Functional Molecules Research Articles

Interrupted Corey-Chaykovsky Reaction of Tethered Bis-Enones to Access 2,3-Epoxy-hexahydrofluoren-9-ones.

The Corey-Chaykovsky reaction is usually employed to synthesize cyclopropanes from activated olefins. We intercepted the intermediates prevailing during this transformation and diverted the process for the creation of intricate molecular motifs. We describe an unusual skeletal remodelling of tethered bis-enones to 2,3-epoxy-hexahydrofluoren-9-ones via an "interrupted Corey-Chaykovsky reaction". The strategy rationally merges the nucleophilic features of sulfur ylides with electronically biased olefins to achieve the regio- and stereoselective synthesis of several new classes of hydrofluorenones. We have demonstrated the synthetic utility of the products in accessing several highly functionalized molecules.

Carbene-Catalyzed Enantioselective Addition of Sulfinate to Ketones.

A carbene-catalyzed enantioselective addition of sulfinate to ketones between 2-benzoylbenzaldehyde and sulfonyl chloride is disclosed. Up to now, the carbon and heteroatom nucleophiles have effectively undergone catalytic enantioselective addition to carbonyl molecules to introduce functionalities and chirality. Sulfone, as an important class of sulfur-containing functional groups, represents highly valuable motifs in medicines and natural products. It remains undeveloped for the catalytic asymmetric addition of sulfinate to carbonyls. Herein we disclosed the first catalytic enantioselective addition of sulfinate to ketones for the synthesis of sulfones via N-heterocyclic carbene (NHC) catalysis. The sulfonyl chloride behaves both as an oxidant and as a nucleophilic substrate in this carbene-catalyzed process. Experimental studies suggested that the Breslow intermediate can be SET oxidized by sulfonyl chloride to generate the sulfonyl radical. This novel synthetic approach for the asymmetric addition of sulfinate to carbonyls can also be used to modify the commercially available functional molecules.

DNA Walker-Driven Mass Nanotag Assembly System for Simultaneously Profiling Dual Markers of Oxidative Stress at Different Cellular Locations.

Simultaneous profiling of redox-regulated markers at different cellular sublocations is of great significance for unraveling the upstream and downstream molecular mechanisms of oxidative stress in living cells. Herein, by synchronizing dual target-triggered DNA machineries in one nanoentity, we engineered a DNA walker-driven mass nanotag (MNT) assembly system (w-MNT-AS) that can be sequentially activated by oxidative stress-associated mucin 1 (MUC1) and apurinic/apyrimidinic endonuclease 1 (APE1) from plasma membrane to cytoplasm and induce recycled assembly of MNTs for multiplex detection of the two markers by matrix-assisted laser desorption ionization mass spectrometry (MALDI MS). In the working cascade, the sensing process governs the separate activation of w-MNT-AS by MUC1 and APE1 in diverse locations, while the assembly process contributes to the parallel amplification of the ion signal of the characteristic mass tags. In this manner, the differences between MCF-7, HeLa, HepG2, and L02 cells in membrane MUC1 expression and cytoplasmic APE1 activation were fully characterized. Furthermore, the oxidative stress level and dynamics caused by exogenous H2O2, doxorubicin, and simvastatin were comprehensively demonstrated by tracking the fate of the two markers across different cellular locations. The proposed w-MNT-AS coupled MS method provides an effective route to probe multiple functional molecules that lie at different locations while participating in the same cellular event, facilitating the mechanistic studies on cellular response to oxidative stress and other disease-related cellular processes.

Neuroimmune modulation by tryptophan derivatives in neurological and inflammatory disorders

The nervous and immune systems are highly developed, and each performs specialized physiological functions. However, they work together, and their dysfunction is associated with various diseases. Specialized molecules, such as neurotransmitters, cytokines, and more general metabolites, are essential for the appropriate regulation of both systems. Tryptophan, an essential amino acid, is converted into functional molecules such as serotonin and kynurenine, both of which play important roles in the nervous and immune systems. The role of kynurenine metabolites in neurodegenerative and psychiatric diseases has recently received particular attention. Recently, we found that hyperactivity of the kynurenine pathway is a critical risk factor for septic shock. In this review, we first outline neuroimmune interactions and tryptophan derivatives and then summarized the changes in tryptophan metabolism in neurological disorders. Finally, we discuss the potential of tryptophan derivatives as therapeutic targets for neuroimmune disorders.

Dipole Moments Regulation of Biphosphonic Acid Molecules for Self-assembled Monolayers Boosts the Efficiency of Organic Solar Cells Exceeding 19.7.

PSS has been widely used as a hole extraction layer (HEL) in organic solar cells (OSCs). However, their acidic nature can potentially corrode the indium tin oxide (ITO) electrode over time, leading to adverse effects on the longevity of the OSCs. Herein, we have developed a class of biphosphonic acid molecules with tunable dipole moments for self-assembled monolayers (SAMs), namely, 3-BPIC(i), 3-BPIC, and 3-BPIC-F, which exhibit an increasing dipole moment in sequence. Compared to centrosymmetric 3-BPIC(i), the axisymmetric 3-BPIC and 3-BPIC-F exhibit higher adsorption energies (Eads) with ITO, shorter interface spacing, more uniform coverage on ITO surface, and better interfacial compatibility with the active layer. Thanks to the incorporation of fluorine atoms, 3-BPIC-F exhibits a deeper highest occupied molecular orbital (HOMO) energy level and a larger dipole moment compared to 3-BPIC, resulting in an enlarged work function (WF) for the ITO/3-BPIC-F substrate. These advantages of 3-BPIC-F could not only improve hole extraction within the device but also lower the interfacial impedance and reduce nonradiative recombination at the interface. As a result, the OSCs using SAM based on 3-BPIC-F obtained a record high efficiency of 19.71%, which is higher than that achieved from the cells based on 3-BPIC(i) (13.54%) and 3-BPIC (19.34%). Importantly, 3-BPIC-F-based OSCs exhibit significantly enhanced stability compared to that utilizing PEDOT:PSS as HEL. Our work offers guidance for the future design of functional molecules for SAMs to realize even higher performance in organic solar cells.

Ion‐Conducting Molecular‐Grafted Sustainable Cellulose Quasi‐Solid Composite Electrolyte for High Stability Solid‐State Lithium‐Metal Batteries

AbstractCellulose‐based solid electrolyte possesses the characteristics of low cost, high strength, and sustainability, and has great potential in the field of solid‐state lithium metal batteries. However, the large hydrogen bonds between cellulose molecules make the molecular chains tightly arranged, and hinder the ion conduction, seriously limiting its further development. Herein, an ion‐conducting molecular grafting strategy is proposed for the fabrication of cellulose acetate quasi‐solid composite electrolyte (CLA‐CN‐LATP QCE) with a superior ionic conductivity of 1.25 × 10−3 S cm−1 at room temperature. Benefited from grafted functional molecules, the assembled symmetrical battery exhibits low polarization voltage and highly stable lithium stripping/plating cycling of more than 1200 h at 0.1 mA cm−2 current density. Moreover, it endows LFP|CLA‐CN‐LATP QCE|Li battery with excellent long‐cycle stability of 1500 cycles at 0.5 C and 25 °C and superior capacity retention of 92.1%. Importantly, this work provides an effective strategy for further opening the ion transport channel between cellulose molecular chains and improving the interface properties of electrolytes and electrodes.

The role of small extracellular vesicles and microRNA as their cargo in the spinal cord injury pathophysiology and therapy

Spinal cord injury (SCI) is a devastating condition with a complex pathology that affects a significant portion of the population and causes long-term consequences. After primary injury, an inflammatory cascade of secondary injury occurs, followed by neuronal cell death and glial scar formation. Together with the limited regenerative capacity of the central nervous system, these are the main reasons for the poor prognosis after SCI. Despite recent advances, there is still no effective treatment. Promising therapeutic approaches include stem cells transplantation, which has demonstrated neuroprotective and immunomodulatory effects in SCI. This positive effect is thought to be mediated by small extracellular vesicles (sEVs); membrane-bound nanovesicles involved in intercellular communication through transport of functional proteins and RNA molecules. In this review, we summarize the current knowledge about sEVs and microRNA as their cargo as one of the most promising therapeutic approaches for the treatment of SCI. We provide a comprehensive overview of their role in SCI pathophysiology, neuroprotective potential and therapeutic effect.

Side Chain Functional Molecule Additives for Efficient and Stable Perovskite Solar Cells

AbstractIn the commercial development of perovskite solar cells, the main challenge lies in achieving efficient devices with high stability. Additive engineering in polycrystalline perovskites is considered as an effective approach to address this challenge by passivating surface defects and reducing carrier losses associated with these defects. In this work, the passivation effect of molecules with different side chain groups on perovskites and the role of binding energy in mitigating carrier loss are studied. The findings reveal that the thiophene group is particularly effective in passivating defects and enhancing hole transport. Consequently, devices treated with 2‐thienylmethylamine hydrochloride (TMAC) demonstrate a champion power conversion efficiency (PCE) of 24.63%. Furthermore, these TMAC‐treated devices exhibit remarkable stability, maintaining over 93.13% of their initial efficiencies after 1200 h of continuous illumination under maximum power point tracking (MPPT). This research presents a pathway to enhance the optoelectronic performance and stability of perovskite solar cells.

A Hadal Streptomyces-Derived Echinocandin Acylase Discovered through the Prioritization of Protein Families

Naturally occurring echinocandin B and FR901379 are potent antifungal lipopeptides featuring a cyclic hexapeptide nucleus and a fatty acid side chain. They are the parent compounds of echinocandin drugs for the treatment of severe fungal infections caused by the Candida and Aspergilla species. To minimize hemolytic toxicity, the native fatty acid side chains in these drug molecules are replaced with designer acyl side chains. The deacylation of the N-acyl side chain is, therefore, a crucial step for the development and manufacturing of echinocandin-type antibiotics. Echinocandin E (ECE) is a novel echinocandin congener with enhanced stability generated via the engineering of the biosynthetic machinery of echinocandin B (ECB). In the present study, we report the discovery of the first echinocandin E acylase (ECEA) using the enzyme similarity tool (EST) for enzymatic function mining across protein families. ECEA is derived from Streptomyces sp. SY1965 isolated from a sediment collected from the Mariana Trench. It was cloned and heterologously expressed in S. lividans TK24. The resultant TKecea66 strain showed efficient cleavage activity of the acyl side chain of ECE, showing promising applications in the development of novel echinocandin-type therapeutics. Our results also provide a showcase for harnessing the essentially untapped biodiversity from the hadal ecosystems for the discovery of functional molecules.

107 Soybean meal energy value under field conditions: Where are we at and where are we going?

Abstract Soybean meal (SBM) is the main protein source for swine diets globally. Considering its wide utilization and relevance to the swine industry, it is critical to accurately characterize its nutritional profile. The net energy (NE) of SBM has been particularly scrutinized as an increasing amount of evidence suggests it may be underestimated. For instance, the NRC (2012) reports the NE of SBM as 2,087 kcal/kg. Recent indirect calorimetry trials suggest, however, that this value could be at least 8% greater. Furthermore, large scale growth assays conducted under the rigors and challenges of field conditions indicate that the energy of SBM may be even greater. The foundation of such growth assays is to relate the energy value of a test ingredient, in this case SBM, to the energy value of a known ingredient it replaces in diet formulation, such as corn. Changes in feed and caloric efficiencies are measured and can then be used to estimate the energy content of SBM relative to corn. Multiple field trials established that when fed increasing levels of SBM, late nursery, growing, and finishing pigs respond with linear improvements in feed and caloric efficiencies, suggesting an underestimation of the energy value of SBM. In those cases, while the NRC value for SBM NE is 78% of corn NE, this value ranges from 100 to 125% under field conditions. It is hypothesized that the discrepancy between NE values derived from academic and commercial facilities could be driven by differences in health and environmental conditions and the functional molecules within SBM. These functional molecules, such as isoflavones and saponins, have been reported to exert anti-inflammatory, anti-viral, and antioxidant properties. In a challenging field environment, such molecules could bolster the immune response, consequently conserving and redirecting energy from the immune system to growth. Although the evidence is robust, it is critical to understand the particularities of such trials. The methodology utilized is clearly not the same as classic NE measurements. Thus, the term productive energy has been proposed to describe the energy value observed in growth assays. Although all studies agree that the energy of SBM should be greater than traditional publications, there is significant variability across studies which should be further investigated. Nevertheless, these findings provide important insight regarding the value of SBM, particularly for practical swine nutritionists.

Comparative Study of the Impurity Effect on SnAgCu and SnZn Solder Joints with Electrodeposited Cu.

Sn-3Ag-0.5Cu (SAC305)- and Sn-9Zn-based alloys (Sn-Zn-X, X = Al, In) are lead-free solders used in the fabrication of solder joints with Cu metallization. Electroplating is a facile technology used to fabricate Cu metallization. However, the addition of functional additive molecules in the plating solution may result in impurity residues in the Cu electroplated layer, causing damage to the solder joints. This study investigates the impurity effect on solder joints constructed by joining various solder alloys to the Cu electroplated layers. Functional additives are formulated to fabricate high-impurity and low-impurity Cu electroplated samples. The as-joined solder joint samples are thermally aged at 120 °C and 170 °C to explore the interfacial reactions between solder alloys and Cu. The results show that the impurity effect on the interfacial reactions between SAC305 and Cu is significant. Voids are massively formed at the SAC305/Cu interface incorporated with a high impurity content, and the Cu6Sn5 intermetallic compound (IMC) grows at a faster rate. In contrast, the growth of the Cu5Zn8 IMC formed in the SnZn-based solder joints is not significantly influenced by the impurity content in the Cu electroplated layers. Voids are not observed in the SnZn-based solder joints regardless of the impurity content, indicative of an insignificant impurity effect. The discrepancy of the impurity effect is rationalized by the differences in the IMC formation and associated atomic interdiffusion in the SAC305- and SnZn-based solder joints.

A potential antiviral role for CCR5+CD8+ T cells in children with hepatitis B.

While dysfunctional exhausted CD8+ T cells hamper viral control when children acquire hepatitis B virus (HBV) infection, it's crucial to recognize that CD8+ T cells have diverse phenotypes and functions. This study explored a subset of CD8+ T cells expressing C-C chemokine receptor type 5 (CCR5) in children with HBV infection.Thirty-six patients in the immune tolerantgroup, 33 patients in the immune activegroup, 55 patients in the combined responsegroup, and 22 healthy controlchildren were enrolled. The frequency, functional molecules, and effector functions of the CCR5+CD8+ T cell population in different groups were evaluated.The frequency of CCR5+CD8+ T cells correlated positively with the frequency of CCR5+CD4+ T cells and patient age, and it correlated negatively with alanine aminotransferase, aspartate transaminase, HBV DNA, hepatitis B surface antigen, and lactic dehydrogenase levels. CCR5+CD8+ T cells had higher levels of inhibitory and activated receptors and produced higher levels of IFN-γ, IL-2, and TNF-α than CCR5-CD8+ T cells.CCR5+CD8+ T cells were partially exhausted but possessed a stronger antiviral activity than CCR5-CD8+ T cells. The identification of this subset increases our understanding of CD8+ T cell functions and serves as a potential immunotherapeutic target for children with HBV infection.

Postassembly Modification of Peptides by Histidine-Directed β-C(sp3)-H Arylation of Alanine at the Internal Positions: Overcoming the Inhibitory Effect of Peptide Bonds.

Peptide modification by C(sp3)-H functionalization of residues at the internal positions remains underdeveloped due to the inhibitory effect of backbone amides. In this study, using histidine (His) as an endogenous directing group, we developed a novel method for the β-C(sp3)-H functionalization of alanine (Ala) at diverse positions of peptides. Through this approach, a wide range of linear peptides were modified on the side-chain of Ala adjacent to His to afford the functionalized peptides in moderate to good yield and excellent position selectivity. Furthermore, conjugation of peptides with functional molecules such as glucuronide, oleanolic acid, dipeptide, and fluorophore derivatives was achieved.

Gut health benefits and associated systemic effects provided by functional components from the fermentation of natural matrices.

Recently, the role of the gut microbiota in metabolic health, immunity, behavioral balance, longevity, and intestine comfort has been the object of several studies from scientific communities. They were encouraged by a growing interest from food industries and consumers toward novel fermented ingredients and formulations with powerful biological effects, such as pre, pro, and postbiotic products. Depending on the selected strains, the operating conditions, the addition of suitable reagents or enzymes, the equipment, and the reactor configurations, functional compounds with high bioactivity, such as short-chain fatty acids, gamma-aminobutyric acid, bioactive peptides, and serotonin, can be enhanced and/or produced through fermentation of several vegetable matrices. Otherwise, their formation can also be promoted directly in the gut after the dietary intake of fermented foods: In this case, fermentation will aim to increase the content of precursor substances, such as indigestible fibers, polyphenols, some amino acids, and resistant starch, which can be potentially metabolized by endogenous gut microorganisms and converted in healthy molecules. This review provides an overview of the main functional components currently investigated in literature and the associated gut health benefits. The current state of the art about fermentation technology as a promising functionalization tool to promote the direct or indirect formation of gut-health-enhancing components was deepened, highlighting the importance of optimizing microorganism selection, system setups, and process conditions according to the target compound of interest. The collected data suggested the possibility of gaining novel functional food ingredients or products rich in functional molecules through fermentation without performing additional extraction and purification stages, which are needed when conventional culture broths are used.

Role of MicroRNA in Hypoxic Tumours and their Potential as Biomarkers for Early Detection of Cancer.

Hypoxia is a pathophysiological condition characterized by oxygen deficiency in tissues, which negatively affects normal biological functions. It is a typical microenvironment character of almost all solid tumours. Noncoding RNA are small functional RNA molecules that regulate gene expression at chromatin and posttranscriptional levels. Micro-RNAs (miRNAs) are a type of noncoding RNA and are ~12-22 nucleotides long that are crucial in regulating gene expression by partnering with the mRNAs of protein-coding genes. It is widely reported that miRs play an important role in various key processes and pathways during tumour formation, as well as advancement in hypoxic tumors by influencing the HIF pathway. The role of miRNAs in hypoxic tumours, namely in pancreatic, kidney, breast, lung and colorectal, are described. These miRNAs have immense potential as diagnostic and prognostic biomarkers for early cancer detection.

Fabrication of chitosan-based fluorescent hydrogel membranes cross-linked with bisbenzaldehyde for efficient selective detection and adsorption of Fe2+

Chitosan, as a natural biomass material, is green, recyclable, sustainable and well biocompatible. The molecular chain is rich in active groups such as amino and hydroxyl groups, and its preparation of fluorescent probes has the advantages of biocompatibility and efficient detection performance. In this study, a bis(benzaldehyde) (BHD) fluorescent functional molecule was designed. Then a series of fluorescent chitosan-based hydrogel films (CSBHD) were prepared using chitosan as raw material and BHD as cross-linking agent. As a fluorescent probe for metal ions, CSBHD was able to efficiently detect Fe2+ with a linear correlation of fluorescence intensity in the range of 0–160 μM, and the limit of detection (LOD) was 0.55 μM. Moreover, it has excellent adsorption performance for Fe2+ ions, with a maximum adsorption capacity of 223.5 g/mg at 500 mg/L Fe2+ concentration. Finally, we characterised the structure and microscopic morphology of CSBHD films and found that CSBHD as a hydrogel film has a high cross-linking density, good water resistance, excellent thermal stability, strong resistance to swelling, and excellent stability in cycling tests. Hence, it has great potential for application in adsorption and detection of Fe2+ ions. It also provides a good strategy for the application of chitosan based fluorescent probe materials in environmental monitoring and heavy metal ion adsorption.

Extracellular vesicles as human therapeutics: A scoping review of the literature.

Extracellular vesicles (EVs) are released by all cells and contribute to cell-to-cell communication. The capacity of EVs to target specific cells and to efficiently deliver a composite profile of functional molecules have led researchers around the world to hypothesize their potential as therapeutics. While studies of EV treatment in animal models are numerous, their actual clinical benefit in humans has more slowly started to be tested. In this scoping review, we searched PubMed and other databases up to 31 December 2023 and, starting from 13,567 records, we selected 40 pertinent published studies testing EVs as therapeutics in humans. The analysis of those 40 studies shows that they are all small pilot trials with a large heterogeneity in terms of administration route and target disease. Moreover, the absence of a placebo control in most of the studies, the predominant local application of EV formulations and the inconsistent administration dose metric still impede comparison across studies and firm conclusions about EV safety and efficacy. On the other hand, the recording of some promising outcomes strongly calls out for well-designed larger studies to test EVs as an alternative approach to treat human diseases with no or few therapeutic options.

Quercetin encapsulated polycaprolactone-polyvinylpyrrolidone electrospun membranes as a delivery system for wound healing applications

The present work focuses on the production of electrospun membranes based on Poly(ε-caprolactone) (PCL) and Polyvinylpyrrolidone (PVP) for the topical release of Quercetin (Q). Membranes were prepared at 0.5, 1.0, 3.0, 7.0 and 15 % wt of Quercetin and studied from a morphological, physical, and biological point of view. The scanning electron microscopy (SEM) evidences micrometric dimensions of the fibres with a good dispersion of the functional molecule. The retention degree of liquids was evaluated by testing four different liquid media while the radical scavenging activity of Quercetin-loaded membranes was evaluated through DPPH analysis. The release kinetics of Quercetin highlights the presence of an initial burst followed by slower release up to attaining an equilibrium state, after roughly 50 h, showing the possibility of a fine-tuning of drug release. Diffusion coefficients were then evaluated by using Fick’s law. Finally, to verify the actual biocompatibility of the systems produced and the possible application in the repair of tissue injury, the biological activity of Quercetin released from drug-loaded membranes was analysed in an immortalized human keratinocyte cell line HaCaT by a wound healing assay. So, the reported preliminary data confirm the possibility of applying the electrospun Quercetin-loaded PCL-PVP membranes for wound healing applications.

Electrochemical sensing strategies for on‐site testing of pathogenic nucleic acids

AbstractRapid and reliable on‐site pathogen testing is crucial for diagnosing and managing human health. Nucleic acids (NAs) containing genetic information are valuable target molecules for pathogen testing, and sensitive and rapid detection of NAs using electrochemical approaches has been intensively investigated. Detection approaches for NAs are diverse and compatible with current gene amplification methods and continue to expand with the development of novel functional materials and molecules. The variety of electrochemical sensing devices also continues to expand, and more practical testing is being pursued. This review outlines the latest detection approaches and basic guidelines for NA detection. Furthermore, this review provides an overview of electrochemical sensing devices that utilize novel and unique materials and functions and comprehensively discusses their advantages.

Augmentation of NK-cell activity and immunity by combined natural polyphenols and saccharides in vitro and in vivo

Curcuma longa and Sargassum coreanum are commonly used in traditional pharmaceutical medicine to improve immune function in chronic diseases. The present study was designed to systematically elucidate the in vitro and in vivo immuno-enhancing effects of a combination of C. longa and S. coreanum extracts (CS) that contain polyphenols and saccharides as functional molecules in a cyclophosphamide (Cy)-induced model of immunosuppression. In primary splenocytes, we observed the ameliorative effects of CS on a Cy-induced immunosuppression model with low cytotoxicity and an optimal mixture procedure. CS treatment enhanced T- and B-cell proliferation, increased splenic natural killer-cell activity, and restored cytokine release. Wistar rats were orally administered low (30 mg/kg), intermediate (100 mg/kg), or high (300 mg/kg) doses of CS for four weeks, followed by oral administration of Cy (5 mg/kg) for four weeks. Compared with the vehicle group, low-, intermediate-, and high-dose CS treatment accelerated dose-dependent recovery of the serum level of tumor necrosis factor-α, interferon-γ, interleukin-2, and interleukin-12. These results suggest that CS treatment accelerates the amelioration of immune deficiency in Cy-treated primary splenocytes and rats, which supports considering it for immunity maintenance. Our findings provide experimental evidence for further research and clinical application in immunosuppressed patients.