardioprotective role in these women, though exactly how it does so remains unclear. In this review, we examine the presence of estrogen receptors within the cardiovascular system, as well as the role they play behind the cardioprotective effect attributed to estrogen. Furthermore, we highlight the underlying mechanisms behind their alleviation of HF, as well as possible treatment approaches, such as hormone replacement therapy and exercise regimens, to manipulate these mechanisms in treating and preventing HF.

Superbinder based phosphoproteomic landscape revealed PRKCD_pY313 mediates the activation of Src and p38 MAPK to promote TNBC progression.

Phosphorylation proteomics is the basis for the study of abnormally activated kinase signaling pathways in breast cancer, which facilitates the discovery of new oncogenic agents and drives the discovery of potential targets for early diagnosis and therapy of breast cancer. In this study, we have explored the aberrantly active kinases in breast cancer development and to elucidate the role of PRKCD_pY313 in triple negative breast cancer (TNBC) progression. We collected 47 pairs of breast cancer and paired far-cancer normal tissues and analyzed phosphorylated tyrosine (pY) peptides by Superbinder resin and further enriched the phosphorylated serine/threonine (pS/pT) peptides using TiO2 columns. We mapped the kinases activity of different subtypes of breast cancer and identified PRKCD_pY313 was upregulated in TNBC cell lines. Gain-of-function assay revealed that PRKCD_pY313 facilitated the proliferation, enhanced invasion, accelerated metastasis, increased the mitochondrial membrane potential and reduced ROS level of TNBC cell lines, while Y313F mutation and low PRKCD_pY313 reversed these effects. Furthermore, PRKCD_pY313 significantly upregulated Src_pY419 and p38_pT180/pY182, while low PRKCD_pY313 and PRKCD_Y313F had opposite effects. Dasatinib significantly inhibited the growth of PRKCD_pY313 overexpression cells, and this effect could be enhanced by Adezmapimod. In nude mice xenograft model, PRKCD_pY313 significantly promoted tumor progression, accompanied by increased levels of Ki-67, Bcl-xl and Vimentin, and decreased levels of Bad, cleaved caspase 3 and ZO1, which was opposite to the trend of Y313F group. Collectively, the heterogeneity of phosphorylation exists in different molecular subtypes of breast cancer. PRKCD_pY313 activates Src and accelerates TNBC progression, which could be inhibited by Dasatinib.

Isolation and identification of a pigeonpox virus strain and study on the integration of reticuloendotheliosis virus sequence.

In order to study the integration of reticuloendotheliosis virus (REV) in pigeonpox virus (PPV), we collected suspected pigeonpox disease material, amplified the 4b core protein gene of PPV, the gp90 gene of REV, and the integrated sequence fragments from the end of the ORF201 segment of PPV to the beginning of the LTR of REV, and sequenced these genes. The results showed that a 4b core protein fragment of 332 bp was amplified and identified as pigeonpox virus, which was named SX/TY/LTR 01/2023. Sequence analysis showed that the pigeonpox virus isolate belonged to genotype A2, which was the closest to the domestic CVL strain, with a identity of 99.4%. A band of 1191 bp was amplified from the gp90 gene of REV, named SX/TY/PPV-REV01/2023, and sequence analysis indicated that REV belonged to genotype III. The sequence analysis showed that REV belonged to genotype III, and belonged to the same large branch as the domestic isolates JSRD0701 and LNR0801, with 99.3% identity. The integrated sequence fragment was amplified to a band of 637 bp, which determined that the REV sequence was integrated in the PPV rather than a mixed infection of the two viruses. This indicates that REV was integrated in this isolation of PPV, suggesting that pigeon farms need to prevent reticuloendotheliosis at the same time when preventing pigeonpox.

Analysis of differential metabolites in serum metabolomics of patients with aortic dissection.

BACKGROUND: Pathogenesis and diagnostic biomarkers of aortic dissection (AD) can be categorized through the analysis of differential metabolites in serum. Analysis of differential metabolites in serum provides new methods for exploring the early diagnosis and treatment of aortic dissection. OBJECTIVES: This study examined affected metabolic pathways to assess the diagnostic value of metabolomics biomarkers in clients with AD. METHOD: The serum from 30 patients with AD and 30 healthy people was collected. The most diagnostic metabolite markers were determined using metabolomic analysis and related metabolic pathways were explored. RESULTS: In total, 71 differential metabolites were identified. The altered metabolic pathways included reduced phospholipid catabolism and four different metabolites considered of most diagnostic value including N2-gamma-glutamylglutamine, PC(phocholines) (20:4(5Z,8Z,11Z,14Z)/15:0), propionyl carnitine, and taurine. These four predictive metabolic biomarkers accurately classified AD patient and healthy control (HC) samples with an area under the curve (AUC) of 0.9875. Based on the value of the four different metabolites, a formula was created to calculate the risk of aortic dissection. Risk score = (N2-gamma-glutamylglutamine × -0.684) + (PC (20:4(5Z,8Z,11Z,14Z)/15:0) × 0.427) + (propionyl carnitine × 0.523) + (taurine × -1.242). An additional metabolic pathways model related to aortic dissection was explored. CONCLUSION: Metabolomics can assist in investigating the metabolic disorders associated with AD and facilitate a more in-depth search for potential metabolic biomarkers.

Clinical characteristics and predictors for cardiovascular system involvement in patients with Behçet's disease.

OBJECTIVES: The purpose of this study is to analyse the clinical characteristics of Behçet's disease (BD) patients in China with or without cardiovascular system involvement, and to develop a risk model to identify factors related to cardiovascular involvement in BD. METHODS: This retrospective cohort study, using the information on BD in Shenzhen People's Hospital from January 2000 to December 2021, included 95 patients: BD patients without cardiovascular system involvement (n=63) and with cardiovascular system involvement (n=32). RESULTS: Patients with BD who were males and had a combination of hypertension and a longer duration of disease were more likely to have cardiovascular involvement (p < 0.05). Compared to patients without cardiovascular involvement, manifestations of genital ulcers are rarely observed in those with cardiovascular involvement (60.32% vs. 37.50%, p=0.035). The binary logistic regression analysis found that ascending aortic widening and a history of hypertension were independent risk factors for BD with cardiovascular system involvement (OR=1.277, 95% CI 1.09, 1.495, p=0.002; OR=11.578, 95% CI 1.308, 102.639, p=0.028). The established prediction model indicated that can help to predict the likelihood of cardiovascular involvement in a patient with BD. CONCLUSIONS: Cardiovascular involvement in BD is not at all rare, however, it is often underreported due to a lack of specificity. BD patients who are male, have a history of combined hypertension, and have a long duration of disease should be focused on the presence of combined cardiovascular system involvement, with particular attention to the patient's ascending aortic internal diameter.

Complete genome sequence analysis and biological characteristics of Newcastle disease viruses from different hosts in China.

Newcastle disease (ND) is one of the most serious diseases affecting poultry worldwide. In 2022, we studied two strains of Newcastle disease virus (NDV) from pigeons and magpies identified by PCR and propagated in SPF chicken embryos. The whole genome of the virus was then expanded and its biological characteristics were studied. The results showed that NDV was isolated from pigeons and magpies. Virus present in the allantoic fluid could agglutinate red blood cells and could not be neutralized by serum positive for avian influenza. Sequencing showed that the gene length of the two isolates was 15,191 bp, had high homology and was located in the same branch of the phylogenetic tree, both belonging to genotype VI.1.1. The sequence of 112-117 amino acids in the F gene sequence was 112R-R-Q-K-R-F117, which constituted virulent strain characteristics. The HN gene contained 577 amino acids, which is also consistent with the characteristics of a virulent strain. The results from the study of biological characteristics revealed that the virulence of SX/TY/Pi01/22 was slightly stronger. There were only four different bases in the complete sequence of the two strains. Comprehensive analysis revealed that the G at 11,847 site of the SX/TY/Ma01/22 strain may change to T, leading to translation of amino acids from R to S, thereby weakening viral virulence. Therefore, NDV was transmitted from pigeons to magpies, indicating that the pathogen could be transmitted between poultry and wild birds.

Dynamic adjustable metalens based on a stretchable substrate with a double-layer metal microstructure.

Based on the impedance-matching theory, a double-layer metal structure dynamical focusing cylindrical metalens with a stretchable substrate was designed at the operation frequency of 0.1 THz. The diameter, initial focal length, and NA of the metalens were 80 mm, 40 mm, and 0.7, respectively. The transmission phase of the unit cell structures could cover 0-2π by changing the size of the metal bars, and then the different unit cells were spatially arranged as the designed phase profile for the metalens. When the stretching range of the substrate was about 100%-140%, the focal length changed from 39.3 mm to 85.5 mm, the dynamic focusing range was about 117.6% of the minimum focal length, and the focusing efficiency decreases from 49.2% to 27.9%. Then, by rearranging the unit cell structures, a dynamically adjustable bifocal metalens was numerically realized. Using the same stretching ratio, compared to a single focus metalens, the bifocal metalens can provide a larger focal length control range.

Mapping Tyrosine Kinases Based on a TK Activity-Representing Peptide Library Reveals a Role for SRC in H1975 Drug Resistance.

Tyrosine kinases (TKs) are prominent targets in cancer therapies, and more than 30 TK inhibitors have been approved for treatments in tumors with abnormal TK. Disappointingly, an incomplete response can occur with the long-term use of TK inhibitors, known as cancer drug resistance, which can be caused by kinome reprogramming. Hence, monitoring the status of TKs is crucial for revealing the underlying drug resistance mechanism. Here, we describe a TK activity-representing peptide library-based multiple reaction monitoring (TARPL-MRM) strategy for directly inferring TK activities. The strategy facilitated the assay of 87 human TKs through target quantification of 301 phosphorylation sites. Using this strategy, we demonstrated the heterogeneity of TK activity in different non-small cell lung cancer (NSCLC) cell lines and assessed the response of TK activities to the EGFR inhibitor AZD9291 in NSCLC cells. We found that the acquired resistance of H1975 cells to AZD9291 requires SRC activity, and inhibition of SRC plays potential roles in overcoming this resistance. In summary, our work reveals that this strategy has the potential to become a powerful tool for TK studies, clinical diagnostics, and the discovery of new therapeutic targets.

Effect of pharmacological treatment on outcomes of heart failure with preserved ejection fraction: an updated systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Optimal treatment strategies for patients with heart failure with preserved ejection fraction (HFpEF) remain uncertain. The goal of this study was to compare the treatment effects of different therapeutic agents for patients with HFpEF. METHODS: Randomized controlled trials (RCTs) published before June 2022 were searched from PubMed, Clinical Trials gov, and the Cochrane Central Register databases. Combined odds ratios (ORs) with 95% confidence intervals (CI) were calculated for the primary and secondary outcomes. All-cause death was the primary endpoint and cardiac death, hospitalization for HF, and worsening HF (WHF) events were secondary endpoints in this meta-analysis. RESULTS: Fifteen RCTs including 31,608 patients were included in this meta-analysis. All-cause and cardiac death were not significantly correlated between drug treatments and placebo. Compared with placebo, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor neprilysin inhibitors (ARNIs), and sodium-glucose cotransporter-2 (SGLT2) inhibitors significantly reduced HF hospitalizations [odds ratio (OR) = 0.64, (95% confidence interval (95%CI 0.43 - 0.96), OR = 0.73, (95%CI 0.61 - 0.86), and OR = 0.74, (95%CI 0.66 - 0.83), respectively] without heterogeneity among studies. Only SGLT2 inhibitors significantly reduced WHF events [OR = 0.75, (95%CI 0.67 - 0.83)]. CONCLUSIONS: No treatments were effective in reducing mortality, but ARNIs, ACEIs or SGLT2 inhibitors reduced HF hospitalizations and only SGLT2 inhibitors reduced WHF events for patients with HFpEF.

Renal Safety and Renin-Angiotensin-Aldosterone System Inhibitors in Patients With Contrast Media Exposure: A Multicenter Randomized Controlled Study.

ABSTRACT: There is no clear consensus on the safety of renin-angiotensin-aldosterone system inhibitors in patients with contrast media exposure. We aimed to assess the safety of renin-angiotensin-aldosterone system inhibitors in patients exposed to contrast media at 1-year follow-up. Patients treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) were recruited and randomly divided into 2 groups (1:1 ratio): with ACEI/ARB group (ACEI/ARB continued throughout the study period) and without ACEI/ARB group (ACEI/ARB stopped 24 hours before and continued 48 hours after the procedure). The primary endpoint was contrast-induced acute kidney injury (CI-AKI) and secondary endpoints were major adverse cardiovascular events (MACEs), and the need for renal replacement therapy during hospitalization and at 1-year follow-up. The occurrence rates of CI-AKI were not comparable in the ACEI/ARB group and the without ACEI/ARB group (2.92% and 2.62%, respectively; P = 0.866). No significant between-group differences were found with respect to the frequency of MACEs or renal replacement therapy during hospitalization and at 1-year follow-up. On subgroup analysis, among patients with estimated glomerular filtration rate (eGFR) < 45 mL/min, the incidence of CI-AKI was significantly higher in the ACEI/ARB group [17.95% (14/78) vs. 6.02% (5/83), P = 0.029]. Among patients with eGFR ≥ 45 mL/min, the incidence of CI-AKI was comparable in the 2 groups [0.87% (5/572) vs. 2.12% (12/567), P = 0.094]. The incidence of MACEs and renal replacement therapy was not comparable in the 2 groups, during hospitalization and at 1-year follow-up. ACEI or ARB treatment can safely be continued after exposure to contrast media, but not in patients with eGFR < 45 mL/min.

Detection of Fe3+ and Hg2+ Ions by Using High Fluorescent Carbon Dots Doped With S And N as Fluorescence Probes.

In this paper, carbon quantum dots (N-S-CDs) containing sulfur and nitrogen were synthesized using citric acid and thiourea. The average particle size of N-S-CDs is 8 nm. The N-S-CDs surface contains various of functional groups, which has good water solubility. The fluorescence quantum yield of N-S-CDs is as high as 36.8%. N-S-CDs emits strong blue fluorescence in aqueous solution and has good photostability in neutral and alkaline NaCl solution. N-S-CDs has unique selectivity and high sensitivity to Fe3+ and Hg2+ ions, and the lowest detection limits are 1.4 µM and 0.16 µM, respectively. Under the interference of other metal ions, Fe3+ and Hg2+ ions can still effectively and stably quench the fluorescence of N-S-CDs. In addition, in the detection of actual samples, N-S-CDs can effectively detect Fe3+ and Hg2+ ions in tap water and lake water.

ANGPTL2 aggravates doxorubicin-induced cardiotoxicity via inhibiting DUSP1 pathway.

Angiopoietin-like protein 2 (ANGPTL2) plays versatile roles in various cardiovascular diseases. Its connection to doxorubicin (DOX)-related cardiomyopathy, however, remains elusive. To determine the role of ANGPTL2, an adeno-associated viral vector was used to overexpress ANGPTL2 in the murine heart 4 weeks before DOX treatment (15 mg/kg). Moreover, mice were injected with adenoviral vectors to knock down ANGPTL2 in the myocardium. Echocardiography and hemodynamics were used to determine the cardiac function. The effect of ANGPTL2 and its downstream target were elucidated by applying molecular and biochemical strategies. We found that ANGPTL2 expression was significantly increased in response to DOX stimulation. Moreover, cardiac-specific ANGPTL2 overexpression exacerbated DOX-related cardiac dysfunction, myocardial apoptosis, and oxidative stress. Mechanistically, ANGPTL2 aggravated DOX-induced cardiac injury via inhibiting the dual specificity phosphatase 1 (DUSP1) pathway and DUSP1 overexpression significantly impeded DOX-induced cardiomyopathy in ANGPTL2-overexpressed mice. Altogether, ANGPTL2 aggravated DOX-related cardiac injury by suppressing the DUSP1 pathway.

Phosphorylation-dependent substrate selectivity of protein kinase B (AKT1).

Protein kinase B (AKT1) is a central node in a signaling pathway that regulates cell survival. The diverse pathways regulated by AKT1 are communicated in the cell via the phosphorylation of perhaps more than 100 cellular substrates. AKT1 is itself activated by phosphorylation at Thr-308 and Ser-473. Despite the fact that these phosphorylation sites are biomarkers for cancers and tumor biology, their individual roles in shaping AKT1 substrate selectivity are unknown. We recently developed a method to produce AKT1 with programmed phosphorylation at either or both of its key regulatory sites. Here, we used both defined and randomized peptide libraries to map the substrate selectivity of site-specific, singly and doubly phosphorylated AKT1 variants. To globally quantitate AKT1 substrate preferences, we synthesized three AKT1 substrate peptide libraries: one based on 84 "known" substrates and two independent and larger oriented peptide array libraries (OPALs) of ∼1011 peptides each. We found that each phospho-form of AKT1 has common and distinct substrate requirements. Compared with pAKT1T308, the addition of Ser-473 phosphorylation increased AKT1 activities on some, but not all of its substrates. This is the first report that Ser-473 phosphorylation can positively or negatively regulate kinase activity in a substrate-dependent fashion. Bioinformatics analysis indicated that the OPAL-activity data effectively discriminate known AKT1 substrates from closely related kinase substrates. Our results also enabled predictions of novel AKT1 substrates that suggest new and expanded roles for AKT1 signaling in regulating cellular processes.

BirA*-protein A fusion protein based BioEnhancer amplifies western blot immunosignal.

Western blot (protein immunoblot) is a widely used analytical technique in molecular biology. Utilizing the specific recognizing primary antibody, proteins immobilized on various matrix are investigated by subsequent visualization steps, for example, by the horse radish peroxidase conjugated secondary antibody incubation. Methods to improve the sensitivity in protein identification or quantification are appreciated by biochemists. Herein, we report a new strategy to amplify Western blot signals by constructing a probe with proximal labeling and IgG targeting abilities. The R118G mutation attenuated the biotin-AMP binding affinity of the bacterial biotin ligase BirA*, offering a proximity-dependent labeling ability, which could be used as a signal amplifier. We built a BirA*-protein A fusion protein (BioEnhancer) that specifically binds to IgG and adds biotin tags to its proximal amine groups, enhancing the immunosignal of target proteins. In our experiments, the BioEnhancer system amplified the immunosignal by tenfold compared to the standard western blot. Additionally, our strategy could couple with other signal enhancement methods to further increase the western blot sensitivity.

Intravenous morphine use in acute heart failure increases adverse outcomes: a meta-analysis.

Intravenous morphine is a controversial treatment for acute heart failure (AHF). This study aimed to evaluate and compare the efficacy of intravenous morphine treatment vs. no morphine treatment in AHF patients. Relevant research conducted before June 2020 was retrieved from electronic databases. One unpublished study of our own was also included. Studies were eligible for inclusion if they compared AHF patients treated with intravenous morphine and patients who did not receive morphine. This meta-analysis included three propensity-matched cohorts and two retrospective analyses, involving a total of 149,967 patients (intravenous-morphine group, n = 22,072; no-morphine group, n = 127,895). There was a non-significant increase in the in-hospital mortality in the morphine group (combined odds ratio [OR] = 2.14, 95% confidence interval [CI]: 0.88-5.23, p = 0.095, I2 = 97.1%). However, subgroup analyse showed that the rate of in-hospital mortality with odds of 1.41 times more likely (95% CI: 1.11-1.80, p = 0.005, I2 = 0%) in those receiving vs. not receiving intravenous morphine. No significant correlation was found between intravenous morphine and invasive mechanical ventilation (OR = 2.19, 95% CI: 0.84-5.73, p = 0.10, I2 = 94.2%; subgroup analysis: OR = 2.24, 95% CI: 0.70-7.21, p = 0.176, I2 = 95.1%) or long-term mortality (hazard ratio = 1.15, 95% CI: 0.96-1.34, p = 0.335; I2 = 8.6%). The administration of intravenous morphine to patients with AHF may be related to in-hospital mortality, but not to invasive mechanical ventilation and long-term mortality.

Validity of SOFA score as a prognostic tool for critically ill elderly patients with acute infective endocarditis.

The prognostic value of the sequential organ failure assessment (SOFA) score for critically ill elderly patients with acute infective endocarditis (IE) remains unknown. From January 2015 to December 2019, 111 elderly (≥65 years) patients with acute IE were consecutively included and divided into a low SOFA (<6) group (n = 71) and a high SOFA (≥6) group (n = 40). Endpoints included in-hospital and long-term (12-36 month) mortality. A high SOFA score was related to higher incidence of in-hospital mortality (30.0%) with an area under the curve (AUC) of 0.796. In multivariate analysis, age [odds ratio (OR) = 2.21, 95% confidence intervals (CI), 1.16-6.79, p = 0.040], SOFA ≥6 (OR = 6.38, 95% CI, 1.80-16.89, p = 0.004) and surgical treatment (OR = 0.21, 95% CI, 0.05-0.80, p = 0.021) were predictive of in-hospital mortality. A Cox proportional-hazards model identified age [Hazard ratios (HR)= 2.85, 95% CI, 1.11-7.37, p = 0.031], diabetes mellitus (HR = 3.99, 95% CI, 1.35-11.80, p = 0.013), SOFA ≥6 (OR = 3.38, 95% CI, 1.26-9.08, p = 0.001) and surgical treatment (HR = 0.24, 95% CI, 0.08-0.68, p = 0.021) as predictors of long-term mortality. A high SOFA score predicts a poor outcome including in-hospital and long-term mortality in critically ill elderly patients with acute IE.

Multicenter clinical evaluation of a piezoresistive-MEMS-sensor rapid-exchange pressure microcatheter system for fractional flow reserve measurement.

OBJECTIVES: This multicenter, prospective clinical study investigates whether the microelectromechanical-systems-(MEMS)-sensor pressure microcatheter (MEMS-PMC) is comparable to a conventional pressure wire in fractional flow reserve (FFR) measurement. BACKGROUND: As a conventional tool for FFR measurement, pressure wires (PWs) still have some limitations such as suboptimal handling characteristics and unable to maintain the wire position during pullback assessment. Recently, a MEMS-PMC compatible with any 0.014″ guidewire is developed. Compared with the existing optical-sensor PMC, this MEMS-PMC has smaller profiles at both the lesion crossing and sensor packaging areas. METHODS: Two hundred and forty-two patients with visually 30-70% coronary stenosis were enrolled at four centers. FFR was measured first with the MEMS-PMC, and then with the PW. The primary endpoint was the Bland-Altman mean bias between the MEMS-PMC and PW FFR. RESULTS: From the 224-patient per-protocol data, quantitative coronary angiography showed 17.9% and 55.9% vessels had diameter < 2.5 mm and stenosis >50%, respectively. The two systems' mean bias was -0.01 with [-0.08, 0.06] 95% limits-of-agreement. Using PW FFR≤0.80 as cutoff, the MEMS-PMC per-vessel diagnostic accuracy was 93.4% [95% confidence interval: 89.4-96.3%]. The MEMS-PMC's success rate was similar to that of PW (97.5 vs. 96.3%, p = .43) with no serious adverse event, and its clinically-significant (>0.03) drift rate was 43% less (9.5 vs. 16.7%, p = .014). CONCLUSIONS: Our study showed the MEMS-PMC is safe to use and has a minimal bias equal to the resolution of current FFR systems. Given the MEMS-PMC's high measurement accuracy and rapid-exchange nature, it may become an attractive new tool facilitating routine coronary physiology assessment.

Satisfactory Long-term Outcomes of Thoracic Endovascular Aortic Repair With a Bare Stent for Acute Complicated Type B Aortic Dissections.

PURPOSE: To compare the clinical outcomes after thoracic endovascular aortic repair (TEVAR) with a bare stent to those after TEVAR alone in patients with complicated acute type B aortic dissection (cATBAD). MATERIALS AND METHODS: A prospective, randomized trial was conducted at 2 medical centers in China between 2010 and 2013. Patients with cATBAD were randomly assigned to receive TEVAR with a bare stent (n=42) or TEVAR only (n=42). Patients were scheduled to undergo computed tomography angiography at 3, 6, and 12 months and then annually to 5 years. The primary endpoint was all-cause mortality at 5 years; secondary outcomes were a composite of complications (endoleak, stent-graft-induced new entry, aortic rupture, and secondary intervention) and aortic remodeling at 1 and 5 years. RESULTS: All-cause death occurred in 1 (2.4%) patient in the TEVAR with bare stent group (lung cancer) and 5 patients (11.9%) in the TEVAR group (4 aorta-related) during the 5-year follow-up (log-rank p=0.025). The 1- and 5-year rates of complications and secondary interventions did not differ between the groups. Patients in the TEVAR with bare stent group had higher increases in the thoracic true lumen diameter (19.7±3.6 vs 17.0±6.2 mm, p=0.018) and abdominal true lumen diameter (13.7±4.8 vs 7.2±6.1 mm, p<0.001) and a higher incidence of complete false lumen thrombosis (80.9% vs 47.6%, p=0.005) at the 1-year follow-up. However, no between-group differences in the changes of aortic remodeling parameters were observed between the 1- and 5-year follow-up periods. CONCLUSION: The addition of a distal bare stent to a thoracic stent-graft during TEVAR was associated with significantly improved long-term survival in cATBAD patients vs TEVAR only, likely due to the prevention of true lumen collapse and improvement of complete false lumen thrombosis of the dissected aorta.

Molecular Insights into the Recruiting Between UCP2 and DDX5/UBAP2L in the Metabolic Plasticity of Non-Small-Cell Lung Cancer.

Mitochondrial uncoupling protein 2 (UCP2) is distributed in tumor cells with a link to the support of systemic metabolic deregulation, and the downregulation of UCP2 has been unveiled as a biomarker of oncogenesis and chemoresistance in non-small-cell lung cancer (NSCLC) cells. However, the underlying mechanism of how UCP2 cooperates with other proteins in this metabolic reprogramming remains largely unsolved. We employed a combined computational and experimental strategy to explore into the recruiting of DDX5 with other proteins, and we unraveled the underlying structural mechanisms. We found that recruiting by ATP-dependent RNA helicase DDX5 (DDX5)/ubiquitin-associated protein 2-like (UBAP2L) might help UCP2 to play the pathological roles in NSCLC cells. According to the view of thermodynamics in physics, UCP2 tends to recruit DDX5 rather than UBAP2L, as shown by the ensemble-based docking, molecular dynamics simulations and molecular mechanics generalized Born surface area (MM/GBSA) approach. Cellular immunofluorescence assays further demonstrated that UCP2 associate with DDX5, and the recruiting of DDX5 with UCP2 at least partially contribute to the metabolic plasticity of NSCLCs via the AKT/mTOR pathway. Our study proposed an efficient way for detecting the protein-protein association via the experimentally validated molecular simulation. Our results shed light on the functional annotation of UCP and DDX family proteins in dysregulated metabolism, and the identification of candidate therapeutic targets for NSCLC.