International Journal of Biological Macromolecules最新文献

In the innate immune system, the cyclic GMP-AMP synthase (cGAS)-interferon gene stimulator (STING) pathway activates the type I interferon (IFN) response and the NF-κB pathway by recognizing double-stranded DNAs, the imbalance of which plays a pivotal role in human diseases, including cancer, autoimmune and inflammatory diseases. Non-coding RNAs (ncRNAs) are a diverse group of transcripts that do not code for proteins but regulate various targets and signaling pathways in physiological and pathological processes. Recently, there has been increasing interest in investigating the interplay between the cGAS-STING pathway and ncRNAs. In this review, we provide a concise overview of the cGAS-STING pathway and ncRNAs. Then, we specifically delve into the regulation of the cGAS-STING pathway by long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), the three major classes of ncRNAs, and the influence of the cGAS-STING pathway on the expression of ncRNAs. Furthermore, we introduce the therapeutic applications targeting the cGAS-STING pathway and ncRNA therapy, and propose the utilization of drug delivery systems to deliver ncRNAs that influence the cGAS-STING pathway. Overall, this review highlights the emerging understanding of the intricate relationship between the cGAS-STING pathway and ncRNAs, shedding light on their potential as therapeutic targets in various diseases.

Although β-xylosidases have broad applications in fields such as food and medicine, there is limited research on cold-active β-xylosidases. This study cloned a novel cold-active β-xylosidase XYL13 from Parabacteroides distasonis. The purified XYL13 exhibited the highest activity at 40 °C, with 42 % and 25 % of its maximum activity at 4 °C and 0 °C, respectively. Meanwhile, XYL13 predominantly produces X1 while degrading X2-X6. Additionally, XYL13 showed a significant synergistic effect (18.5-fold) with endo-xylanase for degrading beechwood xylan at low temperatures. Moreover, the site-directed mutagenesis assay indicated that Ile269 and Glu621 are essential catalytic sites of XYL13. Finally, molecular docking showed that XYL13 has an excellent binding effect with X2-X6, verifying that XYL13 can effectively cut X2-X6 to produce xylose. These results highlight the potential of cold-adapted XYL13 from P. distasonis for application in the food industry.

In recent years, invasive fungal infections have posed a significant threat to human health, particularly due to the limited availability of effective antifungal medications. This study responds to the urgent need for powerful and selective antifungal agents by designing and synthesizing a series of lipopeptides with lipoylation at the N-terminus of the antimicrobial peptide I6. Compared to the parent peptide I6, lipopeptides exhibited selective antifungal efficacy in the presence of Na⁺. Among the variants tested, C₈-I6 emerged as the most effective, with an average effective concentration of 5.3 μM against 12 different fungal species. C₈-I6 combated fungal infections by disrupting both cytoplasmic and mitochondrial membranes, impairing the proton motive force, generating reactive oxygen species, and triggering apoptosis in fungal cells. Importantly, C₈-I6 exhibited minimal hemolysis and cytotoxicity while effectively inhibiting fungal biofilm formation. In vivo experiments further validated the safety and therapeutic potential of C₈-I6 in treating fungal skin infections. These findings underscore the significance of lipoylation in enhancing the efficacy of antimicrobial peptides, positioning C₈-I6 as a promising candidate in fighting against drug-resistant fungal infections.

A novel bionanocomposite of grafted chitosan-phthalic anhydride/Co₂O₃ nanoparticles (CHT-PHT/Co₂O₃) was synthesized and used for the elimination of brilliant green (BG) dye from aquatic systems. The CHT-PHT/Co₂O₃ material underwent several instrumental characterizations including, XRD, BET, FTIR, FESEM-EDX, and pH_pzc examinations. The impact of the key uptake factors, namely A: CHT-PHT/Co₂O₃ dose, B: starting solution pH, and C: contact duration, on the effectiveness of BG removal, was mathematically optimized using the response surface methodology (RSM). The ideal conditions of the maximum BG elimination (96.05 %) according to the desirability function are as follows: A: CHT-PHT/Co₂O₃ dose (0.044 g); B: pH ~ 10; and C: contact duration (34.6 min). The analysis of adsorption kinetics and equilibrium demonstrates a strong fit to the pseudo-first-order model, and the Freundlich isotherm model confirms the occurrence of multilayer adsorption. The highest adsorption capacity of CHT-PHT/Co₂O₃ for BG was determined to be 425.09 mg/g at a temperature of 25 °C. This study highlights the development of a practical bionanocomposite adsorbent that has a favorable ability to absorb organic dyes from wastewater. The current work offers a sustainable and efficient method of reducing the environmental impact of industrial dye pollutants by utilizing the distinctive properties of CHT-PHT/Co₂O₃ bionanocomposite.

D-allulose, a low-calorie functional sweetener, is produced by the enzymatic conversion of d-fructose via D-allulose 3-epimerase (DAE) and holds significant market potential, particularly for individuals with obesity and diabetes. However, the limited reusability and stability of DAE have restricted its industrial application. In this study, we developed functional superparamagnetic supports by integrating diatomite, a biomineralized silica-based material, with cobalt ferrite nanoparticles through a green chemical co-precipitation method. The covalent attachment of DAE enzymes to these magnetic supports resulted in enzyme-metal hybrid catalysts (DAE@mDE-NH₂) that exhibited enhanced stability and facilitated recovery and reuse via magnetic separation. These catalysts showed superior stability in acidic conditions and high temperatures, with a 24-fold increase in half-life at 60 °C compared to free DAE. They also exhibited remarkable durability, retaining 95.36 % of their activity after six months of storage at 4 °C and 70.08 % activity after 12 consecutive cycles. Utilizing this robust and recyclable biocatalyst, 147.7 g/L of D-allulose was obtained from 500 g/L of d-fructose. This study presents a sustainable strategy for advancing the production of high-value functional sweeteners like D-allulose while providing new insights into enzyme immobilization for biocatalytic processes.

Enzymatic PET recycling has emerged as a promising green solution in addition to mechanical recycling, but low soluble expression levels of the inherently hydrophobic PET hydrolases hinder large-scale applications. Here, we propose a novel strategy for enhanced production of FastPETase in Escherichia coli using co-expression of molecular chaperones from Ideonella sakaiensis. Co-expression of cognate DnaK and DnaJ chaperones significantly increased soluble FastPETase expression (up to 2.5-fold), surpassing commercial chaperone plasmids. Furthermore, a combinatorial approach employing co-expression of DnaK/DnaJ chaperones and fusion of FastPETase with the VNp6-tag significantly boosted FastPETase secretion, yielding over 2 g/L of target protein in a 5-l bioreactor. Notably, the crude FastPETase in fermentation broth displayed comparable PET hydrolysis effects to the purified enzyme. This work not only provides new insights into the process of chaperones in protein folding but also suggests a novel and efficient strategy for producing recombinant proteins.

The CRISPR/Cas13 system has garnered attention as a potential tool for RNA editing. However, the degree of collateral activity among various Cas13 orthologs and their cytotoxic effects in mammalian cells remain contentious, potentially impacting their applications. In this study, we observed differential collateral activities for LwaCas13a and RfxCas13d in 293 T and U87 cells by applying both sensitive dual-fluorescence (mRuby/GFP) reporter and quantifiable dual-luciferase (Fluc/Rluc) reporter, with LwaCas13a displaying notable activity contrary to previous reports. However, significant collateral RNA cleavage exerted only a modest impact on cell viability. Furthermore, collateral activity of LwaCas13a mildly impeded, but did not arrest, porcine embryo development. Our findings reveal that distinct collateral RNA cleavage by Cas13 slightly suppresses mammalian cell proliferation and embryo development. This could account for the lack of reported collateral effects in numerous prior studies and offers new insights into the implications of the collateral activity of Cas13 for clinical application.

Traditional tumor treatment faces great challenge owning to inherent drawbacks. Activatable prodrugs with multi-modality therapeutic capacity are highly desired. In this consideration, a responsiveness-released multi-in-one nanoplatform, PLGA-PEG@HC, toward cervical cancer therapy was innovatively developed. Among the nanoplatform, HC was constructed by incorporating chlorambucil, a classic chemotherapy drug into a near-infrared photo- and sono-sensitizer, HCH via ester linker, which can be specifically hydrolyzed by carboxylesterase (CES). HC is scarcely fluorescent and toxic due to the caging of HCH and chlorambucil, thus achieving low background signal and minimal side effects. However, once selectively hydrolyzed by tumor enriched CES, ester bond will be broken. Consequently, HCH and chlorambucil are released so as to achieve near-infrared fluorescence imaging and synergistic photodynamic/sonodynamic/chemo therapy. PLGA-PEG packaging ensures the biocompatibility of HC. The as-obtained nanoplatform, with diameter of 97 nm, achieves tumor targeting capacity via EPR. In vitro and in vivo applications have demonstrated that PLGA-PEG@HC can accumulate in tumor tissues, exhibit CES-activatable near-infrared fluorescence imaging and efficient tumor suppression capacity. Compared with the reported combinational therapy materials which are complex in compositions, PLGA-PEG@HC is simple in formulation but demonstrates near-infrared fluorescence traced and considerable therapy efficacy toward tumors, which may accelerate the clinical translation.