Transcription factor NnMYB5 controls petal color by regulating GLUTATHIONE S-TRANSFERASE2 in Nelumbo nucifera.

Lotus (Nelumbo spp.) is an important aquatic ornamental genus in the family Nelumbonaceae comprising only 2 species: Nelumbo lutea with yellow flowers and Nelumbo nucifera with red or white flowers. The petal color variations between these 2 species have previously been associated with the potential activities of FLAVONOL SYNTHASE (FLS) and MYB5. However, the underlying genetic mechanisms of flower color divergence within the N. nucifera species remain unclear. Here, quantitative trait locus mapping led to the identification of MYB5, a candidate gene controlling petal color in N. nucifera. Genotyping of 213 natural lotus accessions revealed an 80 kb presence/absence variant (PAV) of the NnMYB5 gene that is associated with petal color variation. Transcriptome analysis, dual-luciferase, and yeast 1-hybrid assays showed that NnMYB5 could directly activate the anthocyanin transporter gene GLUTATHIONE S-TRANSFERASE2 (NnGST2). Heterologous expression of NnGST2 in Arabidopsis (Arabidopsis thaliana) and its overexpression in lotus petals induced anthocyanin accumulation. Deletion of the 80 kb PAV within NnMYB5 inactivated NnGST2 expression and blocked anthocyanin accumulation in white N. nucifera petals. In contrast, the anthocyanin deficiency of N. lutea occurred due to pseudogenized NlMYB5 alleles. Our results establish a regulatory link between NnMYB5 and NnGST2 in petal anthocyanin accumulation and demonstrate the independent mechanisms controlling flower coloration in Nelumbo.

Deep-learning-based cross-talk free and high-security compressive encryption with spatially incoherent illumination.

Incoherent optical cryptosystem is promising for its immunity against coherent noise and insensitivity to misalignment, and compressive encryption is desirable considering the increasingly demand on the exchange of encrypted data via Internet. In this paper, we propose a novel optical compressive encryption approach with spatially incoherent illumination based on deep learning (DL) and space multiplexing. For encryption, the plaintexts are individually sent to the scattering-imaging-based encryption (SIBE) scheme where they are transformed to scattering images with noise appearances. Afterwards, these images are randomly sampled and then integrated into a single package (i.e., ciphertext) by space multiplexing. The decryption is basically the inverse of the encryption, while it involves an ill-posed problem (i.e., recovering the noise-like scattering image from its randomly sampled version). We demonstrated that such a problem can be well resolved by DL. The proposal is radically free from the cross-talk noise existing in many current multiple-image encryption schemes. Also, it gets rid of the linearity bothering the SIBE and is hence robust against the ciphertext-only attack based on phase retrieval algorithm. We present a series of experimental results to confirm the effectiveness and feasibility of the proposal.

Carboxybetaine-Based Zwitterionic Polymer Nanogels with Long Blood Circulation for Cancer Therapy.

Given the advantages of antifouling capacity and good biocompatibility, zwitterionic polymers have been profoundly applied for drug delivery to improve the pharmacokinetics profile. Here, a zwitterionic polymer (poly (carboxybetaine methacrylate) (PCBMA)) nanogel was fabricated by one-step reflux precipitation polymerization for doxorubicin (DOX) loading. The obtained nanogels display favorable long blood circulation without priming immune responses as a result of the introduction of the zwitterionic group. Meanwhile, the disulfide bonds deriving from the crosslinker endow nanogels with excellent glutathione-responsive degradation and sufficient drug release under a reduction environment. The carboxylate groups originating from carboxybetaine provide modification sites to conjugate with fluorescent dye to achieve labeling and biodistribution tracking. Overall, under the significantly prolonging circulation and enhanced tumor accumulation through passive targeting, DOX-loaded PCBMA nanogels show a noticeable tumor inhibition effect in mouse colorectal cancer models, which may provide a delivery vehicle with great promise in cancer therapy.

Metabolite profiling and screening of callus browning-related genes in lotus (Nelumbo nucifera).

Callus browning is a major drawback to lotus callus proliferation and regeneration. However, the underlying mechanism of its formation remains largely unknown. Herein, we aimed to explore the metabolic and molecular basis of lotus callus browning by combining histological staining, high-throughput metabolomics, and transcriptomic assays for lotus callus at three browning stages. Histological stained brown callus cross sections displayed severe cell death symptoms, accompanied by an obvious accumulation of polyphenols and lignified materials. Widely targeted metabolomics revealed extensively decreased accumulation of most detected flavonoids and benzylisoquinoline alkaloids (BIAs), as well as a few phenolic acids, amino acids and their derivatives in callus with browning symptoms. Conversely, the contents of most detected tannins were significantly increased. Subsequent comparative transcriptomics identified a set of differentially expressed genes (DEGs) associated with the biosynthesis and regulation of flavonoids and BIAs in lotus. Notably, callus browning was coupled with significantly up-regulated expression of two polyphenol oxidase (PPO) and 17 peroxidase (POD) encoding genes, while the expression of ethylene associated genes remained at marginal levels. These results suggest that lotus callus browning is primarily controlled at the level of metabolism, wherein the oxidation of flavonoids and BIAs is crucially decisive.

Urolithin A ameliorates obesity-induced metabolic cardiomyopathy in mice via mitophagy activation.

Metabolic cardiomyopathy (MC) is characterized by intracellular lipid accumulation and utilizing fatty acids as a foremost energy source, thereby leading to excess oxidative stress and mitochondrial dysfunction. There is no effective therapy available yet. In this study we investigated whether defective mitophagy contributed to MC and whether urolithin A (UA), a naturally occurring microflora-derived metabolite, could protect against MC in experimental obese mice. Mice were fed high fat diet for 20 weeks to establish a diet-induced obese model. We showed that mitochondrial autophagy or mitophagy was significantly downregulated in the heart of experimental obese mice. UA (50 mg·kg-1·d-1, for 4 weeks) markedly activated mitophagy and ameliorated MC in obese mice by gavage. In PA-challenged H9C2 cardiomyocytes, UA (5 µM) significantly increased autophagosomes and decreased autolysosomes. Furthermore, UA administration rescued PINK1/Parkin-dependent mitophagy and relieved mitochondrial defects in the heart of obese mice, which led to improving cardiac diastolic function and ameliorating cardiac remodelling. In PA-challenged primarily isolated cardiomyocytes, both application of mitophagy inhibitor Mdivi-1 (15 µM) and silencing of mitophagy gene Parkin blunted the myocardial protective effect of UA. In summary, our data suggest that restoration of mitophagy with UA ameliorates symptoms of MC, which highlights a therapeutic potential of UA in the treatment of MC.

Assessment of agricultural pesticide inert ingredient transport following modeling approach: Case study of two formulation agents in Sacramento River watershed.

This research provides the first assessment of the environmental fate and transport of agricultural pesticide formulation agents following a dynamic modeling approach. Two formulation agents of toxicological concern, Naphthalene and Solvent Naphtha (Petroleum), Heavy Aromatic, were simulated from their usage in commercially-applied pesticides. The Soil and Water Assessment Tool (SWAT) was applied to simulate these formulation agents during 2011-2014 in the agriculturally intensive Sacramento River watershed. The sensitivity and uncertainty of some key parameters were analyzed. The predicted transport masses of these formulation agents in surface water were strongly associated with rainfall. While predicted transport masses were quite small at the watershed scale (<0.01% of applied masses), they were 26-31 times higher in certain locales at the subbasin level. Since many formulation agents are widely used in pesticides throughout this and other agriculturally impacted watersheds, their potential risks in the environment need more thorough investigation by modeling and monitoring, especially for areas with heavy usage.

Identification of QTLs and a putative candidate gene involved in rhizome enlargement of Asian lotus (Nelumbo nucifera).

KEY MESSAGE: QTL mapping studies identified three reliable QTLs of rhizome enlargement in lotus. NnBEL6 located within the confidence interval of the major QTL cqREI-LG2 is a key candidate gene enhancing rhizome enlargement. Lotus (Nelumbo) is perennial aquatic plant with nutritional, pharmacological, and ornamental significance. Rhizome is an underground lotus stem that acts as a storage organ and as a reproductive tissue for asexual production. The enlargement of lotus rhizome is an important adaptive strategy for surviving the cold winter. The aims of this study were to identify quantitative trait loci (QTLs) for rhizome enlargement traits including rhizome enlargement index (REI) and number of enlarged rhizome (NER), and to uncover their associated candidate genes. A high-density genetic linkage map was constructed, consisting of 2935 markers binned from 236,840 SNPs. A total of 14 significant QTLs were detected for REI and NER, which explained 6.7-22.3% of trait variance. Three QTL regions were repeatedly identified in at least 2 years, and a major QTL, designated cqREI-LG2, with a rhizome-enlargement effect and about 20% of the phenotypic contribution was identified across the 3 climatic years. A candidate NnBEL6 gene located within the confidence interval of cqREI-LG2 was considered to be putatively involved in lotus rhizome enlargement. The expression of NnBEL6 was exclusively induced by rhizome swelling. Sequence comparison of NnBEL6 among lotus cultivars revealed a functional Indel site in its promoter that likely initiates the rhizome enlargement process. Transgenic potato assay was used to confirm the role of NnBEL6 in inducing tuberization. The successful identification QTLs and functional validation of NnBEL6 gene reported in this study will enrich our knowledge on the genetic basis of rhizome enlargement in lotus.

Strain Sensing Behavior of 3D Printable and Wearable Conductive Polymer Composites Filled with Silane-Modified MWCNTs.

3D printing of conductive polymers is an attractive technique for achieving high flexibility, wearability, and sensing characteristics without geometrical limitations. However, there is an urgent need to integrate printability, conductivity, and sensing capability. Herein, a conductive polymer ink for 3D printing that combines the desirable features of high electrical conductivity, flexible stretchability, and strain-sensing monitoring is prepared. The ink matrix is polydimethylsiloxane and synergistically enhanced by acetylene carbon black (ACB) and multi-walled carbon nanotubes (MWCNTs) (silane or un-silane-modified). The inks are screened step-by-step to explore their printability, rheology, mechanical properties, and electrical performance upon loading. The formation of an electrically conductive network, electrical properties upon tensile load, and strain sensing stability under cyclic stretching are investigated intensively. It is demonstrated that conductive polymers filled by ACB and silane-modified, MWCNTs (MWCNTs-MTES) possess superior printability, stretchability, conductivity, and strain sensing behaviors. Finally, a flexible wearable strain-sensing skin patch is printed, and it successfully records joint motion signals on human fingers, wrists, and elbows with good stability and repeatability. Those results show the extent of potential applications in healthcare and motion monitoring fields. This work provides an efficient and simple route to achieve comfortably wearable and high-performance strain sensors.

Role of Sonazoid-based contrast-enhanced ultrasonography in the microwave ablation of primary hyperparathyroidism.

OBJECTIVES: This study aimed to determine the performance of Sonazoid-based contrast-enhanced ultrasound (CEUS) in the microwave ablation (MWA) of primary hyperparathyroidism (pHPT). METHODS: Forty patients with pHPT were enrolled and treated with percutaneous ultrasound (US)-guided MWA assisted by CEUS. All patients underwent immediate CEUS examinations following MWA. On post-ablation day 1, patients who did not display a decrease in intact parathyroid hormone (iPTH) levels to the norm were examined by CEUS to evaluate an incomplete ablation. We compared the serum iPTH and calcium levels and the nodule volumes before and after MWA. The complications were evaluated during and after treatment. RESULTS: Immediately following MWA, CEUS demonstrated complete ablation with all 44 parathyroid nodules. On post-ablation day 1, five nodules in five patients displayed annular enhancement around the ablation zone on CEUS. The average maximum diameters of the nodules and the ablation zone were 1.09 ± 0.28 cm and 1.36 ± 0.23 cm, respectively. An ablation zone larger than the primary lesion (p < 0.05) generated a higher rate of complete ablation. Compared with pre-MWA, serum iPTH and calcium levels were significantly improved. Treatment success was achieved in 38 patients (95%). Hoarseness was a major complication in six patients (15%); however, it improved spontaneously within 1-4 months. We observed two recurrences (2/40, 5%) at 9 months and 11 months following MWA, respectively. CONCLUSION: US-guided percutaneous MWA assisted by CEUS for pHPT is an effective and safe therapy. CEUS can avoid operative failure and improve the cure rate.

Spatial variation of heavy metals and their ecological risk and health risks to local residents in a typical e-waste dismantling area of southeastern China.

There is an increasing concern that soils in e-waste recycling regions are severely contaminated by unregulated e-waste dismantling activities. Hence, it is urgent to reveal the spatial variation of hazardous elements in arable lands close to e-waste stacking and dismantling areas and their potential risks to human beings. We collected 349 topsoil samples based on an intensive grid of 100 m × 100 m in southeastern China. The average concentrations of heavy metals were 1.25 (Cd), 35.44 (Ni), 77.68 (Cr), 77.38 (Pb), 122.14 (Cu), 203.39 (Zn), 0.21 (Hg), and 4.74 (As) mg kg-1, respectively. Compared to the risk screening values of hazardous elements in Chinese agricultural land, Cd and Cu were severely accumulated in the soils. The results of ecological risk analysis revealed that Cd posed the crucial risk among the studied elements. However, the levels of non-carcinogenic and carcinogenic risk were still within the acceptable quantity for adults. Spatial distribution by kriging interpolation displayed that the heavy metals were mainly distributed close to e-waste dismantling sites.

The effects of levothyroxine combined with methimazole on the clinical efficacy of hyperthyroidism treatment.

To investigate the effects of levothyroxine combined with methimazole on the clinical efficacy of hyperthyroidism treatment. A total of 102 patients with hyperthyroidism admitted to our hospital from January 2018 to June 2020 were selected and randomly assigned into the combination group (levothyroxine combined with methimazole) and the control group (methimazole treatment alone). 3 months after treatment, the two groups were compared with regard to clinical efficacy, changes in ultrasound findings, the thyroid hormones, and serum indexes and the adverse reactions rate. The combination group (98.04%) outperformed the control group (86.27%) in total effective rate, and the overall efficacy garnered the similar result. After treatment, the combination group showed advantages in thyroid hormone level, serum index level, thyroid volume, superior thyroid artery diameter, and maximum blood flow rate when compared with those of the control group (P<0.05). As for the adverse reactions rate, the combination group was superior to the control group (3.92%vs15.69%) (P<0.05). Levothyroxine combined with methimazole promotes the clinical efficacy of hyperthyroidism treating, reduces thyroid volume and the diameter of superior thyroid artery, enhances the patient's thyroid function and serum index, with higher safety profile.

The long noncoding RNA PDK1-AS/miR-125b-5p/VEGFA axis modulates human dermal microvascular endothelial cell and human umbilical vein endothelial cell angiogenesis after thermal injury.

Our previous study confirmed the critical role of miR-125b and vascular endothelial growth factor (VEGF) in burn wound repair., The present study was aimed to identify the role of long noncoding RNAs (lncRNAs) related to the function of miR-125b and VEGF in burn wound repair and the underlying mechanism. First, we found that lncRNA PDK1-AS and VEGFA expression was significantly increased in heat-denatured dermal tissue samples and in human dermal microvascular endothelial cells (HDMECs) and human umbilical vein endothelial cells (HUVECs) after thermal injury. PDK1-AS knockdown significantly inhibited cell viability, cumulative tube length, cell migratory ability, and cell invasion of thermally injured HDMECs and HUVECs. PDK1-AS knockdown decreased VEGFA protein levels in HDMECs and HUVECs. While overexpression of PDK1-AS showed the opposite effects. Online tools prediction and luciferase assay confirmed that miR-125b-5p targeted PDK1-AS and VEGFA 3'-untranslated region. miR-125b-5p inhibition significantly increased VEGFA protein levels and enhanced viability, cumulative tube length, migratory ability, and invasion of HUVECs and HDMECs. Furthermore, the effects of PDK1-AS knockdown on VEGFA protein levels in the two cell lines were partially reversed by miR-125b-5p inhibition. Finally, in the tissue samples, PDK1-AS and VEGFA expression was increased, while miR-125b-5p expression was decreased in heat-denatured dermal tissues; the expression of miR-125b-5p had a negative correlation with PDK1-AS and VEGFA, respectively, and PDK1-AS and VEGFA were positively correlated with each other in tissue samples. In conclusion, PDK1-AS relieves miR-125b-5p-induced inhibition on VEGFA by acting as a endogenous RNA, therefore modulating HDMEC and HUVEC angiogenesis after thermal injury.

Interleukin-36γ aggravates macrophage foam cell formation and atherosclerosis progression in ApoE knockout mice.

Atherosclerosis-related cardiovascular diseases are the leading cause of mortality worldwide. Macrophage-derived foam cell formation is a critical early event in atherogenesis. However, the molecular pathways involved in this disease have not been fully elucidated. Interleukin (IL)-36 plays a crucial role in inflammation, and this study was conducted to investigate the possible role of IL-36γ in the pathogenesis and regulation of atherosclerosis. In this study, we show that IL-36γ regulates inflammatory responses and lipoprotein metabolic processes in macrophages and exerts its atherosclerosis-promoting effects by increasing macrophage foam cell formation and uptake of oxidized low-density lipoproteins. Mechanistically, IL-36γ specifically upregulates expression of the scavenger receptor CD36 through the phosphoinositide 3-kinase pathway in macrophages. These results contribute to our understanding of IL-36γ as a novel regulator of foam cell formation and atherogenesis progression.

DRG1 Maintains Intestinal Epithelial Cell Junctions and Barrier Function by Regulating RAC1 Activity in Necrotizing Enterocolitis.

BACKGROUND: An immature intestine is a high-risk factor for necrotizing enterocolitis (NEC), which is a serious intestinal disease in newborns. The regulation of developmentally regulated GTP-binding protein 1 (DRG1) during organ development suggests a potential role of DRG1 in the maturation process of the intestine. AIM: To illustrate the function of DRG1 during the pathogenesis of NEC. METHODS: DRG1 expression in the intestine was measured using immunohistochemistry and q-PCR. Immunoprecipitation coupled with mass spectrometry was used to identify the interacting proteins of DRG1. The biological functions of the potential interactors were annotated with the Database for Annotation, Visualization and Integrated Discovery. Caco2 and FHs74Int cells with stable DRG1 silencing or overexpression were used to investigate the influence of DRG1 on cell junctions and intestinal barrier permeability and to elucidate the downstream mechanism. RESULTS: DRG1 was constitutively expressed during the intestinal maturation process but significantly decreased in the ileum in the context of NEC. Protein interaction analysis revealed that DRG1 was closely correlated with cell junctions. DRG1 deficiency destabilized the E-cadherin and occludin proteins near the cell membrane and increased the permeability of the epithelial cell monolayer, while DRG1 overexpression prevented lipopolysaccharide-induced disruption of E-cadherin and occludin expression and cell monolayer integrity. Further investigation suggested that DRG1 maintained cell junctions, especially adherens junctions, by regulating RAC1 activity, and RAC1 inhibition with NSC23766 attenuated intestinal injury and led to improved barrier integrity in experimental NEC. CONCLUSIONS: Our findings illustrate the mechanism underlying the effect of DRG1 deficiency on epithelial cell permeability regulation and provide evidence supporting the application of RAC1 inhibitors for protection against NEC.

Circular RNA_0001946 is insufficiently expressed in tumor tissues, while its higher expression correlates with less lymph node metastasis, lower TNM stage, and improved prognosis in NSCLC patients.

OBJECTIVE: Circular RNA_0001946 (circ_0001946) inhibits tumor progression but promotes chemosensitivity in non-small-cell lung cancer (NSCLC); however, its correlation with tumor features and prognosis in NSCLC patients is still unclear; therefore, this study aimed to investigate these issues. METHODS: A total of 284 NSCLC patients were retrospectively analyzed. Circ_0001946 expression in tumor (n = 284) and adjacent (n = 125) tissues was detected by the reverse transcription-quantitative polymerase chain reaction. Meanwhile, patients' clinical characteristics, recurrence, and survival data were extracted from the electrical database. RESULTS: Circ_0001946 expression in adjacent tissues was over 3-folds as that in tumor tissues (P < .001). Meanwhile, higher tumor circ_0001946 expression was correlated with less lymph node metastasis (P < .001) and decreased TNM stage (P = .001), but did not correlate with other clinicopathological features. Moreover, higher tumor circ_0001946 expression was associated with prolonged disease-free survival (DFS) (P < .001) and overall survival (OS) (P < .001), respectively. Subgroup analyses revealed that higher tumor circ_0001946 was correlated with improved DFS in patients with TNM stage I, II, or III, respectively (all P < .05), while only correlated with prolonged OS in patients with TNM stage III (P = .037), but not in patients with TNM stage I or II. Further multivariate Cox's proportional hazard regression analyses suggested that higher tumor circ_0001946 expression could independently predict improved DFS (P < .001, hazard ratio (HR) = 0.719) and OS (P < .001, HR = 0.746), respectively. CONCLUSION: Circ_0001946 is insufficiently expressed in tumor tissues, whereas its higher expression correlates with less lymph node metastasis, reduced TNM stage, and improved prognosis in NSCLC patients.

Assessment of pyrethroid contamination and potential mitigation strategies in California Central Coast surface waters.

Increased use of pyrethroids in the Central Coast of California since 2011 has resulted in a dramatic increase in the number and proportion of surface water samples with detectable concentrations at levels of concern to the public and state regulators. The goals of this study were to investigate the relationships between pyrethroid usage and environmental contamination, quantify and assess the potential risks, and recommend mitigation strategies. This study compiled the available pyrethroid use and surface water sampling data for the region, and then applied GIS methods to dynamic simulation modeling and usage-restriction buffer analyses. The results showed that in Monterey County alone, the agricultural usages of bifenthrin and permethrin each increased by ~50%, and the positive detection frequencies of both also increased around 2011-2013. County-wide, bifenthrin positive detections in surface water samples increased precipitously from 8.2% (7/85) for 2008-2012 up to 36.4% (106/291) for 2013-2017, and detections above its crustacean LC50 concentration went from 7.1% (6/85) to 35.7% (104/291). Despite its higher usage by mass, comparable figures for permethrin were more modest for the same time-periods, with positive detections going from 10.6% (9/85) to 14.4% (64/444), and detections above its crustacean LC50 going from 3.5% (3/85) to 7.2% (32/444). The seasonal lag between high bifenthrin usage in spring/summer and high detections in fall/winter samples showed the best correlations with 128- to 182-day lag times. This timing suggests that fallow season rain is likely the main driver of pyrethroid off-site movement into surface waters. SWAT modeling indicated that significant reductions in surface water permethrin concentrations only occurred with buffer distances of 1.6-3.2 km, but not with narrower buffers. However, if those wider buffers were implemented, permethrin could no longer be used on the majority of land where it is currently applied. Specifically, a 1.6-km buffer reduced the instream concentration by 8% but impacted 50% of the cropland, and a 3.2-km buffer reduced the concentration by 50% while impacting 76% of cropland. This study suggested that more promising alternative management practices could include an overall reduction in pyrethroid usage back to 2011 levels or other active mitigation strategies, like planting cover crops during the fallow winter wet season, or installing either vegetated buffer strips and/or sediment check dams on small tributaries to minimize sediment runoff.

A support vector regression model to predict nitrate-nitrogen isotopic composition using hydro-chemical variables.

Nitrate is a prominent pollutant in surface and groundwater bodies worldwide. Isotopes in nitrate provide a powerful approach for tracing nitrate sources and transformations in waters. Given that analytical techniques for determining isotopic compositions are generally time-consuming, laborious and expensive, alternative methods are warranted to supplement and enhance existing approaches. Hence, we developed a support vector regression (SVR) model and explored its feasibility to predict nitrogen isotopic composition of nitrate (δ15N-NO3-) in a rural-urban river system in Southeastern China. A total of 16 easily obtained hydro-chemical variables were measured in the wet season (September 2019) and dry season (January 2020) and used to develop the SVR prediction model. The grading method utilized ~75% (35) of the samples for model building while the remaining 11 samples assessed model performance. Principal component analysis (PCA) extracted 7 principal components for SVR model inputs as PCA reduces superfluous variables. We optimized tuning parameters in the SVR model using a grid search technique coupled with V-fold cross-validation. The optimized SVR model provided accurate δ15N-NO3- predictions with a determination coefficient (R2) of 0.88, Nash-Sutcliffe (NS) of 0.87, and mean square error (MSE) of 0.53‰ in the testing step, and performed much better than the corresponding multivariate linear regression model (R2 = 0.60, NS = 0.58 and MSE = 1.76‰) and general regression neural network model (R2 = 0.66, NS = 0.65 and MSE = 1.45‰). Overall, the SVR model provides a potential indirect method to predict environmental isotope values for water quality management that will complement and enhance the interpretation of direct measurements of δ15N-NO3-.

Association of plasma free fatty acids levels with the presence and severity of coronary and carotid atherosclerotic plaque in patients with type 2 diabetes mellitus.

BACKGROUND: Previous studies have suggested that patients with diabetes mellitus (DM) have higher prevalence of atherosclerotic cardiovascular disease (ASCVD), and plasma levels of free fatty acids (FFAs) are a useful marker for predicting ASCVD. We hypothesized that FFAs could predict both coronary and carotid lesions in an individual with type 2 DM (T2DM). The present study, hence, was to investigate the relation of plasma FFA level to the presence and severity of coronary and carotid atherosclerosis in patients with T2DM. METHODS: Three hundred and two consecutive individuals with T2DM who have received carotid ultrasonography and coronary angiography due to chest pain were enrolled in this study. Plasma FFAs were measured using an automatic biochemistry analyzer. Coronary and carotid severity was evaluated by Gensini score and Crouse score respectively. Subsequently, the relation of FFA levels to the presence and severity of coronary artery disease (CAD) and carotid atherosclerotic plaque (CAP) in whole individuals were also assessed. RESULTS: Increased plasma FFA levels were found in the groups either CAD or CAP compared to those without. Patients with higher level of FFAs had a higher CAD (89.9%) and elevated prevalence of CAP (69.7%). And also, patients with higher level of FFAs had a higher Gensini and Crouse scores. Multivariate regression analysis showed that FFA levels were independently associated with the presence of CAD and CAP (OR = 1.83, 95%CI: 1.27-2.65, P = 0.001; OR = 1.62, 95%CI: 1.22-2.14, P = 0.001, respectively). The area under the curve (AUC) was 0.68 and 0.65 for predicting the presence of CAD and CAP in patients with DM respectively. CONCLUSIONS: The present study firstly indicated that elevated FFA levels appeared associated with both the presence and severity of CAD and CAP in patients with T2DM, suggesting that plasma FFA levels may be a useful biomarker for improving management of patients with T2DM.

Can a barrier zone stop invasion of a population?

We consider an integro-difference model to study the effect of a stationary barrier zone on invasion of a population with a strong Allee effect. It is assumed that inside the barrier zone a certain proportion of the population is killed. A Laplace dispersal kernel is used in the model. We provide a formula for the critical width [Formula: see text] of barrier zone. We show that when a barrier zone is set at the front of a population, if the width of barrier zone is bigger than [Formula: see text] then the barrier zone can stop the population invasion, and if the width of barrier zone is less than [Formula: see text] then the population crosses the barrier zone and eventually occupies the entire space. The results are proven by establishing the existence and attractivity of three types of equilibrium solutions. The mathematical proofs involve phase plane analysis and comparison.

Curcumin inhibits proliferation, migration and neointimal formation of vascular smooth muscle via activating miR-22.

Context: Curcumin has antitumor, antioxidative, anti-inflammatory, and anti-proliferative properties.Objective: To investigate the role of miR-22 during curcumin-induced changes in vascular smooth muscle cells (VSMC) and neointima formation in balloon-injured rat abdominal aorta.Materials and methods: Sprague-Dawley rats were randomised to the sham-operated (n = 10), operated control (injured, n = 10), and curcumin treatment (n = 10) groups. miR-22 expression was determined by real-time PCR. SP1 was assessed by western blot and real-time PCR. Rat aortic smooth muscle A7r5 cells were used to determine VSMC proliferation and migration, which were measured by the MTS, EdU staining, Transwell, and wound healing assays.Results: miR-22 levels declined following arterial balloon injury in vivo (48% at 3d, p < 0.05) and serum stimulation in vitro (45% at 24 h, p < 0.01). Functional studies revealed that miR-22 negatively regulated the proliferation and migration of VSMCs by directly targeting the SP1 transcription factor in VSMCs. Curcumin increased the expression of miR-22 (81%, p < 0.05) and decreased the protein expression of SP1 in VSMCs (25%, p < 0.05). miR-22 inhibition was found to attenuate the effects of curcumin on VSMC functions. Curcumin increased miR-22 (46%, p < 0.01), decreased the SP1 protein (19%, p < 0.05), and inhibited vascular neointimal area (48%, p < 0.01) in vivo.Discussion: The miR-22/SP1 pathway is involved in the protective role of curcumin during arterial balloon injury, but the mechanisms remain unclear.Conclusion: miR-22 is involved in the inhibitory effects of curcumin on VSMCs' proliferation, migration and neointima hyperplasia after arterial balloon injury in rats. Curcumin could be used to prevent neointimal hyperplasia after angioplasty.