No causal effect of genetically determined circulating homocysteine levels on psoriasis in the European population: evidence from a Mendelian randomization study.

Background: Although numerous studies demonstrated a link between plasma homocysteine (Hcy) levels and psoriasis, there still exists a certain level of controversy. Therefore, we conducted a Mendelian randomization study to investigate whether homocysteine plays a causative role in the development or exacerbation of psoriasis. Methods: A two-sample Mendelian randomization (MR) analysis was conducted. Summary-level data for psoriasis were acquired from the latest R9 release results from the FinnGen consortium (9,267 cases and 364,071 controls). Single nucleotide polymorphisms (SNPs) robustly linked with plasma Hcy levels at the genome-wide significance threshold (p < 5 × 10-8) (18 SNPs) were recognized from the genome-wide meta-analysis on total Hcy concentrations (n = 44,147 participants) in individuals of European ancestry. MR analyses were performed utilizing the random-effect inverse variance-weighted (IVW), weighted median, and MR-Egger regression methods to estimate the associations between the ultimately filtrated SNPs and psoriasis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Results: MR analyses revealed no causal effects of plasma Hcy levels on psoriasis [IVW: odds ratio (OR) = 0.995 (0.863-1.146), p = 0.941; weighed median method: OR = 0.985 (0.834-1.164), p = 0.862; MR-Egger regression method: OR = 0.959 (0.704-1.305), p = 0.795]. The sensitivity analyses displayed no evidence of heterogeneity and directional pleiotropy, and the causal estimates of Hcy levels were not influenced by any individual SNP. Conclusion: Our study findings did not demonstrate a causal effect of genetically determined circulating Hcy levels on psoriasis.

The possibilities of LOXL4 as a prognostic marker for carcinomas.

Lysyl oxidase-like 4 (LOXL4), a member of lysyl oxidase family, is a copper and lysine tyrosylquinone-dependent amine oxidase that serves the role of catalyzing the cross-linking of elastin and collagen in the extracellular matrix. Numerous studies have shown a significant association between LOXL4 expression levels and tumor proliferation, migration, invasion and patients' prognosis and overall survival in different types of tumors. Here we review their relationship and the molecular pathogenesis behind them, aiming to explore the possibilities of LOXL4 as a prognostic marker for diverse carcinomas and provide some indications for further research in this field.

Enormously large tippers observed in southwest China: can realistic 3-D EM modeling reproduce them?

Abstract: Vertical magnetic transfer functions (tippers) estimated at a global/continental net of geomagnetic observatories/sites can be used to image the electrical conductivity structure of the Earth's crust and upper mantle (down to around 200 km). We estimated tippers at 54 geomagnetic observatories across China, aiming eventually to invert them in terms of subsurface three-dimensional (3-D) conductivity distribution. Strikingly, we obtained enormously large tippers at three inland observatories in southwest China. Large tippers are often observed at coastal/island observatories due to high conductivity contrasts between resistive bedrock and conductive seawater. However, tippers at those inland observatories appeared to be a few times larger than coastal/island tippers. As far as we know, such large tippers (reaching value 3) were never reported in any region worldwide. We perform electromagnetic simulations in 3-D conductivity models mimicking the geological setting and demonstrate that enormously large tippers are feasible and can be attributed to a current channeling effect.

Bibliometric and visual analysis of vaccination hesitancy research from 2013 to 2022.

Although vaccination is regarded as one of the most significant achievements of public health, there also exists the phenomenon of vaccination hesitancy which refers to delay in acceptance or refusal of vaccination despite availability of vaccination services. In this study, we conducted a bibliometric analysis to provide a comprehensive overview of vaccination hesitancy research from 2013 to 2022. All related publications were retrieved from the Web of Science Core Collection Database. Information on annual publications, countries, organizations, journals, authors, keywords, and documents was analyzed adopting the bibliometix R-package, VOSviewer, and CiteSpace software. A total of 4042 publications were enrolled. The annual publications increased slightly before 2020 but had an extremely dramatic increase from 2020 to 2022. The United States contributed the most articles and had the greatest collaboration with other countries and organizations. The London School of Hygiene & Tropical Medicine was the most active institution. Vaccine was the most cited and influential journal while Vaccines was the most productive journal. It was Dube E who was the most productive authors with the highest h-index. The most frequent keywords were "vaccine hesitancy," "COVID-19," "SARS-CoV2," "immunization," "attitudes," and "willingness." Vaccination hesitancy to some extent hinders the achievement of global public health. The influencing factors vary across time, space, and vaccines. The COVID-19 pandemic and the development of COVID-19 vaccines have made this issue the focus of interest. The complexity and specific contexts of influencing factors of vaccination hesitancy require further study and will potentially be the focus of future research direction.

Antibacterial, antiviral, and biodegradable collagen network mask for effective particulate removal and wireless breath monitoring.

Functional face masks that can effectively remove particulate matter and pathogens are critical to addressing the urgent health needs arising from industrial air pollution and the COVID-19 pandemic. However, most commercial masks are manufactured by tedious and complicated network-forming procedures (e.g., meltblowing and electrospinning). In addition, the materials used (e.g., polypropylene) have significant limitations such as a lack of pathogen inactivation and degradability, which can cause secondary infection and serious environmental concerns if discarded. Here, we present a facile and straightforward method for creating biodegradable and self-disinfecting masks based on collagen fiber networks. These masks not only provide superior protection against a wide range of hazardous substances in polluted air, but also address environmental concerns associated with waste disposal. Importantly, collagen fiber networks with naturally existing hierarchical microporous structures can be easily modified by tannic acid to improve its mechanical characteristics and enable the in situ production of silver nanoparticles. The resulting masks exhibit excellent antibacterial (>99.99%, 15 min) and antiviral (>99.999%, 15 min) capabilities, as well as high PM2.5 removal efficiency (>99.9%, 30 s). We further demonstrate the integration of the mask into a wireless platform for respiratory monitoring. Therefore, the smart mask has enormous promise for combating air pollution and contagious viruses, managing personal health, and alleviating waste issues caused by commercial masks.

Dynamic Metal-Phenolic Coordination Complexes for Versatile Surface Nanopatterning.

We report a general nanopatterning strategy that takes advantage of the dynamic coordination bonds between polyphenols and metal ions (e.g., Fe3+ and Cu2+) to create structures on surfaces with a range of properties. With this methodology, under acidic conditions, 29 metal-phenolic complex-based precursors composed of different polyphenols and metal ions are patterned using scanning probe and large-area cantilever free nanolithography techniques, resulting in a library of deposited metal-phenolic nanopatterns. Significantly, post-treatment of the patterns under basic conditions (i.e., ammonia vapor) triggers a change in coordination state and results in the in situ generation of more stable networks firmly attached to the underlying substrates. The methodology provides control over feature size, shape, and composition, almost regardless of substrate (e.g., Si, Au, and silicon nitride). Under reducing conditions (i.e., H2) at elevated temperatures (180-600 °C), the patterned features have been used as nanoreactors to synthesize individual metal nanoparticles. At room temperature, the ammonia-treated features can reduce Ag+ to form metal nanostructures and be modified with peptides, proteins, and thiolated DNA via Michael addition and/or Schiff base reaction. The generality of this technique should make it useful for a wide variety of researchers interested in modifying surfaces for catalytic, chemical and biological sensing, and template-directed assembly purposes.

Controlling Intracellular Machinery via Polymer Pen Lithography Molecular Patterning.

The plasma membrane and the actomyosin cytoskeleton play key roles in controlling how cells sense and interact with their surrounding environment. Myosin, a force-generating actin network-associated protein, is a major regulator of plasma membrane tension, which helps control endocytosis. Despite the important link between plasma membranes and actomyosin (the actin-myosin complex), little is known about how the actomyosin arrangement regulates endocytosis. Here, nanoscopic ligand arrangements defined by polymer pen lithography (PPL) are used to control actomyosin contractility and examine cell uptake. Confocal microscopy, atomic force microscopy, and flow cytometry suggest that the cytoskeletal tension imposed by the nanoscopic ligand arrangement can actively regulate cellular uptake through clathrin- and caveolin-mediated pathways. Specifically, ligand arrangements that increase cytoskeletal tension tend to reduce the cellular uptakes of cholera toxin (CTX) and spherical nucleic acids (SNAs) by regulating endocytic budding and limiting the formation of clathrin- and caveolae-coated pits. Collectively, this work demonstrates how the cell endocytic fate is regulated by actomyosin mechanical forces, which can be tuned by subcellular cues defined by PPL.

Cyclic polymers: synthesis, characteristics, and emerging applications.

Cyclic polymers with a ring-like topology and no chain ends are a unique class of macromolecules. In the past several decades, significant advances have been made to prepare these fascinating polymers, which allow for the exploration of their topological effects and potential applications in various fields. In this Review, we first describe representative synthetic strategies for making cyclic polymers and their derivative topological polymers with more complex structures. Second, the unique physical properties and self-assembly behavior of cyclic polymers are discussed by comparing them with their linear analogues. Special attention is paid to highlight how polymeric rings can assemble into hierarchical macromolecular architectures. Subsequently, representative applications of cyclic polymers in different fields such as drug and gene delivery and surface functionalization are presented. Last, we envision the following key challenges and opportunities for cyclic polymers that may attract future attention: large-scale synthesis, efficient purification, programmable folding and assembly, and expansion of applications.

Hierarchical collagen fibers complexed with tannic acid and Fe3+ as a heterogeneous catalyst for enhancing sulfate radical-based advanced oxidation process.

Efficient sulfate radical-based advanced oxidation processes (SR-AOPs) are important for treating organic contaminants of industrial wastewater. To achieve this goal, tannic acid (TA)-modified skin collagen fibers (CFs) were prepared for the enhanced immobilization of Fe3+ based on multiple complexation interactions, resulting in a heterogeneous catalyst with more catalytic sites (defined as TA-Fe-CFs) for activating peroxymonosulfate (PMS). During the removal of an organic dye (rhodamine B, RhB) from water, the hierarchical TA-Fe-CFs exhibited excellent adsorption capacity at the early stage before the introduction of PMS, which can be ascribed to the π-π interaction between TA and aromatic RhB. Such improved mass transfer of target contaminants into the catalytic support was proved to be beneficial for improving the utilization efficiency of sulfate radicals in subsequent SR-AOPs. After introducing PMS, the reductive TA moieties of the heterogeneous catalyst were able to accelerate the redox cycle of Fe3+/Fe2+ in Fenton reactions, facilitating the activation of PMS to generate sulfate radicals for the degradation of organic RhB.

Modular penetration and controlled release (MP-CR): improving the internal modification of natural hierarchical materials with smart nanoparticles.

The internal modification of natural hierarchical materials can largely improve their inherent properties and afford them new functions. However, conventional methods using small-molecule agents often encounter poor uniformity and low efficiency. By comparing the penetration of small molecules and nanoparticles into hierarchical collagen fibers, we propose a general strategy, namely modular penetration and controlled release (MP-CR), for the internal modification of 3D biomass materials. We demonstrate that nano-sized aluminum-loaded particles can penetrate into collagen networks more effectively and evenly than small-molecule crosslinkers. After the on-demand pH-triggered release of interactive aluminum ions, enhanced internal crosslinking is achieved. Importantly, we elucidate the mechanism in depth and show that the MP-CR strategy can comprehensively improve the overall performance of natural hierarchical materials. The MP-CR strategy represents a significant step forward for the internal modification of hierarchical materials, which will find broad applications in biomedicine, catalysis, water treatment, soft electronics, and energy storage.

Commercial soft contact lenses engineered with zwitterionic silver nanoparticles for effectively treating microbial keratitis.

The introduction of various drugs onto commercial soft contact lenses (CLs) has emerged as a potentially effective strategy for treating microbial keratitis (MK) because drug-loaded CLs can maintain a controlled drug concentration which leaded to enhanced drug bioavailability and reduced side effects in ocular tissues. In this study, silver nanoparticles modified with zwitterionic poly (carboxybetaine-co-dopamine methacrylamide) copolymer (PCBDA@AgNPs) as novel anti-infective therapeutics were prepared and firmly immobilized onto soft CLs through mussel-inspired surface chemistry. The obtained PCBDA@AgNPs coated CL (PCBDA@AgNPs-CL) remained the excellent transparency of commercial CLs and exhibited strong and broad-spectrum antimicrobial activities. We systematically explored the mechanism and found that the functional CLs can effectively inhibit the growth of microbial biofilms via a synergic "resist-kill-remove" strategy due to the zwitterionic surface and sustained release of silver ions. Significantly, in vitro cell cytotoxicity and in vivo subcutaneous implantation experiments proved the significant biosafety of PCBDA@AgNPs-CL. Furthermore, PCBDA@AgNPs-CL was successfully employed for the in vivo treatment of MK rabbit models, demonstrating excellent abilities to eradicate microbe-induced ocular infections and to prevent the destruction and irreversible structural alterations of corneal tissues. Collectively, PCBDA@AgNPs-CL is therefore a highly promising therapeutic device to significantly boost the efficacy for MK treatment.

Polymer cyclization for the emergence of hierarchical nanostructures.

The creation of synthetic polymer nanoobjects with well-defined hierarchical structures is important for a wide range of applications such as nanomaterial synthesis, catalysis, and therapeutics. Inspired by the programmability and precise three-dimensional architectures of biomolecules, here we demonstrate the strategy of fabricating controlled hierarchical structures through self-assembly of folded synthetic polymers. Linear poly(2-hydroxyethyl methacrylate) of different lengths are folded into cyclic polymers and their self-assembly into hierarchical structures is elucidated by various experimental techniques and molecular dynamics simulations. Based on their structural similarity, macrocyclic brush polymers with amphiphilic block side chains are synthesized, which can self-assemble into wormlike and higher-ordered structures. Our work points out the vital role of polymer folding in macromolecular self-assembly and establishes a versatile approach for constructing biomimetic hierarchical assemblies.

Squaric Ester-Based, pH-Degradable Nanogels: Modular Nanocarriers for Safe, Systemic Administration of Toll-like Receptor 7/8 Agonistic Immune Modulators.

Small-molecular Toll-like receptor 7/8 (TLR7/8) agonists hold promise as immune modulators for a variety of immune therapeutic purposes including cancer therapy or vaccination. However, due to their rapid systemic distribution causing difficult-to-control inflammatory off-target effects, their application is still problematic, in particular systemically. To address this problem, we designed and robustly fabricated pH-responsive nanogels serving as versatile immunodrug nanocarriers for safe delivery of TLR7/8-stimulating imidazoquinolines after intravenous administration. To this aim, a primary amine-reactive methacrylamide monomer bearing a pendant squaric ester amide is introduced, which is polymerized under controlled RAFT polymerization conditions. Corresponding PEG-derived squaric ester amide block copolymers self-assemble into precursor micelles in polar protic solvents. Their cores are amine-reactive and can sequentially be transformed by acid-sensitive cross-linkers, dyes, and imidazoquinolines. Remaining squaric ester amides are hydrophilized affording fully hydrophilic nanogels with profound stability in human plasma but stimuli-responsive degradation upon exposure to endolysosomal pH conditions. The immunomodulatory behavior of the imidazoquinolines alone or conjugated to the nanogels was demonstrated by macrophages in vitro. In vivo, however, we observed a remarkable impact of the nanogel: After intravenous injection, a spatially controlled immunostimulatory activity was evident in the spleen, whereas systemic off-target inflammatory responses triggered by the small-molecular imidazoquinoline analogue were absent. These findings underline the potential of squaric ester-based, pH-degradable nanogels as a promising platform to permit intravenous administration routes of small-molecular TLR7/8 agonists and, thus, the opportunity to explore their adjuvant potency for systemic vaccination or cancer immunotherapy purposes.

Precision Anisotropic Brush Polymers by Sequence Controlled Chemistry.

The programming of nanomaterials at molecular length-scales to control architecture and function represents a pinnacle in soft materials synthesis. Although elusive in synthetic materials, Nature has evolutionarily refined macromolecular synthesis with perfect atomic resolution across three-dimensional space that serves specific functions. We show that biomolecules, specifically proteins, provide an intrinsic macromolecular backbone for the construction of anisotropic brush polymers with monodisperse lengths via grafting-from strategy. Using human serum albumin as a model, its sequence was exploited to chemically transform a single cysteine, such that the expression of said functionality is asymmetrically placed along the backbone of the eventual brush polymer. This positional monofunctionalization strategy was connected with biotin-streptavidin interactions to demonstrate the capabilities for site-specific self-assembly to create higher ordered architectures. Supported by systematic experimental and computational studies, we envisioned that this macromolecular platform provides unique avenues and perspectives in macromolecular design for both nanoscience and biomedicine.

Polymer tube nanoreactors via DNA-origami templated synthesis.

We describe the stepwise synthesis of precise polymeric objects programmed by a 3D DNA tube transformed from a common 2D DNA tile as a precise biotemplate for atom transfer radical polymerization. The catalytic interior space of the DNA tube was utilized for synthesizing a bio-inspired polymer, polydopamine.

Fabrication of Defined Polydopamine Nanostructures by DNA Origami-Templated Polymerization.

A versatile, bottom-up approach allows the controlled fabrication of polydopamine (PD) nanostructures on DNA origami. PD is a biosynthetic polymer that has been investigated as an adhesive and promising surface coating material. However, the control of dopamine polymerization is challenged by the multistage-mediated reaction mechanism and diverse chemical structures in PD. DNA origami decorated with multiple horseradish peroxidase-mimicking DNAzyme motifs was used to control the shape and size of PD formation with nanometer resolution. These fabricated PD nanostructures can serve as "supramolecular glue" for controlling DNA origami conformations. Facile liberation of the PD nanostructures from the DNA origami templates has been achieved in acidic medium. This presented DNA origami-controlled polymerization of a highly crosslinked polymer provides a unique access towards anisotropic PD architectures with distinct shapes that were retained even in the absence of the DNA origami template.

Large-Area Patterning of Metal Nanostructures by Dip-Pen Nanodisplacement Lithography for Optical Applications.

Au nanostructures are remarkably important in a wide variety of fields for decades. The fabrication of Au nanostructures typically requires time-consuming and expensive electron-beam lithography (EBL) that operates in vacuum. To address this challenge, this paper reports the development of massive dip-pen nanodisplacement lithography (DNL) as a desktop fabrication tool, which allows high-throughput and rational design of arbitrary Au nanopatterns in ambient condition. Large-area (1 cm2 ) and uniform (<10% variation) Au nanostructures as small as 70 nm are readily fabricated, with a throughput 100-fold higher than that of conventional EBL. As a proof-of-concept of the applications in the opitcal field, we fabricate discrete Au nanorod arrays that show significant plasmonic resonance in the visible range, and interconnected Au nanomeshes that are used for transparent conductive electrode of solar cells.

Synthesis of Peptide-Functionalized Poly(bis-sulfone) Copolymers Regulating HIV-1 Entry and Cancer Stem Cell Migration.

Peptide-polymer conjugates have been regarded as primary stronghold in biohybrid nanomedicine, which has seen extensive development due to its intrinsic property to provide complementary functions of both the peptide material and the synthetic polymer platform. Here we present an advanced macromolecular therapeutic that targets two exclusive classes of important diseases (namely, the HIV and cancer) that are implicated by extremely different causative agents. Using a facile thiol-reactive monomer, the eventual polymer facilitates multivalent conjugation of an endogenous peptide WSC02 that targets the CXCR4 chemokine receptor. The biohybrid material demonstrated both potent antiviral effects against HIV-1 as well as inhibiting cancer stem cell migration thus establishing the foundation for multimodal nanotherapeutics that simultaneously target more than one class of disease implications.

Arbitrary and Parallel Nanofabrication of 3D Metal Structures with Polymer Brush Resists.

3D polymer brushes are reported for the first time as ideal resists for the alignment-free nanofabrication of complex 3D metal structures with sub-100 nm lateral resolution and sub-10 nm vertical resolution. Since 3D polymer brushes can be serially fabricated in parallel, this method is effective to generate arbitrary 3D metal structures over a large area at a high throughput.