Toward Predicting the Formation of Integral-Asymmetric, Isoporous Diblock Copolymer Membranes.

The self-assembly and nonsolvent-induced phase separation (SNIPS) process of block copolymers and solvents enables the fabrication of integral-asymmetric, isoporous membranes. An isoporous top layer is formed by evaporation-induced self-assembly (EISA) and imparts selectivity for ultrafiltration of functional macromolecules or water purification. This selective layer is supported by a macroporous bottom structure that is formed by nonsolvent-induced phase separation (NIPS) providing mechanical stability. Thereby the permeability/selectivity tradeoff is optimized. The SNIPS fabrication involves various physical phenomena-e.g., evaporation, self-assembly, macrophase separation, vitrification - and multiple structural, thermodynamic, kinetic, and process parameters. Optimizing membrane properties and rationally designing fabrication processes is a challenge which particle simulation can significantly contribute to. Using large-scale particle simulations, it is observed that 1) a small incompatibility between matrix-forming block of the copolymer and nonsolvent, 2) a glassy arrest that occurs at a smaller polymer concentration, or 3) a higher dynamical contrast between polymer and solvent results in a finer, spongy substructure, whereas the opposite parameter choice gives rise to larger macropores with an elongated shape. These observations are confirmed by comparison to experiments on polystyrene (PS)-block-poly(4-vinylpyridine) (P4VP) diblock copolymer membranes, varying the chemical nature of the coagulant or the temperature of coagulation bath.

Transformable Supramolecular Self-Assembled Peptides for Cascade Self-Enhanced Ferroptosis Primed Cancer Immunotherapy.

Immunotherapy has received widespread attention for its effective and long-term tumor-eliminating ability. However, for immunogenic "cold" tumors, such as prostate cancer (PCa), the low immunogenicity of the tumor itself is a serious obstacle to efficacy. Here, this work reports a strategy to enhance PCa immunogenicity by triggering cascade self-enhanced ferroptosis in tumor cells, turning the tumor from "cold" to "hot". This work develops a transformable self-assembled peptide TEP-FFG-CRApY with alkaline phosphatase (ALP) responsiveness and glutathione peroxidase 4 (GPX4) protein targeting. TEP-FFG-CRApY self-assembles into nanoparticles under aqueous conditions and transforms into nanofibers in response to ALP during endosome/lysosome uptake into tumor cells, promoting lysosomal membrane permeabilization (LMP). On the one hand, the released TEP-FFG-CRAY nanofibers target GPX4 and selectively degrade the GPX4 protein under the light irradiation, inducing ferroptosis; on the other hand, the large amount of leaked Fe2+ further cascade to amplify the ferroptosis through the Fenton reaction. TEP-FFG-CRApY-induced immunogenic ferroptosis improves tumor cell immunogenicity by promoting the maturation of dendritic cells (DCs) and increasing intratumor T-cell infiltration. More importantly, recovered T cells further enhance ferroptosis by secreting large amounts of interferon-gamma (IFN-γ). This work provides a novel strategy for the molecular design of synergistic molecularly targeted therapy for immunogenic "cold" tumors.

In Situ Construction of Ferrocene-Containing Membrane-Bound Nanofibers for the Redox Control of Cancer Cell Death and Cancer Therapy.

Precise manipulation of cancer cell death by harnessing reactive oxygen species (ROS) is a promising strategy to defeat malignant tumors. However, it is quite difficult to produce active ROS with spatial precision and regulate their biological outcomes. We succeed here in selectively generating short-lived and lipid-reactive hydroxyl radicals (•OH) adjacent to cancer cell membranes, successively eliciting lipid peroxidation and ferroptosis. DiFc-K-pY, a phosphorylated self-assembling precursor that consists of two branched Fc moieties and interacts specifically with epidermal growth factor receptor, can in situ produce membrane-bound nanofibers and enrich ferrocene moieties on cancer cell membranes in response to alkaline phosphatase. Within the acidic tumor microenvironment, DiFc-K-pY nanofibers efficiently convert tumoral H2O2 to active •OH around the target cell membranes via Fenton-like reactions, leading to lipid peroxidation and ferroptosis with good cellular selectivity. Our strategy successfully prevents tumor progression with acceptable biocompatibility through intratumoral administration.

Role of polymer template in crystal structure and photoactivity of Cu-TiO2 heterojunction nanostructures towards environmental remediation.

Exploring porous heterojunction nanomaterials as a photocatalyst for water depollution strategies towards environmental restoration is exceedingly difficult in the perspective of sustainable chemistry. Herein, we first report a porous Cu-TiO2 (TC40) heterojunction by using microphase separation of a novel penta-block copolymer (PLGA-PEO-PPO-PEO-PLGA) as a template through an evaporation induced self-assembly (EISA) method having nanorod-like particle shape. Furthermore, two types of photocatalyst were made with or without polymer template to clarify the function of that template precursor on the surface and morphology, as well as which variables are the most critical for a photocatalyst. TC40 heterojunction nanomaterial displayed higher BET surface area along with lower band gap value viz.2.98 eV compared to the other and these features make it a robust photocatalyst for wastewater treatment. In order to improve water quality, we have carried out experiments on the photodegradation of methyl orange (MO), highly toxic pollutants that cause health hazards and bioaccumulate in the environment. Our catalyst, TC40 exhibits the 100% photocatalytic efficiency towards MO dye degradation in 40 and 360 min at a rate constant of 0.104 ± 0.007 min-1 and 0.440 ± 0.03 h-1 under UV + Vis and visible light irradiation, respectively.

A Cascade-Targeted Enzyme-Instructed Peptide Self-Assembly Strategy for Cancer Immunotherapy through Boosting Immunogenic Cell Death.

Immunogenic cell death (ICD) approaches by encumbering mitochondrial functions provide great promise for the treatment of malignant tumors, but these kinds of ICD strategies are still in their infancy. Here, one multifunctional drug-loaded, cascade-targeted, and enzyme-instructed self-assembling peptide nanomedicine (Comp. 4) for ICD-based cancer therapy is constructed. Comp. 4 consists of 1) lonidamine (LND) that specifically interferes with mitochondrial functions; 2) a programmed death ligand 1 (PD-L1) binding peptide sequence (NTYYEDQG) and a mitochondria-specific motif (triphenylphosphonium, TPP) that can sequentially control the cell membrane and mitochondria targeting capacities, respectively; and 3) a -GD FD FpD Y- assembly core to in situ organize peptide assemblies responsive to alkaline phosphatase (ALP). Comp. 4 demonstrates noticeable structural and morphological transformations in the presence of ALP and produces peptide assemblies in mouse colon cancer cells (CT26) with high expressions of both ALP and PD-L1. Moreover, the presence of PD-L1- and mitochondria-specific motifs can assist Comp. 4 for effective endocytosis and endosomal escape, forming peptide assemblies and delivering LND into mitochondria. Consequently, Comp. 4 shows superior capacities to in vivo induce abundant mitochondrial oxidative stress, provoke robust ICD responses, and produce an immunogenic tumor microenvironment, successfully inhibiting CT26 tumor growth by eliciting a systemic ICD-based antitumor immunity.

Synthesis of ultra-thin graphene-like nanosheets from lignin based on evaporation induced self-assembly for supercapacitors.

Graphene-like carbon materials are widely used in power devices due to their excellent structural characteristics. In this study, ultra-thin graphene-like nanosheets (LGLNs) with rich surface wrinkles were prepared by classical evaporation induced self-assembly (EISA) using lignin biomass as carbon precursor, followed by chemical activation with KHCO3. The obtained LGLN900 material calcined at 900 °C had a thickness of ca. 3 nm, a large specific surface area of 2886 m2 g-1 with a high specific pore volume of 2.10 cm3 g-1. In addition, a large number of wrinkles on the surface of LGLN900 endows its effective compression resistance. When the LGLN900 material was used as electrode material of supercapacitor, a high specific capacitance of 388 F g-1 was obtained at 0.2 A g-1 current density in 6 M KOH aqueous solution, and 269 F g-1 specific capacitance could be at remained at 40 A g-1. The supercapacitor assembled with LGLN900 afforded a specific energy density of (11.0-13.7) Wh kg-1 at a power density of (128.8-6465) W kg-1. This work provides a facile and green strategy for the synthesis of highly wrinkled ultra-thin graphene-like nanosheets from sustainable biomass resources, which should have wide applications in adsorption, catalysis and energy storage.

Supramolecular Nanofibers Formed by Enzyme-Instructed Self-Assembly for SKBR-3 Cell Selective Inhibition.

Cell-targeted peptides are recommended for precision cancer treatment due to their comparable targeting properties, small molecular size, and good biocompatibility. However, unpredictable bioactivity, low penetration rate and poor stability greatly limit its efficacy. Supramolecular self-assembly based on synthetic peptide has great potential to solve related problems and achieve better therapeutic effects. Herein, we report and compare the effects of two different assembly pathway, heating-cooling, and enzyme instruction, on the penetrability of SKBR-3 cell targeted peptides. It was found that enzyme-instructed self-assembly (EISA) resulted in hydrogels composed of uniform supramolecular nanofibers, whereas heating-cooling resulted in solutions and precipitations composed of slightly different nanoparticles. The nanofibers formed by EISA showed enhanced cellular uptake (2.54 µM), which was significantly higher than the 1.06 µM of the nanoparticles formed by temperature regulation. Thus, EISA is a promising strategy to improve the cell penetration rate of targeted peptides and could provide a better solution for precision cancer treatment.

A Platform Approach to Protein Encapsulates with Controllable Surface Chemistry.

The encapsulation of proteins into core-shell structures is a widely utilised strategy for controlling protein stability, delivery and release. Despite the recognised utility of these microstructures, however, core-shell fabrication routes are often too costly or poorly scalable to allow for industrial translation. Furthermore, many scalable routes rely upon emulsion-techniques implicating denaturing or environmentally harmful organic solvents. Herein, we investigate core-shell protein encapsulation through single-feed, aqueous spray drying: a cheap, industrially ubiquitous particle-formation technology in the absence of organic solvents. We show that an excipient's preference for the surface of the spray dried particle is well-predicted by its hydrodynamic diameter (Dh) under relevant feed buffer conditions (pH and ionic strength) and that the predictive power of Dh is improved when measured at the spray dryer outlet temperature compared to room temperature (R2 = 0.64 vs. 0.59). Lastly, we leverage these findings to propose an adaptable design framework for fabricating core-shell protein encapsulates by single-feed aqueous spray drying.

Optimization of fluoride adsorption from aqueous solution over mesoporous titania-alumina composites using Taguchi method.

The optimization of fluoride removal from aqueous media was studied over the mesoporous titania-alumina composites using Taguchi method-based L25 orthogonal array experimental design. The chemical structure, surface chemistry, and morphology of as-prepared composite adsorbents were studied utilizing various analytical methods. The findings of the characterization demonstrated that the produced composites have high textural qualities, which are conducive to enhanced fluoride adsorption. The optimum conditions for maximum percentage removal of fluoride from aqueous solution were found as adsorbent type as TA75, adsorbent dose 4 g L-1 , initial concentration of fluoride 40 ppm, solution pH 3 with a treatment time of 60 min. Under the optimum conditions, 98% of fluoride adsorption was achieved. Analysis of variance revealed that the solution pH followed by the adsorbent dose was the most significant for fluoride adsorption. The Langmuir model and pseudo-second-order kinetic model fit the adsorption data well, and the TA75 adsorbent had a maximum Langmuir fluoride adsorption capacity of 34.48 mg g-1 at pH = 3. The thermodynamic information suggests that the adsorption was spontaneous and endothermic under the given operating conditions. The synergic combination of Ti-Al nanoparticles demonstrated a high percentage removal of fluoride under the optimized operating conditions. PRACTITIONER POINTS: The Taguchi method-based design of the experimental approach was implemented in the fluoride adsorption process. Mesoporous titania-alumina composites with 0 to 100 wt.% of alumina in titania were prepared and applied to remove fluoride from an aqueous solution. Solution pH was the most influential parameter for the fluoride adsorption process, while the synergistic combination of 75 wt.% alumina in titania showed the maximum adsorption capacity.

Evaporation-Induced Self-Assembly of Small Peptide-Conjugated Silica Nanoparticles.

Self-assembly processes guide disordered molecules or particles into long-range organized structures due to specific supramolecular interactions among the building entities. Herein, we report a unique evaporation-induced self-assembly (EISA) strategy for four different silica nanoparticle systems obtained through peptide functionalization of the particle surface. First, covalent peptide-silica coupling was investigated in detail, starting with the grafting of a single amino acid (L-serine) and expanded to specific small peptides (up to four amino acids) and transferred to different particle types (MCM-48-type MSNs, solid nanoparticles, and newly developed virus-like nanoparticles). These materials were investigated regarding their ability to undergo EISA, which was shown to be independent of particle type and amount of peptide anchored to their surface. This EISA-based approach provides new possibilities for the design of future advanced drug delivery systems, engineered hierarchical sorbents, and nanocatalyst assemblies.

Selectively enhancing radiosensitivity of cancer cells via in situ enzyme-instructed peptide self-assembly.

The radiotherapy modulators used in clinic have disadvantages of high toxicity and low selectivity. For the first time, we used the in situ enzyme-instructed self-assembly (EISA) of a peptide derivative (Nap-GDFDFpYSV) to selectively enhance the sensitivity of cancer cells with high alkaline phosphatase (ALP) expression to ionizing radiation (IR). Compared with the in vitro pre-assembled control formed by the same molecule, assemblies formed by in situ EISA in cells greatly sensitized the ALP-high-expressing cancer cells to γ-rays, with a remarkable sensitizer enhancement ratio. Our results indicated that the enhancement was a result of fixing DNA damage, arresting cell cycles and inducing cell apoptosis. Interestingly, in vitro pre-formed assemblies mainly localized in the lysosomes after incubating with cells, while the assemblies formed via in situ EISA scattered in the cell cytosol. The accumulation of these molecules in cells could not be inhibited by endocytosis inhibitors. We believed that this molecule entered cancer cells by diffusion and then in situ self-assembled to form nanofibers under the catalysis of endogenous ALP. This study provides a successful example to utilize intracellular in situ EISA of small molecules to develop selective tumor radiosensitizers.

Facile Synthesis of Wormhole-Like Mesoporous Tin Oxide via Evaporation-Induced Self-Assembly and the Enhanced Gas-Sensing Properties.

Wormhole-like mesoporous tin oxide was synthesized via a facile evaporation-induced self-assembly (EISA) method, and the gas-sensing properties were evaluated for different target gases. The effect of calcination temperature on gas-sensing properties of mesoporous tin oxide was investigated. The results demonstrate that the mesoporous tin oxide sensor calcined at 400 °C exhibits remarkable selectivity to ethanol vapors comparison with other target gases and has a good performance in the operating temperature and response/recovery time. This might be attributed to their high specific surface area and porous structure, which can provide more active sites and generate more chemisorbed oxygen spices to promote the diffusion and adsorption of gas molecules on the surface of the gas-sensing material. A possible formation mechanism of the mesoporous tin oxide and the enhanced gas-sensing mechanism are proposed. The mesoporous tin oxide shows prospective detecting application in the gas sensor fields.

Self-assembly of mesoporous Bi-S-TiO2 composites for degradation of industrial dinitrotoluene solution under UV light.

Mesoporous Bi-S-TiO2 composites were synthesized by the method combining evaporation-induced self-assembly (EISA) method with impregnation process. Characterization shows mesoporous Bi-S-TiO2 was a highly crystalline anatase, with relatively high thermal stability, large surface area (75-120 m2/g), and large mesopore (10-20 nm). The results also revealed that Bi and S species existed in Bi4+, S2-, S and S6+ forms in the mesoporous TiO2, which allow the mesoporous Bi-S-TiO2 illustrating strong absorption in the ultraviolet region, and the absorption edge shifts to the visible-light region. Photodegradation tests shown that, about 92.3% industrial aqueous dinitrotoluene (DNT) solution could be degraded by 1.5%Bi-S-TiO2 under UV irradiation for 5 h. Concentration of Bi ions and calcination temperature were found to play important roles in its mesoporous properties and photocatalytic activity.

A Syriac Medical Kunnasa of Iso' bar 'Ali (9th c.): First Soundings.

A little-known thirteenth-century manuscript preserved in Damascus contains by far the largest Syriac medical work that has survived till today. Despite the missing beginning, a preliminary study of the text allows us to argue that it is the medical handbook (entitled Kunnasa) of Iso' bar 'Ali, a ninth-century physician and student of Hunayn b. Ishaq. The seven books of the handbook appear to follow the model of Paul of Aegina's Pragmateia both in composition and content. The actual significance of the handbook in the history of Syriac and Arabic medicine is yet to be assessed, but there can be no doubt that it will be a pivotal source that illustrates the development of Syriac medicine during a period of four centuries at the moment when it was being translated to lay the foundations of the nascent medical tradition in Arabic.

Post-transcriptional regulation of photosynthetic genes is a key driver of C4 leaf ontogeny.

C4 photosynthesis allows highly efficient carbon fixation that originates from tightly regulated anatomical and biochemical modifications of leaf architecture. Recent studies showed that leaf transcriptome modifications during leaf ontogeny of closely related C3 (Tarenaya hassleriana) and C4 (Gynandropsis gynandra) species within the Cleomaceae family existed but they did not identify any dedicated transcriptional networks or factors specifically driving C4 leaf ontogeny. RNAseq analysis provides a steady-state quantification of whole-cell mRNAs but does not allow any discrimination between transcriptional and post-transcriptional processes that may occur simultaneously during leaf ontogeny. Here we use exon-intron split analysis (EISA) to determine the extent to which transcriptional and post-transcriptional processes are involved in the regulation of gene expression between young and expanded leaves in both species. C4-specific changes in post-transcriptional regulation were observed for genes involved in the Calvin-Benson cycle and some photosystem components but not for C4 core-cycle genes. Overall, this study provides an unbiased genome-wide insight into the post-transcriptional mechanisms that regulate gene expression through the control of mRNA levels and could be central to the onset of C4 photosynthesis. This mechanism is cytosolic which implies cell-specific modifications of mRNA stability. Understanding this mechanism may be crucial when aiming to transform C3 crops into C4 crops.

Preparation of NASICON-Type Nanosized Solid Electrolyte Li1.4Al0.4Ti1.6(PO4)3 by Evaporation-Induced Self-Assembly for Lithium-Ion Battery.

A simple and practicable evaporation-induced self-assembly (EISA) method is introduced for the first time to prepare nanosized solid electrolyte Li1.4Al0.4Ti1.6(PO4)3 (LATP) for all-solid-state lithium-ion batteries. A pure Na+ super ion conductor (NASICON) phase is confirmed by X-ray diffraction (XRD) analysis, and its primary particle size is down to 70 nm by optimizing evaporation rate of the solvent. Excellent room temperature bulk and total lithium-ion conductivities of 2.09 × 10-3 S cm-1 and 3.63 × 10-4 S cm-1 are obtained, with an ion-hopping activation energy as low as 0.286 eV.

Estimating Nitrogen Load Resulting from Biofuel Mandates.

The Energy Policy Act of 2005 and the Energy Independence and Security Act (EISA) of 2007 were enacted to reduce the U.S. dependency on foreign oil by increasing the use of biofuels. The increased demand for biofuels from corn and soybeans could result in an increase of nitrogen flux if not managed properly. The objectives of this study are to estimate nitrogen flux from energy crop production and to identify the catchment areas with high nitrogen flux. The results show that biofuel production can result in an increase of nitrogen flux to the northern Gulf of Mexico from 270 to 1742 thousand metric tons. Using all cellulosic (hay) ethanol or biodiesel to meet the 2022 mandate is expected to reduce nitrogen flux; however, it requires approximately 25% more land when compared to other scenarios. Producing ethanol from switchgrass rather than hay results in three-times more nitrogen flux, but requires 43% less land. Using corn ethanol for 2022 mandates is expected to have double the nitrogen flux when compared to the EISA-specified 2022 scenario; however, it will require less land area. Shifting the U.S. energy supply from foreign oil to the Midwest cannot occur without economic and environmental impacts, which could potentially lead to more eutrophication and hypoxia.

Evaporation-induced Self-assembly Process Controlled for Obtaining Highly Ordered Mesoporous Materials with Demanded Morphologies.

A large number of periodic mesoporous materials have been reported using amphiphilic organic molecules with increasing development of synthetic methods for mesostructural, morphological, and compositional designs. The evaporation-induced self-assembly (ESIA) process to fabricate ordered mesoporous films is one of the most essential synthetic methods, which has extensively been applied for obtaining a wide variety of samples (e.g., films and monoliths, including powders). It contains complicated physical variations and chemical reactions, but has been simply explained by several research groups. However, a current, exact understanding of such complicated systems should be given with respect to all the variations and reactions. In this article, I have mainly surveyed the exact EISA process by considering the difference between simple and controlled EISA processes on the basis of my own experiments. I believe that the insights are consequently helpful for obtaining highly ordered mesoporous materials with demanded morphologies.

Nanoscale Assemblies of Small Molecules Control the Fate of Cells.

Being driven by non-covalent interactions, the formation of functional assemblies (or aggregates) of small molecules at nanoscale is a more common process in water than one would think. While most efforts on self-assembly in cellular environment concentrate on the assemblies of proteins (e.g., microtubules or amyloid fibers), nanoscale assemblies of small molecules are emerging functional entities that exhibit important biological function in cellular environments. This review describes the increasing efforts on the exploration of nanoscale assemblies of small molecules that largely originate from the serendipitous observations in research fields other than nanoscience and technology. Specifically, we describe that nanoscale assemblies of small molecules exhibit unique biological functions in extracellular and intracellular environment, thus inducing various cellular responses, like causing cell death or promoting cell proliferation. We first survey certain common feature of nanoscale molecular assemblies, then discuss several specific examples, such as, nanoscale assemblies of small peptides accumulated in the cells for selectively inhibiting cancer cells via promiscuous interactions with proteins, and nanoscale assemblies of a glycoconjugate for promoting the proliferation of stem cells or for suppressing immune responses. Subsequently, we emphasize the spatiotemporal control of nanoscale assemblies for controlling the cell fate, particularly illustrate a paradigm-shifting approach-enzyme-instructed self-assembly (EISA), that is, the integration of enzymatic reaction and self-assembly-for generating nanoscale assemblies from innocuous monomers for selectively inhibiting cancer cells. Moreover, we introduce a convenient assay for proteomic study of the proteins that interact with nanoscale assemblies of small molecules in cellular environment. Furthermore, we introduce the use of ligand-receptor interaction to catalyze the formation of nanoscale assemblies. By illustrating these experimental strategies for controlling the formation of nanoscale assemblies of small molecules and for identifying their corresponding protein targets, we aim to highlight that, though not being defined at the genetic level, nanoscale assemblies of small molecules are able to perform many critical biological functions. We envision that nanoscale assemblies of small molecules are a new frontier at the intersection of nanoscience and cell biology and biomedicine. In addition, we discuss the challenges and perspectives of relevant potential biomedical applications of nanoscale assemblies of small molecules.

Effect of variation of average pore size and specific surface area of ZnO electrode (WE) on efficiency of dye-sensitized solar cells.

Mesoporous ZnO nanoparticles have been synthesized with tremendous increase in specific surface area of up to 578 m(2)/g which was 5.54 m(2)/g in previous reports (J. Phys. Chem. C 113:14676-14680, 2009). Different mesoporous ZnO nanoparticles with average pore sizes ranging from 7.22 to 13.43 nm and specific surface area ranging from 50.41 to 578 m(2)/g were prepared through the sol-gel method via a simple evaporation-induced self-assembly process. The hydrolysis rate of zinc acetate was varied using different concentrations of sodium hydroxide. Morphology, crystallinity, porosity, and J-V characteristics of the materials have been studied using transmission electron microscopy (TEM), X-ray diffraction (XRD), BET nitrogen adsorption/desorption, and Keithley instruments.