ABSTRACT
Ion transport is essential to energy storage, cellular signalling and desalination. Polymers have been explored for decades as solid-state electrolytes by either adding salt to polar polymers or tethering ions to the backbone to create less flammable and more robust systems. New design paradigms are needed to advance the performance of solid polymer electrolytes beyond conventional systems. Here the role of a helical secondary structure is shown to greatly enhance the conductivity of solvent-free polymer electrolytes using cationic polypeptides with a mobile anion. Longer helices lead to higher conductivity, and random coil peptides show substantially lower conductivity. The macrodipole of the helix increases with peptide length, leading to larger dielectric constants. The hydrogen bonding of the helix also imparts thermal and electrochemical stability, while allowing for facile dissolution back to monomer in acid. Peptide polymer electrolytes present a promising platform for the design of next-generation ion-transporting materials.
ABSTRACT
Understanding the kinetics of LSD in receptors and subsequent induced signaling is crucial for comprehending both the psychoactive and therapeutic effects of LSD. Despite extensive research on LSD's interactions with serotonin 2A and 2B receptors, its behavior on other targets, including dopamine receptors, has remained elusive. Here, we present cryo-EM structures of LSD/PF6142-bound dopamine D1 receptor (DRD1)-legobody complexes, accompanied by a ß-arrestin-mimicking nanobody, NBA3, shedding light on the determinants of G protein coupling versus ß-arrestin coupling. Structural analysis unveils a distinctive binding mode of LSD in DRD1, particularly with the ergoline moiety oriented toward TM4. Kinetic investigations uncover an exceptionally rapid dissociation rate of LSD in DRD1, attributed to the flexibility of extracellular loop 2 (ECL2). Moreover, G protein can stabilize ECL2 conformation, leading to a significant slowdown in ligand's dissociation rate. These findings establish a solid foundation for further exploration of G protein-coupled receptor (GPCR) dynamics and their relevance to signal transduction.
ABSTRACT
AIM: An analysis of bioinformatics and cell experiments was performed to verify the relationship between gasdermin D (GSDMD), an executive protein of pyroptosis, and Alzheimer's disease (AD). METHODS: The training set GSE33000 was utilized to identify differentially expressed genes (DEGs) in both the AD group and control group, as well as in the GSDMD protein high/low expression group. Subsequently, the weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) regression analysis were conducted, followed by the selection of the key genes for the subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The association between GSDMD and AD was assessed and confirmed in the training set GSE33000, as well as in the validation sets GSE5281 and GSE48350. Immunofluorescence (IF) was employed to detect the myelin basic protein (MBP), a distinctive protein found in the rat oligodendrocytes (OLN-93 cells). A range of concentrations (1-15 µmol/L) of ß-amyloid 1-42 (Aß1-42) were exposed to the cells, and the subsequent observations were made regarding cell morphology. Additionally, the assessments were conducted to evaluate the cell viability, the lactate dehydrogenase (LDH) release, the cell membrane permeability, and the GSDMD protein expression. RESULTS: A total of 7,492 DEGs were screened using GSE33000. Subsequently, WGCNA analysis identified 19 genes that exhibited the strongest correlation with clinical traits in AD. Additionally, LASSO regression analysis identified 13 key genes, including GSDMD, AFF1, and ATOH8. Furthermore, the investigation revealed that the key genes were associated with cellular inflammation based on GO and KEGG analyses. Moreover, the area under the curve (AUC) values for the key genes in the training and validation sets were determined to be 0.95 and 0.70, respectively. Significantly, GSDMD demonstrated elevated levels of expression in AD across both datasets. The positivity of MBP expression in cells exceeded 95%. As the concentration of Aß1-42 action gradually escalated, the detrimental effects on cells progressively intensified, resulting in a gradual decline in cell survival rate, accompanied by an increase in lactate dehydrogenase release, cell membrane permeability, and GSDMD protein expression. CONCLUSION: The association between GSDMD and AD has been observed, and it has been found that Aß1-42 can induce a significant upregulation of GSDMD in OLN-93 cells. This suggests that Aß1-42 has the potential to induce cellular pyroptosis and can serve as a valuable cellular pyroptosis model for the study of AD.
Subject(s)
Alzheimer Disease , Phosphate-Binding Proteins , Pyroptosis , Alzheimer Disease/metabolism , Pyroptosis/drug effects , Phosphate-Binding Proteins/metabolism , Phosphate-Binding Proteins/genetics , Humans , Animals , Rats , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Amyloid beta-Peptides/metabolism , Computational Biology , Peptide Fragments/metabolism , GasderminsABSTRACT
Inhibiting the adhesion and growth of marine microorganisms through photocatalysis is a potentially efficient and environmentally friendly antifouling strategy. However, the undesired "shading effect" caused by resin coatings and microbial deposition reduces the utilization of the catalysts and leads to a failure in the antifouling active substance on the coating surface. Here, we successfully developed a composite coating (DPC-x) combining g-C3N4 nanosheet (g-C-NS) photocatalysts with degradable green poly-Schiff base resins, which integrates the dual functions of enhanced dynamic self-renewal and photocatalytic antibacterial activities towards long-term anti-biofouling. The controllable and complete degradability of the poly-Schiff base polymer chains and the self-renewal mechanism of the DPC-x coating exposed the internal g-C-NS, which provided a constant stream of photocatalytic reactive interfaces for 100% utilization and release of the photocatalysts. g-C-NS were homogeneously dispersed in the degradable resin coating, significantly enhancing and adjusting the self-renewal rate of the poly-Schiff base resin coating in visible light. The degradation reaction rate of DPC-0.2 (20 wt% g-C-NS) was 40 times that of DPC, thus improving the capabilities of surface self-renewal and fouling-release. Due to the synergistic antifouling mechanism of the efficient antibacterial properties and the enhanced degradation/self-renewal, the antimicrobial rates of DPC and DPC-0.2 were 94.58% and 99.31% in the dark, and 98.2% and 99.87% in visible light. DPC-x has excellent all-weather antimicrobial efficacy and could offer a new perspective on eco-friendly marine antifouling strategies.
ABSTRACT
Geopolymers, as a novel cementitious material, exhibit typical brittle failure characteristics under stress. To mitigate this brittleness, fibers can be incorporated to enhance toughness. This study investigates the effects of varying polypropylene fiber (PPF) content and fiber length on the flowability, mechanical properties, and flexural toughness of coal gangue-based geopolymers. Microstructural changes and porosity variations within the Fiber-Reinforced Geopolymer Mortar(GMPF) matrix were observed using scanning electron microscope (SEM) and Low field NMR(LF-NMR) to elucidate the toughening mechanism of PPF-reinforced geopolymers. The introduction of fibers into the geopolymer matrix demonstrated an initial bridging effect in the viscous geopolymer slurry, with a 3.0 vol% fiber content reducing fluidity by 5.6%. Early mechanical properties of GMPF were enhanced with fiber addition; at 1.5 vol% fiber content and 15 mm length, the 3-day flexural and compressive strengths increased by 30.81% and 17.4%, respectively. Furthermore, polypropylene fibers significantly improved the matrix's flexural toughness, which showed an increasing trend with higher fiber content. At a 3.0 vol% fiber content, the flexural toughness index increased by 198.35%. The data indicated that a fiber length of 12 mm yielded the best toughening effect, with an 84.03% increase in the flexural toughness index. SEM observations revealed a strong interfacial bond between fibers and the matrix, with noticeable damage on the fiber surface due to frictional forces, and fiber pull-out being the predominant failure mode. Porosity testing results indicated that fiber incorporation substantially improved the internal pore structure of the matrix, reducing the median pore diameter of mesopores and converting mesopores to micropores. Additionally, the number of harmless and less harmful pores increased by 23.01%, while the number of more harmful pores decreased by 30.43%.
ABSTRACT
Postoperative tumor recurrence and wound infection remain significant clinical challenges in surgery, often requiring adjuvant therapies. The combination treatment of photothermal therapy (PTT) and chemodynamic therapy (CDT) has proven to be effective in cancer treatment and wound infection. However, the hyperthermia during PTT increases the risk of normal tissue damage, severely impeding its application. Moreover, the efficacy of CDT is limited by insufficient hydrogen peroxide (H2O2) and excessive glutathione (GSH) levels at tumor or infection sites. Herein, an injectable and multifunctional CuO2@Au hydrogel system (CuO2@Au Gel) is developed for synergistic CDT and low-temperature PTT (LTPTT) to prevent tumor recurrence and bacterial wound infections. CuO2@Au Gel is constructed by embedding therapeutic CuO2@Au into low-melting point agarose hydrogel. In vitro and in vivo experiments confirm that the CuO2@Au in CuO2@Au Gel is capable of self-supplying H2O2 and depleting GSH, exhibiting effective CDT effect in acidic tumor or bacterial infected microenvironment. Additionally, it exhibits favorable photothermal conversion ability, inducing localized temperature elevation and synergistically enhancing CDT efficiency. The prepared CuO2@Au Gel demonstrates efficient tumor ablation capability in post-surgery recurrence mouse models and exhibits promising anti-infective efficiency in bacterial infection wound models, indicating significant potential in adjuvant therapy for post-surgical treatment and recovery.
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The realm of biomedical materials continues to evolve rapidly, driven by innovative research across interdisciplinary domains. Leveraging big data from the CAS Content Collection, this study employs quantitative analysis through natural language processing (NLP) to identify six emerging areas within nanoscale materials for biomedical applications. These areas encompass self-healing, bioelectronic, programmable, lipid-based, protein-based, and antibacterial materials. Our Nano Focus delves into the multifaceted utilization of nanoscale materials in these domains, spanning from augmenting physical and electronic properties for interfacing with human tissue to facilitating intricate functionalities like programmable drug delivery.
Subject(s)
Biocompatible Materials , Humans , Biocompatible Materials/chemistry , Drug Delivery Systems , Nanostructures/chemistry , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Nanotechnology/methods , Natural Language Processing , Lipids/chemistry , Proteins/chemistryABSTRACT
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.
ABSTRACT
A novel curcumin (CUR) delivery system was developed using soybean whey protein (SWP)-based emulsions, enhanced by pH-adjustment and gum arabic (GA) modification. Modulating electrostatic interactions between SWP and GA at oil/water interface, pH provides favorable charging conditions for stable distribution between droplets. GA facilitated the SWP form a stable interfacial layer that significantly enhanced the emulsifying properties and CUR encapsulation efficiency of the system at pH 6.0, which were 90.15 ± 0.67%, 870.53 ± 3.22 m2/g and 2157.62 ± 115.31%, respectively. Duncan's test revealed significant improvements in thermal, UV, oxidative, and storage stabilities of CUR (P < 0.05). At pH 6.0, GA effectively protected CUR by inhibiting SWP degradation during gastric digestion and promoting the release of CUR by decreasing steric hindrance with oil droplets during intestinal digestion, achieving the highest CUR bioaccessibility (69.12% ± 0.28%) based on Duncan's test. The SWP-GA-CUR emulsion delivery system would be a novel carrier for nutrients.
Subject(s)
Curcumin , Digestion , Drug Delivery Systems , Emulsions , Glycine max , Gum Arabic , Whey Proteins , Emulsions/chemistry , Whey Proteins/chemistry , Hydrogen-Ion Concentration , Gum Arabic/chemistry , Curcumin/chemistry , Curcumin/metabolism , Glycine max/chemistry , Drug Stability , Particle Size , Humans , Drug Carriers/chemistryABSTRACT
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.
ABSTRACT
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.
Subject(s)
Antineoplastic Agents , Breast Neoplasms , Xanthones , Xanthones/chemistry , Xanthones/pharmacology , Humans , Female , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Mice , Drug Screening Assays, Antitumor , Chlorophyll/chemistry , Chlorophyll/analogs & derivatives , Chlorophyll/pharmacology , Cell Survival/drug effects , Nanoparticles/chemistry , Cell Proliferation/drug effects , Photochemotherapy , Particle Size , Mice, Inbred BALB C , Drug Carriers/chemistry , Molecular StructureABSTRACT
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.
ABSTRACT
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.
Subject(s)
Oryza , Resistant Starch , Oryza/chemistry , Yogurt , Starch/chemistry , TemperatureABSTRACT
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.
Subject(s)
Cheminformatics , Drug Design , Polypharmacology , Animals , Mice , Humans , Cheminformatics/methods , Ligands , Receptor, Serotonin, 5-HT2A/metabolism , Receptor, Serotonin, 5-HT2A/chemistry , Receptor, Serotonin, 5-HT1A/metabolism , Receptor, Serotonin, 5-HT1A/chemistry , Male , Binding SitesABSTRACT
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 (DEL) were screened between the 2 milk groups; among these, 6 triacylglycerols (TG), 13 diacylglycerols (DG), 7 free fatty acids (FFA), and 1 monoglyceride (MG) were upregulated in KHM. Carnitine (CAR) was upregulated in HHM. Most DEL showed a single peak distribution in both groups. The correlations, related pathways and diseases of these DEL were further analyzed. The results demonstrated that DG, MG, and FFA showed highly positive correlations with each other (r > 0.8). The most enriched Kyoto Encyclopedia of Genes and Genomes (https://www.kegg.jp/kegg/) and Human Metabolome Database (http://www.hmdb.ca) 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, whereas HHM showed more obesity-related CAR. These data potentially provide lipidome information regarding human milk from different ethnicities in China.
Subject(s)
Lipidomics , Milk, Human , Humans , Milk, Human/chemistry , Female , Lipids , Ethnicity/genetics , Triglycerides/metabolism , China , Republic of Korea , East Asian PeopleABSTRACT
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.
Subject(s)
Central Nervous System Agents , Drug Discovery , Membrane Transport Proteins , Chemistry, Pharmaceutical , Drug DesignABSTRACT
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.
ABSTRACT
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.
Subject(s)
Breast Neoplasms , Cyclin-Dependent Kinase 4 , Cyclin-Dependent Kinase 6 , Immunotherapy , Indoles , Polymers , Indoles/chemistry , Indoles/pharmacology , Polymers/chemistry , Breast Neoplasms/therapy , Breast Neoplasms/pathology , Immunotherapy/methods , Female , Animals , Cyclin-Dependent Kinase 6/antagonists & inhibitors , Cyclin-Dependent Kinase 4/antagonists & inhibitors , Mice , Humans , Cell Line, Tumor , Porosity , Pyridines/chemistry , Pyridines/pharmacology , Piperazines/chemistry , Piperazines/pharmacology , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Photothermal TherapyABSTRACT
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.
Subject(s)
Anti-Bacterial Agents , Bacteria , Anti-Bacterial Agents/pharmacologyABSTRACT
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.