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We develop a coarse-grained Monte Carlo model for the anchoring of cationic polymers onto a phosphatidyl-choline (PC) lipid monolayer, doped with univalent phosphatidylserine (PS) and tetravalent phosphatidylinositol 4, 5-bisphosphate (PIP 2 ) anionic lipids. Using this model, we extensively explore the effects of important factors on the structural alterations of the polymers/monolayer complex, including the polymer concentration, the polymer ionization fraction and the ionic concentration of the salt solution. We find the substantial disparity in the scaling of the anchoring/dissociation transition for polymers/monolayer complex and polyelectrolyte/surface system, which demonstrates that the mobile anionic monolayer exerts stronger attraction on cationic polymers than uniformly charged surface, thereby illustrating the significant predominance of PIP 2 lipids in the anchoring procedure. In the polymer anchoring regime, increasing the polymer ionization fraction drastically strengthens the attractions between polymers and the monolayer at low polymer concentrations, which in turn results in the transformation of individual polymer chains from a brush-like structure to a pancake-like structure and leads to the enhancement of PIP 2 sequestration. Elevating the polymer concentration strengthens the competition of the anchoring between individual polymers, and the fraction of anchored polymers can even saturate at sufficiently high polymer concentrations. At high polymer concentrations, this competition forces both weakly and strongly charged polymers to anchor onto the membrane in the brush-like conformation, thereby sequestering smaller PIP 2 clusters. The PS lipids cluster around the polymer/PIP 2 complexes when the amount of tetravalent PIP 2 lipids is insufficient to neutralize the anchored cationic polymers. We also observe that the monolayer can be overcharged due to the anchoring of polymers at high polymer concentrations. Our work thus approaches an improved understanding of the anchoring processes from a fundamental perspective based on the estimates of the stability and the structural variations of the polymers/monolayer complex with important molecular factors. [ABSTRACT FROM AUTHOR]

[Display omitted] • Four methods were used to decomposed the effects of climate change and human activities effects on sediment discharge (SD). • Human activities had the larger influence on SD , especially dam construction. • Sediment identify factor analysis indicated that sediment concentration greatly influenced SD , accounting for 100% to 154%. • The four quantitative methods were compared and their relative merits were summarized. Quantifying the relative contributions of climate change and human activities to changes in sediment discharge is closely related to regional water resources, soil management, and healthy ecosystem function. However, few studies have used different methods to decompose influences of climatic variability and human activities on changes to sediment discharge, especially in karst regions of southwest China which are experiencing severe soil erosion. This study systematically reviewed four methods (simple linear regression, double mass curve, sediment identify factor analysis, and elastic coefficient method) to separate the contribution of climate change and human activities to sediment discharge variation in four karst watersheds of southwest China during 1955 to 2015. The trend and abrupt change year of sediment discharge in the four watersheds were obtained using a nonparametric Mann-Kendall trend test and sequential test method, respectively. Result showed that the sediment discharge in all four watersheds all decreased significantly (P < 0.05), and the abrupt change years were 2003 or 2004 for these watersheds. The simple linear regression method, double mass curve method, and elastic coefficient method all indicated that the sediment discharge was mainly influenced by human activities, which contributed more than 73% of the observed change. For the sediment identify factor analysis method, sediment concentration was the principal factor influencing sediment discharge variation. The results provide a reference for evaluating the influence of climate and human activities on sediment discharge, and can aid in preparing regional soil conservation policy in karst watersheds. [ABSTRACT FROM AUTHOR]

In this work, separation performance of hierarchically porous membranes (HPMs) with multiple channels have been investigated with the combination of finite element simulation and experiment. The simulation results indicate that in addition to m-channels (i.e., channels in microns) in reference (with only pores in microns), nanopores in HPMs not only contribute to n-channels (channels in nanometers), but also connect them with m-channels, producing mixed channels. In experiment, PVDF HPMs have been prepared in poly(vinylidene fluoride)/poly(methyl methacrylate)/poly(l -lactic acid) (PVDF/PMMA/PLLA) blend based on phase separation and crystallization templates. Phase separation produces bi-continuous structures of PLLA and PVDF/PMMA with size of microns. In the latter, PMMA has been expelled out during the crystallization of PVDF, resulting in the bi-continuous structures of them in nanometers. Upon etching with chloroform, both PLLA and PMMA have been removed, yielding pores in microns and nanometers respectively. Relative to reference, HPMs exhibit enhanced separation performance, which can be attributed to the shorter diffusion length, extra channels, enlarged contact angle difference and enhanced driving force for separation. Both simulation and experiment results indicate that multiple channels play more important role in the improvement of flux in the case of smaller m-channel diameter. Our results provide an efficient solution for trade-off effect in separation based on HPMs with multiple channels. [Display omitted] • Simulation results verify the existence of multiple-channels and shorter diffusion length in the mixed channel. • HPMs have been fabricated based on phase separation and crystallization templates. • The HPMs with multiple channels exhibit higher flux and higher rejection ratio. • Nano and mixed channels lead to more significant improvement of flux in case of smaller micro-channels. [ABSTRACT FROM AUTHOR]

With the finite element method adopted to solve the coupling of the fluid flow, the deformation of viscoelastic membrane and the distribution of electric field, the dynamic behavior of the polyelectrolyte vesicle is investigated through a pore in the electric field. The velocity of the vesicle is reduced significantly when it approaches the pore, with the vesicle showing a bullet-like shape. Then, the velocity reaches its minimum when the vesicle approaches the center of the pore. At this time, it shows a long-strip shape with the diameter of the vesicle being no greater than the pore diameter, otherwise, it shows a slipper-like shape. After the pore is past through, a sharp increase in vesicle velocity is observed. In addition, as the lengths of pores or the diameters of vesicles increase, the minimum velocity of the vesicles along the horizontal direction declines gradually while the translocation time is extended significantly. Our results further demonstrate that the surface potential of membrane increases slowly when the vesicles approach and escape from the pore but rises sharply when they are passing through the pore. The competition of membrane surface potential, fluid resistance, and pore restriction cause the deformation of the vesicles to peak over the course of migration. Our work is believed to lay a theoretical foundation for the migration, rotation, and deformation of vesicles, thus providing valuable information for such applications as drug carrier and the experimentation on biofilm simulation. [ABSTRACT FROM AUTHOR]

Listeria monocytogenes (LM) is a Gram-positive (G + ) bacterium that secretes nanoscale membrane vesicles (MVs). LM MVs comprise various bacterial components and may have potential as an antigen or drug-delivery vehicle; however, the low yield of the LM MVs limits related research. G + -bacterial MVs germinate from the bacterial plasma membrane and must pass through a thick crosslinked peptidoglycan layer for release. Herein, we aimed to increase the release of MVs by reducing the degree of crosslinking of peptidoglycan. We knocked out two genes related to the longitudinal crosslinking of peptidoglycan, dal and dat, and supplemented the knocked-out dal gene through plasmid expression to obtain a stably inherited recombinant strain LMΔdd::pCW633. The structure, particle size, and main protein components of MVs secreted by this recombinant strain were consistent with those secreted from the wild strain, but the yield of MVs was considerably increased (p < 0.05). Furthermore, Listeria ivanovii (LI) was found to secrete MVs that differed in the composition of the main proteins compared with those of LM MVs. The abovementioned method was also feasible for promoting the secretion of MVs from the attenuated LM strain and LI wild-type and attenuated strains. Our study provides a new method to increase the secretion of MVs derived from Listeria that could be extended to other G + bacteria., (© 2024 Wiley Periodicals LLC.)

Tumor immunotherapy has revolutionized cancer treatment, but limitations remain, including low response rates and immune complications. Extracellular vesicles (EVs) are emerging as a new class of therapeutic agents for various diseases. Recent research shows that changes in the amount and composition of EVs can reshape the tumor microenvironment (TME), potentially improving the effectiveness of immunotherapy. This exciting discovery has sparked clinical interest in using EVs to enhance the immune system's response to cancer. In this Review, we delve into the world of EVs, exploring their origins, how they're generated, and their complex interactions within the TME. We also discuss the crucial role EVs play in reshaping the TME during tumor development. Specifically, we examine how their cargo, including molecules like PD-1 and non-coding RNA, influences the behavior of key immune cells within the TME. Additionally, we explore the current applications of EVs in various cancer therapies, the latest advancements in engineering EVs for improved immunotherapy, and the challenges faced in translating this research into clinical practice. By gaining a deeper understanding of how EVs impact the TME, we can potentially uncover new therapeutic vulnerabilities and significantly enhance the effectiveness of existing cancer immunotherapies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Onychomycosis (OM) is a common nail infection treated with amorolfine hydrochloride nail lacquer in China. Monitoring drug concentrations and using dermoscopy to evaluate treatment efficacy may provide new insights., Objective: The study aims to analyse amorolfine concentrations in nails with mild to moderate OM, assess treatment outcomes using dermoscopy and explore factors influencing drug concentrations and efficacy., Methods: Patients with mild to moderate OM confirmed by fungal microscopy were enrolled. Amorolfine nail lacquer was applied twice weekly for 36 weeks. Monthly nail samples measured amorolfine concentrations using liquid chromatography. Dermoscopy was performed before and after treatment to evaluate responses. Mixed-effects models and logistic regression analysed factors affecting drug concentrations and outcomes., Results: Ninety-seven nails were included. Amorolfine concentrations increased over time, with higher levels in females, fingernails, 2nd-5th digits and superficial white OM (p < 0.05). Age was a risk factor, while drug concentration and OM type were protective for clinical efficacy (p < 0.05). Peak concentration correlated with clinical (r = 0.487, p = 0.000) and mycological (r = 0.433, p = 0.000) responses. Dermoscopic features improved significantly in successful cases (p < 0.05)., Limitations: In the assessment of fungal efficacy, only fungal microscopy was used, and fungal cultures were not performed. The study was limited by a small sample size and the lack of a longer follow-up to assess relapse., Conclusion: Amorolfine concentrations vary with patient and nail characteristics, influencing efficacy. Dermoscopy is valuable for monitoring OM treatment., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Coacervates play a pivotal role in protein-based drug delivery research, yet their drug encapsulation and release mechanisms remain poorly understood. Here, we utilized the Martini model to investigate bovine serum albumin (BSA) protein encapsulation and release within polylysine/polyglutamate (PLys/PGlu) coacervates. Our findings emphasize the importance of ingredient addition sequence in coacervate formation and encapsulation rates, attributed to preference contact between oppositely charged proteins and poly(amino acid)s. Notably, coacervates composed of β-sheet poly(amino acid)s demonstrate greater BSA encapsulation efficiency due to their reduced entropy and flexibility. Furthermore, we examined the pH responsiveness of coacervates, shedding light on the dissolution process driven by Coulomb forces. By leveraging machine learning algorithms to analyze simulation results, our research advances the understanding of coacervate-based drug delivery systems, with the ultimate goal of optimizing therapeutic outcomes., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Polymersomes, composed of amphiphilic block copolymers, are self-assembled vesicles that have gained attention as potential drug delivery systems due to their good biocompatibility, stability, and versatility. Various experimental techniques have been employed to characterize the self-assembly behaviors and properties of polymersomes. However, they have limitations in revealing molecular details and underlying mechanisms. Computational modeling techniques have emerged as powerful tools to complement experimental studies and enabled researchers to examine drug delivery mechanisms at molecular resolution. This review aims to provide a comprehensive overview of the state of the art in the field of polymersome-based drug delivery systems, with an emphasis on insights gained from both experimental and computational studies. Specifically, we focus on polymersome morphologies, self-assembly kinetics, fusion and fission, behaviors in flow, as well as drug encapsulation and release mechanisms. Furthermore, we also identify existing challenges and limitations in this rapidly evolving field and suggest possible directions for future research.

Dentin hypersensitivity (DH) is a prevalent dental condition arising from the exposure of dentin tubules (DTs), leading to discomfort upon external stimuli. However, achieving swift and profound occlusion of these exposed DTs for immediate and enduring relief remains challenging due to the intricate dentin structure and oral environment. Herein, a pioneering and facile drop-by-drop strategy involving an in situ generated natural supramolecular hydrogel formed by self-assembling silk fibroin (SF) and tannic acid (TA) within the narrow DT space is proposed. When SF and TA aqueous solutions are applied successively to exposed dentin, they penetrate deeply within DTs and coassemble into compact gels, robustly adhering to DT walls. This yields a rapid and compact occlusion effect with an unprecedented depth exceeding 250 µm, maintaining stable occlusion efficacy even under rigorous in vitro and in vivo erosion and friction conditions for no less than 21 days. Furthermore, the biocompatibility and effective occlusion properties are verified through cell studies in simulated oral settings and an in vivo rabbit model. This study, for the first time, demonstrates the translational potential of hydrogel-based desensitizers in treating DH with prompt action, superior occlusion depth and enduring treatment benefits, holding promise as clinical-friendly restorative solutions for delicate-structured biosystems., (© 2024 Wiley‐VCH GmbH.)

Using a hybrid simulation approach that combines a lattice-Boltzmann method for fluid flow and a molecular dynamics model for polymers, we investigate the inertial migration of star-like and crew-cut polymer micelles in a square microchannel. It is found that they exhibit two types of equilibrium positions, which shift further away from the center of the microchannel when the Reynolds number (Re) increases, as can be observed for soft particles. What differs from the behaviors of soft particles is that here, the blockage ratio is no longer the decisive factor. When the sizes are the same, the star-like micelles are always relatively closer to the microchannel wall as they gradually transition from spherical to disc-like with the increase of Re. In comparison, the crew-cut micelles are only transformed into an ellipsoid. Conversely, when the hydrophobic core sizes are the same, the equilibrium position of the star-like micelles becomes closer to that of the crew-cut micelles. Our results demonstrate that for polymer micelles with a core-shell structure, the equilibrium position is no longer solely determined by their overall dimensions but depends on the core and shell's specific dimensions, especially the hydrophobic core size. This finding opens up a new approach for achieving the separation of micelles in inertial migration.

We explore the escape dynamics of active ring polymers confined in a cylindrical nanochannel using Brownian dynamics. Our simulation results show that the escape time decreases with the increase of the Péclet number, which is not noticeable between the two stages of the escape process, based on whether the center of mass of the polymer is inside or outside the nanochannel. However, the monomer motion trajectory of the active polymer is very different from that of the passive polymer, similar to the snake-like motion with uniform velocity. The passive polymer, however, is in constant fugitive motion with increased velocity at the tail end of the escape. Our work is vital for understanding the escape dynamics of active ring polymers in the confined nanochannel, which provides new perspectives on their characterization and analysis.

The assembly of oligopeptide and polypeptide molecules can reconstruct various ordered advanced structures through intermolecular interactions to achieve protein-like biofunction. Here, we develop a "molecular velcro"-inspired peptide and gelatin co-assembly strategy, in which amphiphilic supramolecular tripeptides are attached to the molecular chain of gelatin methacryloyl via intra-/intermolecular interactions. We perform molecular docking and dynamics simulations to demonstrate the feasibility of this strategy and reveal the advanced structural transition of the co-assembled hydrogel, which brings more ordered β-sheet content and 10-fold or more compressive strength improvement. We conduct transcriptome analysis to reveal the role of co-assembled hydrogel in promoting cell proliferation and chondrogenic differentiation. Subcutaneous implantation evaluation confirms considerably reduced inflammatory responses and immunogenicity in comparison with type I collagen. We demonstrate that bone mesenchymal stem cells-laden co-assembled hydrogel can be stably fixed in rabbit knee joint defects by photocuring, which significantly facilitates hyaline cartilage regeneration after three months. This co-assembly strategy provides an approach for developing cartilage regenerative biomaterials., (© 2024. The Author(s).)

DNA logic operations are accurate and specific molecular strategies that are appreciated in target multiplexing and intelligent diagnostics. However, most of the reported DNA logic operation-based assays lack amplifiers prior to logic operation, resulting in detection limits at the subpicomolar to nanomolar level. Herein, a homogeneous and isothermal AND-logic cascade amplification strategy is demonstrated for optomagnetic biosensing of two different DNA inputs corresponding to a variant of concern sequence (containing spike L452R) and a highly conserved sequence from SARS-CoV-2. With an "amplifiers-before-operator" configuration, two input sequences are recognized by different padlock probes for amplification reactions, which generate amplicons used, respectively, as primers and templates for secondary amplification, achieving the AND-logic operation. Cascade amplification products can hybridize with detection probes grafted onto magnetic nanoparticles (MNPs), leading to hydrodynamic size increases and/or aggregation of MNPs. Real-time optomagnetic MNP analysis offers a detection limit of 8.6 fM with a dynamic detection range spanning more than 3 orders of magnitude. The accuracy, stability, and specificity of the system are validated by testing samples containing serum, salmon sperm, a single-nucleotide variant, and biases of the inputs. Clinical samples are tested with both quantitative reverse transcription-PCR and our approach, showing highly consistent measurement results.

Using hybrid lattice-Boltzmann molecular dynamics simulations, we investigate the flow-driven translocation of comb-like copolymer micelles through a nanochannel, in particular, making a detailed comparison with micelles formed by the corresponding diblock copolymers. Our results demonstrate that the critical flow flux of micelles formed by the comb-like copolymers is higher than that of micelles formed by the corresponding diblock copolymers, which is more pronounced with increasing side chain lengths or grafting densities, as evidenced by the free energy computed by self-consistent field theory. Our work indicates that the impact of chain topology on the stability of micelles, especially with the same size, can be well characterized using the critical flow fluxes, which provides a theoretical basis for designing self-assembling micelles for various applications.

Background: Photodynamic therapy (PDT) for actinic keratosis (AK) is limited by the depth of treatment. Microneedling or fractional CO 2 laser can facilitate the penetration of photosensitizer, while cryotherapy can treat deeper tissues but is not suitable for field cancerization., Objective: To investigate the efficacy of microneedling, fractional CO 2 laser, and cryotherapy in combination with PDT for AK., Methods: Patients with AK were randomized into 4 groups, including group A with microneedling + PDT, group B with fractional CO 2 laser + PDT, group C with cryotherapy + PDT, and group D with PDT. After 12 weeks, the clinical, dermoscopic, and reflectance confocal microscopy (RCM) outcomes were assessed., Results: A total of 129 patients were included in this study, with 31, 30, 35, and 31 patients in each group, yielding clinical response rates of 90.3%, 93.3%, 97.1%, and 74.2%, respectively (P=0.026). The RCM response rates were 71.0%, 80.0%, 85.7%, and 54.8%, respectively (P=0.030). The dermoscopic response rates were 77.4%, 83.3%, 88.6%, and 60.0%, respectively (P=0.039). Group C showed the best efficacy in terms of clinical, dermoscopic, and RCM outcomes., Conclusions: All three treatments improved the efficacy of PDT and were well tolerated, with cryotherapy + PDT showing the best efficacy., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023. Published by Elsevier B.V.)

Self-assembly of block copolymers has recently drawn great attention due to its remarkable performance and wide variety of applications in biomedicine, biomaterials, microelectronics, photoelectric materials, catalysts, etc. Poly(amino acid)s (PAAs), formed by introducing synthetic amino acids into copolymer backbones, are able to fold into different secondary conformations when compared with traditional amphiphilic copolymers. Apart from changing the chemical composition and degree of polymerization of copolymers, the self-assembly behaviors of PAAs could be controlled by their secondary conformations, which are more flexible and adjustable for fine structure tailoring. In this article, we summarize the latest findings on the variables that influence secondary conformations, in particular the regulation of order-to-order conformational changes and the approaches used to manage the self-assembly behaviors of PAAs. These strategies include controlling pH, redox reactions, coordination, light, temperature, and so on. Hopefully, we can provide valuable perspectives that will be useful for the future development and use of synthetic PAAs., (© 2023 Wiley-VCH Verlag GmbH.)

Using Brownian dynamics simulations, we study the ejection dynamics of spherically confined active polymers through a small pore. Although the active force can provide a driving force other than the entropy drive, it also causes the collapse of the active polymer, which in turn reduces the entropy drive. Thus, our simulation results confirm that the active polymer's ejection process can be divided into three stages. In the first stage, the influence of the active force is small, and the ejection is mainly an entropy-driven process. In the second stage, the ejection time satisfies the scaling relationship with the chain length, and the value of obtained scaling exponent is less than 1.0, indicating that the active force accelerates the ejection process. In the third stage, the scaling exponent is maintained at about 1.0, where the active force dominates the ejection process, and the ejection time is inversely proportional to the Péclet number. Furthermore, we find that the ejection velocity of the trailing particles has significant differences at different stages and is the core factor of the ejection mechanism at different stages. Our work helps us understand this non-equilibrium dynamic process and enhances our prediction of the relevant physiological phenomena.

Allosteric transitions can modulate the self-assembly and biological function of proteins. It remains, however, tremendously challenging to design synthetic allosteric polymeric assemblies with spatiotemporally switchable hierarchical structures and functionalities. Here, a photoallosteric polymersome is constructed that undergoes a rapid conformational transition from β-sheet to α-helix upon exposure to near-infrared light irradiation. In addition to improving nanoparticle cell penetration and lysosome escape, photoinduced allosteric behavior reconstructs the vesicular membrane structure, which stimulates the release of hydrophilic cytolytic peptide melittin and hydrophobic kinase inhibitor sorafenib. Combining on-demand delivery of multiple therapeutics with phototherapy results in apoptosis and immunogenic death of tumor cells, remold the immune microenvironment and achieve an excellent synergistic anticancer efficacy in vivo without tumor recurrence and metastasis. Such a light-modulated allosteric transition in non-photosensitive polymers provides new insight into the development of smart nanomaterials for biosensing and drug delivery applications., (© 2023 Wiley-VCH GmbH.)

A novel fabrication process to connect single-stranded DNA (ssDNA)to a silicon substrate based on a mechano-chemical method is proposed. In this method, the single crystal silicon substrate was mechanically scribed in a diazonium solution of benzoic acid using a diamond tip which formed silicon free radicals. These combined covalently with organic molecules of diazonium benzoic acid contained in the solution to form self-assembled films (SAMs). The SAMs were characterized and analyzed by AFM, X-ray photoelectron spectroscopy and infrared spectroscopy. The results showed that the self-assembled films were covalently connected to the silicon substrate by Si-C. In this way, a nano-level benzoic acid coupling layer was self-assembled on the scribed area of the silicon substrate. The ssDNA was further covalently connected to the silicon surface by the coupling layer. Fluorescence microscopy showed that ssDNA had been connected, and the influence of ssDNA concentration on the fixation effect was studied. The fluorescence brightness gradually increased with the gradual increase in ssDNA concentration from 5 μmol/L to 15 μmol/L, indicating that the fixed amount of ssDNA increased. However, when the concentration of ssDNA increased from 15 μmol/L to 20 μmol/L, the detected fluorescence brightness decreased, indicating that the hybridization amount decreased. The reason may be related to the spatial arrangement of DNA and the electrostatic repulsion between DNA molecules. It was also found that ssDNA junctions on the silicon surface were not very uniform, which was related to many factors, such as the inhomogeneity of the self-assembled coupling layer, the multi-step experimental operation and the pH value of the fixation solution.

Based on disulfide-enriched multiblock copolymer vesicles, we present a straightforward sequential drug delivery system with dual-redox response that releases hydrophilic doxorubicin hydrochloride (DOX·HCl) and hydrophobic paclitaxel (PTX) under oxidative and reductive conditions, respectively. When compared to concurrent therapeutic delivery, the spatiotemporal control of drug release allows for an improved combination antitumor effect. The simple and smart nanocarrier has promising applications in the field of cancer therapy.

We study the effect of backbone rigidity on the conformation of comb-like chains in dilute solution by using Brownian dynamics simulations. Our results demonstrate that the backbone rigidity can control the effect of side chains on the conformation of comb-like chains; that is, the relative strength of the excluded-volume interactions from backbone monomer-graft and graft-graft to backbone monomer-monomer gradually weakens with the increase of backbone rigidity. Only when the rigidity of the backbone tends to be flexible and the grafting density is high is the effect of excluded volume of graft-graft on the conformation of comb-like chains significant enough, and other cases can be ignored. Our results show that the radius of gyration of comb-like chains and the persistence length of the backbone are exponentially related to the stretching factor, where the power exponent exhibits an increase with the increase of the strength of bending energy. These finds provide new insights for characterizing the structure properties of comb-like chains., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

The ability of nanocarriers to enter tumor cells can be enhanced by positive surface charge. Nonetheless, the relationship between the spatial distributions of cationic groups and the endocytosis and tumor penetration of nanocarriers remains largely elusive. Here, using quaternary ammonium salt (QAS) as a model cationic group, a series of hybrid micelles (HMs) bearing QAS with different spatial distributions were prepared from star-shaped polymers with well-defined molecular architectures. The structural characteristics of HM, such as spatial location of QAS and local poly(ethylene glycol) (PEG) density near QAS, were investigated by both experimental techniques and dissipative particle dynamics (DPD) simulation. We show that the drug carriers with QAS extending to the micellar outer space allows QAS to facilitate cell surface binding with minimized hindrance, resulting in greatly enhanced endocytosis compared with nanocarriers with QAS attached onto the micellar surface or shielded by a PEG corona. This study offers cues for future development of tumor-penetrating drug delivery systems.

Purpose: To explore the diagnostic value and the prognostic significance of cerebrospinal fluid (CSF) examination by flow cytometry (FC) in children with central nervous system leukemia (CNSL). Method: This is a retrospective observational study. We select 986 pediatric patients with newly diagnosed acute lymphoblastic leukemia from January 2012 to December 2018 as the research objects and analyze the sensitivity and specificity of different methods for diagnosing CNSL. The recurrence rate and survival rate of CNSL in different groups were compared. Results: Among the 986 cases, 31 cases (positive rate of 3.14%) were positive by FC, and the cytospin-based cytomorphology (CC) test was positive in 6 cases (positive rate of 0.61%). CC combined with FC might improve the diagnostic sensitivity (from 30% to 65%, 𝑥 2 value was 5.143, P   =  .016). The 2-year event-free survival (EFS) of 31 FC  +  children was 59.5%  ±  9.2%, and that of 955 FC - children was 74.1%  ±  1.8% ( P   =  .004). The 2-year overall survival (OS) of the 2 groups were 63.6%  ±  9.7% and 80.2%  ±  1.5%, respectively ( P   =  .004). In order to exclude the influence of CNSL, we divided the patients into 3 groups: CNSL group and non-CNSL group with CSF FC + , FC - group. There was no significant difference in EFS between FC - group and non-CNSL group with FC  +  (2-year EFS were 74.1%  ±  1.8% and 68.7%  ±  9.8%, respectively, P   =  .142), and there was a significant difference in OS (2-year OS were 80.2%  ±  1.5% and 67.5%  ±  10.3%, respectively, P   =  .029). Conclusion: The test of FC combined with CC may improve the diagnostic sensitivity of CNSL. The EFS and OS of children with FC  +  are worse than those of children with FC -. However, for those patients with non-CNSL, but only FC  +  at the initial diagnosis, the EFS is not significantly affected by strengthening systemic chemotherapy and increasing the number of intrathecal injections.

Objective: Detect the expression of Interleukin-6 (IL-6) in the serum of patients with systemic sclerosis (SSc) and assess its association with clinical and laboratory features of the disease., Methods: The clinical data from 50 patients with SSc in the affiliated hospital of Xuzhou Medical University, China were retrospectively analyzed. The level of IL-6 in peripheral blood of systemic sclerosis patients was compared between the different clinical phenotypes groups. Spearman correlation test was used to analyze the correlation of the IL-6 with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), creatinine, and cystatin C., Results: Interleukin-6 increased in the disease course ≥5 years, systemic sclerosis-Interstitial lung disease (SSc-ILD), pulmonary arterial hypertension (PAH), gastrointestinal involvement, and cardiac involvement group compared with the group with disease course <5 years, no SSc-ILD, PAH, gastrointestinal involvement, and no cardiac involvement group. The differences were statistically significant (p < 0.05). Correlation analysis showed that IL-6 in the group with disease course ≥5 years had a positive correlation with ESR (Rs = 0.438, p = 0.022) and CRP (Rs = 0.825, P < 0.001), whereas it was negatively correlated with creatinine (Rs = -0.481, p = 0.011). Nevertheless, when it came to disease course <5 years, the figures had no statistically significant difference., Conclusion: Serum IL-6 in patients with systemic sclerosis is related to different clinical phenotypes. IL-6 helps to diagnose various phases of diseases, monitor severities of diseases, and predict the prognosis of patients., (© 2022 Wiley Periodicals LLC.)

Peptidomimetic polymers have attracted increasing interest because of the advantages of facile synthesis, high molecular tunability, resistance to degradation, and low immunogenicity. However, the presence of non-native linkages compromises their ability to form higher ordered structures and protein-inspired functions. Here we report a class of amino acid-constructed polyureas with molecular weight- and solvent-dependent helical and sheet-like conformations as well as green fluorescent protein-mimic autofluorescence with aggregation-induced emission characteristics. The copolymers self-assemble into vesicles and nanotubes and exhibit H-bonding-mediated metamorphosis and discoloration behaviors. We show that these polymeric vehicles with ultrahigh stability, superfast responsivity and conformation-assisted cell internalization efficiency could act as an "on-off" switchable nanocarrier for specific intracellular drug delivery and effective cancer theranosis in vitro and in vivo. This work provides insights into the folding and hierarchical assembly of biomacromolecules, and a new generation of bioresponsive polymers and nonconventional luminescent aliphatic materials for diverse applications., (© 2022. The Author(s).)

We investigate the diffusion dynamics of a single polymer strongly adsorbed on surfaces in an extremely broad chain length and surface roughness by means of molecular dynamics simulations. Our simulations demonstrate that with the increase in chain length, the diffusion dynamics of polymer chains exhibits three regimes: the Rouse dynamics with D ∼ N -1 when the lateral size of polymer chains is smaller than a half of distance between obstacles on rough surfaces; the reptationlike dynamics with D ∼ N -1.5 and τ r ∼ N 3 when the obstacles inhibit the freely Rouse behavior of polymer chains; and the quasi-Rouse dynamics with D ∼ N -1 and τ r ∼ N 2.5 when the height of obstacles is smaller than twice the vertical size of polymer chains, where D, N, and τ r are the diffusion coefficient, chain length, and end-to-end vector relaxation time of polymer chains, respectively. The long chains have sufficient conformation entropy to form loops to hop over short obstacles, which could dramatically reduce the confinement from obstacles on the rough surfaces and changes the diffusion and relaxation dynamics of polymer chains from the reptationlike dynamics to the quasi-Rouse dynamics. Our results reveal the whole diffusion dynamics of polymer chains strongly adsorbed on rough surfaces and clarify the corresponding transition mechanism, which is significant for the understanding of the physical nature and the development of the corresponding applications.

We study the effects of the nanopore size on the flow-induced capture of the star polymer by a nanopore and the afterward translocation, using a hybrid simulation method that couples point particles into a fluctuating lattice-Boltzmann fluid. Our simulation demonstrates that the optimal forward arm number decreases slowly with the increase of the length of the nanopore. Compared to the minor effect of the length of the nanopore, the optimal forward arm number obviously increases with the increase of the width of the nanopore, which can clarify the current controversial issue for the optimal forward arm number between the theory and experiments. In addition, our results indicate that the critical velocity flux of the star polymer is independent of the nanopore size. Our work bridges the experimental results and the theoretical understanding, which can provide comprehensive insights for the characterization and the purification of the star polymers.