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Background and Purpose: Delta-opioid receptors (DOP receptors) could represent a novel target in the treatment of depressive disorders. To explore this new field of interest, the development of highly selective DOP receptor agonists is essential. UFP-512 [H-Dmt-Tic-NH-CH(CH2-COOH)-Bid], was recently shown to behave in vitro as a selective and potent DOP receptor agonist and to promote antidepressant- and anxiolytic-like effects in vivo (Vergura et al., 2007). Here, we have characterized the pharmacological properties of UFP-512 and established a link between desensitization and tolerance.Experimental Approach: Studies were performed in the human neuroblastoma SK-N-BE cells to establish i) binding parameters for UFP-512 ii) signalling pathways activated after acute and chronic treatment iii) regulation (phosphorylation and trafficking) of human DOP (hDOP) receptors after sustained activation by UFP-512. In vivo, we studied UFP-512-induced antidepressant-like effects after acute or chronic treatment in the mouse forced swimming test.Key Results: In vitro, UFP-512 was a high affinity agonist for DOP receptors. While UFP-512 induced marked phosphorylation of DOP receptors on Ser363, we observed a low desensitization of the cAMP pathway, associated with receptor endocytosis and recycling without any reduction on extracellular signal-regulated protein kinase 1/2 activation. In vivo, acute administration of UFP-512 produced an antidepressant-like effect, without any sign of tolerance after chronic administration.Conclusions and Implications: There was a correlation between weak desensitization, significant internalization and recycling of the human DOP receptors and lack of tolerance to UFP-512. This suggests that this compound would be a promising drug prototype for exploring innovative treatments for mood disorders. [ABSTRACT FROM AUTHOR]

The article discusses how to achieve the optimal hedging of a cash flow when facing price risk of the product the company sells. It presents an analytical solution to the optimal hedging strategy in the general case and in some particular situations. It also obtains an expression to measure the efficiency of the hedging strategy.

Se revisan las acciones que se llevan a cabo para sensibilizar a los medios en diversas estrategias internacionales contra el estigma. De la experiencia de la estrategia contra el estigma de Andalucía “1 de cada 4”, iniciada en 2005, se exponen una serie de aspectos que deberían considerarse cuando se trabaja para mejorar la imagen de la enfermedad mental que se proyecta en los medios de comunicación.

The low efficiency for dehydrogenation of steroids has become a starting point for new developments and genetic improvement of microorganisms. Steroid-1,2-dehydrogenase has been studied in several bacterial strains as Mycobacterium, Arthrobacter and Nocardia. There are still possibilities for finding new enzyme properties for reaction yields being improved. The optimum temperature and thermal stability were studied. Cells were irradiated in a microwaves reactor Maxidigest MX 350, 30-90 W power, temperatures were registered from 50 to 90°C with a Digisense CA 862 thermometer. The enzyme activity was higher than in control samples. At temperature as higher as 80 °C, the activity was increased by a 3,6 factor. In all experiments, cell survival was higher in microwaves heated cells (95,9 % survival at 50°C) than for conventional heated cells (0,4 % survival at same temperature). [ABSTRACT FROM AUTHOR]

El artículo explora la conversión de androstadiona (ADD) a androstadiendiona en ciertos cultivos mixtos, específicamente Mycobacterium sp. Fermentaciones con cepas de Mycobacterium se ven limitados por una cierta proporción de AD presente en los caldos fermentativos. Se presenta detalles sobre la conversión a androstadiendiona, añadiendo células de Nocardiodes. Se observó que la eficiencia de la conversión se aumenta si se utilizaron mutantes con actividad incrementada de la enzima en cuestión.

The enzyme steroid 1,2 dehydrogenase in microorganisms degrading sterols catalyzes the formation of androstadien-3,17-dione (ADD) from 4-androsten-3,17-dione (AD). The reaction introduces a double bound at the 1,2 position in ring A of the steroidal nucleus. This paper shows the results of the kinetic study of this enzyme in strains Mycobacterium sp. NRRL-B3683 and Ex4, a derived mutant from the former. Both strains are ADD producers as the main phenotype. Determination of the kinetic parameters includes the Michaelis-Menten constant (Km), the maximal velocity of the enzymatic reaction (Vmax), optimal temperature and pH, as well as its thermostability. Maximal activity was achieved at 25 °C, and pH values from 7,8 to 8,8. On the other hand, Km and Vmax were 4 . 10-4 M and 20 nmol/mL, respectively. The above results are compared to biotransformation behavior of the strains in fermentation experiments having cholesterol, stigmasterol and a phytosterol mixture from sugar cane oil as substrates. ADD yield was similar when cholesterol was used as substrate in both strains. However, the AD/ADD ratio was smaller in Ex4, so that this strain must harbor a higher steroid 1,2 dehydrogenase activity. [ABSTRACT FROM AUTHOR]

Eutrophication is a global problem causing the reduction of water quality and the loss of ecosystem goods and services. The lakes of the "Lagunas de Montebello" National Park (LMNP), Chiapas, Mexico, not only represent unique and beautiful natural scenic sites in southern Mexico but are also a national protected area and RAMSAR site. Unfortunately, some of these lakes started showing eutrophication signs since 2003. Anthropogenic activities ( e.g. , land-use change from forested to agricultural and urban development) are leading to water quality and trophic state alterations of the lakes of the LMNP. This study shows the results of a coupled limnological characterization and high-throughput sequencing of the V4 hypervariable region of the 16S rRNA gene to analyze the microbial composition of the water column in a set of oligotrophic and eutrophic lakes. Chlorophyll a (Chl-a) was the main environmental parameter correlated with the trophic conditions of the lakes. Although the microbial diversity was similar, the microbial composition changed significantly from oligo to eutrophic lakes. Proteobacteria, Firmicutes, and Cyanobacteria were the main components of oligotrophic lakes, and Cyanobacteria, Proteobacteria, and Bacteroidetes of eutrophic lakes. While Acinetobacter (Proteobacteria) and Cyanobium (a unicellular cyanobacterium) dominated in oligotrophic lakes, the filamentous, bloom-forming, and toxin-producing cyanobacteria Planktothrix was the dominant genus in eutrophic lakes. High-throughput sequencing allowed the detection of changes in the composition of the microbial component in oligotrophic lakes, suggesting a shift towards eutrophication, highlighting the relevance of sensitive monitoring protocols of these ecosystems to implement remediation programs for eutrophicated lakes and conservation strategies for those yet pristine., Competing Interests: The authors declare there are no competing interests., (©2022 Yanez-Montalvo et al.)

Background: The median survival of Glioblastoma multiforme (GBM) patients is 14+ months due to poor responses to surgery and chemoradiation. Means to counteract radiation resistance are therefore highly desirable. We demonstrate the membrane bound matrix metalloproteinase MT1-MMP promotes resistance of GBM to radiation, and that using a selective and brain permeable MT1-MMP inhibitor, (R) -ND336, improved tumor control can be achieved in preclinical studies., Methods: Public microarray and RNA-sequencing data were used to determine MT1-MMP relevance in GBM patient survival. Glioma stem-like neurospheres (GSCs) were used for both in vitro and in vivo assays. An affinity resin coupled with proteomics was used to quantify active MT1-MMP in brain tissue of GBM patients. Short hairpin RNA (shRNA)-mediated knockdown of MT1-MMP and inhibition via the MT1-MMP inhibitor (R) -ND336, were used to assess the role of MT1-MMP in radio-resistance., Results: MT1-MMP expression inversely correlated with patient survival. Active MT1-MMP was present in brain tissue of GBM patients but not in normal brain. shRNA- or (R) -ND336-mediated inhibition of MT1-MMP sensitized GSCs to radiation leading to a significant increase in survival of tumor-bearing animals. MT1-MMP depletion reduced invasion via the effector protease MMP2; and increased the cytotoxic response to radiation via induction of replication fork stress and accumulation of double strand breaks (DSBs), making cells more susceptible to genotoxic insult., Conclusions: MT1-MMP is pivotal in maintaining replication fork stability. Disruption of MT1-MMP sensitizes cells to radiation and can counteract invasion. (R) -ND336, which efficiently penetrates the brain, is therefore a novel radio-sensitizer in GBM., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

The inheritance of memory is an adaptive trait. Microbes challenge the immunity of organisms and trigger behavioral adaptations that can be inherited, but how bacteria produce inheritance of a trait is unknown. We use Caenorhabditis elegans and its bacteria to study the transgenerational RNA dynamics of interspecies crosstalk leading to a heritable behavior. A heritable response of C. elegans to microbes is the pathogen-induced diapause (PIDF), a state of suspended animation to evade infection. We identify RsmY, a small RNA involved in quorum sensing in Pseudomonas aeruginosa as a trigger of PIDF. The histone methyltransferase (HMT) SET-18/SMYD3 and the argonaute HRDE-1, which promotes multi-generational silencing in the germline, are also needed for PIDF initiation . The HMT SET-25/EHMT2 is necessary for memory maintenance in the transgenerational lineage. Our work is a starting point to understanding microbiome-induced inheritance of acquired traits, and the transgenerational influence of microbes in health and disease., Competing Interests: The authors declare no competing interests., (© 2022 The Authors.)

Mining uranium from seawater is highly desirable for sustaining the increasing demand for nuclear fuel; however, access to this unparalleled reserve has been limited by competitive adsorption of a wide variety of concentrated competitors, especially vanadium. Herein, we report the creation of a series of uranyl-specific "hooks" and the decoration of them into the nanospace of porous organic polymers to afford uranium nanotraps for seawater uranium extraction. Manipulating the relative distances and angles of amidoxime moieties in the ligands enabled the creation of uranyl-specific "hooks" that feature ultrahigh affinity and selective sequestration of uranium with a distribution coefficient threefold higher compared to that of vanadium, overcoming the long-term challenge of the competing adsorption of vanadium for uranium extraction from seawater. The optimized uranium nanotrap (2.5 mg) can extract more than one-third of the uranium in seawater (5 gallons), affording an enrichment index of 3836 and thus presenting a new benchmark for uranium adsorbent. Moreover, with improved selectivity, the uranium nanotraps could be regenerated using a mild base treatment. The synergistic combination of experimental and theoretical analyses in this study provides a mechanistic approach for optimizing the selectivity of chelators toward analytes of interest., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Communication with bacteria deeply impacts the life history traits of their hosts. Through specific molecules and metabolites, bacteria can promote short- and long-term phenotypic and behavioral changes in the nematode Caenorhabditis elegans . The chronic exposure of C. elegans to pathogens promotes the adaptive behavior in the host's progeny called pathogen-induced diapause formation (PIDF). PIDF is a pathogen avoidance strategy induced in the second generation of animals infected and can be recalled transgenerationally. This behavior requires the RNA interference machinery and specific nematode and bacteria small RNAs (sRNAs). In this work, we assume that RNAs from both species co-exist and can interact with each other. Under this principle, we explore the potential interspecies RNA interactions during PIDF-triggering conditions, using transcriptomic data from the holobiont. We study two transcriptomics datasets: first, the dual sRNA expression of Pseudomonas aeruginosa PAO1 and C. elegans in a transgenerational paradigm for six generations and second, the simultaneous expression of sRNAs and mRNA in intergenerational PIDF. We focus on those bacterial sRNAs that are systematically overexpressed in the intestines of animals compared with sRNAs expressed in host-naïve bacteria. We selected diverse in silico methods that represent putative mechanisms of RNA-mediated interspecies interaction. These interactions are as follows: heterologous perfect and incomplete pairing between bacterial RNA and host mRNA; sRNAs of similar sequence expressed in both species that could mimic each other; and known or predicted eukaryotic motifs present in bacterial transcripts. We conclude that a broad spectrum of tools can be applied for the identification of potential sRNA and mRNA targets of the interspecies RNA interaction that can be subsequently tested experimentally., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Legüe, Aguila and Calixto.)

The Fanconi Anemia (FA) pathway is essential for human cells to maintain genomic integrity following DNA damage. This pathway is involved in repairing damaged DNA through homologous recombination. Cancers with a defective FA pathway are expected to be more sensitive to cross-link based therapy or PARP inhibitors. To evaluate downstream effectors of the FA pathway, we studied the expression of 734 different micro RNAs (miRNA) using NanoString nCounter miRNA array in two FA defective lung cancer cells and matched control cells, along with two lung tumors and matched non-tumor tissue samples that were deficient in the FA pathway. Selected miRNA expression was validated with real-time PCR analysis. Among 734 different miRNAs, a cluster of microRNAs were found to be up-regulated including an important cancer related micro RNA, miR-200C. MiRNA-200C has been reported as a negative regulator of epithelial-mesenchymal transition (EMT) and inhibits cell migration and invasion by promoting the upregulation of E-cadherin through targeting ZEB1 and ZEB2 transcription factors. miRNA-200C was increased in the FA defective lung cancers as compared to controls. AmpliSeq analysis showed significant reduction in ZEB1 and ZEB2 mRNA expression. Our findings indicate the miRNA-200C potentially play a very important role in FA pathway downstream regulation.

A photoactive porphyrinic metal-organic framework (MOF) has been prepared by exchanging Ti into a Zr-based MOF precursor. The resultant mixed-metal Ti/Zr porphyrinic MOF demonstrates much-improved efficiency for gas-phase CO 2 photoreduction into CH 4 and CO under visible-light irradiation using water vapor compared to the parent Zr-MOF. Insightful studies have been conducted to probe the photocatalysis processes. This work provides the first example of gas-phase CO 2 photoreduction into methane without organic sacrificial agents on a MOF platform, thereby paving an avenue for developing MOF-based photocatalysts for application in CO 2 photoreduction and other types of photoreactions., (© 2020 Wiley-VCH GmbH.)

Preorganization is a basic design principle used by nature that allows for synergistic pathways to be expressed. Herein, a full account of the conceptual and experimental development from randomly distributed functionalities to a convergent arrangement that facilitates cooperative binding is given, thus conferring exceptional affinity toward the analyte of interest. The resulting material with chelating groups populated adjacently in a spatially locked manner displays up to two orders of magnitude improvement compared to a random and isolated manner using uranium sequestration as a model application. This adsorbent shows exceptional extraction efficiencies, capable of reducing the uranium concentration from 5 ppm to less than 1 ppb within 10 min, even though the system is permeated with high concentrations of competing ions. The efficiency is further supported by its ability to extract uranium from seawater with an uptake capability of 5.01 mg g -1 , placing it among the highest-capacity seawater uranium extraction materials described to date. The concept presented here uncovers a new paradigm in the design of efficient sorbent materials by manipulating the spatial distribution to amplify the cooperation of functions., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by Wiley‐VCH GmbH.)

To offset the environmental impact of platinum-group element (PGE) mining, recycling techniques are being explored. Porous organic polymers (POPs) have shown significant promise owing to their selectivity and ability to withstand harsh conditions. A series of pyridine-based POP nanotraps, POP-Py, POP-pNH 2 -Py, and POP-oNH 2 -Py, have been designed and systematically explored for the capture of palladium, one of the most utilized PGEs. All of the POP nanotraps demonstrated record uptakes and rapid capture, with the amino group shown to be vital in improving performance. Further testing on the POP nanotrap regeneration and selectivity found that POP-oNH 2 -Py outperformed POP-pNH 2 -Py. Single-crystal X-ray analysis indicated that POP-oNH 2 -Py provided a stronger complex compared to POP-pNH 2 -Py owing to the intramolecular hydrogen bonding between the amino group and coordinated chlorine molecules. These results demonstrate how slight modifications to adsorbents can maximize their performance., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The Industrial Revolution has resulted in social and economic improvements, but unfortunately, with the development of manufacturing and mining, water sources have been pervaded with contaminants, putting Earth's freshwater supply in peril. Therefore, the segregation of pollutants-such as radionuclides, heavy metals, and oil spills-from water streams, has become a pertinent problem. Attempts have been made to extract these pollutants through chemical precipitation, sorbents, and membranes. The limitations of the current remediation methods, including the generation of a considerable volume of chemical sludge as well as low uptake capacity and/or selectivity, actuate the need for materials innovation. These insufficiencies have provoked our interest in the exploration of porous organic polymers (POPs) for water treatment. This category of porous material has been at the forefront of materials research due to its modular nature, i.e. , its tunable functionality and tailorable porosity. Compared to other materials, the practicality of POPs comes from their purely organic composition, which lends to their stability and ease of synthesis. The potential of using POPs as a design platform for solid extractors is closely associated with the ease with which their pore space can be functionalized with high densities of strong adsorption sites, resulting in a material that retains its robustness while providing specified interactions depending on the contaminant of choice.POPs raise opportunities to improve current or enable new technologies to achieve safer water. In this Account, we describe some of our efforts toward the exploitation of the unique properties of POPs for improving water purification by answering key questions and proposing research opportunities. The design strategies and principles involved for functionalizing POPs include the following: increasing the density and flexibility of the chelator to enhance their cooperation, introducing the secondary sphere modifiers to reinforce the primary binding, and enforcing the orientation of the ligands in the pore channel to increase the accessibility and cooperation of the functionalities. For each strategy, we first describe its chemical basis, followed by presenting examples that convey the underlying concepts, giving rise to functional materials that are beyond the traditional ones, as demonstrated by radionuclide sequestration, heavy metal decontamination, and oil-spill cleanup. Our endeavors to explore the applicability of POPs to deal with these high-priority contaminants are expected to impact personal consumer water purifiers, industrial wastewater management systems, and nuclear waste management. In our view, more exciting will be new applications and new examples of the functionalization strategies made by creatively merging the strategies mentioned above, enabling increasingly selective binding and efficiency and ultimately promoting POPs for practical applications to enhance water security.

TP53 and K-ras mutations are two of the major genetic alterations in human nonsmall cell lung cancers. The association between these two genes during lung tumorigenesis is unknown. We evaluated the potential of two common Type I (273H, contact) and Type II (175H, conformational) TP53 mutations to induce lung tumors in transgenic mice, as well as K-ras status, and other driver mutations in these tumors. Among 516 (138 nontransgenic, 207 SPC-TP53-273H, 171 SPC-TP53-175H) mice analyzed, 91 tumors, all adenocarcinomas, were observed. Type II mutants developed tumors more frequently (as compared to nontransgenics, p = 0.0003; and Type I, p = 0.010), and had an earlier tumor onset compared to Type I (p = 0.012). K-ras mutations occurred in 21 of 50 (42%) of murine lung tumors sequenced. For both the nontransgenic and the SPC-TP53-273H transgenics, tumor K-ras codon 12-13 mutations occurred after 13 months with a peak incidence at 16-18 months. However, for the SPC-TP53-175H transgenics, K-ras codon 12-13 mutations were observed as early as 6 months, with a peak incidence between the ages of 10-12 months. Codons 12-13 transversion mutations were the predominant changes in the SPC-TP53-175H transgenics, whereas codon 61 transition mutations were more common in the SPC-TP53-273H transgenics. The observation of accelerated tumor onset, early appearance and high frequency of K-ras codon 12-13 mutations in the Type II TP53-175H mice suggests an enhanced oncogenic function of conformational TP53 mutations, and gains in early genetic instability for tumors containing these mutations compared to contact mutations., (© 2019 UICC.)

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor with a median survival of approximately 14 months. Despite aggressive treatment of surgical resection, chemotherapy and radiation therapy, only 3-5% of GBM patients survive more than 3 years. Contributing to this poor therapeutic response, it is believed that GBM contains both intrinsic and acquired mechanisms of resistance, including resistance to radiation therapy. In order to define novel mediators of radiation resistance, we conducted a functional knockdown screen, and identified the immunoglobulin superfamily protein, PTGFRN. In GBM, PTGFRN is found to be overexpressed and to correlate with poor survival. Reducing PTGFRN expression radiosensitizes GBM cells and potently decreases the rate of cell proliferation and tumor growth. Further, PTGFRN inhibition results in significant reduction of PI3K p110β and phosphorylated AKT, due to instability of p110β. Additionally, PTGFRN inhibition decreases nuclear p110β leading to decreased DNA damage sensing and DNA damage repair. Therefore overexpression of PTGFRN in glioblastoma promotes AKT-driven survival signaling and tumor growth, as well as increased DNA repair signaling. These findings suggest PTGFRN is a potential signaling hub for aggressiveness in GBM., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Spermidine/spermine N1-acetyltransferase 1 (SAT1), the rate-limiting enzyme in polyamine catabolism, has broad regulatory roles due to near ubiquitous polyamine binding. We describe a novel function of SAT1 as a gene-specific transcriptional regulator through local polyamine acetylation. SAT1 expression is elevated in aggressive brain tumors and promotes resistance to radiotherapy. Expression profiling in glioma cells identified SAT1 target genes that distinguish high- and low-grade tumors, in support of the prognostic utility of SAT1 expression. We further discovered mechanisms of SAT1-driven tumor aggressiveness through promotion of expression of both DNA damage response pathways as well as cell cycle regulatory genes. Mechanistically, SAT1 associates specifically with the promoter of the MELK gene, which functionally controls other SAT1 targets, and leads biologically to maintenance of neurosphere stemness in conjunction with FOXM1 and EZH2. CRISPR knockin mutants demonstrate the essentiality of the polyamine acetyltransferase activity of SAT1 for its function as a transcriptional regulator. Together, the data demonstrate that gene-specific polyamine removal is a major transcriptional regulatory mechanism active in high-grade gliomas that drives poor outcomes.

To move nuclear as a primary energy source, uranium resources must be secured beyond what terrestrial reserves can provide. Given the vast quantity of uranium naturally found in the ocean, adsorbent materials have been investigated to recover this vital fuel source. Amidoxime (AO) has been found to be the state-of-the-art functional group for this purpose, however, improvements must still be made to overcome the issues with selectively capturing uranium at such a low concentration found in the ocean. Herein, we report PAF-1 as a platform to study the effects of two amidoxime ligands. The synthesized adsorbents, PAF-1-CH 2 NHAO and PAF-1-NH(CH 2 ) 2 AO, with varying chain lengths and grafting degrees, were investigated for their uranium uptakes and kinetic efficiency. PAF-1-NH(CH 2 ) 2 AO was found to outperform PAF-1-CH 2 NHAO, with a maximum uptake capacity of 385 mg/g and able to reduce a uranium-spiked solution to ppb level within 10 min. Further studies with PAF-1-NH(CH 2 ) 2 AO demonstrated effective elution for multiple adsorption cycles and showed promising results for uranium recovery in the diverse composition of a spiked seawater solution. The work presented here moves forward design principles for amidoxime-functionalized ligands and provides scope for strategies to enhance the capture of uranium as a sustainable nuclear fuel source.

Precise control of the outer-sphere environment around the active sites of heterogeneous catalysts to modulate the catalytic outcomes has long been a challenge. Here, we demonstrate how this can be fulfilled by encapsulating catalytic components into supramolecular capsules, used as building blocks for materials synthesis, whereby the microenvironment of each active site is tuned by the assembled wall. Specifically, using a cationic template equipped with a polymerizable functionality, anionic ligands can be encapsulated by ion pair-directed supramolecular assembly, followed by construction into porous frameworks. The hydrophilic ionic wall enables reactions to be achieved in water that usually requires organic solvents and also facilitates the enrichment of the substrate into the hydrophobic pocket, leading to superior catalytic performances as demonstrated by the industrially relevant hydroformylation. Remarkably, the formation of the supramolecular assembly and catalyst encapsulation further engenders reaction selectivity, which reaches an even greater extent after construction of the porous framework.

Herein, we show how the spatial environment in the functional pores of covalent organic frameworks (COFs) can be manipulated in order to exert control in catalysis. The underlying mechanism of this strategy relies on the placement of linear polymers in the pore channels that are anchored with catalytic species, analogous to outer-sphere residue cooperativity within the active sites of enzymes. This approach benefits from the flexibility and enriched concentration of the functional moieties on the linear polymers, enabling the desired reaction environment in close proximity to the active sites, thereby impacting the reaction outcomes. Specifically, in the representative dehydration of fructose to produce 5-hydroxymethylfurfural, dramatic activity and selectivity improvements have been achieved for the active center of sulfonic acid groups in COFs after encapsulation of polymeric solvent analogues 1-methyl-2-pyrrolidinone and ionic liquid., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The rapid development of supramolecular chemistry provides a powerful bottom-up approach to construct various well-defined nano-architectures with increasing complexity and functionality. Compared to that of small and simple nanometric objects, the self-assembly of larger and more complex nanometric objects, such as nanocages, remains a significant challenge. Herein, we used a discrete nanocage as the monomer to successfully construct a novel three-dimensional (3D) supramolecular architecture, which comprises two types of nanocage building units with different connectivity, using the solvent-assisted coordination-driven assembly approach. The mechanism of this supramolecular assembly process was investigated by electrospray ionization mass spectrometry (ESI-MS) studies, which identified for the first time the formation of a nanocage dimer intermediate during the assembly process. The assembly of discrete nanocages into a 3D supramolecular architecture led to remarkable enhancement of stability and gas adsorption properties.

Frustrated Lewis pairs (FLPs) have recently been advanced as efficient metal-free catalysts for catalytic hydrogenation, but their performance in chemoselective hydrogenation, particularly in heterogeneous systems, has not yet been achieved. Herein, we demonstrate that, via tailoring the pore environment within metal-organic frameworks (MOFs), FLPs not only can be stabilized but also can develop interesting performance in the chemoselective hydrogenation of α,β-unsaturated organic compounds, which cannot be achieved with FLPs in a homogeneous system. Using hydrogen gas under moderate pressure, the FLP anchored within a MOF that features open metal sites and hydroxy groups on the pore walls can serve as a highly efficient heterogeneous catalyst to selectively reduce the imine bond in α,β-unsaturated imine substrates to afford unsaturated amine compounds., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A squaramide-decorated COF was synthesized and used as a highly efficient heterogeneous catalyst for hydrogen-bonding organocatalysis as exemplified in the context of catalyzing Michael addition reactions under mild conditions. Our work lays a foundation for the development of functional COFs as a new platform for biomimetic organocatalysis.

Achieving high-performance biocomposites requires knowledge of the compatability between the immobilized enzyme and its host material. The modular nature of covalent organic frameworks (COFs), as a host, allows their pore geometries and chemical functionalities to be fine-tuned independently, permitting comparative studies between the individual parameters and the performances of the resultant biocomposites. This research demonstrates that dual pores in COFs have profound consequences on the catalytic activity and denaturation of infiltrated enzymes. This approach enforces a constant pore environment by rational building-block design, which enables it to be unequivocally determined that pore heterogeneity is responsible for rate enhancements of up to threefold per enzyme molecule. More so, the enzyme is more tolerant to detrimental by-products when occupying the larger pore in a dual-pore COF compared to a corresponding uniform porous COF. Kinetic studies highlight that pore heterogeneity facilitates mass transfer of both reagents and products. This unparalleled versatility of these materials allows many different aspects to be designed on demand, lending credence to their prospect as next-generation host materials for various enzyme biocomposites catalysts., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Photomechanical molecular crystals are receiving much attention due to their efficient conversion of light into mechanical work and advantages including faster response time; higher Young's modulus; and ordered structure, as measured by single-crystal X-ray diffraction. Recently, various photomechanical crystals with different motions (contraction, expansion, bending, fragmentation, hopping, curling, and twisting) are appearing at the forefront of smart materials research. The photomechanical motions of these single crystals during irradiation are triggered by solid-state photochemical reactions and accompanied by phase transformation. This Minireview summarizes recent developments in growing research into photoresponsive molecular crystals. The basic mechanisms of different kinds of photomechanical materials are described in detail; recent advances in photomechanical crystals for promising applications as smart materials are also highlighted., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The elimination of specific contaminants from competitors poses a significant challenge. Rather than relying on a single direct interaction, the cooperation of multiple functionalities is an emerging strategy for adsorbents design to achieve the required affinity. Here, we describe that the interaction with the target species can be altered by modifying the local environment of the direct contact site, as demonstrated by manipulating the affinity of pyridinium-based anion nanotraps toward pertechnetate. Systematic control of the substituent effect allows the resulting anion nanotraps to combine multiple features, overcoming the long-term challenge of TcO 4 - segregation under extreme conditions of super acidity and basicity, strong irradiation field, and high ionic strength. The top material exhibits the highest sorption capacity together with record-high extraction efficiencies after a single treatment from conditions relevant to the used nuclear fuel (Hanford tank wastes, 95%) and legacy nuclear wastes (Savannah River Sites, 80%) among materials reported thus far.

Breast cancer is the second leading cause of death among women in the US. Targeted therapies exist, however resistance is common and patients resort to chemotherapy. Chemotherapy is also a main treatment for triple negative breast cancer (TNBC) patients; while radiation is delivered to patients with advanced disease to counteract metastasis. Yet, resistance to both chemo- and radiotherapy is still frequent, highlighting a need to provide novel sensitizers. We discovered that MT1-MMP modulates DNA damage responses (DDR) in breast cancer. MT1-MMP expression inversely correlates to chemotherapy response of breast cancer patients. Inhibition of MT1-MMP sensitizes TNBC cells to IR and doxorubicin in vitro, and in vivo in an orthotopic breast cancer model. Specifically, depletion of MT1-MMP causes stalling of replication forks and Double Strand Breaks (DBSs), leading to increased sensitivity to additional genotoxic stresses. These effects are mediated by integrinβ1, as a constitutive active integrinβ1 reverts replication defects and protects cells depleted of MT1-MMP from IR and chemotherapy. These data highlight a novel DNA damage response triggered by MT1-MMP-integrinβ1 and provide a new point of therapeutic targeting that may improve breast cancer patient outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Over millennia, nature has evolved an ability to selectively recognize and sequester specific metal ions by employing a wide variety of supramolecular chelators. Iron-specific molecular carriers-siderophores-are noteworthy for their structural elegance, while exhibiting some of the strongest and most selective binding towards a specific metal ion. Development of simple uranyl (UO 2 2+ ) recognition motifs possessing siderophore-like selectivity, however, presents a challenge. Herein we report a comprehensive theoretical, crystallographic and spectroscopic studies on the UO 2 2+ binding with a non-toxic siderophore-inspired chelator, 2,6-bis[hydroxy(methyl)amino]-4-morpholino-1,3,5-triazine (H 2 BHT). The optimal pK a values and structural preorganization endow H 2 BHT with one of the highest uranyl binding affinity and selectivity among molecular chelators. The results of small-molecule standards are validated by a proof-of-principle development of the H 2 BHT-functionalized polymeric adsorbent material that affords high uranium uptake capacity even in the presence of competing vanadium (V) ions in aqueous medium.

The separation of racemic compounds is important in many fields, such as pharmacology and biology. Taking advantage of the intrinsically strong chiral environment and specific interactions featured by biomolecules, here we contribute a general strategy is developed to enrich chirality into covalent organic frameworks (COFs) by covalently immobilizing a series of biomolecules (amino acids, peptides, enzymes) into achiral COFs. Inheriting the strong chirality and specific interactions from the immobilized biomolecules, the afforded biomolecules⊂COFs serve as versatile and highly efficient chiral stationary phases towards various racemates in both normal and reverse phase of high-performance liquid chromatography (HPLC). The different interactions between enzyme secondary structure and racemates were revealed by surface-enhanced Raman scattering studies, accounting for the observed chiral separation capacity of enzymes⊂COFs., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Covalent organic frameworks (COFs) are an emerging class of functional nanostructures with intriguing properties, due to their unprecedented combination of high crystallinity, tunable pore size, large surface area, and unique molecular architecture. The range of properties characterized in COFs has rapidly expanded to include those of interest for numerous applications ranging from energy to environment. Here, a background overview is provided, consisting of a brief introduction of porous materials and the design feature of COFs. Then, recent advancements of COFs as a designer platform for a plethora of applications are emphasized together with discussions about the strategies and principles involved. Finally, challenges remaining for this type material for real applications are outlined.

Understanding the effect of gas molecules on the framework structures upon gas sorption in porous materials is highly desirable for the development of gas storage and separation technologies. However, this remains challenging for flexible metal-organic frameworks (MOFs) which feature "gate-opening/gate-closing" or "breathing" sorption behaviors under external stimuli. Herein, we report such a flexible Cd-MOF that exhibits "gating effect" upon CO 2 sorption. The ability of the desolvated flexible Cd-MOF to retain crystal singularity under high pressure enables the direct visualization of the reversible closed-/open-pore states before and after the structural transformation as induced by CO 2 adsorption/desorption through in situ single-crystal X-ray diffraction experiments. The binding sites of CO 2 molecules within the flexible MOF under high pressure and room temperature have also been identified via combined in situ single-crystal X-ray diffraction and powder X-ray diffraction studies, facilitating the elucidation of the states observed during gate-opening/gate-closing behaviors. Our work therefore lays a foundation to understand the high-pressure gas sorption within flexible MOFs at ambient temperature, which will help to improve the design efforts of new flexible MOFs for applications in responsive gas sorption and separation., Competing Interests: The authors declare no competing financial interest.

This work describes a facile approach to modify metal-organic frameworks (MOFs) with ionic liquids (ILs), rendering them as useful heterogeneous catalysts for CO 2 chemical fixation. An amino-functionalized imidazolium-based ionic liquid is firmly grafted into the porous MOF, MIL-101-SO 3 H by the acid-base attraction between positively charged ammonium groups on the IL and negatively charged sulfonate groups from the MOF. Analyses by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, 1 H NMR, and N 2 sorption experiments reveal the MOF-supported ionic liquid (denoted as IL@MOF) material remains intact while functioning as a recyclable heterogeneous catalyst that can efficiently convert CO 2 and epichlorohydrin into chloropropene carbonate without the addition of a cocatalyst.

Chemical transformations are highly sensitive toward changes in the solvation environment and solvents have long been used to control their outcome. Reactions display unique performance in solvents like ionic liquids or DMSO, however, isolating products from them is cumbersome and energy-consuming. Here, we develop promising alternatives by constructing solvent moieties into porous materials, which in turn serve as platforms for introducing catalytic species. Due to the high density of the solvent moieties, these porous solid solvents (PSSs) retain solvation ability, which greatly influences the performance of incorporated active sites via concerted non-covalent substrate-catalyst interactions. As a proof-of-concept, the -SO 3 H-incorporated PSSs exhibit high yields of fructose to 5-hydroxymethylfurfural in THF, which exceeds the best results reported using readily separable solvents and even rivals those in ionic liquids or DMSO. Given the wide application, our strategy provides a step forward towards sustainable synthesis by eliminating the concerns with separation unfriendly solvents.

Industrial synthesis is driven by a delicate balance of the value of the product against the cost of production. Catalysts are often employed to ensure product turnover is economically favorable by ensuring energy use is minimized. One method, which is gaining attention, involves cooperative catalytic systems. By inserting a flexible polymer into a metal-organic framework (MOF) host, the advantages of both components work synergistically to create a composite that efficiently fixes carbon dioxide to transform various epoxides into cyclic carbonates. The resulting material retains high yields under mild conditions with full reusability. By quantitatively studying the kinetic rates, the activation energy was calculated, for a physical mixture of the catalyst components to be about 50 % higher than that of the composite. Through the unification of two catalytically active components, a new opportunity opens up for the development of synergistic systems in multiple applications., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Artificial muscles triggered by light are of great importance, especially for the development of non-contact and remotely controlled materials. Common materials for synthesis of photoinduced artificial muscles typically rely on polymer-based photomechanical materials. Herein, we are able to prepare artificial muscles using a mixed-matrix membrane strategy to incorporate photomechanical molecular crystals with connective polymers (e.g. PVDF). The formed hybrid materials inherit not only the advantages of the photomechanical crystals, including faster light response, higher Young's modulus and ordered structure, but also the elastomer properties from polymers. This new type of artificial muscles demonstrates various muscle movements, including lifting objects, grasping objects, crawling and swimming, triggered by light irradiation. These results open a new direction to prepare light-driven artificial muscles based on molecular crystals., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

One of the major health concerns on long-duration space missions will be radiation exposure to the astronauts. Outside the earth's magnetosphere, astronauts will be exposed to galactic cosmic rays (GCR) and solar particle events that are principally composed of protons and He, Ca, O, Ne, Si, Ca, and Fe nuclei. Protons are by far the most common species, but the higher atomic number particles are thought to be more damaging to biological systems. Evaluation and amelioration of risks from GCR exposure will be important for deep space travel. The hematopoietic system is one of the most radiation-sensitive organ systems, and is highly dependent on functional DNA repair pathways for survival. Recent results from our group have demonstrated an acquired deficiency in mismatch repair (MMR) in human hematopoietic stem cells (HSCs) with age due to functional loss of the MLH1 protein, suggesting an additional risk to astronauts who may have significant numbers of MMR deficient HSCs at the time of space travel. In the present study, we investigated the effects gamma radiation, proton radiation, and 56 Fe radiation on HSC function in Mlh1 +/+ and Mlh1 -/- marrow from mice in a variety of assays and have determined that while cosmic radiation is a major risk to the hematopoietic system, there is no dependence on MMR capacity. Stem Cells Translational Medicine 2018;7:513-520., (© 2018 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

The potential consequences of nuclear events and the complexity of nuclear waste management motivate the development of selective solid-phase sorbents to provide enhanced protection. Herein, it is shown that 2D covalent organic frameworks (COFs) with unique structures possess all the traits to be well suited as a platform for the deployment of highly efficient sorbents such that they exhibit remarkable performance, as demonstrated by uranium capture. The chelating groups laced on the open 1D channels exhibit exceptional accessibility, allowing significantly higher utilization efficiency. In addition, the 2D extended polygons packed closely in an eclipsed fashion bring chelating groups in adjacent layers parallel to each other, which may facilitate their cooperation, thereby leading to high affinity toward specific ions. As a result, the amidoxime-functionalized COFs far outperform their corresponding amorphous analogs in terms of adsorption capacities, kinetics, and affinities. Specifically, COF-TpAb-AO is able to reduce various uranium contaminated water samples from 1 ppm to less than 0.1 ppb within several minutes, well below the drinking water limit (30 ppb), as well as mine uranium from spiked seawater with an exceptionally high uptake capacity of 127 mg g -1 . These results delineate important synthetic advances toward the implementation of COFs in environmental remediation., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)