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To investigate the short-term efficacy of enhanced external counterpulsation (EECP) on chronic insomnia. This is a pilot randomized, participant-blind, and sham-controlled study. Forty-six participants with chronic insomnia were randomly assigned in a 1:1 ratio to receive EECP or sham EECP intervention (total of 35 sessions with 45 min each). The primary outcome was Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes included sleep diary, Hospital Anxiety and Depression Scale (HADS), Short-Form Health Survey (SF12), flow mediated dilation (FMD), serum biomarkers of melatonin, cortisol, interleukin-6, and high sensitivity C-reactive protein. Outcomes were assessed after treatment and at 3-month follow-up. The PSQI was significantly decreased in both EECP and sham groups after 35-session intervention (13.74 to 6.96 in EECP and 13.04 to 9.48 in sham), and EECP decreased PSQI more than sham EECP (p = 0.009). PSQI in two groups kept improved at 3-month follow-up. After treatment, the total sleep time, sleep efficiency, FMD value and SF12 mental component of EECP group were significantly improved, and group differences were found for these outcomes. At follow-up, total sleep time, sleep efficiency and SF12 mental component of EECP group remained improved, and group difference for SF12 mental component was found. Post-treatment and follow-up HADS-A significantly decreased in both groups, with no differences between groups. Post-treatment serum biomarkers showed no differences within and between groups. Lack of objective sleep measurement. EECP could improve sleep quality and mental quality of life in chronic insomnia and the therapeutic effect maintained for 3 months. • EECP could improve sleep quality and mental quality of life in chronic insomnia. • EECP significantly improved total sleep time, sleep efficiency, sleep initiation, sleep maintenance. • EECP significantly improved vascular endothelial function and psychological state. • The therapeutic effect of EECP on chronic insomnia maintained for 3 months. [ABSTRACT FROM AUTHOR]

Objective Breast cancer is a malignant tumor in the epithelial tissue of the breast gland. This study aimed to unveil the expression and clinical diagnostic value of lncRNA cervical cancer high-expressed 1 (CCHE1) in breast cancer. Methods CCHE1 expression in breast cancer tissues was evaluated by RT-qPCR. The relationship between the CCHE1 expression and clinicopathological features of breast cancer was analyzed with the chi-square test, and the survival of breast cancer patients was evaluated with the Kaplan–Meier method. The diagnostic value of CCHE1 expression for breast cancer was evaluated by using the receiver operating characteristics (ROC) curve. Breast cancer cell lines (SKBR3, T47D, BT474, and MCF-7) were cultured for detecting CCHE1 expression in the cells. MCF-7 cells were selected for the subsequent experiments, and the small interfering RNA of CCHE1 (si-CCHE1) and CCHE1 overexpression vector (pcDNA-CCHE1) were transfected into MCF-7 cells. The proliferation, migration, and invasive ability were assessed by CCK-8 and Transwell assays. The influence of CCHE1 on the growth of tumors was validated by nude mice xenograft assay. Results CCHE1 was up-regulated in breast cancer tissues and breast cancer cells. The high expression level of CCHE1 in cancer tissues of breast cancer patients was correlated with larger tumor size, advanced TNM stage, Ki-67 status, and lymph node metastasis. The area under the ROC curve for CCHE1 in the diagnosis of breast cancer was 0.983 (95% CI: 0.966–1.000), with a sensitivity of 95.00% and a specificity of 91.70%. The 5-year survival rate was higher in patients with low CCHE1 expression than those with high CCHE1 expression. Furthermore, restrained CCHE1 impeded proliferation, invasion, and migration of MCF-7 cells, as well as tumor growth in mice. Conclusion Our study highlights that elevated expression of CCHE1 in breast cancer tissues, which is closely related to clinicopathologic features, has some clinical value in the diagnosis of the disease. [ABSTRACT FROM AUTHOR]

Controlling the nanoparticle‐cell membrane interaction to achieve easy and fast membrane anchoring and cellular internalization is of great importance in a variety of biomedical applications. Here we report a simple and versatile strategy to maneuver the nanoparticle‐cell membrane interaction by creating a tunable hydrophobic protrusion on Janus particles through swelling‐induced symmetry breaking. When the Janus particle contacts cell membrane, the protrusion will induce membrane wrapping, leading the particles to docking to the membrane, followed by drawing the whole particles into the cell. The efficiencies of both membrane anchoring and cellular internalization can be promoted by optimizing the size of the protrusion. In vitro, the Janus particles can quickly anchor to the cell membrane in 1 h and be internalized within 24 h, regardless of the types of cells involved. In vivo, the Janus particles can effectively anchor to the brain and skin tissues to provide a high retention in these tissues after intracerebroventricular, intrahippocampal, or subcutaneous injection. This strategy involving the creation of a hydrophobic protrusion on Janus particles to tune the cell‐membrane interaction holds great potential in nanoparticle‐based biomedical applications. [ABSTRACT FROM AUTHOR]

Controlling the nanoparticle‐cell membrane interaction to achieve easy and fast membrane anchoring and cellular internalization is of great importance in a variety of biomedical applications. Here we report a simple and versatile strategy to maneuver the nanoparticle‐cell membrane interaction by creating a tunable hydrophobic protrusion on Janus particles through swelling‐induced symmetry breaking. When the Janus particle contacts cell membrane, the protrusion will induce membrane wrapping, leading the particles to docking to the membrane, followed by drawing the whole particles into the cell. The efficiencies of both membrane anchoring and cellular internalization can be promoted by optimizing the size of the protrusion. In vitro, the Janus particles can quickly anchor to the cell membrane in 1 h and be internalized within 24 h, regardless of the types of cells involved. In vivo, the Janus particles can effectively anchor to the brain and skin tissues to provide a high retention in these tissues after intracerebroventricular, intrahippocampal, or subcutaneous injection. This strategy involving the creation of a hydrophobic protrusion on Janus particles to tune the cell‐membrane interaction holds great potential in nanoparticle‐based biomedical applications. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) features the loss of cholinergic neurons in the mesopontine area. There is no available approach to repair the damaged cholinergic neurons. Neural stem cell (NSC)‐based therapy is a promising strategy for the treatment of AD. However, it is a challenge to direct the NSCs to specifically differentiate into cholinergic neurons. Herein, calcium folate (CaFO) nanoparticles are synthesized through a facile nanoprecipitation approach for promoting the differentiation of NSCs into functional cholinergic neurons. After uptake by NSCs, the CaFO nanoparticles are distributed in the lysosomes (pH< 5.5) and can be decomposed into Ca2+ and folic acid in the acidic environment. The Ca2+ can accelerate the differentiation rate of NSCs while the folic acid can direct the NSCs to differentiate into cholinergic neurons. The in vitro experiments demonstrate that under the stimulation of CaFO nanoparticles, the NSCs differentiate into functional cholinergic neurons within 5 d. Animal experiments prove that the CaFO nanoparticles also promote the neuronal differentiation of NSCs in vivo, leading to the improvement in the cognitive memory ability of AD mice. This study provides a new strategy to induce the quick differentiation of NSCs into functional cholinergic neurons, which is promising for the treatment of AD. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) play important roles in organisms and are closely related to various physiological and pathological processes. Due to the short lifetime and easy transformation of ROS, the determination of ROS content in biosystem has always been a challenging task. Chemiluminescence (CL) analysis has been widely used in the detection of ROS due to its advantages of high sensitivity, good selectivity and no background signal, among which nanomaterial-related CL probes are rapidly developing. In this review, the roles of nanomaterials in CL systems are summarized, mainly including their roles as catalysts, emitters, and carriers. The nanomaterial-based CL probes for biosensing and bioimaging of ROS developed in the past five years are reviewed. We expect that this review will provide guidance for the design and development of nanomaterial-based CL probes and facilitate the wider application of CL analysis in ROS sensing and imaging in biological systems. [ABSTRACT FROM AUTHOR]

Chlorpyrifos (CPF) is a widely used organophosphorus pesticide. Increasing evidence has shown that exposure to CPF in early life might induce neurodevelopmental disorders, but the pathogenesis remains uncertain. Synaptic plasticity plays a crucial role in neurodevelopment. This study aimed to investigate the effect of CPF on synaptic plasticity in hippocampal neurons and establish the cellular mechanism underlying these effects. Using CPF-exposed rat and primary hippocampal neurons model, we analyzed the impact of CPF on the synaptic morphology, the expression level of a presynaptic protein, a postsynaptic protein and ionotropic glutamate receptors (iGluRs), as well as the effects on the Wnt/β-catenin pathway. We found that the synapses were shortened, the spines were decreased, and the expression of synaptophysin (Syp), postsynaptic density-95 (PSD-95), GluN1, GluA1 and Wnt7a, as well as active β-catenin in primary hippocampal neurons was decreased. Our study suggests that CPF exposure induced dysregulation of synaptic plasticity in rat hippocampal neurons, which might provide novel information regarding the mechanism of CPF-induced neurodevelopmental disorders. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a very common health problem and currently lacks effective treatments. Cullin RING E3 ligases (CRLs) regulate the turnover of ∼20% of mammalian cell proteins. Neddylation, the process by which NEDD8 is covalently attached to cullin proteins through sequential enzymatic reactions, is critical for the activation of CRLs and was recently found to be elevated in liver fibrosis. NEDD8-activating enzyme E1-specific inhibition led to the reduced liver damage characterized by decreased apoptosis, inflammation, and fibrosis. However, the relevance of a co-E3 ligase, DCN1, in liver fibrosis remains unclear. Here, a novel and potent DCN1–UBC12 interaction inhibitor HZX-960 was discovered with an IC50 value of 9.37 nmol/L, which could inhibit the neddylation of cullin3. Importantly, we identified that HZX-960 treatment could attenuate transforming growth factor β-induced liver fibrotic responses by reducing the deposition of collagen I and α-smooth muscle actin, and upregulating cellular NF-E2-related factor 2, hemeoxygenase 1, and NADPH quinone oxidoreductase-1 levels in two hepatic stellate cell lines. Additionally, DCN1 was shown to be unregulated in CCl4-induced mice liver tissue, and liver fibrotic signaling in mice was reduced by HZX-960. Therefore, our data demonstrated that HZX-960 possessed anti-liver fibrosis ability and that DCN1 may be a potential therapeutic target for liver fibrosis treatment. [ABSTRACT FROM AUTHOR]

Introduction: Limited qualitative studies exist on nurses' experience in terms of communicating with and caring for patients with endemic diseases. The purpose of this study was to describe the working experiences of nurses caring for Tibetan patients with Kashin–Beck disease in China. Method: A qualitative design was used in this study. Sixteen nurses who worked in the orthopedics department of a large tertiary general hospital in Wuhan, China, constituting a purposive sample, were interviewed face-to-face using semi-structured guided questions. Results: Three major themes and nine subthemes were identified. Major themes included the challenge in cross-cultural nursing, stress adjustment in cross-cultural nursing, and reshaping competencies in cross-cultural nursing. Discussion: This study revealed that nurses encountered multifaceted challenges when caring for Tibetan patients with Kashin–Beck disease. In a multiethnic society, communication and language skills, cultural competency and cultural sensitivity, and diverse training methods to improve cross-cultural knowledge could increase ethnic minority patient satisfaction with cross-cultural care. [ABSTRACT FROM AUTHOR]

Polyion complex (PIC) vesicles have attracted considerable attention as soft yet functional delivery vehicles. However, most of the PIC vesicles suffer from insufficient stability and functionality which hinder their applications. Herein, a new type of PIC vesicles obtained by co‐assembly of neutral‐cationic diblock copolymers with a supramolecular coordination polyelectrolyte is reported. The latter exhibits tunable structures and properties that endows regulated stability and functionalities of the vesicles. With lanthanide‐based coordination polymers, PIC vesicles are constructed with not only enhanced stability against salt, but also tunable fluorescent or magnetic properties associated with particular Ln3+ ions. Moreover, the vesicle lumen is applied to load PEGlated indocyanine green as a model photothermal transduction agent. The designed vesicles finally display high stability, good biocompatibility, and efficient photothermal conversion, and therefore behave well for thermal ablation of both tumor cells and tumor in mice. The well‐regulated stability and functions of the PIC vesicles are assigned the adaptive structure and properties of the supramolecular coordination polyelectrolytes, which hardly be achieved with conventional covalent polyelectrolytes. This study therefore demonstrates a facile strategy to regulate the stability and function of PIC vesicles, and shall be inspirational for developing novel vesicular materials for potential biomedical applications. [ABSTRACT FROM AUTHOR]

Background: There are increasing Chinese migrants in sub-Saharan Africa currently. Most of them are engaged in infrastructure construction. Research has shown that they stay at particular risk of HIV and are recommended for HIV testing. However, their HIV testing behavior, and its relevant factors, have not been researched among them by now. This study describes the recent HIV testing behavior and relevant factors among Chinese migrant workers in Kenya.Methods: A cross-sectional survey was conducted among 110 male Chinese workers from six different Chinese infrastructure construction enterprises in Kenya. Furthermore, a two-stage cluster random sampling method was used to select participants. We used a questionnaire that included HIV testing history, demographic characteristics, and putative multilevel facilitators of HIV testing. Logistic regression was used to explore the predictors of recent HIV testing behavior among Chinese migrant workers in Kenya.Result: Of the 110 participants, 30 (27.27%) were tested for HIV in the recent year. All participants were male, and the majority were married (73.2%). The mean age was 37.49 years (SD = 9.73; range: 23 to 63), and a considerable proportion refused to answer questions about transactional sexual behaviors in the last year. Most were able to obtain HIV-related information (91.8%) and were exposed to HIV-related information in the last year (68.2%), but only 47.6% had sufficient HIV knowledge. Nearly one-fifth of them believed that selling sex and paying for sex is acceptable. Multiple logistic regression analysis indicated that participants who could accept the 'pay for sex' (OR: 2.74; 95% CI: 1.02, 7.36) and exposed to HIV related information (OR: 4.75; 95% CI: 1.29, 17.44) were more likely to test for HIV in the recent 1 year.Conclusion: Higher current HIV test rates were associated with a more open sexual attitude towards paying for sex and being exposed to HIV-related information in the last year among Chinese workers in Kenya. More specific attention to HIV should be attached to this population to increase the rate of HIV testing among them. [ABSTRACT FROM AUTHOR]

Regarding the 2- d i s t a n c e coloring of planar graphs, in 1977, Wegner conjectured that for a graph G : (1) χ 2 (G) ≤ 7 if Δ (G) = 3. (2) χ 2 (G) ≤ Δ (G) + 5 if 4 ≤ Δ (G) ≤ 7. (3) χ 2 (G) ≤ ⌊ 3 2 Δ (G) ⌋ + 1 if Δ (G) ≥ 8. In this paper, we proved that for every planar graph with maximum degree Δ (G) ≤ 4 : (1) χ 2 l (G) ≤ 1 0 if g (G) ≥ 6. (2) χ 2 l (G) ≤ 7 if g (G) ≥ 1 0. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by dopaminergic neuron degeneration. Neural stem cell (NSC) therapy offers promise for replacing these neurons and restoring neural function. However, directing NSCs to become dopaminergic neurons is challenging. Retinoic acid (RA) is a potential regulator, but its insolubility in water limits its use in PD therapy. Herein, nanonizing RA with calcium acetate to create calcium‐retinoic acid nanoparticles (Ca‐RA NPs) is proposed. These nanoparticles can be internalized by NSCs and then dissociated in the acidic environment of lysosomes to lead to a burst of Ca2+ and RA. In vitro results showed that the intracellular bursting of Ca2+ and RA accelerated neuronal differentiation and maturation by 5–10 days compared to spontaneous NSC differentiation. Importantly, Ca‐RA NPs uniquely directed NSCs to dopaminergic neurons, involving the interaction between the calcium ion‐mediated MAPK signaling pathway and the RA‐mediated RA signaling pathway. Animal experiments further validated the efficacy of Ca‐RA‐coated NSCs in restoring motor and cognitive functions in PD mice by rapidly forming dopaminergic neural circuits. Given that both RA and calcium acetate are approved by the FDA, this strategy has the potential for translation into a clinical treatment approach for stem cell therapy of PD. [ABSTRACT FROM AUTHOR]

Luminol chemiluminescence (CL) sensing system remains an excellent candidate for application in bioanalysis due to its good water solubility. However, traditional luminol CL system usually requires the addition of oxidizing agents and sensitizers to obtain high efficiency for the improvement of detection sensitivity. Although numerous studies on the nanomaterial-enhanced luminol CL systems have been carried out, there is still great potential to develop inexpensive, readily available and easily handled catalysts to construct simple and effective CL platform for biomolecular sensing. Few-layered MoS 2 nanosheets (NS) prepared by sonication-assisted exfoliation of commercially available bulk MoS 2 were found to significantly enhance the CL of luminol‒dissolved oxygen in the absence of additional oxidants. The mechanism study demonstrated that exfoliated MoS 2 NS could catalyze the decomposition of dissolved oxygen by virtue of its exposed active sites on the surface, generating increased reactive oxygen intermediates, which then oxidize luminol and produce intense CL emission. The proposed high-efficiency luminol CL system was then employed for the extremely sensitive identification of dopamine based on the quenching of CL by dopamine. The limit of detection (LOD) for dopamine can be as low as 2.07 nM. Besides, it also works well in the actual urine sample with good recoveries (99.6–100.6 %), confirming the practicability of the method. As a new type of CL catalyst, MoS 2 NS developed in this work are easy to obtain, simple to prepare and can be produced in large quantities, which lays a foundation for extending applicability of MoS 2 NS in the CL field, and provides a new idea for developing simple and highly sensitive CL sensing system. [Display omitted] • A simple and easily available catalyst was developed for luminol chemiluminescence. • High-efficiency chemiluminescence was achieved without extra oxidizing agents. • Ultrasensitive detection of dopamine was realized. • Successful application in urine samples with high spiking recoveries. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma stem-like cells (GSCs) are hypothesized to contribute to self-renewal and therapeutic resistance in glioblastoma multiforme (GBM) tumors. Constituting only a small percentage of cancer cells, GSCs possess "stem-like", tumor-initiating properties and display resistance to irradiation and chemotherapy. Thus, novel approaches that can be used to suppress GSCs are urgently needed. A new carbon material-graphene oxide (GO), has been reported to show potential for use in tumor therapy. However, the exact effect of GO on GSCs and the inherent mechanism underlying its action are not clear. In this study, we aimed to investigate the usefulness of GO to inhibit the growth and promote the differentiation of GSCs, so as to suppress the malignancy of GBM.Methods: In vitro effects of GO on sphere-forming ability, cell proliferation and differentiation were evaluated in U87, U251 GSCs and primary GSCs. The changes in cell cycle and the level of epigenetic modification H3K27me3 were examined. GO was also tested in vivo against U87 GSCs in mouse subcutaneous xenograft models by evaluating tumor growth and histological features.Results: We cultured GSCs to explore the effect of GO and the underlying mechanism of its action. We found, for the first time, that GO triggers the inhibition of cell proliferation and induces apoptotic cell death in GSCs. Moreover, GO could promote the differentiation of GSCs by decreasing the expression of stem cell markers (SOX2 and CD133) and increasing the expression of differentiation-related markers (GFAP and β-III tubulin). Mechanistically, we found that GO had a striking effect on GSCs by inducing cell cycle arrest and epigenetic regulation. GO decreased H3K27me3 levels, which are regulated by EZH2 and associated with transcriptional silencing, in the promoters of the differentiation-related genes GFAP and β-III tubulin, thereby enhancing GSC differentiation. In addition, compared with untreated GSCs, GO-treated GSCs that were injected into nude mice exhibited decreased tumor growth in vivo.Conclusion: These results suggested that GO could promote differentiation and reduce malignancy in GSCs via an unanticipated epigenetic mechanism, which further demonstrated that GO is a potent anti-GBM agent that could be useful for future clinical applications. [ABSTRACT FROM AUTHOR]

The pervasive communications between vehicles and dynamic mobility may significantly increase data exchange and therefore bring a huge amount of traffic data in InVANETs. Due to some environmental factors, like the vulnerability of wireless connection, limitation of in-car computing ability, and speed of vehicles, it is extremely challenging to design identity authentication protocols satisfying the requirements of both high security and efficiency simultaneously. To this end, the aggregate signature technology has been employed in InVANETs. However, the technology still suffers from high computational overhead due to the management of certificates, as well as the key escrow problem (i.e., the dependence on a fully trusted third party). In this article, we propose the SE-CLASA protocol for InVANETs in order to tackle the aforementioned problems. In addition, a novel factor-contained aggregation mechanism is proposed to resist an information injection attack investigated in our analysis. Moreover, we prove the security of the proposed SE-CLASA and conclude that it meets most known security requirements in a general InVANET scenario. Simulation results show the superiority of the proposed SE-CLASA, in terms of security and efficiency, compared to the most recent authentications in InVANETs. [ABSTRACT FROM AUTHOR]

Objective: Neural tube defects (NTDs) are the most serious and common birth defects in the clinic. The SRY-related HMG box B1 (SoxB1) gene family has been implicated in different processes of early embryogenesis. Sox19b is a maternally expressed gene in the SoxB1 family that is found in the region of the presumptive central nervous system (CNS), but its role and mechanism in embryonic neural stem cells (NSCs) during neural tube development have not yet been explored. Considering that Sox19b is specific to bony fish, we intended to investigate the role and mechanism of Sox19b in neural tube development in zebrafish embryos. Material and methods: Morpholino (MO) antisense oligonucleotides were used to construct a Sox19b loss-of-function zebrafish model. The phenotype and the expression of related genes were analysed by in situ hybridization and immunolabelling. Epigenetic modifications were detected by western blot and chromatin immunoprecipitation. Results: In this study, we found that zebrafish embryos exhibited a reduced or even deleted forebrain phenotype after the expression of the Sox19b gene was inhibited. Moreover, we found for the first time that knockdown of Sox19b reduced the proliferation of NSCs; increased the transcription levels of Ngn1, Ascl1, HuC, Islet1, and cyclin-dependent kinase (CDK) inhibitors; and led to premature differentiation of NSCs. Finally, we found that knockdown of Sox19b decreased the levels of EZH2/H3K27me3 and decreased the level of H3K27me3 at the promoters of Ngn1 and ascl1a. Conclusion: Together, our data demonstrate that Sox19b plays an essential role in early NSC proliferation and differentiation through EZH2-mediated histone methylation in neural tube development. This study established the role of transcription factor Sox19b and epigenetic factor EZH2 regulatory network on NSC development, which provides new clues and theoretical guidance for the clinical treatment of neural tube defects. [ABSTRACT FROM AUTHOR]

Fine-tuned interaction between reacting molecules and metal surface is of great importance in heterogeneous catalysis for the design of highly selective processes. Conventional strategies based on adjusting the intrinsic catalyst properties such as particle size, metal-support interaction and morphology suffer from complicated and time-consuming synthetic procedures. Recently, the modification of metal nanoparticles with non-metallic promoters has been demonstrated as an effective tool to regulate the interfacial environment of metallic catalysis. Herein, we will give an overview of recent progress in this area. A general analysis will be proposed about the electronic, steric effects and new functionalities imposed by non-metallic promoters of metal catalysts. The potential for the selectivity enhancement of the promoted metal catalysts in various industrially important reactions is discussed. [ABSTRACT FROM AUTHOR]

Aiming to provide an approach for finding energy-efficient routes in dynamic and stochastic transportation networks for electric vehicles, this paper addresses the route planning problem in dynamic transportation network where the link travel times are assumed to be random variables to minimize total energy consumption and travel time. The changeable signals are introduced to establish state-space-time network to describe the realistic dynamic traffic network and also used to adjust the travel time according to the signal information (signal cycle, green time, and red time). By adjusting the travel time, the electric vehicle can achieve a nonstop driving mode during the traveling. Further, the nonstop driving mode could avoid frequent acceleration and deceleration at the signal intersections so as to reduce the energy consumption. Therefore, the dynamically adjusted travel time can save the energy and eliminate the waiting time. A multiobjective 0-1 integer programming model is formulated to find the optimal routes. Two methods are presented to transform the multiobjective optimization problem into a single objective problem. To verify the validity of the model, a specific simulation is conducted on a test network. The results indicate that the shortest travel time and the energy consumption of the planning route can be significantly reduced, demonstrating the effectiveness of the proposed approaches. [ABSTRACT FROM AUTHOR]

Reported here is a new class of PICsomes (vesicles formed by polyelectrolyte complexation) in which the anionic/neutral diblock copolymer is replaced by an anionic, reversible, supramolecular polyelectrolyte based on metal–ligand coordination. This supramolecular polyelectrolyte forms exclusively inside the wall of the assembly, and therefore self‐adjusts its length to that of the cationic block provided. Moreover, the supramolecular coordination polyelectrolytes introduce new and tunable properties and functions associated with the specific metal. As a proof‐of‐concept Mn‐based PICsomes were prepared and display high magnetic relaxivity, as well as enhanced contrast in in vitro magnetic resonance imaging tests. The simplicity of our approach, together with the new functions derived from the metal ions, demonstrates a robust strategy for the preparation of a variety of PICsomes with well‐defined and tunable structures and properties. [ABSTRACT FROM AUTHOR]

Reported here is a new class of PICsomes (vesicles formed by polyelectrolyte complexation) in which the anionic/neutral diblock copolymer is replaced by an anionic, reversible, supramolecular polyelectrolyte based on metal–ligand coordination. This supramolecular polyelectrolyte forms exclusively inside the wall of the assembly, and therefore self‐adjusts its length to that of the cationic block provided. Moreover, the supramolecular coordination polyelectrolytes introduce new and tunable properties and functions associated with the specific metal. As a proof‐of‐concept Mn‐based PICsomes were prepared and display high magnetic relaxivity, as well as enhanced contrast in in vitro magnetic resonance imaging tests. The simplicity of our approach, together with the new functions derived from the metal ions, demonstrates a robust strategy for the preparation of a variety of PICsomes with well‐defined and tunable structures and properties. [ABSTRACT FROM AUTHOR]

Cervical cancer is the second most deadly gynecological tumor worldwide. MicroRNAs (miRNAs) play very important roles in tumor oncogenesis and progression. The mechanism of post-transcription regulation of WTX gene is still unknown. A series of differential miRNAs were discovered by microarray analysis comparing three pairs of primary cervical cancer specimens and their relapsed tumors from three patients. Quantitative reverse transcriptase PCR (qRT-PCR), Western Blot (WB) and Immunohistochemistry (IHC) was used to detect the expression of miR-4524b-5p and WTX in cervical cell lines and tissues. The biological function of miR-4524b-5p and WTX was investigated through knockdown and overexpression with inhibitor/siRNA and mimic/plasmid in vitro and in vivo. In this study, we found that miR-4524b-5p is highly expressed in relapsed cervical cancer specimens. Combined in vitro and in vivo experiments, showed that miR-4524b-5p could regulate the migration and invasion ability of cervical cancer. Furthermore, we also found that miR-4524b-5p could regulate the migration and invasion of cervical cancer by targeting WTX and that WTX could regulate the expression of β-catenin. Taken together, our data identified a miR-4524b-5p/WTX/β-catenin regulatory axis for cervical cancer, and miR-4524b-5p may be a potential target for cervical cancer therapy. [ABSTRACT FROM AUTHOR]

To meet the increasing concerns for health, safety, and the environment, traditional solvent coatings are gradually replaced by their waterborne counterparts and the development of robust and self-healing waterborne polymers is showing important application significance. Herein, waterborne polyurethane urea composite coatings (WPUU) with dynamic hindered urea bonds are reported. The dispersion of WPUU synthesized with hindered amine as the chain extender has a smaller particle size. The mussel-inspired polydopamine modification was applied to improve the dispersion and interfacial interactions of carbon nanotubes (CNTs) in the WPUU matrix. Due to the dynamic reversibility of the hindered urea and abundant hydrogen bonding, the resulting WPUU-2T2B can achieve self-healing at 70 °C, also showing good mechanical toughness, the tensile strength of 34.0 MPa and elongation at break of 530 %. After adding the modified CNTs, 10%PDA@CNTs/WPUU demonstrates the tensile strength of 22.4 MPa, elongation at break of 251 % and yield strength of 13.1 M Pa. The self-healing properties of nanocomposites are still retained. The maximum electrical conductivity of the composite coating reaches 56.8 S m−1. The composite coating can recover excellent corrosion resistance in the electrolyte environment after healing, which could ensure its safety and sustainability in the long-term service. We envisage this work offers an idea for the fabrication of environmentally friendly, self-healing, corrosion resistant and electrically conductive coatings with good thermal stability and robust mechanical properties. • Robustness and self-healing of waterborne polyurethane urea is achieved by incorporating dynamic hindered urea. • Polydopamine was applied to improve the dispersion and interfacial interactions of CNTs in the WPUU matrix. • The composite coating shows increased electrical conductivity and corrosion resistance as well as self-healing capability. [ABSTRACT FROM AUTHOR]

Objectives The aim of this study was to perform a histomorphometric evaluation of the healing characteristics and jawbone remodeling processes in the peri-implant bone tissue of three commonly used implant surfaces, during the early weeks of osseointegration. Material and methods Dental implants with three different surfaces (anodically modified, hydroxyapatite ( HA)-coated and machined) were inserted into the mandibular side-tooth region of twelve adult mini-pigs. Histomorphometric analyses were performed to evaluate remodeling processes 3, 6 and 12 weeks post-implantation. Results Only a few very early bone remodeling-resorption sites were found at 3 weeks. After 6 weeks, additional signs of remodeling-related reversal and bone formation were detectable in all three groups, which steadily increased until 12 weeks. At the latter time point, the amount of remodeled bone was significantly higher for the anodized and HA-coated surfaces than for the machined implants. Conclusion The results of this study demonstrate that peri-implant bone remodeling can start as early as 3 weeks after implantation and continues at a substantial level up to 12 weeks. The anodic modification or HA coating of implant surfaces appears to accelerate the conversion of primary regenerated bone into more mature secondary lamellar bone. If this observation is of clinical relevance, it has to be clarified in studies that include longer observational time periods. [ABSTRACT FROM AUTHOR]

Unmanned aerial vehicle (UAV) path planning plays an important role in the flight process of an UAV, which needs an effective algorithm to deal with UAV path planning problem. The search and rescue optimization algorithm (SAR) is easy to implement and has the characteristics of flexible, but it has slow convergence speed and has not been applied to UAV path planning. To address these problems, a heuristic crossing search and rescue optimization algorithm (HC-SAR) is proposed. HC-SAR combines a heuristic crossover strategy with the basic SAR to improve the convergence speed and maintain the population diversity in the optimization process. Furthermore, a real-time path adjustment strategy is proposed to straighten the UAV flight path. In addition, cubic B-spline interpolation is used to smooth the generated path. Comprehensive experiments including two-dimensional and three-dimensional environments for different threat zone are conducted to validate the performance of HC-SAR. The results show that HC-SAR has a high convergence speed and can successfully obtain a safe and efficient path, and it significantly outperforms SAR, differential evolution (DE), ant lion optimizer (ALO), squirrel search algorithm (SSA) and salp swarm algorithm (SSA) in all the cases. These results suggest that the proposed algorithm can effectively serve as an alternative for solving UAV path planning problem. • A hybrid algorithm named HC-SAR is proposed for UAV path planning. • A heuristic crossover strategy is combined with SAR to greatly improve SAR. • A real-time path adjustment strategy is proposed to straighten the UAV flight path. • HC-SAR outperforms the competitors in convergence speed and solution quality. [ABSTRACT FROM AUTHOR]

A simple and time-saving strategy was developed for the amplification of electrochemiluminescence (ECL) by dropping the noncoplanar tetraphenylethylene (TPE) solution on the surface of gold electrode. The self-assembled TPE aggregates exhibited inherent porous structures, endowing them with high specific surface area and oxygen adsorption capability. Therefore, the fabricated porous structures could lead to a 50-fold increase in the ECL signal of luminol in neutral aqueous solution, in comparison to that on the bare electrode. In contrast, the aggregates of the two typical coplanar polycyclic aromatic hydrocarbons (PAHs), perylene and pyrene, gave a weaker ECL enhancement, owing to their disc-like molecular structure and densely packed layers under aggregated conditions. The proposed ECL system has been successfully applied for the detection of hydrogen peroxide (H2O2) in the linear range of 0.25-1000 μM with a detection limit (S/N = 3) of 0.1 μM. Our findings provide inspiration for revealing the role of inherent molecular structure in the aggregate configuration, and they provide attractive perspectives for the usage of noncoplanar molecules in analytical applications. [ABSTRACT FROM AUTHOR]

Ecological discourse, as object of ecolinguistics and cultural discourse studies, has far-reaching implications for fostering human beings’ ecological consciousness. However, European ecological discourse is inapt for promoting ecological consciousness due to its roots in critical discourse, Eurocentralization and Cartesianism. This paper aims to pursue a Confucian–Daoist inquiry to Chinese ecological discourse concerning its Confucian–Daoist dimensions in Chinese discursive, cultural and philosophical traditions. This Confucian–Daoist inquiry can be conducted in three parts: a conceptual inquiry into Chinese ecological discourse, a comparative inquiry into Sino-European ecological discourses and a constructive inquiry into a harmonious discourse based on harmosophy. This approach has an important twofold role: first, it can offer profound discursive and spiritual recourses for fostering ecological consciousness in addressing the global ecological crisis. Second, and more importantly, it can help European ecological discourse transcend the negative influences from its roots, which may underplay its role in ecological consciousness. By so doing, an intercultural dialogue for a harmonious world can arise for mutually dealing with ecological problems. [ABSTRACT FROM PUBLISHER]

In this paper, I argue that only dialogue that links science, aesthetics, and axiology can solve the ecological crisis' moral concerns. Serious consideration can thus be given to raising bio-ecological awareness (Section 1). The paper traces three global waves in the emerging field of ecolinguistics (Section 2). Their divergences and disharmony have hindered awareness of the bio-ecology and the benign development of the discipline (Section 3). To bring clarity to the field, it is therefore proposed that the roots of disharmony tap into the moral and ethical harmony of Chinese worldview (Section 4). By adopting a harmonious view of language, mind and the world, a future harmonious ecolinguistics can be realized to become a life science (Section 5). In short, a synthesis of science, axiology and aesthetics can bring new harmony to European and Chinese ecolinguistics. Such an outcome would be a significant step in improving human bio-ecological awareness and resolving the ecological crisis (Section 6). [ABSTRACT FROM AUTHOR]

Alloxan has been used as a diabetogenic agent to induce diabetes. It selectively induces pancreatic β-cell death. The specific toxicity, however, is not fully understood. In this study, we observed the effect of alloxan on proteasome function. We found that alloxan caused the accumulation of ubiquitinated proteins in NRK cells through the inhibition of the proteolytic activities of the proteasome. Biochemistry experiments with purified 26S and 20S proteasomes revealed that alloxan directly acts on the chymotrypsin- and trypsin-like peptidase activities. These results demonstrate that alloxan is a proteasome inhibitor, which suggests that its specific toxicity toward β-cell is at least in part through proteasome inhibition. [ABSTRACT FROM AUTHOR]

The surface states of carbon nanodots (CDs) were engineered by controlling the chemical structure on the surface of the CDs, which play an important role in the chemiluminescence sensing properties of CDs towards peroxynitrite. Their application in monitoring exogenous and endogenous release of peroxynitrite in living cells is demonstrated. [ABSTRACT FROM AUTHOR]

The utilization of semiconductor quantum dots (QDs) as optical labels for biosensing and biorecognition has made substantial progress. However, the development of a suitable QD-based luminescent probe that is capable of detecting individual reactive oxygen species (ROS) represents a great challenge, mainly because the fluorescence of QDs is quenched by a wide variety of ROS. To overcome this limitation, a novel QD-based turn-on luminescent probe for the specific detection of .OH has been designed, and its application in monitoring the endogenous release of .OH species in living cells is demonstrated. Metal citrate complexes on the surfaces of the QDs can act as electron donors, injecting electrons into the LUMO of the QDs, while .OH can inject holes into the HOMO of the QDs. Accordingly, electron-hole pairs are produced, which could emit strong luminescence by electron-hole recombination. Importantly, this luminescent probe does not respond to other ROS. [ABSTRACT FROM AUTHOR]

The utilization of semiconductor quantum dots (QDs) as optical labels for biosensing and biorecognition has made substantial progress. However, the development of a suitable QD-based luminescent probe that is capable of detecting individual reactive oxygen species (ROS) represents a great challenge, mainly because the fluorescence of QDs is quenched by a wide variety of ROS. To overcome this limitation, a novel QD-based turn-on luminescent probe for the specific detection of .OH has been designed, and its application in monitoring the endogenous release of .OH species in living cells is demonstrated. Metal citrate complexes on the surfaces of the QDs can act as electron donors, injecting electrons into the LUMO of the QDs, while .OH can inject holes into the HOMO of the QDs. Accordingly, electron-hole pairs are produced, which could emit strong luminescence by electron-hole recombination. Importantly, this luminescent probe does not respond to other ROS. [ABSTRACT FROM AUTHOR]

In this study, we focused on measuring levels of nurse burnout and job dissatisfaction in the daily practice of nurses in Hunan province, China, analyzed factors related to nurse burnout and job dissatisfaction, and explored the relationship between them. Previous studies have shown a high level of burnout and job dissatisfaction among nurses worldwide. A cross-sectional survey of 1100 nurses was conducted. The nurses worked at 20 hospitals in 11 cities and counties throughout China's Hunan province. Nurse burnout was measured by the Maslach Burnout Inventory. Nurse-rated job dissatisfaction was described using a four point scale, and work environment was measured using the Nursing Work Index - Practice Environment Scale. The results showed that nurses had high burnout scores and were dissatisfied with their jobs. Staffing, work environment, and work hours were all significantly associated with nurse burnout and job dissatisfaction. Adequate staffing, improved work environment, and reasonable work hours are related to decreasing nurse burnout and job dissatisfaction. [ABSTRACT FROM AUTHOR]

As a well-known environmental pollutant but also an important gaseous transmitter, the specific detection of hydrogen sulfide (H2S) is significant in biological systems. In this study, fluorosurfactant functionalized gold nanorods (FSN-AuNRs) have been proposed to act as selective colorimetric nanoprobes for H2S. With the combination of strong gold–S interactions and small FSN bilayer interstices, FSN-AuNRs demonstrate favorable selectivity and sensitivity toward H2S over other anions and small biological molecules. The practical application of the present method in biological H2S detection was validated with human and mouse serum samples. Moreover, the proposed nanoprobe can also be used for evaluating the activity of H2S synthetase. [ABSTRACT FROM AUTHOR]

Luminescent films have received great interest for chemo-/bio-sensing applications due to their distinct advantages over solution-based probes, such as good stability and portability, tunable shape and size, non-invasion, real-time detection, extensive suitability in gas/vapor sensing, and recycling. On the other hand, they can achieve selective and sensitive detection of chemical/biological species using special luminophores with a recognition moiety or the assembly of common luminophores and functional materials. Nowadays, the extensively used assembly techniques include drop-casting/spin-coating, Langmuir–Blodgett (LB), self-assembled monolayers (SAMs), layer-by-layer (LBL), and electrospinning. Therefore, this review summarizes the recent advances in luminescent films with these assembly techniques and their applications in chemo-/bio-sensing. We mainly focused on the discussion of the relationship between the sensing properties of the films and their architecture. Furthermore, we discussed some critical challenges existing in this field and possible solutions that have been or are being developed to overcome these challenges. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) is a major threat to public health worldwide. The relationship between CVD and temperature has been widely reported in developed countries and regions. However, there are few studies of severe CVD in poor rural areas of developing countries. Therefore, this study aimed to explore the relationship between CVD and apparent temperature (AT) in a rural area of Linxia Hui Autonomous Prefecture, China. Daily CVD admission data and meteorological data were collected from Linxia between 2014 and 2015. The media of AT was used as the reference temperature to estimate the cumulative relative risk (RR) of CVD admission. The distributed lag non-linear models were used to examine the association between AT and cumulative RR of CVD admission at lag 0–21 days. In Linxia, high AT (20 °C) had a persistent adverse effect on cumulative RR of CVD admissions, and the RR increased with increasing lag days. Cold (− 10 °C) had a protective effect on the first and later lag days (lag 0–14 and lag 0–21). Adults (aged < 65 years) and females were more susceptible to the effects of heat than males and the elderly (aged ≥ 65 years). In Linxia, China, extremely high AT is an important risk factor for CVD hospitalizations in suburban and rural populations. [ABSTRACT FROM AUTHOR]

Polyurethane elastomer nanocomposites are strategically important due to their indispensable applications in daily life and high-tech fields. Herein, a series of nanocomposites with extraordinary strength, toughness and energy dissipation are reported, which are enabled by multiple dynamic moieties including dynamic boronic ester covalent bonds, boron-nitrogen coordination bonds in the matrix and on the interface. The surface-modified silica nanoparticles with amino-silane coupling agent (D-SiO 2) were added to the polyurethane matrix that contains boron-nitrogen coordination. The presence of interfacial coordination significantly improves the dispersion of D-SiO 2 and enhances the interface interaction of polyurethane composites (SPU/D-SiO 2), which is evidenced by scanning electron microscopy, transmission electron microscopy and rheological investigation. Through mechanical experiment analysis, these modified polyurethane composites exhibit high tensile strength and toughness. The tensile strength of SPU/10D-SiO 2 increases to 19.5 ± 0.2 MPa and its tensile toughness achieves 216.9 MJ/m3, which is 35% of increase as compared with the pristine SPU that had a record-high toughness. In addition, the coordination bonds in the matrix and interface in the composites provide versatile and efficient energy dissipation during the tensile process. This work offers a facile method to improve the mechanical robustness of the newly developed supramolecular polyurethane elastomers. [Display omitted] • The interfacial coordination significantly improves the dispersion of D-SiO 2 and enhances the interfacial interaction. • The tensile toughness of SPU/10D-SiO 2 achieves 216.9 MJ/m3, which is 35% of increase as compared with the pristine SPU. • The extraordinary strength, toughness and energy dissipation are enabled by multiple dynamic moieties. [ABSTRACT FROM AUTHOR]

Purpose The aim of this project is to investigate the impact of diabetes mellitus and different glycemic control times on early osseointegration of dental implants by expression and significance of serum bone Gla protein ( BGP) and alkaline phosphatase ( ALP) levels in Zucker diabetic fatty ( ZDF) rats after implantation. Materials and Methods The animals were divided into three groups, each group with 11 rats and each rat with two dental implants (33 rats and 66 implants in total): group A, diabetic rats with dental implants (controls); group B, diabetic rats treated with insulin and implants placed simultaneously; and group C, diabetic rats treated with insulin until serum glucose at a constant level and then implants be placed. Levels of BGP and ALP in the serum were measured by enzyme-linked immunosorbent assay in each group. The software program SPSS (version 17.0 for Windows) was used to analyze all data; p < .05 was set as the level of statistical significance. Results At the 7th day, serum levels of BGP in group B and C were lower than that in group A ( p > 0.05). At the 14th day, serum levels of BGP in group C were significantly higher ( p < 0.05). After 30 days, compared with group A, the serum levels of BGP in group B and C seems to be lower. Compared with group A, the serum levels of ALP in group B and C were significantly higher, whereas the serum levels of ALP in group C seems to be higher than B ( p < 0.05). Conclusions The present results suggest that injection of delayed release microsphere of exenatide on ZDF rats can release exenatide at a steady rate and the blood glucose can be controlled at a constant level. Implant survival rates could be enhanced in DM subjects when blood plasma glucose level is under control; the serum levels of BGP in this study seems to have no relationship with local osseointegration, whereas the serum levels of ALP might offer insights into the activity of osseointegration around the implant surface. [ABSTRACT FROM AUTHOR]

Abstract: In this work, Mg–Al CO3-layered double hydroxides (LDHs) were used as adsorbent materials for sodium dodecyl benzene sulfonate (SDBS) in aqueous solutions, the enriched SDBS can be directly detected by IO4 −–H2O2 chemiluminescence (CL) system. The commonly existing cations cannot be enriched by Mg–Al CO3-LDHs due to the structurally positively charged layers of LDHs, while other adsorbed anionic interferents had no effect on the IO4 −–H2O2 CL reaction. The corresponding linear regression equation was established in the range of 0.1–10μM for SDBS. The detection limit at a signal-to-noise (S/N) ratio of 3 for SDBS was 0.08μM. The relative standard deviation (RSD) for nine repeated measurements of 0.5μM SDBS was 2.6%. This proposed method has been successfully applied to the determination of SDBS in river water samples. To the best of our knowledge, we have first time coupled the high enrichment capacity of LDHs towards anions with CL detection for analytes. [Copyright &y& Elsevier]

[Display omitted] • Achieving full degradability of polylactide blends using biodegradable polyurethane elastomers as the toughening modifier. • The morphology of minor phase and matrix crystallization in PLLA blends is regulated significantly by interfacial sc-PLA. • The superior toughness is achieved at the optimized D-PU content after thermal annealing. • The toughening mechanism and degradation performance reveal the importance of interfacial stereocomplexation of PLA. The degradable polyurethane elastomers containing poly (L-lactide) (L-PU) and poly (D-lactide) (D-PU) were synthesized and incorporated in commercial PLLA as the toughening modifier. The stereocomplexation of PLA (sc-PLA) is successfully achieved at the interface of PU and PLLA domains in a single melt-blending process. The morphology and matrix crystallization in PLLA/D-PU blends is significantly improved by the presence of interfacial sc-PLA, showing morphological evolution to strip-shaped dispersion of PU phase and remarkable acceleration in matrix crystallization kinetics. After incorporating D-PU, the mechanical properties of blends are improved by interfacial sc-PLA, demonstrating that the notched Izod impact strength increases from 11.8 ± 3.1 KJ/m2 of PLLA/L-PU15 to 27.0 ± 5.8 KJ/m2 of PLLA/D-PU15 and even greater enhancement after thermal annealing is achieved. By observing the morphology of the impact fracture surface, the toughening mechanism of D-PU is investigated, revealing that the superior interfacial strength facilitates shear yielding of non-annealed sample and further prohibits de-bonding of rubber phase after thermal annealing. Hydrolysis tests in alkaline environment show that although interfacial sc-PLA can retard the hydrolysis rate, the blends still experience rapid weight loss to achieve full degradation. This work provides a highly effective strategy to toughen PLLA without sacrificing its degradability. [ABSTRACT FROM AUTHOR]

MXene quantum dots (MQDs), an emerging zero‐dimensional nanomaterial, have garnered significant attention from researchers due to their distinctive physical and chemical properties. In this study, cysteine‐functionalized Ti3C2 MQDs were synthesized using a facile hydrothermal methods, resulting in the functionalized Ti3C2 MQDs exhibiting intense blue fluorescence attributed to size‐dependent effects and surface defects. Furthermore, the cysteine‐functionalized Ti3C2 MQDs exhibit excitation wavelength‐dependent emission behavior and serve as a highly sensitive fluorescent probe for Ag+ detection with an impressive low limit of detection (LOD) of 0.015 μM. Moreover, they demonstrate exceptional sensitivity and selectivity in determining Ag+. This study presents a novel approach for the detection of Ag+ and highlights the immense potential of cysteine‐functionalized Ti3C2 MQDs in environmental applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • Both HIIT and MICT improved PIA-induced depression and anxiety by inhibiting glial activation. • HIIT was superior to MICT in alleviating anxiety-like and depresive-like behaviors in PIA mice. • HIIT ameliorated PIA-induced abnormalities and increases glia-derived IL-4 and BDNF release by specifically regulating KDM6B. Postnatal immune activation (PIA) induces persistent glial activation in the brain and causes various neuropathologies in adults. Exercise training improves stress-related mood disorders; however, the role of exercise in psychiatric disorders induced by early-life immune activation and the association between exercise training and glial activation remain unclear. We compared the effects of different exercise intensities on the PIA model, including high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT). Both HIIT and MICT in adolescent mice inhibited neuroinflammation, remodeled synaptic plasticity, and improved PIA-induced mood disorders in adulthood. Importantly, HIIT was superior to MICT in terms of reducing inflammation and increasing body weight. RNA-seq of prefrontal cortex (PFC) tissues revealed a gene expression pattern, confirming that HIIT was more effective than MICT in improving brain glial cell activation through epigenetic modifications of KDM6B. We investigated the role of KDM6B, a specific histone lysine demethylation enzyme — histone 3 lysine 27 demethylase, in inhibiting glial activation against PIA-induced depression and anxiety by regulating the expression of IL-4 and brain-derived neurotrophic factor (BDNF). Overall, our data support the idea that HIIT improves PIA-induced mood disorders by regulating KDM6B-mediated epigenetic mechanisms and indicate that HIIT might be superior to MICT in improving mood disorders with PIA in mice. Our findings provide new insights into the treatment of anxiety and depression disorders. [ABSTRACT FROM AUTHOR]

AbstractDiabetic wound is one of the most challenge in healthcare, requiring innovative approaches to promote efficient healing. In recent years, lipid nanoparticle-based drug delivery systems have emerged as a promising strategy for enhancing diabetic wound repair by stimulating angiogenesis. These nanoparticles offer unique advantages, including improved drug stability, targeted delivery, and controlled release, making them promising in enhancing the formation of new blood vessels. In this review, we summarize the emerging advances in the utilization of lipid nanoparticles to deliver angiogenic agents and promote angiogenesis in diabetic wounds. Furthermore, we provide an in-depth exploration of key aspects, including the intricate design and fabrication of lipid nanoparticles, their underlying mechanisms of action, and a comprehensive overview of preclinical studies. Moreover, we address crucial considerations pertaining to safety and the translation of these innovative systems into clinical practice. By synthesizing and analyzing the available knowledge, our review offers valuable insights into the future prospects and challenges associated with utilizing the potential of lipid nanoparticle-based drug delivery systems for promoting robust angiogenesis in the intricate process of diabetic wound healing. [ABSTRACT FROM AUTHOR]

Defective in cullin neddylation 1(DCN1) is a co-E3 ligase that is important for cullin neddylation. Dysregulation of DCN1 highly correlates with the development of various cancers. Herein, from the initial high-throughput screening, a novel hit compound 5a containing a phenyltriazole thiol core (IC 50 value of 0.95 μM for DCN1-UBC12 interaction) was discovered. Further structure-based optimization leads to the development of SK-464 (IC 50 value of 26 nM). We found that SK-464 not only directly bound to DCN1 in vitro , but also engaged cellular DCN1, suppressed the neddylation of cullin3, and hindered the migration and invasion of two DCN1-overexpressed squamous carcinoma cell lines (KYSE70 and H2170). These findings indicate that SK-464 may be a novel lead compound targeting DCN1-UBC12 interaction. [Display omitted] • A hit compound 5a containing a phenyltriazole thiol core was discovered as DCN1-UBC12 interaction inhibitor in initial HTS. • 38 phenyltriazole thiol derivatives were further designed, synthesized and evaluated. • SK-464 could significantly inhibit DCN1-UBC12 interaction at both protein and cellular levels. • SK-464 effectively inhibits the migration and invasion of two DCN1-overexpressed squamous cell carcinoma cell lines. [ABSTRACT FROM AUTHOR]

• The self-compacting road concrete incorporating nano-silica was prepared. • The optimum content of nano-silica is 1% based on grey relational analysis. • Incorporation of nano-silica improves the flexural fatigue performance of samples. • Nano-silica can promote the secondary hydration reaction and fill the micropores. In this study, the mix proportion of self-compacting road concrete with ternary cementitious materials was optimized by incorporating nano-silica particles to improve its flexural fatigue performance. The filling property and compressive strength were selected as evaluating indicators to design L 9 (33) orthogonal test, and then four kinds of mix proportions were selected to prepare the nano-modified self-compacting concrete (SCC) according to the results of grey relational analysis and comprehensive weighting method. The four-point flexural fatigue tests were conducted to establish the probabilistic fatigue equations of nano-modified SCC based on the two-parameter Weibull distribution with survival rates of 50% and 95%, respectively. The modification mechanism was revealed with the help of scanning electron microscopy and X-ray diffraction phase analysis. The results indicate that the optimal mix proportion of self-compacting road concrete could be obtained when nano-silica accounts for 1% of the mass of cementitious materials. The specimens with 1% nano-silica particles showed the best flexural fatigue performance, with the reduction factor of flexural strength increased by 1.5%–5.0% and the sensitivity of fatigue life to the stress levels decreased by 2.1%–9.7% at survival rate of 50%. The nanoparticles provided a physical filling effect and facilitated the formation of low-density calcium silicate hydrate gel, filling the internal micro-pores to make the structure more compact. Nano-silica improved the flexural fatigue performance of self-compacting road concrete to a certain extent. [ABSTRACT FROM AUTHOR]

Broca's area is composed of the pars opercularis (PO) and the pars triangularis (PTR) of the inferior frontal gyrus; the anterior ascending ramus of the lateral sulcus (aals) separates the PO from the PTR, and the horizontal ascending ramus of the lateral sulcus (hals) separates the PTR from the pars orbitalis. The morphometry of these two sulci maybe has potential effects on the various functions of Broca's area. Exploring the morphological variations, hemispheric differences and sex differences of these two sulci contributed to a better localization of Broca's area. BrainVISA was used to reconstruct and parameterize these two sulci based on data from 3D MR images of 90 healthy right-handed subjects. The 3D anatomic morphologies of these two sulci were investigated using 4 sulcal parameters: average depth (AD), average width (AW), outer length (OL) and inner length (IL). The aals and hals could be identified in 98.89% and 98.33%, respectively, of the hemispheres evaluated. The morphological patterns of these two sulci were categorized into four typical types. There were no statistically significant interhemispheric or sex differences in the frequency of the morphological patterns. There was statistically significant interhemispheric difference in the IL of the aals. Significant sex differences were found in the AD and the IL of the aals and OL of the hals. Our results not only provide a structural basis for functional studies related to Broca's area but also are helpful in determining the precise position of Broca's area in neurosurgery. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) has a significant burden on healthcare systems worldwide, and is associated with high morbidity and mortality rates in patients. In 2020, the estimated new cases of colon cancer in the United States are 78,300 in men and 69,650 in women. Thus, developing effective and novel alternative agents and adjuvants with reduced side effects is important to reduce the lethality of the disease and improve the quality of life of patients. Melatonin, a pineal hormone that possesses numerous physiological functions, including anti-inflammatory and antitumor activities, can be found in various tissues, including the gastrointestinal tract. Melatonin exerts anticarcinogenic effects via various mechanisms; however, the identified underlying molecular mechanisms do not explain the full breadth of anti-CRC effects mediated by melatonin. MicroRNAs (miRs) serve critical roles in tumorigenesis, however, whether melatonin can inhibit CRC by regulating miRs is not completely understood. In the present study, the roles and mechanism underlying melatonin in CRC were investigated. The proliferation of human CRC cells was tested by CCK8, EDU and colony formation assay. The apoptosis of cancer cells was detected by flow cytometry and western blotting. A xenograft mouse model was constructed and the proliferation and apoptosis of tumor tissue was detected by Ki-67 and TUNEL staining assay respectively. Reverse transcription-quantitative PCR and western blotting were performed to measure the regulation of miRs on mRNA, and the dual-luciferase report analysis experiment was used to verify the direct target genes of miRs. Compared with the control group, melatonin inhibited viability and proliferation, and induced apoptosis in CRC cells. Additionally, the effect of melatonin in a xenograft mouse model was assessed. Compared with the control group, melatonin significantly enhanced the expression levels of the miR-34a/449a cluster, reduced CRC cell proliferation and viability, and increased CRC cell apoptosis. Finally, the dual-luciferase reporter assay indicated that Bcl-2 and Notch1 were the target mRNAs of the miR-34a/449a cluster. To the best of our knowledge, the present study was the first to suggest that melatonin inhibited proliferation and viability, and promoted apoptosis in CRC cells via upregulating the expression of the miR-34a/449a cluster in vitro and in vivo. Therefore, melatonin may serve as a potential therapeutic for CRC. [ABSTRACT FROM AUTHOR]

• 30 compounds containing triazolopyrimidine and hydrazone were synthesized. • Anticancer activity was evaluated against five cancer cell lines. • Compound 34 displayed potent inhibitory activity against PC3 cell lines. • Compound 34 exhibited selectivity between PC3 and the other tested cell lines. • Compound 34 increased ROS level, down-regulated EGFR and induced apoptosis. In this paper, based on molecular hybridization, a series of [1,2,3]triazolo[4,5- d pyrimidine derivatives containing hydrazine was synthesized and their antiproliferative activities against 5 cancer cell lines (MGC-803, PC3, PC9, EC9706 and SMMC-7721) were evaluated. We found that most of them exhibited obvious growth inhibition effects on these tested cancer cells, especially compound 34 on PC3 cells (IC 50 = 26.25 ± 0.28 nM). Meanwhile, compound 34 displayed best selectivity on PC3, compared with the other cancer cell lines, as well as excellent selectivity towards normal cell lines (Het-1A, L02 and GES-1). Further investigations demonstrated that 34 could significantly inhibit PC3 cells' colony formation, increase cellular ROS content, suppress EGFR expression and induce apoptosis. Our findings indicate that 34 may serve as a novel lead compound for the discovery of more triazolopyrimidine derivatives with improved anticancer potency and selectivity. [ABSTRACT FROM AUTHOR]