High Structural Diversity Research Articles

Evolutionary Dynamics of Polintons: A Rarely Investigated Superfamily of DNA Transposons

Polintons, also known as ‘Maverick’ is a rarely investigated superfamily of DNA transposons. Although, discovered in recent decades, these elements are now found in several eukaryotic genomes due to the advancements and expansions in genome sequencing projects. The current study was conducted to investigate the evolutionary genomics and distribution of Polintons in various genomes. Approximately, 102 Polinton elements from various species were collected from Repbase – GIRI database. They have shown a high structural diversity and ranged in sizes from 03 to 42kb. The phylogenetic relationship and evolutionary history of the Polinton superfamily was investigated using bioinformatics software. Phylogenetic trees were created based on two major protein coding domains, such as RVE integrase and DNA POL B. In both cases, the sequences were clustered in 2 clades, several sub-clades, and groups with variable number of elements in each group. The cladograms represented the extensive genetic diversity and evolutionary history of these elements and allowed to observe the intricate branching patterns and relationships within the Polinton superfamily. The cladogram provides a roadmap to explore the relationships and dynamics of the Polinton superfamily in detail. The current study aimed to enhance the understanding of evolutionary dynamics of Polintons found in different organisms.

Dune Hares: Population Indices, Home Range Size, and Habitat Selection of the European Hare on a Danish Island.

Population indices, such as transect counts of animals, can provide important information concerning population changes over time. Moreover, data concerning the home range size and habitat selection of individuals can provide valuable insight into spatial requirements of animals and how they can adapt to variable environments. Here, we describe the population development of European hares (Lepus europaeus) and investigated home range sizes and habitat selection of six radio-tagged individuals on the small (80 ha) Danish Wadden Sea island Langli. The average minimum hare population density from 1983 to 1997 was 64 ± 36 (mean ± SD) hares/km2, with hare numbers varying among years and seasons. The average home range size was 23.3 (CI: 18.9-28.7) ha, which is comparable to agricultural areas of high structural diversity. Moreover, hare habitat selection was generally bimodal, with hares moving over larger areas and selecting marsh habitat for foraging during nighttime, and dune and grassland habitat for resting during daytime, especially during winter. Combined, our results indicate that hare abundance and space use in the dunal landscape of Langli Island were similar to agricultural areas of comparatively high habitat quality. Thus, dunal marsh landscapes offer high-quality habitat for hares and might be of importance as population strongholds at a time when hare populations are declining in many agricultural areas across Europe.

Cancer Prevention and Treatment with Polyphenols: Type IV Collagenase-Mediated Mechanisms.

Polyphenols are natural compounds found in many plants and their products. Their high structural diversity bestows upon them a range of anti-inflammatory, anti-oxidant, proapoptotic, anti-angiogenic, and anti-metastatic properties, and a growing body of research indicates that a polyphenol-rich diet can inhibit cancer development in humans. Polyphenolic compounds may modulate the expression, secretion, or activity of compounds that play a significant role in carcinogenesis, including type IV collagenases, such as matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), by suppressing cellular signaling pathways such as nuclear factor-kappa B. These enzymes are responsible for the degradation of the extracellular matrix, thus promoting the progression of cancer. This review discusses the current state of knowledge concerning the anti-cancer activity of polyphenols, particularly curcumin, resveratrol, epigallocatechin-3-gallate, genistein, and quercetin, with a specific focus on their anti-invasive and anti-metastatic potential, based on the most recent in vitro and in vivo studies. It appears that polyphenols may be valuable options for the chemoprevention and treatment of cancer via the inhibition of MMP-2 and MMP-9 and the suppression of signaling pathways regulating their expression and activity.

From Data to Discovery: Recent Trends of Machine Learning in Metal-Organic Frameworks.

Renowned for their high porosity and structural diversity, metal-organic frameworks (MOFs) are a promising class of materials for a wide range of applications. In recent decades, with the development of large-scale databases, the MOF community has witnessed innovations brought by data-driven machine learning methods, which have enabled a deeper understanding of the chemical nature of MOFs and led to the development of novel structures. Notably, machine learning is continuously and rapidly advancing as new methodologies, architectures, and data representations are actively being investigated, and their implementation in materials discovery is vigorously pursued. Under these circumstances, it is important to closely monitor recent research trends and identify the technologies that are being introduced. In this Perspective, we focus on emerging trends of machine learning within the field of MOFs, the challenges they face, and the future directions of their development.

Lattice Manipulation with Di-Tertiary Ammonium Spacer in Bismuth Bromide Perovskite Directs Efficient Charge Transport and Suppressed Ion Migration for Photodetector Applications.

Bismuth halide hybrid perovskites have emerged as promising alternatives to their lead halide homologs because of high chemical stability, low toxicity, and structural diversity. However, their advancements in optoelectronic field are plagued with poor charge transport, due to considerable microstrain triggered by bulky spacer. Herein, the di-tertiary ammonium spacer (N,N,N',N'-tetramethyl-1,4-butanediammonium, TMBD) is explored to direct stable 1D bismuth bromide lattice structure with relaxed microstrain. Compared to the primary pentamethylenediamine (PD)2+, the (TMBD)2+ adopting alternating alignment enables a unique H-bonds mode to distort the configuration of inorganic layers to form corner-sharing [BiBr5] near-regular chains with narrower bandgap, lower exciton binding energy, and reduced carrier-lattice interactions, thereby facilitating charge-carrier transport. Moreover, the (TMBD)2+ spacers largely suppress ion migration in perovskite lattice, as substantiated by the experimental and theoretical investigations. Consequently, (TMBD)BiBr5 single crystal photodetector delivers a 185-fold increase in current on/off ratio with respect to (PD)BiBr5 under white light irradiation, considerable responsivity (≈82.97mA W-1), detectivity (≈8.06 ×1011 Jones) under weak light (0.02mW cm-2) irradiation, in the top rank of the reported hybrid bismuth halide perovskites. This finding offers novel design criterion for high-performance lead-free perovskites.

A review of locomotion of snake robots

In this review paper, we demonstrate the high structural flexibility and motion diversity of snake robots, which are important indicators to measure the performance of the mechanism. And animals in nature, especially reptiles, often have a high degree of flexibility and a variety of modes of movement in order to be able to shift through various terrains. Thus, making a robot with excellent performance, a bionic robot is a suitable choice. Currently, we have reviewed the state of the act in the snake-like machine. In the end, we conclude that with the simplicity of design and practice, it can be designed easily with unique constructures to complete modes of locomotion. Furthermore, we also provide the perspectives of future work.

Oxygen sensing performance modulation using luminescent ionic copper iodide clusters based on Mn(Ⅱ) crystal field intensity

Copper iodide (CuI) clusters have continued been to arouse increasing attention in many fields due to their high cost-performance, abundant reserves, hypotoxicity and structural diversity. Despite the oxygen sensing capability of coordinate CuI clusters has been demonstrated, the ionic counterparts with better structural stability hold potential to construct more durable sensing platform. However, the optical applications of the ionic CuI clusters have been hindered largely by their prominently weak emission. With the progress of ion assembly in recent years, ionic CuI clusters with specific emission properties can be attainable. Herein, two ionic dinuclear CuI clusters with Mn(Ⅱ) crystal field are introduced through fabricating sensing films to exhibit their oxygen sensing performance for the first time. The results reveal that both sensing films presented good reversibility, fast response associated with wide linear responses in the range from 0 % to 90 % gaseous O2. When the sensing behaviors of the two clusters were compared, different I0/I100 ratios of 6.6 and 2.1 are observed. Through investigating EPR spectra and time-resolved luminescence spectra, we highlight that different Mn(Ⅱ) crystal field intensity in corresponding clusters lead to distinct oxygen sensing behaviors. In our perception, the possible mechanism could offer new performance modulation strategy based on CuI clusters with multi-emission centers. Owing to the good structural stability of such materials, one of the clusters is used to demonstrate the dissolved oxygen sensing capability of the platform. The study constructs a stable sensing system and will pave the new way for optical application of the family of ionic CuI clusters.

Identification of heparin-binding amino acid residues in antibody HS4C3 with the potential to design antibodies against heparan sulfate domains.

Heparan sulfate (HS) is a linear polysaccharide with high structural and functional diversity. Detection and localization of HS in tissues can be performed using single chain variable fragment (scFv) antibodies. Although several anti-HS antibodies recognizing different sulfation motifs have been identified, little is known about their interaction with HS. In this study the interaction between the scFv antibody HS4C3 and heparin was investigated. Heparin-binding lysine and arginine residues were identified using a protect and label methodology. Site-directed mutagenesis was applied to further identify critical heparin-binding lysine/arginine residues using immunohistochemical and biochemical assays. In addition, computational docking of a heparin tetrasaccharide towards a 3-D homology model of HS4C3 was applied to identify potential heparin-binding sites. Of the 12 lysine and 15 arginine residues within the HS4C3 antibody, 6 and 9, respectively, were identified as heparin-binding. Most of these residues are located within one of the complementarity determining regions (CDR) or in their proximity. All basic amino acid residues in the CDR3 region of the heavy chain were involved in binding. Computational docking showed a heparin tetrasaccharide close to these regions. Mutagenesis of heparin-binding residues reduced or altered reactivity towards HS and heparin. Identification of heparin-binding arginine and lysine residues in HS4C3 allows for better understanding of the interaction with HS and creates a framework to rationally design antibodies targeting specific HS motifs.

The Lreu_1276 protein from Limosilactobacillus reuteri represents a third family of dihydroneopterin triphosphate pyrophosphohydrolases in bacteria.

The identification of a structurally novel DHNTP pyrophosphohydrolase in L. reuteri provides valuable information in understanding tetrahydrofolate biosynthesis in bacteria that possess lreu_1276 homologs. Interestingly, however, even with the identification of a third family of DHNTP pyrophosphohydrolases, there are still a number of bacteria that do not harbor homologs for any of the three genes while possessing other genes involved in the biosynthesis of the pterin ring structure. This suggests the presence of an unrecognized DHNTP pyrophosphohydrolase gene in bacteria. As humans do not harbor DHNTP pyrophosphohydrolase, the high structural diversity of enzymes responsible for a reaction in tetrahydrofolate biosynthesis may provide an advantage in designing inhibitors targeting a specific group of bacteria in the intestinal microbiota.

Unveiling the Potential of Covalent Organic Frameworks for Energy Storage: Developments, Challenges, and Future Prospects

AbstractCovalent organic frameworks (COFs) are porous structures emerging as promising electrode materials due to their high structural diversity, controlled and wide pore network, and amenability to chemical modifications. COFs are solely composed of periodically arranged organic molecules, resulting in lightweight materials. Their inherent properties, such as extended surface area and diverse framework topologies, along with their high proclivity to chemical modification, have positioned COFs as sophisticated materials in the realm of electrochemical energy storage (EES). The modular structure of COFs facilitates the integration of key functions such as redox‐active moieties, fast charge diffusion channels, composite formation with conductive counterparts, and highly porous network for accommodating charged energy carriers, which can significantly enhance their electrochemical performance. However, ascribing intricate porosity and redox‐active functionalities to a single COF structure, while maintaining long‐term electrochemical stability, is challenging. Efforts to overcome these hurdles embrace strategies such as the implementation of reversible linkages for structural flexibility, stimuli‐responsive functionalities, and incorporating chemical groups to promote the formation of COF heterostructures. This review focuses on the recent progress of COFs in EES devices, such as batteries and supercapacitors, through a meticulous exploration of the latest strategies aimed at optimizing COFs as advanced electrodes in future EES technologies.

Accelerating PROTACs Discovery Through a Direct-to-Biology Platform Enabled by Modular Photoclick Chemistry.

Proteolysis targeting chimeras (PROTACs) have emerged as a promising strategy for drug discovery and exploring protein functions, offering a revolutionary therapeutic modality. Currently, the predominant approach to PROTACs discovery mainly relies on an empirical design-synthesis-evaluation process involving numerous cycles of labor-intensive synthesis-purification and bioassay data collection. Therefore, the development of innovative methods to expedite PROTAC synthesis and exploration of chemical space remains highly desired. Here, a direct-to-biology strategy is reported to streamline the synthesis of PROTAC libraries on plates, enabling the seamless transfer of reaction products to cell-based bioassays without the need for additional purification. By integrating amide coupling and light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) photoclick chemistry into a plate-based synthetic process, this strategy produces PROTAC libraries with high efficiency and structural diversity. Moreover, by employing this platform for PROTACs screening, wesmoothly found potent PROTACseffectively inhibit triple-negative breast cancer (TNBC) cell growth and induce rapid, selective targeted degradation of cyclin-dependent kinase 9 (CDK9). The study introduces a versatile platform for assembling PROTACs on plates, followed by direct biological evaluation. This approach provides a promising opportunity for high-throughput synthesis of PROTAC libraries, thereby enhancing the efficiency of exploring chemical space and accelerating the discovery of PROTACs.

Asymmetric non-fused ring acceptor with low energy loss for efficient organic solar cells

Non-fused ring acceptors (NFRA) show high structural diversity with low synthesis complexities and high cost-effectiveness, which holds the potential to boost the performance of organic solar cells (OSCs). For OSCs, it is crucial to broaden the absorption range while minimizing energy loss. One strategy involves creating acceptors with asymmetric structures. However, to date, there have been relatively few reports on NFRA with asymmetric backbones. Here, we designed a new NFRA molecule UF-ATT-2F with asymmetric π-bridges (thieno [3,2-b] thiophene and thiophene) and studied its performance in OSC. Compared with two symmetric reference molecules UF-T-2F and UF-TT-2F, the device based on the asymmetric acceptor UF-ATT-2F exhibits much lower energy loss, more appropriate phase separation scale and broader absorption range, consequently achieving a higher open-circuit voltage (Voc) exceeding 0.9 V and a decent PCE of 13.26 %. This work demonstrates that incorporating asymmetric π-bridge is an effective strategy for the design low-energy loss and high-performance organic photovoltaic acceptor.

Hordatines, dimerised hydroxycinnamoylagmatine conjugates of barley (Hordeum vulgare L.): an appraisal of the biosynthesis, chemistry, identification and bioactivities

AbstractHydroxycinnamoylamides are specialised metabolites widely distributed in the plant kingdom. These are phenolic moieties covalently linked to mono- or polyamines through amide bonds. Their oxidative coupling (dimerisation) leads to neolignanamides, a group of compounds showing high chemical, structural and functional diversity. Typical to barley, dehydro dimers of hydroxycinnamoylagmatines, hordatines are primarily found in germinated seeds and at the seedling stage. The first step in the biosynthesis of hordatines is catalysed by acyl-coenzyme A-dependent N-hydroxycinnamoyltransferases, and lead to the formation of hydroxycinnamoylagmatines (HCAgms). The oxidative homo- or hetero-dimerisation of the latter results in different hordatines (A, B, C or D). Hordatines can also undergo various types of conjugation and form hydroxylated, methylated or glycosylated derivatives. Although the research on the bioactivities of the hordatines is still nascent, the in planta antifungal properties have long been recognised. While hordatines are naturally and uniquely synthesised in barley plants, these molecules or lead compounds derived therefrom, also exhibit medicinal and pharmaceutical uses important for human health, stimulating research into the utilisation of biotechnology in alternative production hosts and to enhance agricultural yields and value-added production. This review summarises the older and recent knowledge about hordatines and derivatives and may serve as a springboard for future research on this intriguing class of secondary plant metabolites.

Covalent Organic Frameworks for Water Harvesting from Air.

Despite approximately 70 % of the earth being covered by water, water shortage has emerged as an urgent social challenge. Sorbent-based atmospheric water harvesting stands out as a potent approach to alleviate the situation, particularly in arid regions. This method requires adsorbents with ample working capacity, rapid kinetics, low energy costs, and long-term stability under operating conditions. Covalent organic frameworks (COFs) are a novel class of crystalline porous materials and offer distinct advantages due to their high specific surface area, structural diversity, and robustness. These properties enable the rational design and customization of their water-harvesting capabilities. Herein, the basic concepts about the water sorption process within COFs, including the parameters that qualitatively or quantitatively describe their water isotherms and the mechanism are summarized. Then, the recent methods used to prepare COFs-based water harvesters are reviewed, emphasizing the structural diversity of COFs and presenting the common empirical understandings of these endeavors. Finally, challenges and research concepts are proposed to help develop next-generation COFs-based water harvesters.

Covalent Organic Frameworks as Single-Site Photocatalysts for Solar-to-Fuel Conversion.

Single-site photocatalysts (SSPCs) are well-established as potent platforms for designing innovative materials to accomplish direct solar-to-fuel conversion. Compared to classical inorganic porous materials, such as zeolites and silica, covalent organic frameworks (COFs)─an emerging class of porous polymers that combine high surface areas, structural diversity, and chemical stability─are attractive candidates for SSPCs due to their molecular-level precision and intrinsic light harvesting ability, both amenable to structural engineering. In this Perspective, we summarize the design concepts and state-of-the-art strategies for the construction of COF SSPCs, and we review the development of COF SSPCs and their applications in solar-to-fuel conversion from their inception. Underlying pitfalls concerning photocatalytic characterization are discussed, and perspectives for the future development of this burgeoning field are given.

Copper-doped ZIF-67/wood aerogel for effective peroxymonosulfate activation

Metal-organic frameworks (MOFs), composed of metal ions and organic linkers, have garnered enormous attention in catalytic application due to their exceptional characteristics such as high specific surface area, low density, large porosity and structural diversity. However, the recycling and performance improvement of MOF should be taken into account in material design. In this work, we fabricated copper-doped metal-organic framework/wood aerogel composites to enhance the activation of peroxymonosulfate (PMS) for the degradation of organic contaminants. Wood Aerogel (WA) was used as suitable carrier to solve the recycling problem, and copper-doped ZIF-67 was developed to enhance the catalytic performance. Copper-doped ZIF-67 (ZIF-67B) was loaded into the cavities of a wood aerogel by in situ wet chemical precipitation, followed by freeze drying to obtain the composite. The effects of copper doping ratio, temperature, catalyst dosage, initial pH and other operational parameters on the degradation of organic pollutants were comprehensively investigated. The catalytic capacity of ZIF-67B@WA (CoxCu(1-x)) was investigated by activating PMS for the removal of Rhodamine B (RhB). The results demonstrate that the degradation efficiency of ZIF-67B@WA (CoxCu(1-x)) towards RhB can achieve 100 % within 15 min, showing exceptional catalytic performance compared with ZIF-67@WA. Even after four consecutive cycles, the degradation efficiency remains at 87.5 %, indicating that the catalyst has good cycle stability. Additionally, possible degradation mechanisms are proposed in this study, in which WA provides high loading active site/area for MOF catalyst and Cu doping can accelerate electron transfer and facilitate the redox cycling of Co2+ and Co3+, thereby enhancing catalytic efficiency. This work expands the application scope of MOF materials in environmental remediation and holds promising prospects.

Purification, Molecular Docking and Cytotoxicity Evaluation of Bioactive Pentacyclic Polyhydroxylated Triterpenoids from Salvia urmiensis.

Triterpenoids, as one of the largest classes of naturally occurring secondary metabolites in higher plants, are of interest due to their high structural diversity and wide range of biological activities. In addition to several promising pharmacological activities such as antimicrobial, antiviral, antioxidant, anti-inflammatory and hepatoprotective effects, a large number of triterpenoids have revealed high potential for cancer therapy through their strong cytotoxicity on cancer cell lines and, also, low toxicity in normal cells. So, this study was aimed at discovering novel and potentially bioactive triterpenoids from the Salvia urmiensis species. For this, an ethyl acetate fraction of the acetone extract of the aerial parts of the plant was chromatographed to yield five novel polyhydroxylated triterpenoids (1: -5: ). Their structure was elucidated by extensive spectroscopic methods including 1D (1H, 13C, DEPT-Q) and 2D NMR (COSY, HSQC, HMBC, NOESY) experiments, as well as HRESIMS analysis. Cytotoxic activity of the purified compounds was also investigated by MTT assay against the MCF-7 cancer cell line. Furthermore, a molecular docking analysis was applied to evaluate the inhibition potential of the ligands against the nuclear factor kappa B (NF-κB) protein, which promotes tumor metastasis or affects gene expression in cancer disease. The 1β,11β,22α-trihydroxy-olean-12-ene-3-one (compound 4: ) indicated the best activity in both in vitro and in silico assays, with an IC50 value of 32 µM and a docking score value of - 3.976 kcal/mol, respectively.

Electron-activated dissociation (EAD) for the complementary annotation of metabolites and lipids through data-dependent acquisition analysis and feature-based molecular networking, applied to the sentinel amphipod Gammarus fossarum.

The past decades have marked the rise of metabolomics and lipidomics as the -omics sciences which reflect the most phenotypes in living systems. Mass spectrometry-based approaches are acknowledged for both quantification and identification of molecular signatures, the latter relying primarily on fragmentation spectra interpretation. However, the high structural diversity of biological small molecules poses a considerable challenge in compound annotation. Feature-based molecular networking (FBMN) combined with database searches currently sets the gold standard for annotation of large datasets. Nevertheless, FBMN is usually based on collision-induced dissociation (CID) data, which may lead to unsatisfying information. The use of alternative fragmentation methods, such as electron-activated dissociation (EAD), is undergoing a re-evaluation for the annotation of small molecules, as it gives access to additional fragmentation routes. In this study, we apply the performances of data-dependent acquisition mass spectrometry (DDA-MS) under CID and EAD fragmentation along with FBMN construction, to perform extensive compound annotation in the crude extracts of the freshwater sentinel organism Gammarus fossarum. We discuss the analytical aspects of the use of the two fragmentation modes, perform a general comparison of the information delivered, and compare the CID and EAD fragmentation pathways for specific classes of compounds, including previously unstudied species. In addition, we discuss the potential use of FBMN constructed with EAD fragmentation spectra to improve lipid annotation, compared to the classic CID-based networks. Our approach has enabled higher confidence annotations and finer structure characterization of 823 features, including both metabolites and lipids detected in G. fossarum extracts.

Toward Bicalutamide Analogues with High Structural Diversity Using Catalytic Asymmetric Oxohydroxylation.

A catalytic enantioselective synthesis of bicalutamide derivatives with promising potentials in prostate cancer treatment has been disclosed. The key intermediates, α-hydroxy-β-keto esters, were efficiently constructed through cinchoninium-mediated asymmetric oxohydroxylation of easily accessible alkenes with potassium permanganate. Good yields and high levels of asymmetric induction are achieved. This method provides a new synthetic route to bicalutamide analogues with high structural diversity, which will beneficially support subsequent structure-activity relationship studies and boost prostate cancer drug development.

Identification of SARS-CoV-2 Main Protease Inhibitors Using Chemical Similarity Analysis Combined with Machine Learning.

SARS-CoV-2 Main Protease (Mpro) is an enzyme that cleaves viral polyproteins translated from the viral genome, which is critical for viral replication. Mpro is a target for anti-SARS-CoV-2 drug development. Herein, we performed a large-scale virtual screening by comparing multiple structural descriptors of reference molecules with reported anti-coronavirus activity against a library with >17 million compounds. Further filtering, performed by applying two machine learning algorithms, identified eighteen computational hits as anti-SARS-CoV-2 compounds with high structural diversity and drug-like properties. The activities of twelve compounds on Mpro's enzymatic activity were evaluated by fluorescence resonance energy transfer (FRET) assays. Compound 13 (ZINC13878776) significantly inhibited SARS-CoV-2 Mpro activity and was employed as a reference for an experimentally hit expansion. The structural analogues 13a (ZINC4248385), 13b (ZNC13523222), and 13c (ZINC4248365) were tested as Mpro inhibitors, reducing the enzymatic activity of recombinant Mpro with potency as follows: 13c > 13 > 13b > 13a. Then, their anti-SARS-CoV-2 activities were evaluated in plaque reduction assays using Vero CCL81 cells. Subtoxic concentrations of compounds 13a, 13c, and 13b displayed in vitro antiviral activity with IC50 in the mid micromolar range. Compounds 13a-c could become lead compounds for the development of new Mpro inhibitors with improved activity against anti-SARS-CoV-2.