Preparation of high yield lignin-containing cellulose nanofibrils from alkaline peroxide mechanical pulp by deep eutectic solvents pretreatment
The presence of lignin endows lignin-containing cellulose nanofibrils (LCNFs) with special properties. Nevertheless, the conventional methods for cellulose nanofibrils (CNFs) fabrication are confronted with challenges of environmental and economic considerations. In presence work, an environmentally sustainable process of deep eutectic solvents (DES) pretreatment followed by ultrasonic treatment was explored for fabrication of LCNFs from alkaline peroxide mechanical pulp (APMP). In addition, the effects of pulp refining on the properties of the LCNFs were discussed. The results shows that the LCNFs of 68.23 % yield can be obtained as pretreating APMP with DES compose of choline chloride/lactic acid (ChCl/LA) at 100 °C for 8 h followed by ultrasonic treatment for 30 min. The prepared LCNFs have a width of 6.90 nm and 8.65 % lignin content. The pulp refining before DES treatment affects the properties of the LCNFs. When the pulp is refined by PFI mill for 2500 revolutions before DES pretreatment, compared to the LCNFs obtained without refining, the LCNFs obtained from the refined pulp has a similar yield (64.37 %) and smaller width at milder DES treatment conditions (100 °C and 4 h), which indicates that the process of combination of the pulp refining and DES pretreatment improves the LCNFs fabrication efficiency.
Study on the ameliorative effect of marine fungus Hansfordia sinuosae extracellular polysaccharide on DSS-induced ulcerative colitis and depression-like behavior
Colitis has become a public health problem in recent years due to its high incidence rate. The extracellular polysaccharides produced by microorganisms were reported to possess the ability to alleviate colitis. A mannan (HPA) was isolated from the fermented broth of the marine fungus Hansfordia sinuosae, and its effect on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) was investigated in vivo. The results showed that HPA could relieve the disease symptoms and colon pathological injury of UC mice. Further mechanism analysis indicated that HPA repressed the level of NLRP3 inflammasome and inflammatory mediators TNF-α and IL-1β, and promoted the production of IL-10. HPA repaired the colonic barrier by increasing the expression of tight junction proteins ZO-1 and occludin, as well as the number of goblet cells. It also restored the imbalance of the gut microbiota caused by DSS treatment by enhancing the abundance of beneficial bacteria such as Clostridia UCG-014 and Bifidobacterium, while reducing the abundance of potentially harmful bacteria like Escherichia-Shigella and Enterococcus. Besides, HPA relieved the depression-like behavior of UC mice by inhibiting inflammatory response and activation of astrocyte and microglia in brain tissues. In short, HPA had the potential to be developed as functional foods or drugs for the treatment of colitis and accompanied depression-like behavior.
Long-acting antibacterial nanochitin/nanocellulose bioplastic packaging film
Ensuring antimicrobial safety and durability remains a critical challenge in bioplastic packaging. In this study, a silver-loaded lignin/laponite antimicrobial agent (Lap@LAg) with outstanding long-term antibacterial properties was synthesized and subsequently incorporated with nanocellulose and nanochitin to fabricate a bioplastic film (CTF/Lap@LAg). The lignin-coated silver nanoparticles (AgNPs) were effectively immobilized on the laponite and uniformly dispersed throughout the matrix. The combined effects of laponite's confinement and electronegativity, along with the encapsulation capability of lignin, conferred prolonged antibacterial activity to Lap@LAg, achieving over 99.99 % bacteriostatic efficacy against E. coli and S. aureus. Furthermore, Lap@LAg demonstrated a remarkable long-lasting antibacterial effect, effectively protecting wood powder from mold contamination for 14 days. Moreover, the electrostatic and hydrogen bonding interactions among nanocellulose, nanochitin, and laponite, coupled with their multidimensional interwoven structure, imparted exceptional mechanical strength (Increased by 57.2 %) and superior barrier properties (WVP 0.082 g⋅mm/m⋅d⋅kPa, OTR 0.077 cm/m⋅24h⋅0.1 MPa) to the film. This study provides valuable insights into the design of safe and long-lasting antibacterial bioplastic packaging.
Carboxymethyl cellulose/alginate/chitosan-based polyelectrolyte complex hydrogel with irregularly shaped multi-metallic nanowires for efficient continuous-flow Cr(VI) remediation
The efficient removal of hexavalent chromium (Cr(VI)) from industrial wastewater is a pressing environmental challenge. A natural polyelectrolyte complex (PEC) hydrogel composed of carboxymethyl cellulose, alginate and chitosan, was developed to support Pd/Au/Ag/Pt nanowires for the continuous-flow catalytic reduction of Cr(VI) to the less toxic Cr(III). PEC hydrogels are formed through the association of oppositely charged polyelectrolytes, a process that is primarily driven by entropy gain due to the release of counterions, resulting in highly porous networks with tunable physical and chemical properties. These characteristics make them ideal platforms for nanoparticle stabilization and catalytic applications. Crosslinking with glutaraldehyde, citric acid and calcium ions further improved the stability and porosity of the hydrogels. Pd/Au/Ag/Pt nanowires, synthesised through galvanic replacement and co-reduction of Pd/Au/Ag nanowires formed via an oriented attachment mechanism, exhibit a distinctive, irregular, undulating morphology that enhances their suitability for introduction into hydrogel matrices. These multi-metallic nanowires achieved complete Cr(VI) reduction within 15 min. When incorporated into a nanocomposite hydrogel, the Pd/Au/Ag/Pt nanowires significantly enhanced catalytic activity while maintaining structural integrity and high catalytic efficiency. Notably, the system achieved complete Cr(VI) reduction within 5 h of continuous-flow operation, highlighting its potential as a robust and scalable solution for industrial wastewater remediation.
Injectable thermosensitive hydrogel based on hyaluronic acid and poloxamer for sustained bupivacaine release and prolonged analgesia
Local anesthetics are commonly used for postoperative pain relief but have limited effectiveness due to their short half-life and low molecular weight. Various sustained-release systems have been explored but face challenges such as low encapsulation efficiency in liposomes, rapid degradation and limited release durations of hydrogel, and difficulties with injectability in combined microsphere/hydrogel. This study presents a double cross-linked hydrogel (Bup/PO) made from aminated poloxamer 407 (P407) and oxidized hyaluronic acid (OHA), cross-linked via oxime bonds and hydrophobic interactions. Rheological analysis showed that the hydrogel exhibited temperature sensitivity, with a storage modulus of up to 10,000 Pa at 37 °C, significantly higher than pure P407. In vitro, the hydrogel provided sustained bupivacaine release for up to 8 days. In vivo, a rat sciatic nerve block model demonstrated that the Bup/PO hydrogel significantly extended the mechanical pain threshold for 32 h and thermal pain threshold for 48 h. The hydrogel was fully biodegradable within 21 days, with mild reversible inflammation and no neurotoxicity. This study introduces a double-cross-linking mechanism that improves hydrogel stability, mechanical properties, and drug release, offering a promising solution for long-term postoperative pain management and regional anesthesia.
Piezoelectric properties of collagen films: Insights into their potential for electroactive biomedical applications
Electroactive biomaterials and, in particular, piezoelectric ones are gaining insight into tissue engineering and biomedical applications. Collagen is one of the most available biomaterials found in nature, and the present study focus on the evaluation of its piezoelectric response. Collagen extracted from bovine skin was used and the piezoelectric response was correlated to the physicochemical, thermal, morphological and mechanical properties. A dense fibrillar microstructure was observed and the mechanical properties, which depend on the specific amino acids composition, showed tensile strength and maximum strain values of 34 MPa and 18 %, respectively. Collagen films exhibited approximately 25 % weight loss after 1 day in PBS solution, increasing to about 30 % and 100 % at day 2 and 4, respectively. A piezoelectric response of 0.44 pm/V was obtained, demonstrating the collagen film suitability for electroactive materials in biomedical applications.
Advances and challenges in polyhydroxyalkanoates (PHA) production using Halomonas species: A review
Plastic waste pollution is one of the major threats to sustainable development. Biodegradable polymers and biopolymers such as polyhydroxyalkanoates (PHAs) offer suitable alternatives for replacing synthetic plastics. PHAs are produced by diverse bacteria species and archaea as storage compounds for utilization as carbon and energy sources. Halomonas species have emerged as attractive microbial cell factories for biosynthesis of PHAs due to their metabolic versality, ability to valorize diverse feedstock materials, and tolerance to high salinity and pH that allows fermentation in contamination-resistant conditions. In recent years, there has been great attention to the use of Halomonas species in PHA biosynthesis and genetic engineering efforts for enhanced production. This article provides a discussion of the current state of knowledge on production of polyhydroxyalkanoates by Halomonas species. It includes an overview of PHA biosynthesis mechanisms, fermentation strategies, production with cheap substrates, exploitation of open and unsterile conditions, co-production of PHAs and other products, and advances genetic engineering efforts.
Enhancing circular bioeconomy: Alginate-cellulose nanofibre films/coatings functionalized with encapsulated pomegranate peel extract for postharvest preservation of pomegranate arils
This study investigated the properties of alginate-cellulose nanofiber (AL-CNF) bio-composite coatings functionalized with pomegranate peel extract powder (PPEP) at 0.1, 0.3, and 0.5 % (w/v) and their effects on the postharvest shelf life of pomegranate arils stored at 5 °C and 95 ± 2 % RH for 15 days. The results demonstrated that PPEP incorporation enhanced the physical, functional, and antioxidant properties of the coatings while reducing their mechanical strength. Microstructural analysis revealed that CNF contributed to a rougher surface, whereas PPEP addition improved homogeneity and smoothness. The 0.5 % PPEP concentration exhibited the highest thickness, antioxidant activity, and phenolic content. Application of AL-CNF bio-composite coatings significantly (p < 0.05) reduced weight loss, delayed respiration, and maintained firmness compared to the control. PPEP incorporation increased total soluble solids (TSS) and preserved the visual quality of arils. Additionally, 0.5 % PPEP retained higher phenolic content, anthocyanin levels, and DPPH activity while reducing microbial growth. These findings suggest that AL-CNF nanocomposite coatings enriched with PPEP (0.1-0.5 %) effectively preserve quality and extend the shelf life of minimally processed pomegranate arils, offering a sustainable postharvest preservation strategy.
Smart nanocomposite of carbon quantum dots in double hydrogel (carboxymethyl cellulose/chitosan) for effectively adsorb and remove diquat herbicide: Characterization, thermodynamics, isotherms, kinetics, and optimizing through Box-Behnken Design
This research synthesized carbon quantum dots (CQDs) encapsulated in a chitosan (CS) and carboxymethyl cellulose (CMC) matrix. The crosslinking with epichlorohydrin formed (CQDs-CS/CMC) hydrogel beads for effective removal of diquat (DQ) herbicides. Various techniques like XRD, FT-IR, FESEM, EDX, XPS, and nitrogen adsorption/desorption isotherm analysis were used to evaluate the textural properties. The textural properties of the CQDs-CS/CMC were investigated through nitrogen adsorption/desorption isotherms. The surface area was found to be 95.72 m/g, pore size 6.57 nm, and pore volume 0.313 cc/g. Post-DQ adsorption, these values decreased to 68.44 m/g, 4.2 nm, and 0.162 cc/g, indicating DQ blocked mesopores and adsorption sites. The study also examined the effects of dosage, pH, temperature, and initial DQ concentration on adsorption, employing equilibrium and kinetic studies. The system conformed to pseudo-second-order kinetics and Langmuir isotherm models. Chemisorption was the main adsorption process, with an energy of 32.3 kJ/mol. Increased metal uptake at higher temperatures shows the process is spontaneous and endothermic. The Box-Behnken Design software identified optimal adsorption parameters: a pH of 8 and a dosage of 0.02 g of CQDs-CS/CMC per 25 mL of DQ solution, achieving 449.6 mg/g adsorption capability. Extensive testing using Design-Expert software substantially improved the adsorption procedure. The assessment of adsorbent stability involved six cycles of adsorption/desorption. Results showed consistent reusability with no significant reduction in removal efficacy. It maintained its initial chemical configuration before and after repurposing, exhibited consistent performance, and reliable XRD results.
Carrageenan-xanthan gum composite gel achieves the elimination of bitterness and easy swallowability of Coptis chinensis based on electrostatic induction and interpenetrating network interaction
Natural polysaccharides possess the potential function of masking bitterness due to their three-dimensional network structures. However, they also have relatively high mechanical strength, which is not conducive to swallowing. Taking Coptis chinensis as an example, this study developed a composite gel composed of 0.17 % iota-carrageenan, 0.13 % lambda-carrageenan and 0.17 % xanthan gum. This composite gel can eliminate the bitterness and achieve good swallowability. Compared with the Coptis chinensis decoction, the bitterness of this gel is reduced by 60 %. Its hardness and crispness are only 1 % and 0.7 % of those of iota-carrageenan used alone. In addition, 60 % of the berberine in the composite gel can be released in artificial gastric juice within 10 min, and it has no significant impact on the hypoglycemic effects of Coptis chinensis. Further mechanism studies revealed that the sulfate group of iota-carrageenan disperses the electron cloud density of the bitter group of alkaloids through electrostatic induction, thus realizing the masking of bitterness. Meanwhile, the formation of an interpenetrating network structure between xanthan gum and carrageenan improves the swallowability. This study has developed a Coptis chinensis composite gel with excellent taste and easy swallowability, providing evidence for expanding the new applications of polysaccharides in masking taste.
Flexible composite films constructed of MXene/cellulose nanofibers/natural fiber-based activated carbon fibers for high-performance flexible supercapacitors
Traditional activated carbon fibers (CF) based supercapacitors suffer from low mechanical strength, inherent brittleness that induces stress concentrations, and bulky architectures from binder/conductive additive requirements. To overcome these limitations, cellulose nanofibers (CNF) are synergistically integrated with Ti₃C₂Tₓ MXene and CF, forming a mechanically reinforced composite film via hydrogen bonding and van der Waals interactions. The CNF/CF network expands the interlayer spacing of MXene, which enhances the ion-accessible surface area and enables rapid ion transport. The resulting Ti₃C₂Tₓ/CNF/CF composite film demonstrates exceptional electrochemical performance, achieving a specific capacitance of 420.99 F g at 0.5 A g, with 84.56 % retention at 10 A g. As a self-supporting flexible electrode (0.49 mm thickness), it delivers an areal capacitance of 214 mF cm at 0.3 mA cm and an energy density of 14.5 μWh cm at 30.2 μW cm. The hierarchical CNF/CF network simultaneously suppresses MXene restacking through spatial confinement while optimizing mechanical flexibility and stress distribution via interfacial bonding. This assembly strategy enables scalable fabrication of ultrathin MXene-based supercapacitors suitable for flexible electronics and grid-scale storage systems.
Recent developments in non-starch Ipomoea batatas (L.) Lam. polysaccharides: extractions and purifications, structural characteristics, pharmacological activities, structure-activity relationships, and applications A review
Ipomoea batatas (L.) Lam. (I. batatas) is highly regarded by consumers and researchers in medicine and food due to their high yield and rich nutritional value. Due to the difficulty in applying starch polysaccharides from I. batatas in drug development, non-starch polysaccharides with rich pharmacological activity have become a research hotspot in recent years. Non-starch I. batatas polysaccharide has been proven to contain a variety of pharmacological activities, including immune regulation, improvement of intestinal microbiota, gastric protection, liver protection, anti-tumor, anti-inflammatory, anti-oxidant, anti-glycosylation, and anti-diabetes. At the same time, in addition to traditional extraction methods, researchers have also utilized various new extraction methods such as isoelectric point precipitation, hot reflux extraction, and ultra-high pressure extraction to obtain non-starch I. batatas polysaccharides with various conformational features, including cyclic and chain structures. Its rich pharmacological activities and diverse chemical structures provide clear guidance for elucidating of its structure-activity relationships and developing products in fields such as medicine and food. Based on this, this article reviews the research progress on the extraction and purification methods, structural characteristics, pharmacological activities, structure-activity relationships, and applications of non-starch I. batatas polysaccharides in recent years, providing theoretical guidance for future research on non-starch I. batatas polysaccharides.
Evaluating the role of targeted silymarin loaded hyaluronic acid/protein nanoparticles in activating hepatic progenitor stem cells for liver regeneration after CCl-induced liver damage
Silymarin is a natural flavonoid component isolated from the Silybum Marianum (Milk Thistle) plant with multiple pharmacological activities. We investigated its anti-fibrotic effect on the liver and demonstrated its role in activating hepatic progenitor stem cells during liver regeneration.
Temperature-responsive hydrogel prepared from N-vinyl-ε-caprolactam Pickering emulsions stabilized by cationic cellulose nanocrystals for preservative delivery in food packaging
Hydrogels show potential for application in the anti-corrosion of food preservation packaging. However, hydrogels capable of modulating the release rate kinetics of preservatives under elevated temperature conditions for food preservation packaging remain underexplored. Herein, cationic cellulose nanocrystals (AH-CNCs) were employed as emulsifiers to stabilize N-vinyl-ε-caprolactam (NVCL) and the temperature-responsive hydrogel was fabricated via free radical polymerization. This novel hydrogel enables control the release rate of preservatives by adjusting the addition amount of AH-CNCs under conditions exceeding the lower critical solution temperature (LCST). Below the LCST, increasing AH-CNC contents systematically enhance the swelling rate, concurrently reducing pore size and augmenting the structural stability of the hydrogel matrix. Upon surpassing the LCST, the release rate of preservative salicylaldehyde (SA) can be controlled by tuning the AH-CNCs contents and leveraging electrostatic adsorption between AH-CNCs with positive properties and negatively charged SA. Notably, fruit visualization assays validated that the temperature-responsive hydrogel matrix effectively extends the shelf life of fruits via dual-mode preservative delivery. Consequently, this temperature-responsive hydrogel demonstrates significant potential for practical implementation in smart food preservation packaging applications.
Dietary supplementation of yeast polysaccharides enhance lamb growth performance by improving immune and intestinal barrier function and the abundance of cecal microbiota
Weaning stress can affect the growth performance and intestinal health of lambs. Yeast polysaccharides are green and safe feed additives that have been shown to improve growth performance and intestinal health in other animals. The aim of this study was to explore the effects of dietary yeast polysaccharides on the growth performance and intestinal health of weaned lambs. Twenty-four healthy lambs were randomly divided into four groups and fed different doses of yeast polysaccharides (Y) with a basal diet: 0 g/day (control, C), 0.5 g/day (low dose, LY), 1 g/day (medium dose, MY), and 2 g/day (high dose, HY). Results showed that the MY group had a significantly higher average daily gain and a lower feed-to-gain ratio than the control group. Yeast polysaccharide supplementation significantly increased the immunoglobin G (IgG), immunoglobin A (IgA), and β-defensin contents in serum, as well as the secretory immunoglobulin A (SIgA) content in the intestinal mucosa. It also enhanced intestinal villus development, increased the villus height-to-crypt depth ratio, and upregulated the mRNA and protein expression of Claudin1, Occludin, and ZO1. Cecal microbiota analysis revealed an increased relative abundance of Firmicutes, Ruminococcus, Clostridium, Butyrivibrio and Adlercreutzia, along with elevated volatile fatty acid levels. Taken together, these findings suggest that yeast polysaccharides improve growth performance, immune function and intestinal healthy in weaned lambs. Under the conditions of this experiment, 0.5-1 g/d is the optimal dose for production.
Xylooligosaccharides, monosaccharides, and pH-sensitive carbon dots production from Toona sinensis branches using organic acid hydrolysis and hydrothermal treatment
The present study focused on exploring the effectiveness of delignification of the lignocellulosic biomass and pH-controlled organic acid hydrolysis in the cascade utilization of Toona sinensis branches (TB) for the production of xylooligosaccharides (XOS), monosaccharides and carbon dots (CDs). The hydrolysis of delignified TB with propionic acid (PA) resulted in a high XOS yield of 48.1 % at pH 3.0, 170 °C for 60 min. The PA hydrolyzates upon hydrolysis with xylanase yielded 61.2 % XOS. The solid residue from XOS production was subjected to cellulase hydrolysis, resulting in a glucose yield of 87.8 %. Furthermore, CDs were synthesized through a green hydrothermal method using the solid residue from cellulase hydrolysis as a precursor. These CDs exhibited excitation-independent and pH-dependent fluorescence properties. This study demonstrated the integrated utilization of TB for efficient production of XOS, monosaccharides, and pH-sensitive CDs.
Non-coding RNAs modulate pyroptosis in diabetic cardiomyopathy: A comprehensive review
Diabetic cardiomyopathy (DCM) is a leading cause of heart failure (HF) among individuals with diabetes, presenting a significant medical challenge due to its complex pathophysiology and the lack of targeted therapies. Pyroptosis, a pro-inflammatory form of programmed cell death (PCD), is the predominant mode of cell death in the primary resident cells involved in DCM. It has been reported to be critical in DCM's onset, progression, and pathogenesis. Non-coding RNAs (ncRNAs), diverse transcripts lacking protein-coding potential, are essential for cellular physiology and the progression of various diseases. Increasing evidence indicates that ncRNAs are pivotal in the pathogenesis of DCM by regulating pyroptosis. This observation suggests that targeting the regulation of pyroptosis by ncRNAs may offer a novel therapeutic approach for DCM. However, a comprehensive review of this topic is currently lacking. Our objective is to elucidate the regulatory role of ncRNAs in pyroptosis associated with DCM and to elucidate the relationships among these factors. Additionally, we explored how ncRNAs influence pyroptosis and contribute to the pathophysiology of DCM. By doing so, we aim to identify new research targets for the clinical diagnosis and treatment of DCM.
Novel LacdiNAc-specific lectin from Dioclea reflexa seeds exhibits inflammatory and hyper nociceptive properties
Diocleinae lectins are well known for their prevalent affinity for glycomannosides. However, a rare subset displays specificity towards galactosides. This study describes the characterization of a novel N,N'-diacetyl-lactosamine (LacdiNAc)-specific lectin, DrfL II, isolated from Dioclea reflexa seeds. Purified via lactose-affinity chromatography, DrfL II exists as a single 29 kDa chain and potently agglutinates rabbit erythrocytes, an activity inhibited by α-lactose. Interestingly, DrfL II exhibits preferential binding to LacdiNAc (GalNAcβ1-4GlcNAc) over N-acetyl-lactosamine (LacNAc, Galβ1-4GlcNAc), functioning optimally between pH 6-8 and retaining stability up to 60 °C. Partial protein sequencing reveals homology with other legume lectins. Beyond its distinct carbohydrate specificity, DrfL II induces significant inflammatory and hypernociceptive effects in mice, as indicated by paw edema and von Frey assays, while remaining non-toxic to Artemia sp. This finding broadens our understanding of the galactoside-specific lectins within the Diocleinae subtribe, suggesting potential roles in physiological processes yet to be fully elucidated and potential biological application within the inflammation field.
Polysaccharides from Brasenia schreberi alleviated the toxicity induced by acrylamide on cells and Caenorhabditis elegans
Acrylamide (AC), a widely used chemical compound in industrial production and the food industry, has been shown to exhibit reproductive toxicity, neurotoxicity, and genotoxicity. While no specific treatment has been developed to alleviate its harmful effects, identifying an effective therapeutic agent is necessary. In our previous work, polysaccharides from Brasenia schreberi (PSBS) demonstrated strong antioxidant activity, suggesting that PSBS may relieve AC-induced toxicity. In this study, we employed cellular models and Caenorhabditis elegans to evaluate the protective effects of PSBS against AC toxicity. The findings revealed that PSBS significantly reduced reactive oxygen species (ROS) levels and cell apoptosis through the activation of the MAPK signaling pathway. Furthermore, PSBS markedly improved the survival of C. elegans exposed to AC. Quantitative PCR (qPCR) analysis indicated that PSBS downregulated the insulin and PI3K/AKT pathways while upregulating the AMPK and MAPK pathways. Additionally, PSBS enhanced the expression of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST) by activating skn-1 and daf-16. These results suggest that PSBS is a promising natural drug for mitigating acrylamide-induced toxicity.
Structural and functional insights into StnY, a ribbon-helix-helix (RHH) family transcription factor regulating antibiotic resistance in Streptomyces flocculus CGMCC4.1223
Deciphering how bacteria respond to antibiotic stress is essential for developing strategies to combat the increasing global antibiotic resistance gene (ARG) crisis. Here, we identified an unprecedented antibiotic resistance operon characterized by a single-domain transcription factor (TF) StnY, which responds to streptonigrin (STN) antibiotic and controls the activation of resistance genes stnK4 and stnG4 in Streptomyces flocculus CGMCC4.1223. To the best of our knowledge, StnY represents the first RHH family TF regulating ARG and it helically wraps around the promoter of the resistance operon in an octameric form. Unlike conventional TFs with distinct effector-binding domains, StnY utilizes its DNA-binding domain to bind the STN effector, facilitating the dissociation of StnY-DNA complex. Consequently, the vicinal oxygen chelates (VOC) family protein StnK4 sequesters STN to prevent cellular damage, while the major facilitator superfamily (MFS) protein StnG4 effluxes STN out of the cell. Furthermore, genome analysis reveals the widespread distribution of RHH-VOC-MFS gene cassettes in actinomycetes, the primary source of antibiotics. This study elucidates function mode of a resistance operon governed by a TF lacking an effector-binding domain, offering new insights into ARG regulation and the potential of ARG-guided antibiotics discovery, highlighting TFs as promising targets for addressing ARG.
Nose-to-brain delivery of sorafenib-loaded lipid-based poloxamer-carrageenan nanoemulgel: Formulation and therapeutic investigation in glioblastoma-induced orthotopic rat model
Glioblastoma multiforme (GBM) has a poor clinical prognosis, where conventional treatment offers therapeutic limitations. Therefore, the current study introduces a first-of-its-kind sorafenib (SOR) nanoemulsion (SNE) loaded with poloxamer-carrageenan nanoemulgel (SPCNEG), a novel dual-functional and natural polymer-based payload system for effective intranasal chemotherapeutic administration. The nanoformulation was developed using carrageenan (a natural gelling agent), poloxamer (a mucoadhesive agent), glyceryl caprate as lipid, and Cremophor EL:PEG 400 blend as surfactant system. The improved biopharmaceutical attributes of developed formulations were confirmed from the release experiments, revealing augmentation in drug release from SNE (84.56 ± 3.78 %) and SPCNEG (68.62 ± 4.11 %) up to 3.41- and 8.12-fold compared to plain SOR. The ex vivo experiments showed a similar enhancement in drug permeation. Moreover, the SNE also showed superior performance on glioma cell lines, as indicated by lower IC (2.23 μg/mL) than plain SOR (16.61 μg/mL). The pharmacokinetic study revealed a 2.52- and 3.24-fold increase in SNE and SPCNEG brain concentration, respectively, compared to Soranib®. Additionally, a high correlation was also observed between in vitro drug release and in vivo absorption at prespecified time intervals for developed formulations. In conclusion, the current research promising and non-invasive alternative to existing interventions for enhanced brain targeting potential.