Transcatheter targeted myocardial restoration using hydrogel-based cell-free compound: Toward an adoptable clinical protocol.

Background: There is a need for a targeted, comprehensive, minimally invasive myocardial restoration treatment aimed at patients with chronic postinfarction heart failure that can provide a sustained effect and be conveniently adopted with transcatheter techniques. Here we evaluated the effectiveness of a platelet-rich plasma hydrogel-based, cell-free therapeutic compound delivered with the aid of a 3-dimensional electromechanical mapping and catheter-based technique (NOGA) in a porcine translational model. Methods: We assessed the feasibility of targeted, minimally invasive transcatheter NOGA-guided injections of the therapeutic compound in myocardial infarction (MI) survivors at 8 weeks post-MI. Results: Animals undergoing NOGA-guided hydrogel injections at 8 weeks post-MI demonstrated a significant improvement of the selected left ventricular parameters at a 12-week follow-up. Compared to nonintervention, the hydrogel-based therapy provided significant improvements in end-diastolic volume (-11.0% ± 11.1% vs 6.3% ± 15.2%; P = .008) and ejection fraction (-9.1% ± 16% vs 12.7% ± 18.6%; P = .009). In the slice closest to the apex, significant differences in scar area were observed; the treatment group demonstrated a smaller mean scar area in the infarcted zone compared with the control group (47.1% ± 7.0% vs 59% ± 8.2%;  P = .013) and a smaller mean scar area in the border zone compared with the saline group (31.4% ± 8.3% vs 42.6% ± 9.0%; P = .016). Conclusions: The study implies a translational potential of the hydrogel-based therapy and should trigger clinical trials focused on establishing a restoration therapy that can be integrated into a clinical protocol.

QTL mapping and candidate gene analysis for yield and grain weight/size in Tartary buckwheat.

BACKGROUND: Grain weight/size influences not only grain yield (GY) but also nutritional and appearance quality and consumer preference in Tartary buckwheat. The identification of quantitative trait loci (QTLs)/genes for grain weight/size is an important objective of Tartary buckwheat genetic research and breeding programs. RESULTS: Herein, we mapped the QTLs for GY, 1000-grain weight (TGW), grain length (GL), grain width (GW) and grain length-width ratio (L/W) in four environments using 221 recombinant inbred lines (XJ-RILs) derived from a cross of 'Xiaomiqiao × Jinqiaomai 2'. In total, 32 QTLs, including 7 for GY, 5 for TGW, 6 for GL, 11 for GW and 3 for L/W, were detected and distributed in 24 genomic regions. Two QTL clusters, qClu-1-3 and qClu-1-5, located on chromosome Ft1, were revealed to harbour 7 stable major QTLs for GY (qGY1.2), TGW (qTGW1.2), GL (qGL1.1 and qGL1.4), GW (qGW1.7 and qGW1.10) and L/W (qL/W1.2) repeatedly detected in three and above environments. A total of 59 homologues of 27 known plant grain weight/size genes were found within the physical intervals of qClu-1-3 and qClu-1-5. Six homologues, FtBRI1, FtAGB1, FtTGW6, FtMADS1, FtMKK4 and FtANT, were identified with both non-synonymous SNP/InDel variations and significantly differential expression levels between the two parents, which may play important roles in Tatary buckwheat grain weight/size control and were chosen as core candidate genes for further investigation. CONCLUSIONS: Two stable major QTL clusters related to grain weight/size and six potential key candidate genes were identified by homology comparison, SNP/InDel variations and qRT‒qPCR analysis between the two parents. Our research provides valuable information for improving grain weight/size and yield in Tartary buckwheat breeding.

Research progress on vegetation restoration of road slopes in China.

China is the largest country in road construction due to rapid economy growth, which results in a large number of exposed slopes. Vegetation restoration of these road slopes has become the dominant method in ecological restoration. We reviewed research progress from three aspects, including key technologies for road slope vegetation restoration, application of vegetation restoration engineering, and factors influencing the vegetation restoration efforts. The slope protection technologies commonly used in road slope vegetation restoration include soil spraying technology, vegetation concrete slope protection technology, thick base material technology, and hydraulic spraying technology. In engineering applications, slope vegetation has the functions such as soil and water conservation, air purification, and landscape restoration. Currently, the most common community configuration is shrub and grass configuration. The main influencing factors of vegetation restoration on road slopes are climate, soil substrate, slope direction, plant species and community configuration used, human factors, and other natural factors (such as hydrology, altitude, microtopography, and wildlife). Future researches should focus on the mechanisms of different factors affecting road slope vegetation restoration, and study ecological substrates and slope protection technologies, plant species and diverse community configuration models suitable for road slope restoration in different climatic regions and site conditions.

Analysis of Dual Combination Therapies Used in Treatment of Hypertension in a Multinational Cohort.

Importance: More than 1 billion adults have hypertension globally, of whom 70% cannot achieve their hypertension control goal with monotherapy alone. Data are lacking on clinical use patterns of dual combination therapies prescribed to patients who escalate from monotherapy. Objective: To investigate the most common dual combinations prescribed for treatment escalation in different countries and how treatment use varies by age, sex, and history of cardiovascular disease. Design, Setting, and Participants: This cohort study used data from 11 electronic health record databases that cover 118 million patients across 8 countries and regions between January 2000 and December 2019. Included participants were adult patients (ages ≥18 years) who newly initiated antihypertensive dual combination therapy after escalating from monotherapy. There were 2 databases included for 3 countries: the Iqvia Longitudinal Patient Database (LPD) Australia and Electronic Practice-based Research Network 2019 linked data set from South Western Sydney Local Health District (ePBRN SWSLHD) from Australia, Ajou University School of Medicine (AUSOM) and Kyung Hee University Hospital (KHMC) databases from South Korea, and Khoo Teck Puat Hospital (KTPH) and National University Hospital (NUH) databases from Singapore. Data were analyzed from June 2020 through August 2021. Exposures: Treatment with dual combinations of the 4 most commonly used antihypertensive drug classes (angiotensin-converting enzyme inhibitor [ACEI] or angiotensin receptor blocker [ARB]; calcium channel blocker [CCB]; ß-blocker; and thiazide or thiazide-like diuretic). Main Outcomes and Measures: The proportion of patients receiving each dual combination regimen, overall and by country and demographic subgroup. Results: Among 970 335 patients with hypertension who newly initiated dual combination therapy included in the final analysis, there were 11 494 patients from Australia (including 9291 patients in Australia LPD and 2203 patients in ePBRN SWSLHD), 6980 patients from South Korea (including 6029 patients in Ajou University and 951 patients in KHMC), 2096 patients from Singapore (including 842 patients in KTPH and 1254 patients in NUH), 7008 patients from China, 8544 patients from Taiwan, 103 994 patients from France, 76 082 patients from Italy, and 754 137 patients from the US. The mean (SD) age ranged from 57.6 (14.8) years in China to 67.7 (15.9) years in the Singapore KTPH database, and the proportion of patients by sex ranged from 24 358 (36.9%) women in Italy to 408 964 (54.3%) women in the US. Among 12 dual combinations of antihypertensive drug classes commonly used, there were significant variations in use across country and patient subgroup. For example starting an ACEI or ARB monotherapy followed by a CCB (ie, ACEI or ARB + CCB) was the most commonly prescribed combination in Australia (698 patients in ePBRN SWSLHD [31.7%] and 3842 patients in Australia LPD [41.4%]) and Singapore (216 patients in KTPH [25.7%] and 439 patients in NUH [35.0%]), while in South Korea, CCB + ACEI or ARB (191 patients in KHMC [20.1%] and 1487 patients in Ajou University [24.7%]), CCB + ß-blocker (814 patients in Ajou University [13.5%] and 217 patients in KHMC [22.8%]), and ACEI or ARB + CCB (147 patients in KHMC [15.5%] and 1216 patients in Ajou University [20.2%]) were the 3 most commonly prescribed combinations. The distribution of 12 dual combination therapies were significantly different by age and sex in almost all databases. For example, use of ACEI or ARB + CCB varied from 873 of 3737 patients ages 18 to 64 years (23.4%) to 343 of 2292 patients ages 65 years or older (15.0%) in South Korea's Ajou University database (P for database distribution by age < .001), while use of ACEI or ARB + CCB varied from 2121 of 4718 (44.8%) men to 1721 of 4549 (37.7%) women in Australian LPD (P for drug combination distributions by sex < .001). Conclusions and Relevance: In this study, large variation in the transition between monotherapy and dual combination therapy for hypertension was observed across countries and by demographic group. These findings suggest that future research may be needed to investigate what dual combinations are associated with best outcomes for which patients.

Latexin deficiency attenuates adipocyte differentiation and protects mice against obesity and metabolic disorders induced by high-fat diet.

Obesity is a risk factor for many chronic diseases, and is associated with increased incidence rate of type 2 diabetes, hypertension, dyslipidemia and cardiovascular diseases. Adipocyte differentiation play critical role during development of obesity. Latexin (LXN), a mammalian carboxypeptidase inhibitor, plays important role in the proliferation and differentiation of stem cells, and highlights as a differentiation-associated gene that was significantly downregulated in prostate stem cells and whose expression increases through differentiation. However, it is unclear whether LXN is involved in adipocyte differentiation. The aim of this study was to evaluate the role of LXN on adipocyte differentiation, as well as its effects on high fat-induced obesity and metabolic disorders. In this study, we determine the expression of LXN in adipose tissue of lean and fat mice by Western blot, qPCR and immunohistochemistry. We found that LXN in fat tissues was continuous increased during the development of diet-induced obesity. We fed wild-type (WT) and LXN-/-mice with high-fat diet (HFD) to study the effects of LXN on obesity and related metabolic functions. We found that mice deficient in LXN showed resistance against high-fat diet (HFD)-induced obesity, glucose tolerance, insulin tolerance and hepatic steatosis. In vitro studies indicated that LXN was highly induced during adipocyte differentiation, and positively regulated adipocyte differentiation and adipogenesis in 3T3-L1 cells and primary preadipocytes. Functional analysis revealed that the expression of LXN was positively regulated by mTOR/RXR/PPARɤ signaling pathway during the differentiation of adipocytes, while LXN deletion decreased the protein level of PPARɤ in adipocyte through enhancing FABP4 mediated ubiquitination, which led to impaired adipocyte differentiation and lipogenesis. Collectively, our data provide evidence that LXN is a key positive regulator of adipocyte differentiation, and therapeutics targeting LXN could be effective in preventing obesity and its associated disorders in clinical settings.

Sleep apnea and diabetes mellitus are independently associated with cardiovascular events and hospitalization for heart failure after coronary artery bypass grafting.

The relative and combined effects of sleep apnea with diabetes mellitus (DM) on cardiovascular outcomes in patients undergoing coronary artery bypass grafting (CABG) remain unknown. In this secondary analysis of data from the SABOT study, 1007 patients were reclassified into four groups based on their sleep apnea and DM statuses, yielding 295, 218, 278, and 216 patients in the sleep apnea (+) DM (+), sleep apnea (+) DM (-), sleep apnea (-) DM (+), and sleep apnea (-) DM (-) groups, respectively. After a mean follow-up period of 2.1 years, the crude incidence of major adverse cardiac and cerebrovascular event was 18% in the sleep apnea (+) DM (+), 11% in the sleep apnea (+) DM (-), 13% in the sleep apnea (-) DM (+), and 5% in the sleep apnea (-) DM (-) groups. Using sleep apnea (-) DM (-) as the reference group, a Cox regression analysis indicated that sleep apnea (+) and DM (+) independently predicted MACCEs (adjusted hazard ratio, 3.2; 95% confidence interval, 1.7-6.2; p = 0.005) and hospitalization for heart failure (adjusted hazard ratio, 12.6; 95% confidence interval, 3.0-52.3; p < 0.001). Sleep apnea and DM have independent effects on the prognosis of patients undergoing CABG.Clinical trial registration: ClinicalTrials.gov identification no. NCT02701504.

Sleep apnoea and cardiovascular outcomes after coronary artery bypass grafting.

OBJECTIVE: Patients with advanced coronary artery disease are referred for coronary artery bypass grafting (CABG) and it remains unknown if sleep apnoea is a risk marker. We evaluated the association between sleep apnoea and major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing non-emergent CABG. METHODS: This was a prospective cohort study conducted between November 2013 and December 2018. Patients from four public hospitals referred to a tertiary cardiac centre for non-emergent CABG were recruited for an overnight sleep study using a wrist-worn Watch-PAT 200 device prior to CABG. RESULTS: Among the 1007 patients who completed the study, sleep apnoea (defined as apnoea-hypopnoea index ≥15 events per hour) was diagnosed in 513 patients (50.9%). Over a mean follow-up period of 2.1 years, 124 patients experienced the four-component MACCE (2-year cumulative incidence estimate, 11.3%). There was a total of 33 cardiac deaths (2.5%), 42 non-fatal myocardial infarctions (3.7%), 50 non-fatal strokes (4.9%) and 36 unplanned revascularisations (3.2%). The crude incidence of MACCE was higher in the sleep apnoea group than the non-sleep apnoea group (2-year estimate, 14.7% vs 7.8%; p=0.002). Sleep apnoea predicted the incidence of MACCE in unadjusted Cox regression analysis (HR 1.69; 95% CI 1.18 to 2.43), and remained statistically significant (adjusted HR 1.57; 95% CI 1.09 to 2.25), after adjustment for age, sex, body mass index, left ventricular ejection fraction, diabetes mellitus, hypertension, chronic kidney disease and excessive daytime sleepiness. CONCLUSION: Sleep apnoea is independently associated with increased MACCE in patients undergoing CABG. TRIAL REGISTRATION NUMBER: NCT02701504.

Down-regulation of MAP2K1 by miR-539 inhibits hepatocarcinoma progression.

Liver cancer has been considered as one of the major leading causes of cancer-related mortality. The incidence of liver cancer tends to increase in less developed regions. Increasing evidences have demonstrated that mircoRNAs (miRNAs) play crucial roles in the modulation of tumor growth and progression. Whereas, the functional role of miR-539 in hepatocellular carcinoma (HCC) is not well established. In our present study, we sought to explore biological role of miR-539 in HCC progression. qRT-PCR was utilized to evaluate the expression level of miR-539. Immunoblotting analysis, qRT-PCR and luciferase reporter assays were used for the identification of the potential target of miR-539. Proliferation, migration and invasion assays and flow cytometric were performed to assess the biological functional role of miR-539. The molecular signaling pathways related to the integration of miR-539 were also evaluated. MiR-539 was reduced in human HCC. Mitogen-activated protein kinase 1, also known as MAP2K1 was verified as the target of miR-539. Overexpression of miR-539 inhibited migration, invasion and cell proliferation, while apoptosis rate was increased. Knockdown or overexpression of MAP2K1 in HCC cell transfected with ag-miR-539 or in-miR-539 indicated that miR-539 suppresses the progression of HCC by directly targeting and regulating MAP2K1. Our results reveal that miR-539 might be a tumor suppressor in HCC, supporting a potential target for advanced therapeutic strategy for this disease.

Epidermal growth factor receptor-targeted immune magnetic liposomes capture circulating colorectal tumor cells efficiently.

AIM: To compare the capacity of newly developed epidermal growth factor receptor (EGFR)-targeted immune magnetic liposomes (EILs) vs epithelial cell adhesion molecule (EpCAM) immunomagnetic beads to capture colorectal circulating tumor cells (CTCs). METHODS: EILs were prepared using a two-step method, and the magnetic and surface characteristics were confirmed. The efficiency of capturing colorectal CTCs as well as the specificity were compared between EILs and EpCAM magnetic beads. RESULTS: The obtained EILs had a lipid nanoparticle structure similar to cell membrane. Improved binding with cancer cells was seen in EILs compared with the method of coupling nano/microspheres with antibody. The binding increased as the contact time extended. Compared with EpCAM immunomagnetic beads, EILs captured more CTCs in peripheral blood from colorectal cancer patients. The captured cells showed consistency with clinical diagnosis and pathology. Mutation analysis showed same results between captured CTCs and cancer tissues. CONCLUSION: EGFR antibody-coated magnetic liposomes show high efficiency and specificity in capturing colorectal CTCs.

Carbon nanotube signal amplification for ultrasensitive fluorescence polarization detection of DNA methyltransferase activity and inhibition.

A versatile sensing platform based on multiwalled carbon nanotube (MWCNT) signal amplification and fluorescence polarization (FP) is developed for the simple and ultrasensitive monitoring of DNA methyltransferase (MTase) activity and inhibition in homogeneous solution. This method uses a dye-labeled DNA probe that possess a doubled-stranded DNA (dsDNA) part for Mtase and its corresponding restriction endonuclease recognition, and a single-stranded DNA part for binding MWCNTs. In the absence of MTase, the dye-labeled DNA is cleaved by restriction endonuclease, and releases very short DNA carrying the dye that cannot bind to MWCNTs, which has relatively small FP value. However, in the presence of MTase, the specific recognition sequence in the dye-labeled DNA probe is methylated and not cleaved by restriction endonuclease. Thus, the dye-labeled methylated DNA product is adsorbed onto MWCNTs via strong π-π stacking interactions, which leads to a significant increase in the FP value due to the enlargement of the molecular volume of the dye-labeled methylated DNA/MWCNTs complex. This provides the basic of a quantitative measurement of MTase activity. By using the MWCNT signal amplification approach, the detection sensitivity can be significantly improved by two orders of magnitude over the previously reported methods. Moreover, this method also has high specificity and a wide dynamic range of over five orders of magnitude. Additionally, the suitability of this sensing platform for MTase inhibitor screening has also been demonstrated. This approach may serve as a general detection platform for sensitive assay of a variety of DNA MTases and screening potential drugs.

Virtual-image generation in 360-degree viewable image-plane disk-type multiplex holography.

By shifting the rotational axis of the recording film and recording the individual image-plane holograms in reversed sequence with the real-image holographic system [Opt. Express 18, 14012 (2010)], the disk-type multiplex hologram can be made to generate virtual image for walk-around viewing if the recording reference source point is maintained on the symmetry axis of hologram disk. Theoretical formulation and numerical simulation show the characteristics of the reconstructed image. Experimental results are also shown for qualitative comparison.

A gold nanoparticle-enhanced fluorescence polarization biosensor for amplified detection of T4 polynucleotide kinase activity and inhibition.

A novel fluorescence polarization (FP) nanosensor based on λ exonuclease cleavage reaction and FP enhancement effect of gold nanoparticles (AuNPs) has been developed for the detection of T4 polynucleotide kinase activity and inhibition. This FP sensor exhibits higher detection sensitivity over traditional fluorescence sensors by two orders of magnitude.