Search

Dendritic cells (DCs) are crucial in initiating and shaping both innate and adaptive immune responses. Clinical studies and experimental models have highlighted their significant involvement in various autoimmune diseases, positioning them as promising therapeutic targets. Nicotinamide (NAM), a form of vitamin B3, with its anti-inflammatory properties, has been suggested, while the involvement of NAM in DCs regulation remains elusive. Here, through analyzing publicly available databases, we observe substantial alterations in NAM levels and NAM metabolic pathways during DCs activation. Furthermore, we discover that NAM, but not Nicotinamide Mononucleotide (NMN), significantly inhibits DCs over-activation in vitro and in vivo. The suppression of DCs hyperactivation effectively alleviates symptoms of psoriasis. Mechanistically, NAM impairs DCs activation through a Poly (ADP-ribose) polymerases (PARPs)-NF-κB dependent manner. Notably, phosphoribosyl transferase (NAMPT) and PARPs are significantly upregulated in lipopolysaccharide (LPS)-stimulated DCs and psoriasis patients; elevated NAMPT and PARPs expression in psoriasis patients correlates with higher psoriasis area and severity index (PASI) scores. In summary, our findings underscore the pivotal role of NAM in modulating DCs functions and autoimmune disorders. Targeting the NAMPT-PARP axis emerges as a promising therapeutic approach for DC-related diseases. [ABSTRACT FROM AUTHOR]

Roots are fundamental for plants to adapt to variable environmental conditions. The development of a robust root system is orchestrated by numerous genetic determinants and, among them, the MADS‐box gene ANR1 has garnered substantial attention. Prior research has demonstrated that, in chrysanthemum, CmANR1 positively regulates root system development. Nevertheless, the upstream regulators involved in the CmANR1‐mediated regulation of root development remain unidentified. In this study, we successfully identified bric‐a‐brac, tramtrack and broad (BTB) and transcription adapter putative zinc finger (TAZ) domain protein CmBT1 as the interacting partner of CmANR1 through a yeast‐two‐hybrid (Y2H) screening library. Furthermore, we validated this physical interaction through bimolecular fluorescence complementation and pull‐down assays. Functional assays revealed that CmBT1 exerted a negative influence on root development in chrysanthemum. In both in vitro and in vivo assays, it was evident that CmBT1 mediated the ubiquitination of CmANR1 through the ubiquitin/26S proteasome pathway. This ubiquitination subsequently led to the degradation of the CmANR1 protein and a reduction in the transcription of CmANR1‐targeted gene CmPIN2, which was crucial for root development in chrysanthemum. Genetic analysis suggested that CmBT1 modulated root development, at least in part, by regulating the level of CmANR1 protein. Collectively, these findings shed new light on the regulatory role of CmBT1 in degrading CmANR1 through ubiquitination, thereby repressing the expression of its targeted gene and inhibiting root development in chrysanthemum. [ABSTRACT FROM AUTHOR]

To explore the effects of “hospital–community integrated transitional care” model on quality of life in patients with chronic obstructive pulmonary disease (COPD).

The process of jatropha oil transesterification was studied for biodiesel production. Rhizomucor miehei lipase (RML) immobilized on 3-aminopropyltriethoxysilane functionalized magnetic Fe3O4 was employed as a biocatalyst. The immobilized lipase was confirmed by scanning electron microcopy (SEM), Fourier transform infrared spectra (FT-IR), thermogravimetric analysis (TGA), vibrating sample magnetometer (VSM), and confocal laser scanning microscopy (CLSM) techniques. The efficient biodiesel synthesis in ionic liquids using immobilized RML was demonstrated. Fifteen kinds of ionic liquids based on different alkyl chain lengths of the methyl imidazolium cation ([C2MIM], [C4MIM], [C8MIM], [C12MIM], and [C16MIM]) combined with [NTf2], [N(CN)2], [PF6] or [BF4] anions were assayed as reaction media for RML producing biodiesel. The highest synthetic activity of immobilized RML appeared in [BMIM][PF6], which is more than five times higher than the free enzyme. The enzyme catalytic activity remained 60% even after the magnetic nano-biocatalyst and ionic liquid had been reused 5 times in a 48-h reaction cycle. In addition, the immobilized enzyme exhibited excellent storage stability with almost no decrease in catalytic activity after storing at − 20 °C for 98 days. [ABSTRACT FROM AUTHOR]

Peroxidase (POD)-like nanozymes have been found to act as nanoreactors for the generation of reactive oxygen species (ROS) to resolve drug resistance in the tumor microenvironment (TME). Amplifying cellular oxidative stress is considered to be a drug-free strategy to efficiently induce apoptosis in tumor cells. However, the limited content of intracellular hydrogen peroxide (H2O2) extremely restricts the performance of POD-like nanozymes to amplify cellular oxidative stress. Moreover, additional operational processes combined with exogenous reagents to achieve oxidative stress lead to a dilemma of extra cytotoxicity. Here, an integrated iron-porphyrin-MOF-based nanozyme composite named HA@GOx@PCN-224(Fe) (HGPF) was precisely designed and constructed. Generally, the POD-like nanozyme PCN-224(Fe) was used as a platform to immobilize glucose oxidase (GOx), and further embedded with hyaluronic acid (HA) to enable the targeting ability of tumor cells. When endocytosed by tumor cells, intracellular glucose was oxidized to H2O2 and gluconic acid catalyzed by immobilized GOx of HGPF. Afterwards, inspired by heme analogs, H2O2 was catalyzed by iron-porphyrin active sites of the HGPF nanozyme to generate hydroxyl radicals (˙OH). Under light irradiation, the iron-porphyrin of HGPF acted as a photosensitizer to facilely produce singlet oxygen (1O2). Such a synergistic generation of ROS strikingly amplified oxidative stress and induced severe apoptosis in tumor cells. HGPF was expected to integrate intracellular oxygen sources and overcome the dilemma of limited intracellular H2O2 content. Consequently, HGPF was constructed as an integrated nanoreactor to simultaneously achieve light-enhanced catalytic oxidation cascades, providing a promising strategy for a synergistic amplification of cellular oxidative stress. [ABSTRACT FROM AUTHOR]

The common method for the determination of Au in geological samples is by Atomic Absorption Spectrometry (AAS) and Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) after enrichment by polyurethane foam (PUF). Compared with activated carbon, PUF has a good selectivity but has a low absorption capacity. PUF loaded by different extraction agents or modified with different functional groups can improve the absorption capacity. PUF was treated with hydrochloric acid to prepare PUF-NH2. Infrared Spectrum and Scanned Electron Microscope results show the peak of PUF-NH2 shows obvious red shift, and the amount of amino group increases obviously. Macromolecule of PUF-NH2 shows obvious fracture. The amino group after hydrolysis is reduced, which is easy to achieve in an oxide-reduction reaction with Au ions during the absorption of Au to form Au nanoparticles. Modified PUF-NH2 achieved absorption capacity of 96 mg/g, which is an 8-fold improvement compared to PUF. Using PUF-NH2 to enrich Au in geological samples, the samples were first ashed and then digested by 50% aqua regia. Gold was determined by ICP-OES. The recovery by standard-addition ranged from 95.0% to 105.0% and the detection limit was 0.15 μg/g. The experimental results show that the enrichment degree and analytical sensitivity are improved by using PUF-NH2, which is suitable for the determination Au in low grade ores.