Lotus leaf-inspired thermal insulation and anti-icing topography.

Porous sandwich-like structures with surface roughness possess the capacity to sustain droplets, diminish the area of contact between solids and liquids, and augment heat conductivity, and thus delay ice formation when the temperature drops below the freezing point. The prevalence of this combination of surface roughness and a hollow sandwich structure has been observed in several organisms, such as lotus leaves, which have developed these features as a result of environmental adaptation. This study introduces a new design for a surface consisting of a micro-nano conical array and a foam structure with a gradient of pores. The primary components of this design were isocyanate and polyether. The hollow gradient sandwich structure was created by manipulating the water content to increase the porosity, resulting in the formation of a conical-pit morphology on the underside of the specimen. This configuration significantly decreased the amount of heat lost and the modulus of elasticity of the sample. Additionally, the micro-nano hydrophobic structure on the upper surface hindered the transmission of temperature and delayed the formation of ice. This concept, inspired by natural structures, has significant potential applications in the areas of anti-icing, energy conservation, and environmental preservation.

Stability, Digestion, and Cellular Transport of Soy Isoflavones Nanoparticles Stabilized by Polymerized Goat Milk Whey Protein.

Soy isoflavones (SIF) are bioactive compounds with low bioavailability due to their poor water solubility. In this study, we utilized polymerized goat milk whey protein (PGWP) as a carrier to encapsulate SIF with encapsulation efficiency of 89%, particle size of 135.53 nm, and zeta potential of -35.16 mV. The PGWP-SIF nanoparticles were evaluated for their stability and in vitro digestion properties, and their ability to transport SIF was assessed using a Caco-2 cell monolayer model. The nanoparticles were resistant to aggregation when subjected to pH changes (pH 2.0 to 8.0), sodium chloride addition (0-200 mM), temperature fluctuations (4 °C, 25 °C, and 37 °C), and long-term storage (4 °C, 25 °C, and 37 °C for 30 days), which was mainly attributed to the repulsion generated by steric hindrance effects. During gastric digestion, only 5.93% of encapsulated SIF was released, highlighting the nanoparticles' resistance to enzymatic digestion in the stomach. However, a significant increase in SIF release to 56.61% was observed during intestinal digestion, indicating the efficient transport of SIF into the small intestine for absorption. Cytotoxicity assessments via the MTT assay showed no adverse effects on Caco-2 cell lines after encapsulation. The PGWP-stabilized SIF nanoparticles improved the apparent permeability coefficient (Papp) of Caco-2 cells for SIF by 11.8-fold. The results indicated that using PGWP to encapsulate SIF was an effective approach for delivering SIF, while enhancing its bioavailability and transcellular transport.

Natural gambogic acid-tuned self-assembly of nanodrugs towards synergistic chemophototherapy against breast cancer.

Gambogic acid (GA) as a naturally derived chemotherapeutic agent is of increasing interest for antitumor therapy. However, current research mainly focuses on improving the pharmacological properties to overcome the shortcomings in clinical applications or as a synergistic anticancer agent in combination with chemotherapy and chemophototherapy. Yet, the material properties of GA (e.g., self-assembly) are often neglected. Herein, we validated the self-assembly function of GA and its huge potential as a single-component active carrier for synergistic delivery using pyropheophorbide-a (PPa) as a drug model. The results showed that self-assembled GA drives the formation of nano-GA/PPa mainly through noncovalent interactions such as π-π stacking, hydrophobic interactions, and hydrogen bonding. Additionally, although no significant differences in cytotoxicity were found between the individual in vitro chemotherapy and combined chemophototherapy, the as-prepared nano-GA/PPa exhibits remarkably improved water solubility and multiple favorable therapeutic features, leading to a prominent in vivo photochemotherapy efficiency of 89.3% inhibition rate with reduced hepatotoxicity of GA. This work highlights the potential of self-assembled GA as a drug delivery carrier for synergistic biomedical applications.

Flexible scaffold-based cheminformatics approach for polypharmacological drug design.

Effective treatments for complex central nervous system (CNS) disorders require drugs with polypharmacology and multifunctionality, yet designing such drugs remains a challenge. Here, we present a flexible scaffold-based cheminformatics approach (FSCA) for the rational design of polypharmacological drugs. FSCA involves fitting a flexible scaffold to different receptors using different binding poses, as exemplified by IHCH-7179, which adopted a "bending-down" binding pose at 5-HT2AR to act as an antagonist and a "stretching-up" binding pose at 5-HT1AR to function as an agonist. IHCH-7179 demonstrated promising results in alleviating cognitive deficits and psychoactive symptoms in mice by blocking 5-HT2AR for psychoactive symptoms and activating 5-HT1AR to alleviate cognitive deficits. By analyzing aminergic receptor structures, we identified two featured motifs, the "agonist filter" and "conformation shaper," which determine ligand binding pose and predict activity at aminergic receptors. With these motifs, FSCA can be applied to the design of polypharmacological ligands at other receptors.

Comparison of lipidome profiles in human milk from Chinese Han and Korean ethnic groups based on UPLC-QTRAP-MS/MS.

The composition of milk lipids varies across different ethnic sources. The lipidome profiles of Chinese Han human milk (HHM) and Chinese Korean human milk (KHM) were investigated in this study. A total of 741 lipids were identified in HHM and KHM. Twenty-eight differentially expressed lipids (DELs) were screened between the 2 milk groups; among these, 6 triacylglycerols (TGs), 13 diacylglycerols (DGs), 7 free fatty acids (FFAs), and 1 monoglyceride (MG) were upregulated in KHM. Carnitine (CAR) was upregulated in HHM. Most DELs showed a single peak distribution in both groups. The correlations, related pathways and diseases of these DELs were further analyzed. The results demonstrated that DG, MG, and FFAs showed highly positive correlations with each other (r >0.8). The most enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) and Human Metabolome Database (HMDB) pathways were inositol phosphate metabolism, and α-linolenic acid and linolenic acid metabolism, respectively. Major depressive disorder-related FFA (20:5) and FFA (22:6) were more abundant in KHM, while HHM showed more obesity-related CAR. These data potentially provide lipidome information regarding human milk from different ethnicities in China.

The properties of the rice resistant starch processing and its application in skimmed yogurt.

Extrusion is typically employed to prepare resistant starch (RS). However, the process is complicated. In this study, the effects of twin-screw extrusion on the crystallinity, thermal properties, and functional properties of starch formed in different extrusion zones were investigated. The effects of this process on the rheological properties and microstructure of RS-added skimmed yogurt were also studied. According to the results, the RS content increased from 7.40 % in the raw material to 33.79 % in the extrudate. The A-type crystal structure of the starch was not observed. The dissociation temperature of the extruded starch ranged from 87.76 °C to 100.94 °C. The glycemic index (GI) of skimmed yogurt fortified with 0.4 % RS was 48.7, and the viscosity was also improved. The microstructure exhibited a uniform network of the starch-protein structure. The findings may serve as a theoretical basis for the application of RS in the food industry.

Evaluation of flavor substances of rice bran kvass based on electronic nose and gas chromatography-mass spectrometry.

In this paper, the electronic nose (E-nose) and headspace-solid phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS) were used to analyze the volatiles of rice bran kvass (RBK) with the reference of Qiulin kvass (QLK). Meanwhile, the flavor amino acids of RBK before and after fermentation were determined. The results showed that the kinds of kvass remained consistent in terms of the overall category of volatiles while there were differences in content between them (p < 0.05). A total of 35 volatile compounds, mainly including esters, alcohols, phenols, aldehydes, and acids, were identified by GC-MS in the two kinds of kvass. In addition, the total essential amino acid content and the total sweet amino acid content of RBK increased significantly (p < 0.05) after fermentation. RBK contains both the main flavor of kvass and its own unique characteristics, making it a new member of the Kvass family.

2-Phenylcyclopropylmethylamine (PCPMA) as a privileged scaffold for central nervous system drug design.

The use of privileged scaffolds in medicinal chemistry is an effective way to accelerate the drug discovery process, especially at the hit/lead optimization stage. 2-Phenylcyclopropylmethylamine (PCPMA) is a less commonly used chemical scaffold in medicinal chemistry, but many PCPMA-containing compounds exert therapeutic effects for various diseases, in particular central nervous system (CNS) diseases such as depression, schizophrenia, sleep disorder, and Parkinson's disease. The backbone of the PCPMA scaffold enables a unique structure of an amino group linked to a benzene ring through an alkyl linker, making it a useful template for the design of bioactive compounds especially for CNS drug targets including aminergic GPCRs and transporters. This review summarizes the medicinal chemistry studies of PCPMA-containing drugs and drug-like molecules, their mechanisms of action, and biological activities. We conclude that PCPMA is a unique and useful privileged scaffold for CNS drug design.

Effects of Panax notoginseng Saponins Encapsulated by Polymerized Whey Protein on the Rheological, Textural and Bitterness Characteristics of Yogurt.

Panax notoginseng saponins (PNSs) have been used as a nutritional supplement for many years, but their bitter taste limits their application in food formulations. The effects of PNS (groups B, C, and D contained 0.8, 1.0 and 1.2 mg/mL of free PNS, respectively) or Panax notoginseng saponin-polymerized whey protein (PNS-PWP) nanoparticles (groups E, F, and G contained 26.68, 33.35 and 40.03 mg/mL of PNS-PWP nanoparticles, respectively) on the rheological, textural properties and bitterness of yogurt were investigated. Group G yogurt showed a shorter gelation time (23.53 min), the highest elastic modulus (7135 Pa), higher hardness (506 g), higher apparent viscosity, and the lowest syneresis (6.93%) than other groups, which indicated that the yogurt formed a stronger gel structure. The results of the electronic tongue indicated that the bitterness values of group E (-6.12), F (-6.56), and G (-6.27) yogurts were lower than those of group B (-5.12), C (-4.31), and D (-3.79), respectively, which might be attributed to PNS being encapsulated by PWP. The results indicated that PWP-encapsulated PNS could cover the bitterness of PNS and improve the quality of yogurt containing PNS.

Mesoporous polydopamine Targeting CDK4/6 Inhibitor toward Brilliant Synergistic Immunotherapy of Breast Cancer.

Immunotherapy utilizing anti-PD-L1 blockade has achieved dramatic success in clinical breast cancer management but is often hampered by the limited immune response. Increasing evidence shows that immunogenic cell death (ICD) recently arises as a promising strategy for enlarging tumor immunogenicity and eliciting systemic anti-tumor immunity effectively. However, developing simple but versatile, highly efficient but low-toxic, biosafe, and clinically available transformed ICD inducers remains a huge demand and is highly desirable. Herein, a multifunctional ICD inducer is purposefully developed A6-MPDA@PAL by integrating photothermal therapy (PTT) nanoplatforms mesoporous polydopamine (MPDA), CDK4/6 inhibitor palbociclib (PAL), and CD44-specific targeting A6 peptide in a simple way for augmenting the immune antitumor efficacy of anti-PD-L1 therapy. Remarkably, the light-inducible nanoplatforms exhibit multiple favorable therapeutic features ensuring a superior and biosafe PTT/chemotherapy efficacy. Together with stronger accumulative ICD induction, single administration of A6-MPDA@PAL can trigger robust systemic antitumor immunity and abscopal effect with the assistance of anti-PD-L1 blockade by fascinating the intratumoral infiltration of T lymphocytes and reversing the immunosuppressive tumor microenvironment simultaneously, therapy achieving brilliant synergistic immunotherapy with effective tumor ablation. This study presents a simple and smart ICD inducer opening up attractive clinical possibilities for reinforcing the anti-PD-L1 therapy against breast cancer.

Strategies for the eradication of intracellular bacterial pathogens.

Intracellular pathogens affect a significant portion of world population and cause millions of deaths each year. They can invade host cells and survive inside them and are extremely resistant to immune systems and antibiotics. Current treatments have limitations, and therefore, new effective therapies are needed to combat this ongoing health challenge. Active research efforts have been made to develop many new strategies to eradicate these intracellular pathogens. In this review, we focus on the intracellular bacterial pathogens and first introduce several representative intracellular bacteria and the diseases they cause. We then discuss the challenges in eradicating these bacteria and summarize the current therapeutics for intracellular bacteria. Finally, recent advances in intracellular bacteria eradication are highlighted.

Tailoring Synthetic Polypeptide Design for Directed Fibril Superstructure Formation and Enhanced Hydrogel Properties.

The biological significance of self-assembled protein filament networks and their unique mechanical properties have sparked interest in the development of synthetic filament networks that mimic these attributes. Building on the recent advancement of autoaccelerated ring-opening polymerization of amino acid N-carboxyanhydrides (NCAs), this study strategically explores a series of random copolymers comprising multiple amino acids, aiming to elucidate the core principles governing gelation pathways of these purpose-designed copolypeptides. Utilizing glutamate (Glu) as the primary component of copolypeptides, two targeted pathways were pursued: first, achieving a fast fibrillation rate with lower interaction potential using serine (Ser) as a comonomer, facilitating the creation of homogeneous fibril networks; and second, creating more rigid networks of fibril clusters by incorporating alanine (Ala) and valine (Val) as comonomers. The selection of amino acids played a pivotal role in steering both the morphology of fibril superstructures and their assembly kinetics, subsequently determining their potential to form sample-spanning networks. Importantly, the viscoelastic properties of the resulting supramolecular hydrogels can be tailored according to the specific copolypeptide composition through modulations in filament densities and lengths. The findings enhance our understanding of directed self-assembly in high molecular weight synthetic copolypeptides, offering valuable insights for the development of synthetic fibrous networks and biomimetic supramolecular materials with custom-designed properties.

Construction and properties of a carbon dots-decorated gelatin-dialdehyde starch hydrogel with pH response release and antibacterial activity.

An antibacterial carbon dot hydrogel (GDSS-PCD) was constructed based on gelatin, dialdehyde starch (DS) and carbon dots (S-PCDs). The formation mechanism of GDSS-PCD hydrogels was attributed to the synergistic cross-linking of hydrogen bonds and dynamic covalent bonds. With increasing S-PCD content, the mechanical and rheological properties of GDSS-PCD hydrogels can be improved, and the micropore size becomes denser. GDSS-PCD hydrogels had pH-dependent swelling and degradation behavior, with a high swelling rate under acidic conditions and relatively low swelling under neutral and alkaline conditions. The cumulative release of S-PCDs from the same hydrogel in an acidic environment was higher than that in an alkaline environment, indicating that the GDSS-PCD hydrogel had a pH-dependent controlled release ability. The release behavior of S-PCDs conformed to the first-order kinetic release model (R2 > 0.95), and the release mechanism was related to Fickian diffusion. The synergistic antibacterial mechanism of GDSS-PCD hydrogels against Staphylococcus aureus suggested that bacterial metabolism leads to an acidic culture environment, which releases S-PCDs and destroys the bacterial cell membrane for antibacterial purposes. In GDSS-PCD hydrogels, S-PCDs play the main antibacterial role, and the hydrogel plays a synergistic role in trapping bacteria. Carbon dot hydrogels are promising materials to fulfil the functions of antibacterial and controlled release in the food and biomedical fields.

Impact of soybean protein isolate concentration on chitosan-cellulose nanofiber edible films: Focus on structure and properties.

Chitosan and cellulose nanofiber films are frequently employed as biodegradable materials for food packaging. However, many exhibit suboptimal hydrophobicity and antioxidant properties. To address these shortcomings, we enhanced the performance by adding different concentrations of soybean protein isolate (SPI) to chitosan-cellulose nanofiber (CS-CNF) films. As SPI concentration varied, the turbidity, particle size, and ζ-potential of the film-forming solutions initially decreased and subsequently increased. This suggests that 1 % SPI augments the electrostatic attraction and compatibility. Rheological analysis confirmed a pronounced apparent viscosity at this concentration. Analyses using Fourier transform infrared spectra, Raman spectra, X-ray diffraction, and Scanning electron microscope revealed the presence of hydrogen bonds and electrostatic interactions between SPI and CS-CNF, indicative of superior compatibility. When SPI concentration was set at 1 %, notable enhancements in film attributes were observed: improvements in tensile strength and elongation at break, a reduction in water vapor permeability by 8.23 %, and an elevation in the contact angle by 18.85 %. Furthermore, at this concentration, the ABTS+ and DPPH scavenging capacities of the film surged by 61.53 % and 46.18 %, respectively. Meanwhile, the films we prepare are not toxic. This research offers valuable insights for the advancement and application of protein-polysaccharide-based films.

Effect of different salts on the foaming properties of model protein systems for infant formula.

This multiscale study aimed to evaluate the effects of different salts (NaCl, KCl, MgCl2, and CaCl2) on the foaming capacity (FC) and foam stability (FS) of model protein systems (MPS) for infant formula via changes in surface and structural properties. Our results showed that the FC and FS of MPS were increased with the addition of NaCl, KCl, and MgCl2, whereas CaCl2 significantly decreased FC (79.5 ± 10.6%) and increased FS (93.2 ± 2.2%). The surface hydrophobicity was increased and the net charge and surface tension were reduced after the addition of salts. Structural analysis revealed the reduction of intensity of intrinsic fluorescence spectroscopy and UV absorption, and the conversion of α-helix into ß-strand, which was attributed to protein agglomeration. Additionally, MgCl2 and CaCl2 exhibited larger size and lower net charge compared with NaCl and KCl, indicating a greater ability to bind to charged amino acids and form larger aggregates. Correlation analysis indicated that FC was positively related to adsorbed protein and ß-turn and negatively correlated with particle size. In addition, FS showed a positive correlation with ß-strand, apparent viscosity, and zeta potential. However, it exhibited a negative correlation with ß-turn, α-helix, and sulfhydryl content. These results provide a theoretical reference for further understanding of the effect of salts on the foaming properties of MPS.

pH-induced physiochemical and structural changes of milk proteins mixtures and its effect on foaming behavior.

Milk proteins are well known to produce aerated food due to the amphiphilicity. However, milk proteins are commonly added in blends for the desirable properties in food industry. In this study, the foaming properties of milk protein mixtures (MPM), a mixtures of whey protein isolated (WPI) and milk protein concentrate (MPC), was studied through foaming capacity (FC), foam stability (FS), and foam morphology at pH 3.0-9.0. Physiochemical, structural, surface properties, and Pearson correlation analysis were measured to gain insight into foaming behavior. Results indicated that MPM showed excellent FC (113.0-114.3 %) and FS (90.7-93.0 %) at pH 6.0-9.0, and foam displayed a smaller size and uniform distribution. MPM solutions showed smaller particles, higher solubility, and lower apparent viscosity at pH 6.0-9.0, which resulted in an increase in surface pressure and adsorption rate (Kdiff), facilitating more protein absorbed to interface. To further investigate structural changes, various spectral methods were used, in which the structure of MPM was changed with pH. Correlation analysis further suggests that Kdiff and solubility positively affect the formation of foam, while free sulfhydryl and ß-sheet contributed to stabilizing foams. These findings provide valuable information on MPM as ingredients for aerated foods under acidic, neutral, and alkaline conditions.

Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants.

Psychedelics make up a group of psychoactive compounds that induce hallucinogenic effects by activating the serotonin 2A receptor (5-HT2AR). Clinical trials have demonstrated the traditional psychedelic substances like psilocybin as a class of rapid-acting and long-lasting antidepressants. However, there is a pressing need for rationally designed 5-HT2AR agonists that possess optimal pharmacological profiles in order to fully reveal the therapeutic potential of these agonists and identify safer drug candidates devoid of hallucinogenic effects. This Perspective provides an overview of the structure-activity relationships of existing 5-HT2AR agonists based on their chemical classifications and discusses recent advancements in understanding their molecular pharmacology at a structural level. The encouraging clinical outcomes of psychedelics in depression treatment have sparked drug discovery endeavors aimed at developing novel 5-HT2AR agonists with improved subtype selectivity and signaling bias properties, which could serve as safer and potentially nonhallucinogenic antidepressants. These efforts can be significantly expedited through the utilization of structure-based methods and functional selectivity-directed screening.

Functional Identification of Olfactory Receptors of Cnaphalocrocis medinalis (Lepidoptera: Crambidae) for Plant Odor.

Cnaphalocrocis medinalis (Lepidoptera: Crambidae) is a migratory insect pest on rice crops. The migratory C. medinalis population in a particular location may be immigrants, local populations, emigrants, or a mix of these. Immigrants are strongly attracted to plant odor. We conducted research to identify the olfactory receptors in a floral scent mixture that is strongly attractive to C. medinalis. Through gene cloning, 12 olfactory receptor (OR) genes were amplified and expressed in Xenopus oocytes in vitro, and three of them were found to be responsive to plant foliar and floral volatiles. These were CmedOR31, a specific receptor for geraniol; CmedOR32, a broad-spectrum OR gene that responded to both foliar and floral odors; and CmedOR1, which strongly responded to 10-4 M phenylacetaldehyde. The electrophysiological response to phenylacetaldehyde was extremely high, with a current of 3200 ± 86 nA and an extremely high sensitivity. We compared the phylogenetic tree and sequence similarity of CmedOR genes and found that CmedOR1 belonged to a uniquely conserved OR pedigree in the evolution of Glossata species, and the ORs of this pedigree strongly responded to phenylacetaldehyde. The expression of OR1 was significantly higher in the females than in the males. Localization of CmedOR1 in the antennae of C. medinalis by fluorescence in situ hybridization showed that CmedOR1 was expressed in both males and females. CmedOR1 may be an odor receptor used by females to locate food sources. The function of these ORs and their role in pest monitoring were discussed.

Physicochemical and Functional Properties of Thermal-Induced Polymerized Goat Milk Whey Protein.

Goat milk whey protein products are a hard-to-source commodity. Whey protein concentrate was directly prepared from fresh goat milk. The effects of the heating temperature (69-78 °C), time (15-30 min), and pH (7.5-7.9) on the physicochemical and functional properties of the goat milk whey protein were investigated. The results showed that the particle size of the samples significantly increased (p < 0.05) after heat treatment. The zeta potential of polymerized goat milk whey protein (PGWP) was lower than that of native goat milk whey protein. The content of the free sulfhydryl groups of PGWP decreased with increasing heating temperature and time, while an increase in surface hydrophobicity and apparent viscosity of PGWP were observed after heat treatment. Fourier Transform Infrared Spectroscopy analysis indicated that heat treatment and pH had considerable impacts on the secondary structure of goat milk whey protein. Transmission electron microscope images revealed that heat induced the formation of a large and uniform protein network. Additionally, the changes in the physicochemical and structural properties contributed to the improvement of the emulsifying and foaming properties of goat milk whey protein after heat treatment. The results may provide a theoretical basis for the applications of polymerized goat milk whey protein in related products.

Design and Synthesis of Novel GPR139 Agonists with Therapeutic Effects in Mouse Models of Social Interaction and Cognitive Impairment.

The GPR139 receptor is an orphan G-protein-coupled receptor (GPCR) mainly found in the central nervous system and is a potential therapeutic target for the treatment of schizophrenia and drug addiction. Guided by the reported structure of GPR139, we conducted medicinal chemistry optimizations of TAK-041, the GPR139 agonist in clinical trials. New compounds with three different core structures were designed and synthesized, and their activity at GPR139 was evaluated. Among them, compounds 15a (EC50 = 31.4 nM) and 20a (EC50 = 24.7 nM) showed potent agonist activity at GPR139 and good pharmacokinetic properties. In murine schizophrenia models, both compounds rescued the social interaction deficits observed in BALB/c mice. Compound 20a also alleviated cognitive deficits in mice with a pharmacologically induced model of schizophrenia. These findings further demonstrated the potential of GPR139 agonists in alleviating the negative symptoms and cognitive deficits of schizophrenia. Compound 20a is worth further evaluation as an antischizophrenia drug candidate.