Sustainable efficient utilization of magnetic porous biochar for adsorption of orange G and tetracycline: Inherent roles of adsorption and mechanisms.

Iron-doped biochar has been widely used as an adsorbent to remove contaminants due to the high adsorption performance, but it still suffers from complicated preparation methods, unstable iron loading, unsatisfactory specific surface area, and uneven distribution of active sites. Here, a novel magnetic porous biochar (FeCS800) with nanostructure on surface was synthesized by one-pot pyrolysis method of corn straw with K2FeO4, and used in orange G (OG) and tetracycline (TC) adsorption. FeCS800 exhibited outstanding adsorption capacities for OG and TC after K2FeO4 activation and the adsorption data were fitted satisfactorily to Langmuir isotherm and Pseudo-second-order kinetic model. The maximum adsorption capacities of FeCS800 for OG and TC were around 303.03 mg/g and 322.58 mg/g, respectively, at 25 °C and pH 7.0, which were 16.27 and 24.61 times higher than that before modification. Thermodynamic studies showed that the adsorption of OG/TC by FeCS800 were thermodynamically favorable and highly spontaneous. And the adsorption capacity of OG and TC by FeCS800 remained 77% and 81% after 5 cycles, respectively, indicating that FeCS800 had good stability. The outstanding adsorption properties and remarkable reusability of FeCS800 show its great potential to be an economic and environmental adsorbent in contaminants removal.

Oxidative stress resistance prompts pyrroloquinoline quinone biosynthesis in Hyphomicrobium denitrificans H4-45.

Pyrroloquinoline quinone (PQQ) is a natural antioxidant with diverse applications in food and pharmaceutical industries. A lot of effort has been devoted toward the discovery of PQQ high-producing microbial species and characterization of biosynthesis, but it is still challenging to achieve a high PQQ yield. In this study, a combined strategy of random mutagenesis and adaptive laboratory evolution (ALE) with fermentation optimization was applied to improve PQQ production in Hyphomicrobium denitrificans H4-45. A mutant strain AE-9 was obtained after nearly 400 generations of UV-LiCl mutagenesis, followed by an ALE process, which was conducted with a consecutive increase of oxidative stress generated by kanamycin, sodium sulfide, and potassium tellurite. In the flask culture condition, the PQQ production in mutant strain AE-9 had an 80.4% increase, and the cell density increased by 14.9% when compared with that of the initial strain H4-45. Moreover, batch and fed-batch fermentation processes were optimized to further improve PQQ production by pH control strategy, methanol and H2O2 feed flow, and segmented fermentation process. Finally, the highest PQQ production and productivity of the mutant strain AE-9 reached 307 mg/L and 4.26 mg/L/h in a 3.7-L bioreactor, respectively. Whole genome sequencing analysis showed that genetic mutations in the ftfL gene and thiC gene might contribute to improving PQQ production by enhancing methanol consumption and cell growth in the AE-9 strain. Our study provided a systematic strategy to obtain a PQQ high-producing mutant strain and achieve high production of PQQ in fermentation. These practical methods could be applicable to improve the production of other antioxidant compounds with uncleared regulation mechanisms. KEY POINTS: • Improvement of PQQ production by UV-LiCl mutagenesis combined with adaptive laboratory evolution (ALE) and fermentation optimization. • A consecutive increase of oxidative stress could be used as the antagonistic factor for ALE to enhance PQQ production. • Mutations in the ftfL gene and thiC gene indicated that PQQ production might be increased by enhancing methanol consumption and cell growth.

Harnessing tetrahedral framework nucleic acids for enhanced delivery of microRNA-149-3p: A new frontier in oral squamous cell carcinoma therapy.

Oral squamous cell carcinoma (OSCC), a type of malignant tumour that primarily occurs in the oral mucosa, has drawn considerable attention owing to its aggressive growth and potentially high metastatic rate. Surgical resection is the primary treatment method for OSCC and is typically combined with radiation therapy and chemotherapy. microRNA-149-3p (miR-149) is a negative regulator of the Pi3k/Akt pathway and can effectively inhibit the proliferation of tumour cells. However, the application of miR-149 is limited owing to its relatively low efficiency of cellular uptake and poor stability when used alone. To overcome these challenges, this study adopted a novel nucleic acid nanostructured material, tetrahedral framework nucleic acids (tFNAs). The use of tFNAs as carriers to assemble the T-miR-149 complex reduced the expression of Pi3k and Akt involved in tumorigenesis and alterations in proteins related to cell apoptosis. The results indicated that the bionic drug delivery system has an effective tumour suppressive effect on OSCC in mice, revealing its potential clinical value in the treatment of OSCC.

Chloroplast genome analysis and evolutionary insights in the versatile medicinal plant Calendula officinalis L.

Calendula officinalis L.is a versatile medicinal plant with numerous applications in various fields. However, its chloroplast genome structure, features, phylogeny, and patterns of evolution and mutation remain largely unexplored. This study examines the chloroplast genome, phylogeny, codon usage bias, and divergence time of C. officinalis, enhancing our understanding of its evolution and adaptation. The chloroplast genome of C. officinalis is a 150,465 bp circular molecule with a G + C content of 37.75% and comprises 131 genes. Phylogenetic analysis revealed a close relationship between C. officinalis, C. arvensis, and Osteospermum ecklonis. A key finding is the similarity in codon usage bias among these species, which, coupled with the divergence time analysis, supports their close phylogenetic proximity. This similarity in codon preference and divergence times underscores a parallel evolutionary adaptation journey for these species, highlighting the intricate interplay between genetic evolution and environmental adaptation in the Asteraceae family. Moreover unique evolutionary features in C. officinalis, possibly associated with certain genes were identified, laying a foundation for future research into the genetic diversity and medicinal value of C. officinalis.

Identification of oleic acid as an endogenous ligand of GPR3.

Although GPR3 plays pivotal roles in both the nervous system and metabolic processes, such as cold-induced thermogenesis, its endogenous ligand remains elusive. Here, by combining structural approach (including cryo-electron microscopy), mass spectrometry analysis, and functional studies, we identify oleic acid (OA) as an endogenous ligand of GPR3. Our study reveals a hydrophobic tunnel within GPR3 that connects the extracellular side of the receptor to the middle of plasma membrane, enabling fatty acids to readily engage the receptor. Functional studies demonstrate that OA triggers downstream Gs signaling, whereas lysophospholipids fail to activate the receptor. Moreover, our research reveals that cold stimulation induces the secretion of OA in mice, subsequently activating Gs/cAMP/PKA signaling in brown adipose tissue. Notably, brown adipose tissues from Gpr3 knockout mice do not respond to OA during cold stimulation, reinforcing the significance of GPR3 in this process. Finally, we propose a "born to be activated and cold to enhance" model for GPR3 activation. Our study provides a starting framework for the understanding of GPR3 signaling in cold-stimulated thermogenesis.

Structural basis of ligand recognition and design of antihistamines targeting histamine H4 receptor.

The histamine H4 receptor (H4R) plays key role in immune cell function and is a highly valued target for treating allergic and inflammatory diseases. However, structural information of H4R remains elusive. Here, we report four cryo-EM structures of H4R/Gi complexes, with either histamine or synthetic agonists clobenpropit, VUF6884 and clozapine bound. Combined with mutagenesis, ligand binding and functional assays, the structural data reveal a distinct ligand binding mode where D943.32 and a π-π network determine the orientation of the positively charged group of ligands, while E1825.46, located at the opposite end of the ligand binding pocket, plays a key role in regulating receptor activity. The structural insight into H4R ligand binding allows us to identify mutants at E1825.46 for which the agonist clobenpropit acts as an inverse agonist and to correctly predict inverse agonism of a closely related analog with nanomolar potency. Together with the findings regarding receptor activation and Gi engagement, we establish a framework for understanding H4R signaling and provide a rational basis for designing novel antihistamines targeting H4R.