Replacing of sedentary behavior with physical activity and the risk of mortality in people with prediabetes and diabetes: a prospective cohort study.

BACKGROUND: Sedentary behavior is prevalent among people with diabetes and is associated with unfavorable cardiometabolic health. However, there is limited evidence regarding the impact of replacing sedentary time (ST) with physical activity on mortality in people with prediabetes and diabetes. We prospectively examined the association between accelerometer-measured ST and mortality among people with prediabetes and diabetes after adjusting for demographic characteristics, lifestyle factors, and moderate- to vigorous-intensity PA (MVPA). We further determined the effect of replacing ST with equal time of different types of physical activities on all-cause mortality. METHODS: We included 1242 adults with prediabetes and 1037 with diabetes from the National Health and Nutrition Examination Survey. Restricted cubic splines were fitted to determine the dose-response association between ST and overall mortality. Isotemporal substitution modeling was used to explore the hazard ratio (HR) effects of ST replacement. RESULTS: During a median follow-up of 14.1 years, 424 adults with prediabetes and 493 with diabetes died. Compared with the lowest tertile of ST, the multivariable-adjusted HRs for all-cause mortality in the highest tertile were 1.76 (95% confidence interval [CI] 1.19, 2.60) for participants with prediabetes and 1.76 (1.17, 2.65) for those with diabetes. Additionally, a linear association between ST and all-cause mortality was observed in adults with prediabetes and diabetes, with HRs for each 60 min/day increment in ST of 1.19 (1.10, 1.30) and 1.25 (1.12, 1.40), respectively. Isotemporal substitution results indicated that individuals with prediabetes whose ST was replaced by 30 min of light-intensity physical activity (LPA) and MVPA had 9% and 40% lower all-cause mortality, respectively. In people with diabetes, replacing sedentary behavior with an equivalent time of LPA and MVPA was also associated with mortality risk reduction (HR 0.89; 95% CI 0.84, 0.95 for LPA; HR 0.73; 95% CI 0.49, 1.11 for MVPA). CONCLUSIONS: Higher ST was associated in a dose-response manner with an increased risk of premature mortality among adults with prediabetes and diabetes. Statistically replacing ST with LPA was potentially beneficial for health in this high-risk population.

Amputation and limb salvage following endovascular and open surgery for the treatment of peripheral artery illnesses: A meta-analysis.

A meta-analysis investigation was executed to measure the outcome of endovascular surgery (ES) and open surgery (OS) for the management of peripheral artery diseases (PADs) on amputation and limb salvage (LS). A comprehensive literature inspection till February 2023 was applied and 3451 interrelated investigations were reviewed. The 31 chosen investigations enclosed 19 948 individuals with PADs were in the chosen investigations' starting point, 8861 of them were utilising ES, and 11 087 were utilising OS. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were utilised to compute the value of the effect of ES and OS for the management of PADs on amputation and LS by the dichotomous approaches and a fixed or random model. ES had significantly lower amputation (OR, 0.80; 95% CI, 0.68-0.93, P = 0.005) compared with those with OS in individuals with PADs. No significant difference was found between ES and OS in 30-day LS (OR, 0.95; 95% CI, 0.64-1.42, P = 0.81), 1-year LS (OR, 1.06; 95% CI, 0.81-1.39, P = 0.68), and 3-year LS (OR, 0.86; 95% CI, 0.61-1.19, P = 0.36) in individuals with PADs. ES had significantly lower amputation, 30-day LS, 1-year LS, and 3-year LS compared with those with OS in individuals with PADs. However, care must be exercised when dealing with its values because of the low sample size of some of the nominated investigations for the meta-analysis.

Empirical Variational Mode Decomposition Based on Binary Tree Algorithm.

Aiming at non-stationary signals with complex components, the performance of a variational mode decomposition (VMD) algorithm is seriously affected by the key parameters such as the number of modes K, the quadratic penalty parameter α and the update step τ. In order to solve this problem, an adaptive empirical variational mode decomposition (EVMD) method based on a binary tree model is proposed in this paper, which can not only effectively solve the problem of VMD parameter selection, but also effectively reduce the computational complexity of searching the optimal VMD parameters using intelligent optimization algorithm. Firstly, the signal noise ratio (SNR) and refined composite multi-scale dispersion entropy (RCMDE) of the decomposed signal are calculated. The RCMDE is used as the setting basis of the α, and the SNR is used as the parameter value of the τ. Then, the signal is decomposed into two components based on the binary tree mode. Before decomposing, the α and τ need to be reset according to the SNR and MDE of the new signal. Finally, the cycle iteration termination condition composed of the least squares mutual information and reconstruction error of the components determines whether to continue the decomposition. The components with large least squares mutual information (LSMI) are combined, and the LSMI threshold is set as 0.8. The simulation and experimental results indicate that the proposed empirical VMD algorithm can decompose the non-stationary signals adaptively, with lower complexity, which is O(n2), good decomposition effect and strong robustness.

Concurrent Single-Cell RNA and Targeted DNA Sequencing on an Automated Platform for Comeasurement of Genomic and Transcriptomic Signatures.

BACKGROUND: The comeasurement of both genomic and transcriptomic signatures in single cells is of fundamental importance to accurately assess how the genetic information correlates with the transcriptomic phenotype. However, existing technologies have low throughput and laborious work flows. METHODS: We developed a new method for concurrent sequencing of the transcriptome and targeted genomic regions (CORTAD-seq) within the same single cell on an automated microfluidic platform. The method was compatible with the downstream library preparation, allowing easy integration into existing next-generation sequencing work flows. We incorporated a single-cell bioinformatics pipeline for transcriptome and mutation analysis. RESULTS: As proof of principle, we applied CORTAD-seq to lung cancer cell lines to dissect the cellular consequences of mutations that result in resistance to targeted therapy. We obtained a mean detection of 6000 expressed genes and an exonic rate of 50%. The targeted DNA-sequencing data achieved a 97.8% detection rate for mutations and allowed for the identification of copy number variations and haplotype construction. We detected expression signatures of tyrosine kinase inhibitor (TKI) resistance, epidermal growth factor receptor (EGFR) amplification, and expansion of the T790M mutation among resistant cells. We also identified characteristics for TKI resistance that were independent of EGFR T790M, indicating that other alterations are required for resistance in this context. CONCLUSIONS: CORTAD-seq allows assessment of the interconnection between genetic and transcriptomic changes in single cells. It is operated on an automated, commercially available single-cell isolation platform, making its implementation straightforward.

Kinectin-dependent ER transport supports the focal complex maturation required for chemotaxis in shallow gradients.

Chemotaxis in shallow gradients of chemoattractants is accomplished by preferential maintenance of protrusions oriented towards the chemoattractant; however, the mechanism of preferential maintenance is not known. Here, we test the hypothesis that kinectin-dependent endoplasmic reticulum (ER) transport supports focal complex maturation to preferentially maintain correctly oriented protrusions. We knocked down kinectin expression in MDA-MB-231 cells using small interfering RNA and observed that kinectin contributes to the directional bias, but not the speed, of cell migration. Kymograph analysis revealed that the extension of protrusions oriented towards the chemoattractant was not affected by kinectin knockdown, but that their maintenance was. Immunofluorescence staining and live-cell imaging demonstrated that kinectin transports ER preferentially to protrusions oriented towards the chemoattractant. ER then promotes the maturation of focal complexes into focal adhesions to maintain these protrusions for chemotaxis. Our results show that kinectin-dependent ER distribution can be localized by chemoattractants and provide a mechanism for biased protrusion choices during chemotaxis in shallow gradients of chemoattractants.

Near-infrared light-activated IR780-loaded liposomes for anti-tumor angiogenesis and Photothermal therapy.

Tumor angiogenesis is a key step in the process of tumor development, and antitumor angiogenesis has a profound influence on tumor growth. Herein we report a dual-function drug delivery system comprising a Near-infrared (NIR) dye and an anti-angiogenic drug within liposomes (Lip-IR780-Sunitinib) for enhanced antitumor therapy. The hydrophobic NIR dye IR780 was loaded into the liposome phospholipid bilayer, and the bilayer would be disrupted by laser irradiation so that anti-angiogenic drug sunitinib release would be activated remotely at the tumor site. The released hydrophilic sunitinib could potentially target multiple VEGF receptors on the tumor endothelial cell surface to inhibit angiogenesis. Meanwhile, IR780-loaded liposomes kill the cancer cells by photothermal therapy. Lip-IR780-Sunitinib exhibited enhanced anti-tumor and anti-angiogenic effects in vitro and in vivo. This system facilitates easy and controlled release of cargos to achieve anti-tumor angiogenesis and photothermal therapy.

Mitoxantrone- and Folate-TPGS2k Conjugate Hybrid Micellar Aggregates To Circumvent Toxicity and Enhance Efficiency for Breast Cancer Therapy.

Mitoxantrone (MTO) is a potent drug used to treat breast cancer; however, efforts to expand its clinical applicability have been restricted because of its high risk for cardiotoxicity. In this study, we successfully conjugated MTO or folic acid (FA) to a synthesized D-α-tocopheryl polyethylene glycol 2000 succinate (TPGS2k), herein, shortened to MCT and FCT, respectively. The two produced conjugates could self-assemble to form MCT micelles or MCT/FCT mixed micelles (FMCT) aiming to lower systemic toxicity, enhance entrapment efficiency, and provide a platform for targeted delivery. Moreover, these micellar materials showed a significantly low CMC and could be used to load MTO. The diameters of MTO-loaded micelles (MTO-MCT and MTO-FMCT) were less than 100 nm with a negative zeta potential. We further characterized the pH-responsive drug release of MTO-MCT and MTO-FMCT and then assessed their cellular uptake and antitumor efficacy in human breast cancer cell lines (MCF-7) via confocal microscopy, flow cytometry, and cytotoxicity studies. All the results revealed that both MTO-MCT and MTO-FMCT increased drug loading and entrapment efficiency and possessed sufficient pH-sensitive release. Additionally, MTO-FMCT displayed an improved uptake through folate-mediated endocytosis, resulting in a higher cytotoxic effect on MCF-7 cells compared with that of MTO-MCT. Meanwhile, both MTO-MCT and MTO-FMCT exhibited a low toxicity on hCMEC/D3 normal cells. More importantly, pharmacokinetic study demonstrated that, in comparison with free MTO injection, MTO-MCT and MTO-FMCT, respectively, achieved half-lives 11.5 and 13 times longer and a 9.7- and 5.8-fold increase in AUC. In vivo, both MTO-MCT and MTO-FMCT formulations significantly prolonged the survival time of MCF-7 tumor-bearing mice and had a better efficacy/toxicity ratio. Promisingly, MTO-FMCT micelles remarkably increased MTO accumulation in tumors in vivo, induced higher tumor cell apoptosis, and showed lower toxicity toward major organs. These results imply that MTO-FMCT may be used as a potential drug delivery system for breast cancer targeted therapy.

CXCR4-Targeted and Redox Responsive Dextrin Nanogel for Metastatic Breast Cancer Therapy.

The unsatisfied results of cancer therapy are caused by many issues and metastasis of cancer cells is one of the major challenge. It has been reported that inhibiting the SDF1/CXCR4 interaction can significantly reduce the metastasis of breast cancer cells to regional lymph nodes and lung. Herein, a nanogel system equipped with the FDA-approved CXCR4 antagonist AMD3100 was developed and evaluated for its combined antimetastatic and tumor targeting effects. Briefly, a bioreducible cross-linked dextrin nanogel (DNG) coated with AMD3100 was designed to possess multiple functions, including CXCR4 chemokine targeting, inhibition of tumor metastasis, and reduction-responsive intracellular release of doxorubicin (DOX) to reduce the cells proliferation. The in vitro results confirmed that the DOX-loaded AMD3100-coated dextrin nanogel (DOX-AMD-DNG) was more effectively taken up by 4T1 breast cancer cells than DOX-DNG and was significantly more cytotoxic to 4T1 cells than DOX-DNG. In biodistribution studies, the stronger fluorescence intensity of Cy7-AMD-DNG than Cy7-DNG further confirmed that AMD3100 mediated tumor targeting in vivo. AMD3100-coated DOX-DNG also exhibited a distinct antimetastatic effect and CXCR4 antagonistic activity by inhibiting CXCR4-mediated cell invasion in 4T1 and U2OS cells. Moreover, DOX-AMD-DNG displayed superior anticancer activity and antimetastatic effects in orthotopic breast cancer-bearing Balb/C mice. In summary, the multifunctional DOX-AMD-DNG can effectively target the tumor site and dually impede cancer progression and metastasis.

Development of a tannic acid- and silicate ion-functionalized PVA-starch composite hydrogel for in situ skeletal muscle repairing.

The repair capacity of skeletal muscle is severely diminished in massive skeletal muscle injuries accompanied by inflammation, resulting in muscle function loss and scar tissue formation. In the current work, we developed a tannic acid (TA)- and silicate ion-functionalized tissue adhesive poly(vinyl alcohol) (PVA)-starch composite hydrogel, referred to as PSTS (PVA-starch-TA-SiO32-). It was formed based on the hydrogen bonding of TA to organic polymers, as well as silicate-TA ligand interaction. PSTS could be gelatinized in minutes at room temperature with crosslinked network formation, making it applicable for injection. Further investigations revealed that PSTS had skeletal muscle-comparable conductivity and modulus to act as a temporary platform for muscle repairing. Moreover, PSTS could release TA and silicate ions in situ to inhibit bacterial growth, induce vascularization, and reduce oxidation, paving the way to the possibility of creating a favorable microenvironment for skeletal muscle regeneration and tissue fibrosis control. The in vivo model confirmed that PSTS could enhance muscle fiber regeneration and myotube formation, as well as reduce infection and inflammation risk. These findings thereby implied the great potential of PSTS in the treatment of formidable skeletal muscle injuries.

Single-cell transcriptomes reveal the heterogeneity and microenvironment of vestibular schwannoma.

BACKGROUND: Vestibular schwannoma (VS) is the most common benign tumor in the cerebellopontine angle and internal auditory canal. Illustrating the heterogeneous cellular components of VS could provide insights into its various growth patterns. METHODS: Single-cell RNA sequencing was used to profile transcriptomes from 7 VS samples and 2 normal nerves. Multiplex immunofluorescence was employed to verify the data set results. Bulk RNA sequencing was conducted on 5 normal nerves and 44 VS samples to generate a prediction model for VS growth. RESULTS: A total of 83 611 cells were annotated as 14 distinct cell types. We uncovered the heterogeneity in distinct VS tumors. A subset of Schwann cells with the vascular endothelial growth factor biomarker was significantly associated with fast VS growth through mRNA catabolism and peptide biosynthesis. The macrophages in the normal nerves were largely of the M2 phenotype, while no significant differences in the proportions of M1 and M2 macrophages were found between slow-growing and fast-growing VS. The normal spatial distribution of fibroblasts and vascular cells was destroyed in VS. The communications between Schwann cells and vascular cells were strengthened in VS compared with those in the normal nerve. Three cell clusters were significantly associated with fast VS growth and could refine the growth classification in bulk RNA. CONCLUSIONS: Our findings offer novel insights into the VS microenvironment at the single-cell level. It may enhance our understanding of the different clinical phenotypes of VS and help predict growth characteristics. Molecular subtypes should be included in the treatment considerations.

A phthalocyanine-based porous organic polymer for a lithium-ion battery anode.

Porous organic polymers (POPs) are a novel class of polymeric materials with high flexibility and designability for building structures. Herein, a phthalocyanine-based porous organic polymer (PcPOP) was constructed in situ on copper foil from H2Pc(ethynyl)4 [Pc(ethynyl)4 = 2(3),9(10),16(17),23(24)-tetra(ethynyl)phthalocyanine] by the coupling reaction. Benefiting from the uniformly distributed electron-rich nitrogen atoms in the Pc structure and the sp-hybridized carbons in the acetylenic linkage, Li intercalation in the porous organic polymer would be improved and stabilized. As a result, PcPOP showed remarkable electrochemical performance in lithium-ion batteries as the anode, including high specific capacity (a charge capacity of 1172 mA h g-1 at a current density of 150 mA g-1) and long cycling stability (a reversible capacity of 960.1 mA h g-1 can be achieved even after 600 cycles at a current density of 1500 mA g-1). The result indicates that the intrinsic doping of electron-rich sites of the building molecules is beneficial for the electrochemical performance of the porous organic polymer.

Characterization and source apportionment for light absorption amplification of black carbon at an urban site in eastern China.

The mass absorption efficiency (MAE) of black carbon (BC) could be amplified by both internal mixing and the lensing effect from non-absorbing coating, which could intensify the global warming effect of BC. In this study, a two-year-long continuous campaign with measurements of aerosol optical properties and chemical composition were conducted in Nanjing, a typical polluted city in the Yangtze River Delta (YRD) region. Relatively large MAE values were observed in 2016, and the high BC internal mixing level could be the main cause. The strong positive correlation between the ratio of non-absorbing particulate matter (NAPM) over elemental carbon (EC) and the MAE value indicated that the coating thickness of BC largely promotes its light absorption ability. The impacts of chemical component coating on MAE amplification in autumn and winter were greater than in other seasons. Multiple linear regression was performed to estimate the MAE amplification effect by internal mixing and the coating of different chemical components. Nitrate coating had the strongest impact on MAE amplification, followed by organic matter. The effects of organic matter and nitrate coatings on MAE amplification increased with the internal mixing index (IMI). Based on the positive matrix factorization (PMF) model, it was found that large decrease in the contribution of industrial emissions and coal combustion to PM2.5 from 2016 to 2017 was the main cause for MAE reduction. The novel statistical model developed in this study could be a useful tool to separate the impacts of internal mixing and non-absorbing coating.

Photoactive "Bionic Virus" Robustly Elicits the Synergy Anticancer Activity of Immunophotodynamic Therapy.

Coronavirus represents an inspiring model for designing drug delivery systems due to its unique infection machinery mechanism. Herein, we have developed a biomimetic viruslike nanocomplex, termed SDN, for improving cancer theranostics. SDN has a unique core-shell structure consisting of photosensitizer chlorin e6 (Ce6)-loaded nanostructured lipid carrier (CeNLC) (virus core)@poly(allylamine hydrochloride)-functionalized MnO2 nanoparticles (virus spike), generating a virus-mimicking nanocomplex. SDN not only prompted cellular uptake through rough-surface-mediated endocytosis but also achieved mitochondrial accumulation by the interaction of cationic spikes and the anionic mitochondrial surface, leading to mitochondria-specific photodynamic therapy. Meanwhile, SDN could even mediate oxygen generation to relieve tumor hypoxia and, consequently, improve macrophage-associated anticancer immune response. Importantly, SDN served as a robust magnetic resonance imaging (MRI) contrast agent due to the fast release of Mn2+ in the presence of intracellular redox components. We identified that SDN selectively accumulated in tumors and released Mn2+ to generate a 5.71-fold higher T1-MRI signal, allowing for effectively detecting suspected tumors. Particularly, SDN induced synergistic immunophotodynamic effects to eliminate malignant tumors with minimal adverse effects. Therefore, we present a novel biomimetic strategy for improving targeted theranostics, which has a wide range of potential biomedical applications.

Cell Membrane Camouflaged Metal Oxide-Black Phosphorus Biomimetic Nanocomplex Enhances Photo-chemo-dynamic Ferroptosis.

Despite the availability of various treatment options, the inherent complexity of tumors significantly impairs therapeutic efficacy. Recently, combination treatments exhibited great anticancer potential due to low cross-resistance and good therapeutic additivity. Herein, a photoactive metal oxide-black phosphorus biomimetic nanocomplex (photophage) is developed for improving the antitumor combination of ferroptosis and photodynamic therapy (PDT). The photophage is composed of M1 macrophage membrane camouflaged MnO2 and Fe3O4 nanoparticles anchored black phosphorus nanosheets (BPNs), which together trigger a synergistic antitumor action. Fe3O4 acts as an iron source to activate Fenton-reaction-dependent ferroptosis, which can be further strengthened by BPN-mediated PDT. Besides the original antitumor effects, PDT also generates reactive oxygen species to enhance lipid peroxidation and glutathione depletion, which in turn reinforce ferroptosis and PDT efficacy. Importantly, MnO2 can in situ generate oxygen to relieve tumor hypoxia and consequently leverage cell behaviors to improve therapeutic responses. Particularly, M1 macrophage membrane modification endows the photophage with good tumor targeting capability and tumor penetration, which promote synergistic ferroptosis and PDT to destroy tumors while reducing systemic side effects, resulting in the prolonged survival of tumor-bearing mice. Therefore, we present a biomimetic nanoplatform for overcoming tumor barriers and advancing tumor-targeted treatment.

Steady states and dynamics of urokinase-mediated plasmin activation in silico and in vitro.

Plasmin (PLS) and urokinase-type plasminogen activator (UPA) are ubiquitous proteases that regulate the extracellular environment. Although they are secreted in inactive forms, they can activate each other through proteolytic cleavage. This mutual interplay creates the potential for complex dynamics, which we investigated using mathematical modeling and in vitro experiments. We constructed ordinary differential equations to model the conversion of precursor plasminogen into active PLS, and precursor urokinase (scUPA) into active urokinase (tcUPA). Although neither PLS nor UPA exhibits allosteric cooperativity, modeling showed that cooperativity occurred at the system level because of substrate competition. Computational simulations and bifurcation analysis predicted that the system would be bistable over a range of parameters for cooperativity and positive feedback. Cell-free experiments with recombinant proteins tested key predictions of the model. PLS activation in response to scUPA stimulus was found to be cooperative in vitro. Finally, bistability was demonstrated in vitro by the presence of two significantly different steady-state levels of PLS activation for the same levels of stimulus. We conclude that ultrasensitive, bistable activation of UPA-PLS is possible in the presence of substrate competition. An ultrasensitive threshold for activation of PLS and UPA would have ramifications for normal and disease processes, including angiogenesis, metastasis, wound healing, and fibrosis.

Copper niobate nanowires immobilized on reduced graphene oxide nanosheets as rate capability anode for lithium ion capacitor.

Binary metal niobium oxides can offer a higher specific capacity compared to niobium pentoxide (Nb2O5) and thus are ideal anode candidates for lithium ion capacitors (LICs). However, their lower electronic conductivity limits their ability to achieve high energy and power densities. In this paper, one-dimensional (1D) copper niobate (CuNb2O6) nanowires are successfully prepared by electrospinning technology and then immobilized on two-dimensional (2D) reduced graphene oxide (rGO) nanosheets to form a unique 1D nanowire/2D nanosheet CuNb2O6/rGO structure. The 1D/2D CuNb2O6/rGO electrode exhibits a high specific capacity of 312.2 mAh g-1 at 100 mA g-1 as the anode of LICs. The proposed Li+ storage mechanism of the CuNb2O6 anode involves CuNb2O6 decomposition into lithium niobate (Li3NbO4) and copper (Cu) during the initial lithium insertion process. The intercalation-type Li3NbO4 will further serve as the host to Li+ and the inactive Cu phase will act as a conductive network for electron transportation. Furthermore, the energy density of the assembled CuNb2O6/rGO//activated carbon (CuNb2O6/rGO//AC) device could achieve a value as high as 92.1 Wh kg-1 and could thus be considered as a possible alternative electrode material for high energy and power LICs.

Giotto: a toolbox for integrative analysis and visualization of spatial expression data.

Spatial transcriptomic and proteomic technologies have provided new opportunities to investigate cells in their native microenvironment. Here we present Giotto, a comprehensive and open-source toolbox for spatial data analysis and visualization. The analysis module provides end-to-end analysis by implementing a wide range of algorithms for characterizing tissue composition, spatial expression patterns, and cellular interactions. Furthermore, single-cell RNAseq data can be integrated for spatial cell-type enrichment analysis. The visualization module allows users to interactively visualize analysis outputs and imaging features. To demonstrate its general applicability, we apply Giotto to a wide range of datasets encompassing diverse technologies and platforms.

LncRNA LBX2-AS1 facilitates abdominal aortic aneurysm through miR-4685-5p/LBX2 feedback loop.

Long noncoding RNAs (LncRNAs) are involved in multiple processes of human malignancy, and emerge as crucial molecules in RNA biology. However, the function of lncRNAs has not been well illustrated in abdominal aortic aneurysm (AAA). In this research, the effects of dysregulated ladybird homeobox 2 antisense RNA 1 (LBX2-AS1) or ladybird homeobox 2 (LBX2) on vascular smooth muscle cell (VSMC) biological processes were surveyed via cell counting kit-8 (CCK-8), methyl thiazolyl tetrazolium (MTT), terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and caspase-3 activity assays. LBX2-AS1 and LBX2 both possessed pro-apoptosis and anti-proliferation functions in AAA. Mechanically, the regulation role of LBX2-AS1 on miR-4685-5p or that of miR-4685-5p on LBX2 was investigated by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the competing endogenous RNA (ceRNA) network was confirmed by luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. LBX2-AS1 sequestered miR-4685-5p to release LBX2 expression via ceRNA mechanism. Further, LBX2 could act as a transcriptional activator of LBX2-AS1. A positive feedback loop was formed by LBX2-AS1, miR-4685-5p and LBX2, deteriorating AAA formation and progression. To sum up, our data suggested that LBX2-AS1, miR-4685-5p and LBX2 constituted a positive feedback loop in promoting AAA development, implying a potential usage of LBX2-AS1/miR-4685-5p/LBX2 axis in AAA management.

[Pollution Characteristics and Ozone Formation Potential of Ambient Volatile Organic Compounds(VOCs)in Summer and Autumn in Different Functional Zones of Lianyungang, China].

Atmospheric volatile organic compounds (VOCs) were collected from different functional zones of Lianyungang during the summer and autumn of 2018. One-hundred-seven VOCs species were measured by cryogenic pre-concentration and gas chromatography-mass spectrometry (GC/MS). The ozone generation potential (OFP) of VOCs was estimated by maximum incremental reactivity (MIR). Results showed that the average volume fraction of VOCs was (22.1±13.1)×10-9. Alkanes and alkenes from C2-C4 as well as acetone and ethyl acetate were the predominant species, accounting for 59.8%-75.8% of TVOCs. The mean volume fraction in the industrial zone was the largest[(28.4±13.5)×10-9], followed by the scenic zone[(21.7±4.4)×10-9] and the traffic and residential mixed zone[(20.8±7.2)×10-9]. The concentration of VOCs in autumn was significantly higher than that in summer. The industrial zone was the site with the highest volume fraction in autumn (35.4×10-9), while the scenic zone had the highest volume fraction in summer (21.5×10-9). Alkane, sulfur, or oxygen containing compounds and halogenated hydrocarbons were the predominant components of VOCs, accounting for 35.3%, 26.9%, and 15.6% of the total amount, respectively. Due to industrial emissions, the content of sulfur or oxygen containing compounds in the industrial zone was significantly higher than that in scenic zone and the traffic and residential mixed zone. The average ratio of T/B (toluene/benzene) indicated that vehicle and solvent use were the main sources of VOCs in the urban area. The highest OFP was found in the industrial zone, followed by the traffic and residential mixed zone and the scenic zone. Alkenes and aromatics were the largest contributors to OFP.

"Star" miR-34a and CXCR4 antagonist based nanoplex for binary cooperative migration treatment against metastatic breast cancer.

Invasion and metastasis of tumor cells is one of the major obstacles in cancer therapy. The process of tumor metastasis and diffusion is coordinated by multiple pathways associated with chemokine signals and migration microenvironment. In our previous work, chemokine CXC receptor 4 (CXCR4) antagonists showed significant anti-metastatic effects by blocking the CXCR4/stromal cell-derived factor-1(SDF-1) axis in pancreatic cancer and breast cancer. Here, we proposed to achieve migration chain-treatment for metastatic tumors by introducing a cell adhesion molecules CD44 inhibitor (Star miR-34a) to deprive of cell migration capability on the basis of CXCR4 antagonism (cyclam monomer, CM). Dextrin modified 1.8 k PEI with CM-end was prepared to deliver therapeutic miR-34a (named DPC/miR-34a) for efficient anti-metastasis by downregulating adhesion protein CD44 and targeting the CXCR4/SDF-1 axis. Additionally, reduced expression of the anti-apoptotic protein Bcl2 caused by miR-34a could enhance the anti-tumor efficacy of DPC/miR-34a nanoplex administration. Compared with inhibition of the CXCR4/SDF-1 axis or CD44 expression, the multidimensional therapy (DPC/miR-34a) exhibited considerable suppression of cancer cell invasion as assessed by an in vitro cell invasion assay and in vivo anti-metastasis model. Moreover, DPC/miR-34a demonstrated a superior antitumor and anti-metastatic efficacy both in lung metastatic model and orthotopic MDA-MB-231 tumor models, thus providing an efficient approach for combating metastatic tumors.