Utilization of the Shensheng-Piwen changed medicinal powder extracts combines metal-organic frameworks as an antibacterial agent.

Introduction: Widespread opportunistic pathogens pose a serious threat to global health, particularly in susceptible hospital populations. The escalating crisis of antibiotic resistance highlights the urgent need for novel antibacterial agents and alternative treatment approaches. Traditional Chinese Medicine (TCM) and its compounds have deep roots in the treatment of infectious diseases. It has a variety of active ingredients and multi-target properties, opening up new avenues for the discovery and development of antimicrobial drugs. Methods: This study focuses on assessing the efficacy of the Shensheng-Piwen changed medicinal powder (SPC) extracts against opportunistic pathogen infections by broth microdilution and agar disc diffusion methods. Additionally, biofilm inhibition and eradication assays were performed to evaluate the antibiofilm effects of SPC extracts. Results: Metabolite profiles were analyzed by LC-MS. Furthermore, the potential synergistic effect between SPC and Metal-Organic Framework (MOF) was investigated by bacterial growth curve analysis. The results indicated that the SPC extracts exhibited antibacterial activity against S. aureus, with a minimum inhibitory concentration (MIC) of 7.8 mg/mL (crude drug concentration). Notably, at 1/2 MIC, the SPC extracts significantly inhibited biofilm formation, with over 80% inhibition, which was critical in tackling chronic and hospital-acquired infections. Metabolomic analysis of S. aureus revealed that SPC extracts induced a notable reduction in the levels of various metabolites, including L-proline, L-asparagine. This suggested that the SPC extracts could interfere with the metabolism of S. aureus. Meanwhile, the growth curve experiment proved that SPC extracts and MOFs had a synergistic antibacterial effect. Discussion: In conclusion, the present study highlights the potential of SPC extracts as a novel antibacterial agent against S. aureus infections, with promising biofilm inhibition properties. The observed synergistic effect between SPC extracts and MOFs further supports the exploration of this combination as an alternative treatment approach.

Integration of Enzyme and Covalent Organic Frameworks: From Rational Design to Applications.

Manufacturing is undergoing profound transformations, among which green biomanufacturing with low energy consumption, high efficiency, and sustainability is becoming one of the major trends. However, enzymes, as the "core chip" of biomanufacturing, are often handicapped in their application by their high cost, low operational stability, and nonreusability. Immobilization of enzymes is a technology that binds or restricts enzymes in a certain area with solid materials, allows them to still carry out their unique catalytic reaction, and allows them to be recycled and reused. Compared with free enzymes, immobilized enzymes boast numerous advantages such as enhanced storage stability, ease of separation, reusability, and controlled operation. Currently, commonly used supports for enzyme immobilization (e.g., mesoporous silica, sol-gel hydrogels, and porous polymer) can effectively improve enzyme stability and reduce product inhibition. However, they still face drawbacks such as potential leaching or conformational change during immobilization and poor machining performance. Especially, most enzyme carrier solid materials possess disordered structures, inevitably introducing deficiencies such as low loading capacity, hindered mass transfer, and unclear structure-property relationships. Additionally, it remains a notable challenge to meticulously design immobilization systems tailored to the specific characteristics of enzyme/reaction. Therefore, there is a significant demand for reliable solid materials to overcome the above challenges. Crystalline porous materials, particularly covalent organic frameworks (COFs), have garnered significant interest as a promising platform for immobilizing enzymes due to their unique properties, such as their crystalline nature, high porosity, accessible active sites, versatile synthetic conditions, and tunable structure. COFs create a stabilizing microenvironment that protects enzymes from denaturation and significantly enhances reusability. Nevertheless, some challenges still remain, including difficulties in loading large enzymes, reduced enzyme activities, and the limited functionality of carriers. Therefore, it is essential to develop innovative carriers and novel strategies to broaden the methods of immobilizing enzymes, enabling their application across a more diverse array of fields.The integration of enzymes with advanced porous materials for intensified performance and diverse applications is still in its infancy, and our group has done a series of pioneering works. This Account presents a comprehensive overview of recent research progress made by our group, including (i) the development of innovative enzyme immobilization strategies utilizing COFs to make the assembly and integration of enzymes and carriers more effective; (ii) rational design and construction of functional carriers for enzyme immobilization using COFs; and (iii) extensions of immobilized enzyme applications based on COFs from industrial catalysis to biomedicine and chiral separation. The integration of enzymes with functional crystalline materials offers mutual benefits and results in a performance that surpasses what either component can achieve individually. Additionally, immobilized enzymes exhibit enhanced functionality and intriguing characteristics that differ from those of free enzymes. Consistent with our research philosophy centered on integration, platform development, and engineering application, this Account addresses the critical challenges associated with enzyme immobilization using COFs while extending the applications of COFs and proposing future design principles for biomanufacturing and enzyme industry.

Inhibition of CK2α accelerates skin wound healing by promoting endothelial cell proliferation through the Hedgehog signaling pathway.

Diabetes is a chronic disease characterized by perturbed glucose and lipid metabolism, resulting in high blood glucose levels. Many complications induced by endothelial dysfunction can cause disability and even death of diabetic patients. Here, we found that the protein level of casein kinase 2α (CK2α) was increased in the endothelium of mice with type I diabetes (T1D) induced by streptozotocin (STZ) injection. Although a potential correlation between the protein level of CK2α and endothelial dysfunction in diabetes was established, the contribution of CK2α to the progression of endothelial dysfunction in diabetes remained largely unknown. By using CX4945 (a selective CK2α antagonist) and Si-csnk2a1 (small interfering RNA targeting CK2α), we found that inhibition of CK2α accelerated skin wound healing in T1D mice by promoting proliferation of endothelial cells. Administration of CX4945 or Si-csnk2a1 rescued the impaired Hedgehog signaling pathway in high glucose-treated human umbilical vein endothelial cells (HUVECs). Exploration of the underlying molecular mechanism revealed that the protective effect of CK2α inhibition on angiogenesis, which contributes to skin wound healing in diabetic mice, was blocked by administration of GANT61 (an inhibitor targeting the Hedgehog signaling pathway). Our findings establish CK2α as a regulator of endothelial dysfunction in diabetes and demonstrate that inhibition of CK2α accelerates skin wound healing in T1D mice by promoting endothelial cell proliferation via the Hedgehog signaling pathway.

A Convenient All-Cell Optical Imaging Method Compatible with Serial SEM for Brain Mapping.

The mammalian brain, with its complexity and intricacy, poses significant challenges for researchers aiming to understand its inner workings. Optical multilayer interference tomography (OMLIT) is a novel, promising imaging technique that enables the mapping and reconstruction of mesoscale all-cell brain atlases and is seamlessly compatible with tape-based serial scanning electron microscopy (SEM) for microscale mapping in the same tissue. However, currently, OMLIT suffers from imperfect coatings, leading to background noise and image contamination. In this study, we introduced a new imaging configuration using carbon spraying to eliminate the tape-coating step, resulting in reduced noise and enhanced imaging quality. We demonstrated the improved imaging quality and validated its applicability through a correlative light-electron imaging workflow. Our method successfully reconstructed all cells and vasculature within a large OMLIT dataset, enabling basic morphological classification and analysis. We also show that this approach can perform effectively on thicker sections, extending its applicability to sub-micron scale slices, saving sample preparation and imaging time, and increasing imaging throughput. Consequently, this method emerges as a promising candidate for high-speed, high-throughput brain tissue reconstruction and analysis. Our findings open new avenues for exploring the structure and function of the brain using OMLIT images.

Efficient selective removal of uremic toxin precursor by olefin-linked covalent organic frameworks for nephropathy treatment.

Indoxyl sulfate is a protein-bound uremic toxin synthesized from indole that cannot be efficiently removed by the hemodialysis method and thus becomes a key risk factor for the progression of chronic kidney disease. Here, we develop a non-dialysis treatment strategy to fabricate an ultramicroporous olefin-linked covalent organic framework with high crystallinity in a green and scalable fashion for selectively removing the indoxyl sulfate precursor (i.e., indole) from the intestine. Various analyses show that the resulting material exhibits excellent gastrointestinal fluid stability, high adsorption efficiency, and good biocompatibility. Notably, it realizes the efficient and selective removal of indole from the intestine and significantly attenuates serum indoxyl sulfate level in vivo. More importantly, the selective removal efficacy of indole is substantially higher than that of the commercial adsorbent AST-120 used in the clinic. The present study opens up a new avenue to eliminate indoxyl sulfate by a non-dialysis strategy and further expands the in vivo applications of covalent organic frameworks.

The complete mitochondrial genome of Laudakia wui (Iguania; Agamidae).

In this study, the complete mitochondrial genome of Laudakia wui, has been firstly determined by shotgun sequencing. The overall length of mitogenome is 16,455 bp and contains 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 2 control regions. Majority of the genes (13 protein-coding genes, 2 rRNA and 14 tRNA) were distributed on the H-strand, in addition to the two ND6 genes and eight tRNA genes, which were encoded on the L-strand. The phylogenetic tree was built by L. wui and 13 other related species. The DNA data presented here will be useful to study the evolutionary relationships and genetic diversity of L. wui.