Deep eutectic solvent: Synthesis, classification, properties and application in macromolecular substances.

Deep eutectic solvent (DES) is a kind of solvent prepared by mixing hydrogen bond donors and hydrogen bond acceptors, and have become a hot topic in ecological civilization construction due to its low toxicity and sustainability. Its excellent properties such as low volatility, thermal stability and biodegradability make it stand out among many organic solvents and widely used in fields including medicine, chemical industry and agriculture, with broad development prospects. In recent years, the application of DES in the food field has mostly focused on the extraction of small molecular substances, and there are few summaries on the application of DES in macromolecular substances. In this review, we introduced the synthesis, classification and properties of DES, and summarized the application of DES in the food industry for macromolecular substances, including the extraction of macromolecular substances such as chitosan and pectin, as well as the preparation of related macromolecular substrate films. At the same time, we analyzed the characteristics of DES and its advantages and limitations in application, and provided prospects for future development.

A Supramolecular Biosensor for Rapid and High-Throughput Quantification of a Disease-Associated Niacin Metabolite.

Metabolic abnormalities play a pivotal role in various pathological conditions, necessitating the quantification of specific metabolites for diagnosis. While mass spectrometry remains the primary method for metabolite measurement, its limited throughput underscores the need for biosensors capable of rapid detection. Previously, we reported that pillar[6]arene with 12 carboxylate groups (P6AC) forms host-guest complexes with 1-methylnicotinamide (1-MNA), which is produced in vivo by nicotinamide N-methyltransferase (NNMT). P6AC acts as a biosensor by measuring the fluorescence quenching caused by photoinduced electron transfer upon 1-MNA binding. However, the low sensitivity of P6AC makes it impractical for detecting 1-MNA in unpurified biological samples. In this study, we found that P6A with 12 sulfonate groups (P6AS) is a specific and potent supramolecular host for 1-MNA interactions even in biological samples. The 1-MNA binding affinity of P6AS in water was found to be (5.68 ± 1.02) × 106 M-1, which is approximately 700-fold higher than that of P6AC. Moreover, the 1-MNA detection limit of P6AS was determined to be 2.84 × 10-7 M, which is substantially lower than that of P6AC. Direct addition of P6AS to culture medium was sufficient to quantify 1-MNA produced by cancer cells. Furthermore, this sensor was able to specifically detect 1-MNA even in unpurified human urine. P6AS therefore enables rapid and high-throughput quantification of 1-MNA, and further improvement of our strategy will contribute to the establishment of high-throughput screening of NNMT inhibitors, diagnosis of liver diseases, and imaging of human cancer cells in vivo.

Odd-even effect in chiral side-chain cyanobiphenyl block copolymer assemblies prepared by polymerization-induced chiral self-assembly.

The precise control of the chirality of polymer assemblies is a challenge faced by scientists and has received significant attention in recent years. In this study, we employed the polymerization-induced chiral self-assembly (PICSA) method to create chiral side-chain cyanobiphenyl (CB) block copolymer (BCP) assemblies. The flexible spacers in chiral CB monomers were regulated to exhibit two distinct odd-even effects in the supramolecular asymmetrical arrangement of the CB mesogens inside BCP assemblies. The research results indicated that the liquid crystalline properties of CB mesogens significantly influence the magnitude and sign of their chiroptical properties. These findings have significant implications for the design of polymer assemblies with designable chiroptical functions.

Regulating the Chiroptical Expression of Aggregated Solvophobic Core by Solvophilic Segments.

The investigation of chiral supramolecular stacking is of essential significance for the understanding of the origin of homochirality in nature. Unlike structurally well-defined amphiphilic liposomes, it remains unclear whether the solvophilic segments of the amphiphilic block copolymer play a decisive role in the construction of asymmetric superstructures. Herein, insights are presented into the stacking patterns and morphological regulation in azobenzene-containing block copolymer assemblies solely by modulating the solvophilic chain length. The solvophilic poly(methacrylic acid) (PMAA) segments of different molecular weights could cause multi-mode chirality inversions involving stacking transitions between intra-chain π-π stacking, inter-chain H- and J-aggregation. Furthermore, the length of the solvophilic PMAA also affects the morphology of the chiral supramolecular assemblies; rice grain-like micelles, worms, nanofibers, floccules, and lamellae can be prepared at different solvophilic-solvophobic balance. The comprehensive mechanism is collectively revealed by utilizing various measurement methods, such as including circular dichroism (CD), small-angle X-ray scattering (SAXS), and wide-angle X-ray diffraction (WAXD). This study highlights the critical importance of fully dissolved solvophilic segments for the chiroptical regulation of the aggregated core, providing new insights into the arrangement of chiral supramolecular structures in polymer systems.

Up-regulated PLA2G10 in cancer impairs T cell infiltration to dampen immunity.

T cells are often absent from human cancer tissues during both spontaneously induced immunity and therapeutic immunotherapy, even in the presence of a functional T cell-recruiting chemokine system, suggesting the existence of T cell exclusion mechanisms that impair infiltration. Using a genome-wide in vitro screening platform, we identified a role for phospholipase A2 group 10 (PLA2G10) protein in T cell exclusion. PLA2G10 up-regulation is widespread in human cancers and is associated with poor T cell infiltration in tumor tissues. PLA2G10 overexpression in immunogenic mouse tumors excluded T cells from infiltration, resulting in resistance to anti-PD-1 immunotherapy. PLA2G10 can hydrolyze phospholipids into small lipid metabolites, thus inhibiting chemokine-mediated T cell mobility. Ablation of PLA2G10's enzymatic activity enhanced T cell infiltration and sensitized PLA2G10-overexpressing tumors to immunotherapies. Our study implicates a role for PLA2G10 in T cell exclusion from tumors and suggests a potential target for cancer immunotherapy.

Precise Modulation of Circularly Polarized Luminescence via Polymer Chiral Co-assembly and Contactless Dynamic Chiral Communication.

Circularly polarized luminescence (CPL) plays a pivotal role in cutting-edge display and information technologies. Currently achieving precise color control and dynamic signal regulation in CPL still remains challenging due to the elusory relationship between fluorescence and chirality. Inspired by the natural mechanisms governing color formation and chiral interaction, we proposed an addition-subtraction principle theory to address this issue. Three fluorene-based polymers synthesized by Suzuki polycondensation with different electron-deficient monomers exhibit similar structures and UV/Vis absorption, but distinct fluorescence emissions due to intramolecular charge transfer. Based on this, precise-color CPL-active films are obtained through quantitative supramolecular co-assembly directed by addition principle. Particularly, an ideal white-emitting CPL film (CIE coordinates: (0.33, 0.33)) is facilely fabricated with a high quantum yield of 80.8 % and a dissymmetry factor (glum) of 1.4×10-2. Structural analysis reveals that the ordered stacking orientation favors higher glum. Furthermore, to address the dynamically regulated challenge, the comparable subtraction principle is proposed, involving a contactless chiral communication between excited and ground states. The representative system consisting of as-prepared fluorene-based polymers and chirality-selective absorption azobenzene (Azo)-containing polymers is constructed, achieving CPL weakening, reversal, and enhancement. Finally, a switchable quick response code is realized based on trans-cis isomerization of Azo moiety.

Revealing Pathway Complexity and Helical Inversion in Supramolecular Assemblies Through Solvent-Induced Radical Disparities.

New insights are raised to interpret pathway complexity in the supramolecular assembly of chiral triarylamine tris-amide (TATA) monomer. In cosolvent systems, the monomer undergoes entirely different assembly processes depending on the chemical feature of the two solvents. Specifically, 1,2-dichloroethane (DCE) and methylcyclohexane (MCH) cosolvent trigger the cooperative growth of monomers with M helical arrangement, and hierarchical thin nanobelts are further formed. But in DCE and hexane (HE) combination, a different pathway occurs where monomers go through isodesmic growth to generate twisted nanofibers with P helical arrangement. Moreover, the two distinct assemblies exhibit opposite excited-state chirality. The driving force for both assemblies is the formation of intermolecular hydrogen bonds between amide moieties. However, the mechanistic investigation indicates that radical and neutral triarylamine species go through distinct assembly phases by changing solvent structures. The neutralization of radicals in MCH plays a critical role in pathway complexity, which significantly impacts the overall supramolecular assembly process, giving rise to inversed supramolecular helicity and distinct morphologies. This differentiation in pathways affected by radicals provides a new approach to manipulate chiral supramolecular assembly process by facile solvent-solute interactions.

Characterization and Function Analysis of Soluble Dietary Fiber Obtained from Radish Pomace by Different Extraction Methods.

Soluble dietary fiber (SDF) benefits human health, and different extraction methods might modify the structure and functions of the SDFs. Radish is rich in dietary fiber. To assess the impact of various extraction techniques on the properties and functions of radish SDF, the SDFs were obtained from white radish pomace using alkaline, ultrasonic-assisted, and fermentation-assisted extraction methods. Analysis was conducted on the structure, physicochemical characteristics, thermal properties, and functional attributes of the SDFs. The study revealed that various extraction techniques can impact the monosaccharides composition and functionality of the SDFs. Compared with the other two extraction methods, the surface structures of SDFs obtained by fermentation-assisted extraction were looser and more porous, and the SDF had better water solubility and water/oil holding capacity. The adsorption capacities of glucose and cholesterol of the SDFs obtained from fermentation-assisted extraction were also improved. Wickerhamomyces anomalus YFJ252 seems the most appropriate strain to ferment white radish pomace to acquire SDF; the water holding, oil holding, glucose absorption capacity, and cholesterol absorption capacity at pH 2 and pH 7 have a 3.06, 1.65, 3.19, 1.27, and 1.83 fold increase than the SDF extracted through alkaline extraction method.

Unraveling Dynamic Helicity Inversion and Chirality Transfer through the Synthesis of Discrete Azobenzene Oligomers by an Iterative Exponential Growth Strategy.

Unraveling the chirality transfer mechanism of polymer assemblies and controlling their handedness is beneficial for exploring the origin of hierarchical chirality and developing smart materials with desired chiroptical activities. However, polydisperse polymers often lead to an ambiguous or statistical evaluation of the structure-property relationship, and it remains unclear how the iterative number of repeating units function in the helicity inversion of polymer assemblies. Herein, we report the macroscopic helicity and dynamic manipulation of the chiroptical activity of supramolecular assemblies from discrete azobenzene-containing oligomers (azooligomers), together with the helicity inversion and morphological transition achieved solely by changing the iterative chain lengths. The corresponding assemblies also differ from their polydisperse counterparts in terms of thermodynamic properties, chiroptical activities, and morphological control.

Explicit learning based on reward prediction error facilitates agile motor adaptations.

Error based motor learning can be driven by both sensory prediction error and reward prediction error. Learning based on sensory prediction error is termed sensorimotor adaptation, while learning based on reward prediction error is termed reward learning. To investigate the characteristics and differences between sensorimotor adaptation and reward learning, we adapted a visuomotor paradigm where subjects performed arm movements while presented with either the sensory prediction error, signed end-point error, or binary reward. Before each trial, perturbation indicators in the form of visual cues were presented to inform the subjects of the presence and direction of the perturbation. To analyse the interconnection between sensorimotor adaptation and reward learning, we designed a computational model that distinguishes between the two prediction errors. Our results indicate that subjects adapted to novel perturbations irrespective of the type of prediction error they received during learning, and they converged towards the same movement patterns. Sensorimotor adaptations led to a pronounced aftereffect, while adaptation based on reward consequences produced smaller aftereffects suggesting that reward learning does not alter the internal model to the same degree as sensorimotor adaptation. Even though all subjects had learned to counteract two different perturbations separately, only those who relied on explicit learning using reward prediction error could timely adapt to the randomly changing perturbation. The results from the computational model suggest that sensorimotor and reward learning operate through distinct adaptation processes and that only sensorimotor adaptation changes the internal model, whereas reward learning employs explicit strategies that do not result in aftereffects. Additionally, we demonstrate that when humans learn motor tasks, they utilize both learning processes to successfully adapt to the new environments.

Upregulation of CELSR1 expression promotes ovarian cancer cell proliferation, migration, and invasion.

Cadherin epidermal growth factor and laminin-G seven-pass G-type receptor 1 (CELSR1) is a planar cell polarity protein involved in the transmission of directional cues to align either individual cells within an epithelial sheet or multicellular clusters. CELSR1 has been suggested to play a role in glioma, breast cancer, and chronic lymphocytic leukemia development; however, whether it has a role in the pathogenesis of ovarian cancer remains unknown. The aim of this study was to determine the role of CELSR1 in ovarian cancer and elucidate its underlying molecular mechanisms. By analyzing gene expression data downloaded from the Cancer Genome Atlas database, we found that CELSR1 expression was upregulated in ovarian cancer tissues compared to that in normal ovarian tissues. High CELSR1 expression levels were associated with poor prognosis in patients with ovarian cancer. Cell proliferation, scratch, and transwell assays revealed that CELSR1 promoted the proliferation, migration, and invasion of ovarian cancer cells in vitro. In addition, transcriptome sequencing analysis revealed that CELSR1 knockdown in T29H cells resulted in the dysregulation of the expression of 1320 genes. Further analysis revealed that genes involved in proliferation- and migration-associated signaling pathways were regulated by CELSR1. Our study demonstrates that CELSR1 is highly expressed in ovarian cancer cells and regulates their proliferation and migration, suggesting its potential as a diagnostic marker and therapeutic target.

A virtual reality platform to evaluate the effects of supernumerary limbs' appearance.

Supernumerary robot limbs (SL) can expand the ability of users by increasing the number of degrees of freedom that they control. While several SLs have been designed and tested on human participants, the effect of the limb's appearance on the user's acceptance, embodiment and device usage is not yet understood. We developed a virtual reality platform with a three-arm avatar that enabled us to systematically investigate the effect of the supernumerary limb's appearance on their perception and motion control performance. A pilot study with 14 participants exhibited similar performance, workload and preference in human-like or robot-like appearance with a trend of preference for the robotic appearance.

Mutual communication between radiosensitive and radioresistant esophageal cancer cells modulates their radiosensitivity.

Radiotherapy is an important treatment modality for patients with esophageal cancer; however, the response to radiation varies among different tumor subpopulations due to tumor heterogeneity. Cancer cells that survive radiotherapy (i.e., radioresistant) may proliferate, ultimately resulting in cancer relapse. However, the interaction between radiosensitive and radioresistant cancer cells remains to be elucidated. In this study, we found that the mutual communication between radiosensitive and radioresistant esophageal cancer cells modulated their radiosensitivity. Radiosensitive cells secreted more exosomal let-7a and less interleukin-6 (IL-6) than radioresistant cells. Exosomal let-7a secreted by radiosensitive cells increased the radiosensitivity of radioresistant cells, whereas IL-6 secreted by radioresistant cells decreased the radiosensitivity of radiosensitive cells. Although the serum levels of let-7a and IL-6 before radiotherapy did not vary significantly between patients with radioresistant and radiosensitive diseases, radiotherapy induced a more pronounced decrease in serum let-7a levels and a greater increase in serum IL-6 levels in patients with radioresistant cancer compared to those with radiosensitive cancer. The percentage decrease in serum let-7a and the percentage increase in serum IL-6 levels at the early stage of radiotherapy were inversely associated with tumor regression after radiotherapy. Our findings suggest that early changes in serum let-7a and IL-6 levels may be used as a biomarker to predict the response to radiotherapy in patients with esophageal cancer and provide new insights into subsequent treatments.

Hypoxia promotes the growth and metastasis of ovarian cancer cells by suppressing ferroptosis via upregulating SLC2A12.

BACKGROUND: Ovarian cancer has been a worldwide health burden for women and its progression is highly hypoxia-independent. Here, we investigated the exact mechanisms by which hypoxia contributes to the malignant progression of ovarian cancer. METHOD: MTT, transwell, colony formation, and scratch wound healing assays were carried out for cellular functions. The underlying mechanism by which hypoxia functions was explored by RNA-seq, enrichment analysis, western blotting, qRT-PCR, flow cytometry, ChIP, luciferase reporter, and ELISA. Finally, animal experiments including the xenograft model and tumor metastasis model were constructed to validate the role of SLC2A12 in vivo. RESULTS: Hypoxia treatment promoted the cell proliferation, mobility, and colony growth abilities of the two ovarian cancer cell lines HO-8910 and A2780. RNA-seq and enrichment analysis showed that SLC2A12 was hyper-expressed under hypoxia condition and it may be related to glutathione and lipid metabolism. Besides, the expression of SLC2A12 was negatively correlated with overall survival. Hypoxia suppressed ferroptosis by SLC2A12 because silencing SLC2A12 declined the cell viability of HO-8910 and A2780 cells under hypoxia conditions, while the ferroptosis inhibitor ferrostatin-1 (Fer-1) breached that result and upregulated the expression of glutathione peroxidase 4 (GPX4). Moreover, hypoxia increased the expression of hypoxia inducible factor 1 A (HIF-1A), and the accumulated HIF-1A binds to hypoxia inducible factor 1 B (HIF1B) to form HIF-1 complex, then promoted the binding of hypoxic response elements (HRE) to SLC2A12 promoter by HIF-1/HRE signal. Subsequently, SLC2A12 regulated glutathione metabolism and in turn inhibited ferroptosis. The animal experiments indicated that silencing SLC2A12 could significantly inhibit tumor growth and metastasis in vivo. CONCLUSION: Hypoxia promoted ovarian cancer progression by upregulating SLC2A12 and then regulating glutathione metabolism to inhibit ferroptosis.

A Subtle Change in the Flexible Achiral Spacer Does Matter in Supramolecular Chirality: Two-Fold Odd-Even Effect in Polymer Assemblies.

Precise control over the chirality and morphologies of polymer assemblies, a remaining challenge for both chemists and materials scientists, is receiving ever-increasing attention in the recent years. Herein, we report the subtle manipulation of the achiral spacers from the chiral stereocenter to the azobenzene (Azo) unit, of which the chiroptical consistency or chiroptical inversion of self-assemblies could be successfully controlled and present "two-fold" odd-even effect. Furthermore, morphological transitions from 0D spherical micelles, 1D worms, and nanowires to 3D vesicles, spindle- and dumbbell-shaped vesicles were also unexpectedly found to exhibit odd-even correlations. These observations were collectively elucidated by mesomorphic properties, stacking modes, chiroptical dynamics, and stimuli-responsive behaviors. Negligible modifications to the spacer structures can enable remarkable modulation of supramolecular chirality and anisotropic topologies in polymer assemblies, which is of great significance for the design of complex chiral functional polymers.

Simultaneous Chiral Fixation and Chiral Regulation Endowed by Dynamic Covalent Bonds.

The construction of chiral superstructures through the self-assembly of non-chiral polymers usually relies on the interplay of multiple non-covalent bonds, which is significantly limited by the memory ability of induced chirality. Although the introduction of covalent crosslinking can undoubtedly enhance the stability of chiral superstructures, the concurrent strong constraining effect hinders the application of chirality-smart materials. To address this issue, we have made a first attempt at the reversible fixation of supramolecular chirality by introducing dynamic covalent crosslinking into the chiral self-assembly of side-chain polymers. After chiral induction, the reversible [2+2] cycloaddition reaction of the cinnamate group in the polymer chains can be further controlled by light to manipulate inter-chain crosslinking and decrosslinking. Based on this photo-programmable and dynamic chiral fixation strategy, a novel pattern-embedded storage mechanism of chiral polymeric materials was established for the first time.

Design and evaluation of gastro-swelling/gastro-floating sustained-release tablets of brivaracetam for epilepsy therapy.

To prolong the absorption of the drug and achieve the effect of gastric retention, new brivaracetam tablets together with the characteristics of rapid swelling and sustained floating have been developed here. The tablets were optimized and prepared by direct compression techniques using Kollidon® SR and cross-linked polyvinylpyrrolidone (PVPP) XL as the matrix and disintegrant respectively, and carbomer 71G NF and polyethylene oxide (PEO) N60K as the gel materials to achieve sustained release effect. The characteristics of static expansion, floating time, drug release and dynamic swelling performance in vitro of the tablets were evaluated. The optimized formulations (F5 and F10) exhibited satisfactory swelling and floating properties, mechanical strength, and in vitro sustained-release characteristic with diffusion and matrix erosion mechanisms. X-ray images of beagle dogs showed that the tablet F5 could be retained in the stomach for more than 6 h. Furthermore, the pharmacokinetic studies in volunteers exhibited that the bioavailability of F5 and F10 was 95.70% (90% CI, 83.80%-109.28%) and 103.39% (90% CI, 87.61%-122.01%), respectively, relative to commercial tablets, with Tmax prolonged, demonstrating an excellent sustained-release effect. Therefore, the present system can reduce dosing frequency and improve patient compliance, which is expected to be a promising treatment option for epilepsy patients.

Small cytosolic double-stranded DNA represses cyclic GMP-AMP synthase activation and induces autophagy.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a major mediator of inflammation following stimulation with >45 bp double-stranded DNA (dsDNA). Herein, we identify a class of ∼20-40 bp small cytosolic dsDNA (scDNA) molecules that compete with long dsDNA (200-1,500 bp herring testis [HT]-DNA) for binding to cGAS, thus repressing HT-DNA-induced cGAS activation. The scDNA promotes cGAS and Beclin-1 interaction, releasing Rubicon, a negative regulator of phosphatidylinositol 3-kinase class III (PI3KC3), from the Beclin-1-PI3KC3 complex. This leads to PI3KC3 activation and induces autophagy, causing degradation of STING and long cytosolic dsDNA. Moreover, DNA damage decreases, and autophagy inducers increase scDNA levels. scDNA transfection and treatment with autophagy inducers attenuate DNA damage-induced cGAS activation. Thus, scDNA molecules serve as effective brakes for cGAS activation, preventing excessive inflammatory cytokine production following DNA damage. Our findings may have therapeutic implications for cytosolic DNA-associated inflammatory diseases.

Estimating heterogeneous effects of internet use on environmental knowledge: Taking population heterogeneity into consideration.

The recent decades have witnessed the rise of digital media; as an essential informal way of environmental education, the internet has become an important source where public acquire environmental knowledge. The current study investigates the heterogeneous treatment effects of internet use on environmental knowledge across members of the Chinese population. Based on a nationwide survey in China, the propensity score approach, a series of statistical techniques that are often used in the counterfactual framework to understand the causal relationship between an intervention and an outcome, is employed to adjust for population heterogeneity and to estimate heterogeneous treatment effects. The findings reveal highly significant positive associations between internet access/use and environmental knowledge. More importantly, this study shows that individuals who are least likely to access the internet benefit most from the knowledge returns to internet access and use, indicating a positive outlook for the potential of the digital media to narrow the environmental knowledge gap.