Week-long normoglycaemia in diabetic mice and minipigs via a subcutaneous dose of a glucose-responsive insulin complex.

Glucose-responsive formulations of insulin can increase its therapeutic index and reduce the burden of its administration. However, it has been difficult to develop single-dosage formulations that can release insulin in both a sustained and glucose-responsive manner. Here we report the development of a subcutaneously injected glucose-responsive formulation that nearly does not trigger the formation of a fibrous capsule and that leads to week-long normoglycaemia and negligible hypoglycaemia in mice and minipigs with type 1 diabetes. The formulation consists of gluconic acid-modified recombinant human insulin binding tightly to poly-L-lysine modified by 4-carboxy-3-fluorophenylboronic acid via glucose-responsive phenylboronic acid-diol complexation and electrostatic attraction. When the insulin complex is exposed to high glucose concentrations, the phenylboronic acid moieties of the polymers bind rapidly to glucose, breaking the complexation and reducing the polymers' positive charge density, which promotes the release of insulin. The therapeutic performance of this long-acting single-dose formulation supports its further evaluation and clinical translational studies.

Identifying potential pathogenesis and immune infiltration in diabetic foot ulcers using bioinformatics and in vitro analyses.

BACKGROUND: Diabetic foot ulcers (DFU) are among the fastest-growing diseases worldwide. Recent evidence has emphasized the critical role of microRNA (miRNA)-mRNA networks in various chronic wounds, including DFU. In this study, we aimed to clarify the miRNA-mRNA axes associated with the occurrence of DFU. METHODS: Expression profiles of miRNAs and mRNAs were extracted from the Gene Expression Omnibus. Differentially expressed genes and differentially expressed miRNAs were identified, and miRNA-mRNA regulatory axes were constructed through integrated bioinformatics analyses. We validated the miRNA-mRNA axes using quantitative real-time PCR (qPCR) and dual-luciferase reporter assays. We conducted an immune infiltration analysis and confirmed the bioinformatics results using immunofluorescence staining. Single-sample gene set enrichment analysis (ssGSEA) was used to analyze the metabolic mechanisms. RESULTS: miR-182-5p-CHL1/MITF and miR-338-3p-NOVA1 interactions were identified using in silico analysis. The qPCR results showed apparent dysregulation of these miRNA-mRNA axes in DFU. The dual-luciferase reporter assay confirmed that miR-182-5p targeted CHL1 and MITF, and miR-338-3p targeted NOVA1. We conducted an immune infiltration analysis and observed that key genes correlated with decreased infiltration of M1 macrophages and resting mast cells in DFU. Immunofluorescence staining verified the co-localization of CHL1 and tryptase, while MITF and CD68 showed weak positive correlations. Metabolic pathways related to these three genes were identified using ssGSEA. CONCLUSIONS: In summary, the miR-182-5p-CHL1/MITF and miR-338-3p-NOVA1 pathway interactions and decreased infiltration of M1 macrophages and resting mast cells may provide novel clues to the pathogenesis of DFU. TRIAL REGISTRATION: The clinical trial included in this study was registered in the Chinese Clinical Trial Registry ( ChiCTR2200066660 ) on December 13, 2022.

Exploring release mechanisms by disrupting π-π stacking regions in stable micelles.

π-π stacking strategies can enhance the stability performance of delivery platforms but are often restricted by incomplete drug release performance, even with the help of crosslinking strategies. Therefore, there has been considerable interest in enhancing the drug release performance by disrupting the π-π stacking region (structural rearrangements). Herein, we synthesized poly(3-(isobutyloxy)-2-oxopropyl benzoate)-b-poly(2-hydroxybutyl methacrylate)-co-poly((ethylene glycol)methylether methacrylate) [PBOOPMA-b-P(HBMA-co-PEGMA), PHB] and revealed the drug release mechanism of PHB-based micelles. The structural rearrangements derived from the crosslinking strategy were revealed to improve the early release performance by 43-55% using micellar dissolutions. Moreover, the esterase-responsive strategy was elucidated to induce reassembly with 77-79% size variation, intensifying the structural rearrangements, which was also synergistic with the crosslinking strategy. Based on the advantages of improving drug release performance, the esterase-responsive strategy was considered a promising candidate for enhancing late release performance. Meanwhile, it is believed that such responsive modulation (crosslinking, esterase-responsive) in the π-π stacking region will become highly promising for subsequent research. Finally, the biosafety of 95.81% at 400 mg L-1 and drug cytotoxicity of IC50 ≈ 2.5 mg L-1 of PHB-EDE@CPT were also validated, confirming the broad application prospects of PHB-based crosslinked micelles.

Association between childhood trauma and affective lability among adolescents: A moderated mediation model.

BACKGROUND: Affective lability is an important feature of psychopathology. However, there is limited relevant research involving adolescents. To fill this research gap, the present study assessed the relationship between childhood trauma and affective lability among adolescents using a moderated mediation model. METHODS: A total of 3738 students were recruited from four high schools in Shenzhen, China, between September and December 2019. The participants completed self-reported questionnaires measuring childhood trauma, affective lability, body image dissatisfaction, and the experience of being bullied. Linear regression and moderated mediation analyses were used in this study. RESULTS: Linear regression analysis showed that emotional abuse and body image dissatisfaction positively predicted affective lability in boys and girls (all p < 0.001). Body image dissatisfaction mediated the relationship between emotional abuse and affective lability. In the moderated mediation model, being bullied moderated the direct path from emotional abuse to affective lability (p = 0.0236, p = 0.0188), and gender did not have a significant moderating effect on any direct or indirect path (all p > 0.05). LIMITATIONS: A causal relationship could not be ascertained due to the cross-sectional design, and the results cannot be generalized to other populations. CONCLUSIONS: The findings support that childhood trauma has an impact on affective lability in adolescents. Specifically, body image dissatisfaction and being bullied affect the relationship between emotional abuse and affective lability.

Template-Directed Synthesis of Colloidal Hollow Particles: Mind the Material Used for the Template.

The dissolution of a polymeric solid typically starts with the absorption of solvent molecules, followed by swelling and volume expansion. Only when the extent of swelling reaches a threshold can the polymer chains be disentangled and then dissolved into the solvent. When the polymeric solid is encapsulated in a rigid shell, the swelling process will be impeded. Despite the widespread use of this process, it is rarely discussed in the literature how the polymeric solid is dissolved from the core for the generation of colloidal hollow particles. Recent studies have started to shed light on the mechanistic details involved in the formation of hollow particles through a template-directed process. Depending on the nature of the material used for the template, the removal of the template may involve different mechanisms and pathways, leading to the formation of distinct products. Here, a number of examples are used to illustrate this important phenomenon that is largely neglected in the literature. This article also discusses how the swelling of a polymeric template encapsulated in a rigid shell can be leveraged to fabricate new types of functional colloidal particles.

Copolymer-Functionalized Cellulose Nanocrystals as a pH- and NIR-Triggered Drug Carrier for Simultaneous Photothermal Therapy and Chemotherapy of Cancer Cells.

As a class of biocompatible and biodegradable naturally derived nanomaterials, cellulose nanocrystals (CNCs) with diverse surface functionalization have aroused considerable attention for a range of biomedical applications in drug or gene delivery, as a fluorescent nanoprobe, in cancer targeting, and in photothermal cancer therapy, among others. Herein, we construct the copolymer-functionalized CNCs as a pH- and near-infrared (NIR)-triggered drug carrier for simultaneous photothermal therapy and chemotherapy of cancer cells. Poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (PCL-b-PDMAEMA) was conjugated onto the surface of CNCs through ring-opening polymerization, followed by activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP). The resultant CNC-based drug carrier can encapsulate doxorubicin (DOX) as a therapeutic agent and indocyanine green (ICG) as an NIR dye in the PCL core and the PDMAEMA shell, respectively, via hydrophobic and electrostatic interactions. In addition to the intrinsic pH response, the release profile of DOX can also be controlled by the duration of laser irradiation due to collapse of the crystal structure of the PCL domain with the increase of temperature induced by photothermal conversion. The drug carrier can exhibit enhanced cytotoxicity toward HepG2, human hepatocyte carcinoma, cells upon laser irradiation, which can be attributed to the synergistic effect arising from NIR-triggered burst release of DOX and photothermal heating. The rod-like morphology of the CNC-based drug carrier may help accelerate the endocytosis in cell membranes compared with its common spherical counterpart. Based on the abovementioned advantages, copolymer-functionalized CNCs can serve as a promising candidate for effective cancer treatment.

Morphological transitions of micelles induced by the block arrangements of copolymer blocks: dissipative particle dynamics simulation.

Polymer micelles with distinct morphologies and unique microphase separation microstructures can exhibit different properties and functions, holding great promise for a range of biomedical applications. In the current work, the topological effects of grafted triblock copolymers on the morphologies and microphase separation microstructures of micelles, including block arrangements and grafting arrangements of hydrophobic side chains, are systematically studied. Using common copolymer components of typical drug carriers, micelles with interesting geometries are achieved, such as raspberry, multicompartment, ellipsoidal and dumbbell shapes, in which the relationship between micelle morphology and copolymer topology is verified. With further exploration of the grafting position and amount of hydrophobic side chains, the microstructure influencing mechanism of copolymer micelles in self-assembly is discussed. The block arrangements of hydrophobic side chains determine the configurations of copolymers (zigzag/bridge) inside micelles, which in turn affect the morphological transitions (from spherical to ringed short-rods and then to cylinders) and the size of the hydrophobic ring, which further gradually change into hydrophobic cage. This study provides insight into the microstructure of hydrophobic side chain grafted copolymer micelles and further helps to understand the mechanism of controlling the morphology of micelles, which might be useful to guide the molecular design and experimental preparation of micelles with controllable morphology for drug encapsulation and delivery.

Clinical intervention effect of TACE combined with 3DCRT in patients with primary liver cancer.

OBJECTIVE: To investigate the clinical intervention effect of transcatheter arterial chemoembolization (TACE) combined with three-dimensional conformal radiotherapy (3DCRT) in patients with primary liver cancer (PLC). METHODS: A total of 110 PLC patients admitted to our hospital were selected and divided into the study group (SG, n=60, treated with TACE combined with 3DCRT) and the control group (CG, n=50, treated with TACE alone) in accordance with the different clinical intervention measures. The clinical intervention effect and the changes of tumor factors and quality of life scores were compared between the two groups before and after intervention, and the three-year survival and the incidence of adverse reactions were evaluated. RESULTS: The objective response rate (ORR) and disease control rate (DCR) in the SG (78.33% and 95.00%) were higher than those in the CG (38.00% and 80.00%), whereas the carcinoembryonic antigen (CEA) and alpha fetoprotein (AFP) levels in the SG were lower than those in the CG (P < 0.05). After intervention, the quality of life score in the SG was higher than that in the CG (P < 0.05). The SG was superior to the CG in follow-up survival (P < 0.05). CONCLUSION: TACE combined with 3DCRT has a high safety and leads to remarkable clinical intervention effects, marked improvement of the serological indices, better quality of life, as well as satisfactory long-term survival.

Self-assembly of cyclic grafted copolymers with rigid rings and their potential as drug nanocarriers.

Enhancing the performance of polymer micelles by purposeful regulation of their structures is a challenging topic that receives widespread attention. In this study, we systematically conduct a comparative study between cyclic grafted copolymers with rigid and flexible rings in the self-assembly behavior via dissipative particle dynamics (DPD) simulation. With a focus on the possible stacking ways of rigid rings, we propose the energy-driven packing mechanism of cyclic grafted copolymers with rigid rings. For cyclic grafted copolymers with large ring size (14 and 21-membered rings), rigid rings present a novel channel-layer-combination layout, which is determined by the balance between the potential energy of micelles (Emicelle) and the interaction energy between water and micelles (Eint). Based on this mechanism, we further regulate a series of complex self-assembling structures, including curved rod-like, T-shape, annular and helical micelles. Compared with flexible copolymers, cyclic grafted copolymers with rigid rings provide a larger and loose hydrophobic core and higher structural stability with micelles due to the unique packing way of rigid rings. Therefore, their micelles have a great potential as drug nanocarriers. They possess a better drug loading capacity and disassemble more quickly than flexible counterparts under acidic tumor microenvironment. Furthermore, the endocytosis kinetics of rigid micelles is faster than the flexible counterparts for the adsorption and wrapping process. This study may provide a reasonable idea of structural design for polymer micelles to enhance their performance in biomedical applications.

Maternal Diabetes-Induced Suppression of Oxytocin Receptor Contributes to Social Deficits in Offspring.

Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterized by impaired skills in social interaction and communication in addition to restricted and repetitive behaviors. Many different factors may contribute to ASD development; in particular, oxytocin receptor (OXTR) deficiency has been reported to be associated with ASD, although the detailed mechanism has remained largely unknown. Epidemiological study has shown that maternal diabetes is associated with ASD development. In this study, we aim to investigate the potential role of OXTR on maternal diabetes-mediated social deficits in offspring. Our in vitro study of human neuron progenitor cells showed that hyperglycemia induces OXTR suppression and that this suppression remains during subsequent normoglycemia. Further investigation showed that OXTR suppression is due to hyperglycemia-induced persistent oxidative stress and epigenetic methylation in addition to the subsequent dissociation of estrogen receptor ß (ERß) from the OXTR promoter. Furthermore, our in vivo mouse study showed that maternal diabetes induces OXTR suppression; prenatal OXTR deficiency mimics and potentiates maternal diabetes-mediated anxiety-like behaviors, while there is less of an effect on autism-like behaviors. Additionally, postnatal infusion of OXTR partly, while infusion of ERß completely, reverses maternal diabetes-induced social deficits. We conclude that OXTR may be an important factor for ASD development and that maternal diabetes-induced suppression of oxytocin receptor contributes to social deficits in offspring.

Nanobottles for Controlled Release and Drug Delivery.

Nanobottles refer to colloidal particles with a hollow interior and a single opening in the wall. These unique features make them ideal carriers for the loading, encapsulation, release, and delivery of various types of theranostic agents in an array of biomedical applications. The hollow interior gives them a high loading capacity while the opening enables quick loading and controlled release of the payload(s). More significantly, on-demand release can be readily achieved by adding a stimuli-responsive material as the inner matrix or cork stopper. This progress report begins with an introduction to the general structures and properties of nanobottles, followed by a brief discussion on the methods developed for their fabrication. The use of nanobottles for loading different types of payloads is then showcased, including small-molecule drugs, biomacromolecules, imaging contrast agents, and functional nanoparticles. The strategies explored for controlling the release by varying the size of the opening and/or integrating with a stimuli-responsive material are also highlighted. This paper concludes with some perspectives on future directions for this class of nanomaterials in terms of fabrication, functionalization, and application.

Maternal Diabetes Induces Immune Dysfunction in Autistic Offspring Through Oxidative Stress in Hematopoietic Stem Cells.

Autism spectrum disorders (ASD) have been found to be associated with immune dysfunction and elevated cytokines, although the detailed mechanism remains unknown. In this study, we aim to investigate the potential mechanisms through a maternal diabetes-induced autistic mouse model. We found that maternal diabetes-induced autistic offspring have epigenetic changes on the superoxide dismutase 2 (SOD2) promoter with subsequent SOD2 suppression in both hematopoietic stem cells (HSC) and peripheral blood mononuclear cells (PBMC). Bone marrow transplantation of normal HSC to maternal diabetes-induced autistic offspring transferred epigenetic modifications to PBMC and significantly reversed SOD2 suppression and oxidative stress and elevated inflammatory cytokine levels. Further, in vivo human study showed that SOD2 mRNA expression from PBMC in the ASD group was reduced to ~12% compared to typically developing group, and the SOD2 mRNA level-based ROC (Receiver Operating Characteristic) curve shows a very high sensitivity and specificity for ASD patients. We conclude that maternal diabetes induces immune dysfunction in autistic offspring through SOD2 suppression and oxidative stress in HSC. SOD2 mRNA expression in PBMC may be a good biomarker for ASD diagnosis.

[Moderated mediation analysis for symptoms of attention deficit/hyperactivity disorder with the symptoms of anxiety in children].

OBJECTIVE: To study the moderated mediation for attention deficit/hyperactivity disorder (ADHD) with the symptoms of anxiety in children. METHODS: A total of 12 271 students were included with an average age of 8.9±1.9 years, including 6 743 male students and 5 508 female students, and 20 students with missing data on gender. Child psychological trauma questionnaires (parents version) and Conners questionnaires (parent version) were completed by the parents of primary school students. The data was studied by univariate analysis, multivariate analysis and moderated mediation analysis. RESULTS: The results of the univariate analysis showed that in all subjects, boys, and girls, the scores of hyperactivity index and childhood trauma were positively correlated with the score of anxiety (P<0.01), and ADHD and childhood trauma positively predicted anxiety disorder (P<0.001). The results of the multivariate analysis showed that in all subjects, boys, and girls, the scores of hyperactivity index (ADHD symptoms) and childhood trauma positively predicted the score of anxiety (P<0.001), and both ADHD and childhood trauma positively predicted anxiety disorder (P<0.001). The results of the moderated mediation analysis showed that childhood trauma was a mediating factor for the relationship between hyperactivity index and anxiety index in boys and girls (P<0.05), and sex moderated the relationship between hyperactivity index and anxiety index (P<0.001). CONCLUSIONS: ADHD symptoms/ADHD are closely associated with anxiety symptoms/anxiety disorder. Childhood trauma exerts a mediating effect on the relationship between ADHD symptoms and anxiety symptoms, and sex moderates the relationship between ADHD symptoms and anxiety symptoms.

Internet addiction mediates the association between cyber victimization and psychological and physical symptoms:moderation by physical exercise.

BACKGROUND: The potential mechanisms underlying cyber victimization and the resulting psychological and physical symptoms remain unclear. Thus, the present study investigated whether Internet addiction mediates the association between peer victimization (e.g., cyberbullying) and psychological and physical symptoms. Furthermore, it was assessed whether physical exercise moderates the hypothetical mediation. METHODS: 1854 students from 11 middle and high schools in Shenzhen, Guangdong Province, China, were sampled for this study. Psychological and physical symptoms were assessed using the World Health Organization Quality of Life-BREF, while Internet addiction was evaluated using the Internet addiction test by Young. Cyber victimization was measured using a single question. In addition, this study examined whether Internet addiction mediated the association between cyber victimization and both psychological and physical symptoms. Additional work was conducted to test if physical exercise played a moderating role in the mediation hypothesized above. Mediation and moderation were analyzed using PROCESS macro for SPSS. RESULTS: Regression analysis showed that both cyber victimization (ß = - 0.102, p < 0.05) and Internet addiction (ß = - 0.278, p < 0.05) significantly predicted psychological and physical symptoms and demographic variables were controlled. Further mediation analysis suggested that Internet addiction mediated the relationship between cyber victimization and psychological and physical symptoms. The 95% CI (confidence interval) of the direct effect was (- 4.283, - 1.696) and the indirect effect (- 1.904, - 0.820), respectively, excluding zero. Finally, moderation analysis indicated that physical exercise moderated the relationship between Internet addiction and psychological and physical symptoms (p = 0.047). CONCLUSIONS: Internet addiction plays a mediating role in the association between cyber victimization and both psychological and physical symptoms, Thus, addressing Internet addiction among cyberbullying victims is worthwhile. Furthermore, physical exercise alleviates negative impacts on health and should thus be promoted.

The relationship between mobile phone use and suicide-related behaviors among adolescents: The mediating role of depression and interpersonal problems.

BACKGROUND: This study examined (a) the relationship that interpersonal problems and depression share with the intensity of mobile phone use and (b) their effects on suicide-related behaviors (SRBs) and self-harming behaviors among adolescents. METHODS: In this cross-sectional study, adolescents were recruited from 11 middle and high schools in Shenzhen, China. They completed self-reported measures that assessed mobile phone use, their history of SRBs (i.e., suicidal ideation, suicidal planning, and attempted suicide) and self-harming behaviors, depression, and interpersonal problems. RESULTS: Interpersonal problems and depression mediated the relationship between high-intensity mobile phone use and the risk for SRBs and self-harming behaviors among Chinese adolescents. CONCLUSIONS: The findings delineate the pathways through which interpersonal problems and depression increase the risk for SRBs and self-harming behaviors among adolescents who report high-intensity mobile phone use. Future studies should develop interventions that alleviate interpersonal problems and depressive symptoms to reduce the risk for SRBs and self-harming behaviors among adolescents who report high-intensity mobile phone use.

Reversible Cross-Linked Mixed Micelles for pH Triggered Swelling and Redox Triggered Degradation for Enhanced and Controlled Drug Release.

Good stability and controlled drug release are important properties of polymeric micelles for drug delivery. A good candidate for drug delivery must have outstanding stability in a normal physiological environment, followed with low drug leakage and side effects. Moreover, the chemotherapeutic drug in the micellar core should also be quickly and "on-demand" released in the intracellular microenvironment at the tumor site, which is in favor of overcoming multidrug resistance (MDR) effects of tumor cells. In this work, a mixed micelle was prepared by the simple mix of two amphiphilic copolymers, namely PCL-SS-P(PEGMA-co-MAEBA) and PCL-SS-PDMAEMA, in aqueous solution. In the mixed micelle's core-shell structure, PCL blocks were used as the hydrophobic core, while the micellar hydrophilic shell consisted of two blocks, namely P(PEGMA-co-MAEBA) and PDMAEMA. In the micellar shell, PEGMA provided hydrophilicity and stability, while MAEBA introduced the aldehyde sites for reversible crosslinking. Meanwhile, the PDMAEMA blocks were also introduced in the micellar shell for pH-responding protonation and swelling of the micelle. The disulfide bonds between the hydrophobic core and hydrophilic shell had redox sensitive properties. Reversible cross-linked micelles (RCLMs) were obtained by crosslinking the micellar shell with an imine structure. RCLMs showed good stability and excellent ability against extensive dilution by aqueous solution. In addition, the stability in different conditions with various pH values and glutathione (GSH) concentrations was studied. Then, the anticancer drug doxorubicin (DOX) was selected as the model drug to evaluate drug entrapment and release capacity of mixed micelles. The in vitro release profiles indicated that this RCLM had controlled drug release. In the simulated normal physiological environment (pH 7.4), the drug release of the RCLMs was restrained obviously, and the cumulative drug release content was only 25.7 during 72 h. When it came to acidic conditions (pH 5.0), de-crosslinking of the micelles occurred, as well as protonation of PDMAEMA blocks and micellar swelling at the same time, which enhanced the drug release to a large extent (81.4%, 72 h). Moreover, the drug release content was promoted further in the presence of the reductant GSH. In the condition of pH 5.0 with 10 mM GSH, disulfide bonds broke-up between the micelle core and shell, followed by shedding of the shell from the inner core. Then, the micellar disassembly (degradation) happened based on the de-crosslinking and swelling, and the drug release was as high as 95.3%. The MTT assay indicated that the CLSMs showed low cytotoxicity and good biocompatibility against the HepG2 cells. In contrast, the DOX-loaded CLSMs could efficiently restrain the proliferation of tumor cells, and the cell viability after 48 h incubation was just 13.2%, which was close to that of free DOX. This reversible cross-linked mixed micelle with pH/redox responsive behaviors is a potential nanocarrier for chemotherapy.

The self-assembly behavior of polymer brushes induced by the orientational ordering of rod backbones: a dissipative particle dynamics study.

Dissipative particle dynamics (DPD) simulations were used to study the self-assembly behavior of polymer brushes with rod-coil backbones, polycaprolactone-b-poly(2-(dimethylamino)ethyl methacrylate)-grafted cellulose nanocrystals (CNC-g-PCL-b-PDMAEMA), and to further examine the influences of polymer concentration, rod-block proportion and distribution of backbones and the grafting density of side chains on the resulting aggregate conformations. We proposed the "rod-coil competitive mechanism" for the self-assembly of polymer brushes with rod-coil backbones. The results indicated that the micellar structures mainly depend on the relative intensity between the orientational ordering of rod blocks and the disordered packing of the flexible blocks. The cylindrical micelles were formed when the orientational order of the rod blocks predominates, while the disorder of the flexible blocks contributes to the formation of spherical micelles. We further proved that the competitive relationship is affected by polymer concentration, rod-block proportion and distribution of backbones and the grafting density of side chains. The increasing rod-block proportion, the rod-coil-rod backbones and the asymmetric grafting side chains are beneficial to the orientation order of the brush-like polymer in the self-assembly process, thereby inducing the formation of the cylindrical micelles. The self-assembly mechanism of the rod-coil copolymer proposed in this study provides guidance and a theoretical basis for the design and regulation of novel and complex polymer aggregates.

Directed Self-Assembly of Patchy Microgels into Anisotropic Nanostructures.

Multi-geometry nanostructures with high-order, complex, and controllable geometries have attracted extensive attention in the development of functional nanomaterials. A simple and versatile strategy is proposed to construct various anisotropic nanostructures through the directed self-assembly (DSA) of patchy microgels. A general criterion for interaction parameters is developed by the variance analysis method to achieve the formation of 1D nanorods by the single directional DSA process, and 2D or 3D polymorphs including V/T/h/cross shapes, multiple arms, multi-directional bending, single/multiple rings, nanocages, etc., by the multi-directional DSA process of binary microgel blends. At the optimum interaction parameters, the nanorods exhibit the quickest formation process and the most thermodynamically stable geometry, while the various 2D or 3D assemblies exhibit controlled jointing behaviors for versatile assembly geometries. The number of recognition sites on the patchy microgel surface guides the aggregation modes of microgels during the DSA process. These assemblies can bear large curvature variance with the increase of shear rates due to the high flexibility and the ability of adjusting orientation spontaneously. The DSA behavior of patchy microgels differs from the traditional self-assembly process of block copolymers, which may open a new route for guiding the formation of controllable nanoparticle architectures.

Mesoscopic simulations of drug-loaded diselenide crosslinked micelles: Stability, drug loading and release properties.

Intelligent reversible crosslinked micelles that have a good balance of structure stability in normal tissue and controlled drug release responded to the tumor microenvironment are highly promising novel drug delivery systems. However, to date, there have been very few reports about mesoscale simulations of drug-loaded polymeric reversible crosslinked micelles. Here, dissipative particle dynamics (DPD) simulation, the nearest-neighbor bonding principle, and the nearest media-bead bond breaking principle were used to investigate the influence of physiological environment along with low tumor pH and reduction microenvironment on the stability and doxorubicin (DOX) distribution of the star polymer [PCL-b-P(HEMA-Se-Se˜)-b-PPEGMA]6 diselenide crosslinked micelles with different diselenide crosslinking levels (CLs). The self-assembly process results obtained by DPD simulations reveal the formation of three-layer spherical micelles with the loaded DOX mainly distributed at the interfacial regions of the inner PCL core and middle HEMA layer. The structural stability and DOX loading capacity of the micelles can be improved by appropriately increasing the CL based on the nearest-neighbor bonding principle due to the effect of the pressure exerted by the crosslink that squeezes the loaded drugs from the intermediate and interfacial layers into the micelle core. Furthermore, the effect of breaking of the diselenide bond on the drug release properties was investigated through the use of the nearest media-bead bond breaking principle. A low CL gives rise to intense drug release, increasing the toxic side effects on the system. With the increase in the CL, the micelles show the transformation from local crosslinking to compact crosslinking, leading to slower drug release. Therefore, this work can provide some guidance on the mesoscale for the structural design and controlled construction of reversible crosslinked micelles for smart drug delivery systems.

Effect of Degree of Silicification on Silica/Silicic Acid Binding Cd(II) and Its Mechanism.

Heavy metal pollution in farmland soil reduces crop yield and quality and also potentially causes the crisis to human health. Formerly, the fact that silicon fertilizer could effectively reduce the residual concentration of heavy metal in crops has been identified at the tissue level. In this paper, molecular dynamics simulation was employed to investigate the effects of the degree of silicification of silicic acids [namely, the molar ratio of Si(OH)4 and SiO2] on the Cd(II) bound in the aspect of radial distribution functions and mean square displacements. The results demonstrated that Si(OH)4 attracted Cd(II) through the coordination, while SiO2 attracted Cd(II) by the adsorption. In particular, when the degree of silicification was 0, both the bound Cd(II) amount and strength were the maximum value, indicating that the silicon fertilizer had the best efficiency of Cd(II) bound as Si(OH)4. By comparing the adsorption energy and electronic transfer of Cd(II) and Si(OH)4 adsorption onto the SiO2 surface through the quantum chemical simulation, we concluded that Cd(II) adsorption onto the SiO2 surface was chemisorption, while the Si(OH)4 adsorption onto SiO2 surface was physisorption. Consequently, the adsorption capacity of Cd(II) on the SiO2 surface was higher than that of Si(OH)4 adsorption on the SiO2 surface. Moreover, the compact hydration layers around Cd(II) prevented the process of Cd(II) adsorption on the SiO2 surface; even so, the counterion Cl- in the system promoted the adsorption process. The mechanism of silicon fertilizer binding heavy metal Cd(II) was investigated and revealed at the molecular and electronic level. This work has expanded the possibility of theoretical guidance for the design of silicon fertilizer.