Ultra-Dense Supported Ruthenium Oxide Clusters via Directed Ion Exchange for Efficient Valorization of 5-Hydroxymethylfurfural.

Maximizing the loading of active centers without aggregation for a supported catalyst is a grand challenge but essential for achieving high gravimetric activity, especially toward multi-step reactions. The oxidation of 5-hydroxymethylfurfural (HMF), a key biomass-derived platform molecule, into 2,5-furandicarboxylic acid (FDCA), a promising alternative to polyester monomer, is such a multi-step reaction that involves 6 electron transfers. Herein, we devised a strategy of creating ultra-dense supported Ru oxide clusters on a Co hydroxyanion (CoHA) support. Pyrimidine ligands were first incorporated into the CoHA interlayers, and their subsequent evacuation created porous channels for the directed ion exchange with the built-in anions in CoHA, which allows the dense and mono-disperse functionalization of RuCl62- anions and their resulting Ru oxide clusters. These ultra-dense Ru oxide clusters not only enable high HMF electrooxidation currents under neutral conditions but also create microscopic channels in-between the clusters for the expedited re-adsorption and oxidation of intermediates toward highly oxidized product, such as 5-formyl-2-furoic acid (FFCA) and FDCA. A two-stage HMF oxidation process, consisting of ambient conversion of HMF into FFCA and FFCA oxidation into FDCA under 60 oC, was eventually developed to first achieve a high FDCA yield of 92.1% with significantly reduced polymerization.

Exogenous Co-Reactant-Free Electrochemiluminescent Biosensor for Ratiometric Measurement of α-Glucosidase Based on a ZIF-67-Regulated Hydrogen-Bonded Organic Framework.

The development of highly sensitive and selective analytical approaches for monitoring enzymatic activity is critical for disease diagnosis and biomedical research. Herein, we develop an exogenous co-reactant-free electrochemiluminescence (ECL) biosensor for the ratiometric measurement of α-glucosidase (α-Glu) based on a zeolitic imidazolate framework (ZIF-67)-regulated pyrene-based hydrogen-bonded organic framework (HOF-101). Target α-Glu can hydrolyze maltose to α-d-glucose, which can subsequently react with GOx to produce gluconic acid. The resultant gluconic acid can dissolve ZIF-67, leading to the recovery of the HOF-101 cathodic ECL signal and the decrease of the luminol anodic ECL signal. The long-range ordered structure of HOF-101 can speed up charge transfer, resulting in a stable and strong cathodic ECL signal. Moreover, ZIF-67 can not only efficiently quench the ECL signal of HOF-101 due to ECL resonance energy transfer between HOF-101 and ZIF-67 as well as the steric hindrance effect of ZIF-67 but also enhance the anodic ECL emission of luminol in dissolved O2 system because of its ordered and porous crystalline structure and the atomically dispersed Co2+. Notably, HOF-101 possesses a higher ECL efficiency (32.22%) compared with the Ru(bpy)32+ standard. Importantly, this ratiometric ECL biosensor shows high sensitivity (a detection limit of 0.19 U L-1) and a broad linear range (0.2-50 U L-1). This biosensor can efficiently eliminate systematic errors and enhance detection reliability without the involvement of exogenous co-reactants, and it displays good assay performance in human serum samples, holding great promise in biomedical research studies.

Lipid metabolism-related gene signatures for predicting the prognosis of lung adenocarcinoma.

Background: Lung cancer is one of the most common epithelial malignancies worldwide, accounting for the highest number of new cases and deaths. Metabolism is the sum of chemical reactions that produce energy to keep an organism alive. Several studies have shown that glucose and lipid metabolic disorders are common phenomena related to cancer cell genesis and progression. Methods: We screened the differentially expressed genes (DEGs) of lung adenocarcinoma (LUAD) samples of The Cancer Genome Atlas (TCGA) database, the Gene Set Enrichment Analysis (GSEA), and Gene Card database metabolism-related data, the metabolism-related DEGs of LUAD, as well as the univariate Cox regression analysis genes, for identifying significant outcome-related genes. The least absolute shrinkage and gene selection operator (LASSO) analysis was performed to establish the best risk model. Results: Our study aimed to establish a lipid metabolism-related model for predicting LUAD prognosis. Furthermore, our model's prognosis prediction power was evaluated by survival analysis. This study finally identified 11 DEGs related to lipid metabolism that were significantly associated with the prognosis of lung adenocarcinoma. It provided a new idea for the treatment of high-risk lung adenocarcinoma patients. Conclusions: The constructed clinical prognosis model of lung adenocarcinoma related to lipid metabolism provides a new idea for clinical treatment of lung adenocarcinoma.

Electrode/Electrolyte Synergy for Concerted Promotion of Electron and Proton Transfers toward Efficient Neutral Water Oxidation.

Neutral water oxidation is a crucial half-reaction for various electrochemical applications requiring pH-benign conditions. However, its sluggish kinetics with limited proton and electron transfer rates greatly impacts the overall energy efficiency. In this work, we created an electrode/electrolyte synergy strategy for simultaneously enhancing the proton and electron transfers at the interface toward highly efficient neutral water oxidation. The charge transfer was accelerated between the iridium oxide and in situ formed nickel oxyhydroxide on the electrode end. The proton transfer was expedited by the compact borate environment that originated from hierarchical fluoride/borate anions on the electrolyte end. These concerted promotions facilitated the proton-coupled electron transfer (PCET) events. Due to the electrode/electrolyte synergy, Ir-O and Ir-OO- intermediates could be directly detected by in situ Raman spectroscopy, and the rate-limiting step of Ir-O oxidation was determined. This synergy strategy can extend the scope of optimizing electrocatalytic activities toward more electrode/electrolyte combinations.

Molecular Dynamics Simulations Reveal the Conformational Transition of GH33 Sialidases.

Sialidases are increasingly used in the production of sialyloligosaccharides, a significant component of human milk oligosaccharides. Elucidating the catalytic mechanism of sialidases is critical for the rational design of better biocatalysts, thereby facilitating the industrial production of sialyloligosaccharides. Through comparative all-atom molecular dynamics simulations, we investigated the structural dynamics of sialidases in Glycoside Hydrolase family 33 (GH33). Interestingly, several sialidases displayed significant conformational transition and formed a new cleft in the simulations. The new cleft was adjacent to the innate active site of the enzyme, which serves to accommodate the glycosyl acceptor. Furthermore, the residues involved in the specific interactions with the substrate were evolutionarily conserved in the whole GH33 family, highlighting their key roles in the catalysis of GH33 sialidases. Our results enriched the catalytic mechanism of GH33 sialidases, with potential implications in the rational design of sialidases.

[Eleutheroside B induces apoptosis and autophagy of lung cancer cells by regulating PI3K/Akt/mTOR pathway].

This study investigated the effect of eleutheroside B on apoptosis and autophagy of lung cancer A549 and H460 cells and its molecular mechanism. MTT assay was used to detect the cytotoxicity of eleutheroside B at 5, 10, 15, 20, 25, 30, 35, 40, and 45 mmol·L~(-1) on lung cancer cells. Trypan blue exclusion assay was used to detect the effect of eleutheroside B on the survival rate of lung cancer A549 and H460 cells at different time. Colony formation assay was used to detect the effect of eleutheroside B on the proliferation of lung cancer A549 and H460 cells. AO/EB fluorescence double staining and Hoechst 33342 fluorescence staining were used to detect the effect of eleutheroside B on apoptosis of lung cancer A549 and H460 cells, and Western blot was used to detect apoptosis-related proteins to explore the apoptosis-related molecular mechanism. AO fluorescence staining and Western blot were used to detect the expression of autophagic vesicles and autophagy-related proteins P62 and LC3. The results showed that compared with the control group, eleutheroside B inhibited the growth of lung cancer A549 and H460 cells in a concentration-dependent manner. The optimal effect time of eleutheroside B on lung cancer A549 and H460 cells was 24 h, and the optimal concentrations were 28.64 and 22.16 mmol·L~(-1), respectively. Eleutheroside B could inhibit the colony formation of A549 and H460 cells. Compared with the control group, eleutheroside B could promote the formation of apoptotic bodies and induce cell apoptosis, as well as induce the expression of mitochondrial pathway-related proteins. Under the effect of eleutheroside B, the acidic autophagy vacuole in lung cancer cells increased, LC3Ⅱ expression increased, P62 protein expression decreased, and PI3K, p-Akt, and p-mTOR protein expression decreased in the PI3K/Akt/mTOR pathway. Studies have shown that eleutheroside B can inhibit the growth of lung cancer cells, reduce colony formation, induce apoptosis of lung cancer cells through mitochondrial pathway, and induce autophagy. The mechanism may be related to the PI3K/Akt/mTOR pathway.

A Novel ß-Glucosidase From Chryseobacterium scophthalmum 1433 for Efficient Rubusoside Production From Stevioside.

As a natural sweetening and solubilizing agent, rubusoside has great potential in the application of healthy beverages and pharmaceuticals. However, the direct extraction and purification of rubusoside from raw materials is inefficient. In this work, a novel ß-glucosidase (CsBGL) was obtained from Chryseobacterium scophthalmum 1433 through screening of the environmental microorganisms. CsBGL markedly hydrolyzed sophorese (Glcß1-2Glc) and laminaribiose (Glcß1-3Glc), but for steviol glycosides, it only hydrolyzed the C-13/C-19-linked sophorese, instead of the C-13/C-19-linked Glcß1-2[Glcß1-3]Glc trisaccharide and Glcß1-monosaccharide. It efficiently hydrolyzed stevioside (240 g/L) to produce rubusoside (99% yield) at 47.5°C for 70 min. Even when using a crude steviol glycosides extract (500 g/L) containing ∼226 g/L stevioside as the substrate, CsBGL could also convert stevioside to rubusoside (99% yield) at 47.5°C for 2 h, in which the rubusoside concentration increased from the initial 42 g/L to the final 222 g/L. These results reveal that CsBGL would be a promising biocatalyst for the industry-scale production of rubusoside from stevioside or/and the crude steviol glycosides extract.

NanoFe3O4 accelerates anoxic biodegradation of 3, 5, 6-trichloro-2-pyridinol.

3, 5, 6-trichloro-2-pyridinol (TCP) is a widespread organic pollutant with persistent, mobile and high antimicrobial effects. Here, nanoFe3O4 was firstly introduced into the anoxic biodegradation of TCP. It was found that nanoFe3O4 significantly accelerated TCP biodegradation. The removal rate of TCP (100 mg L-1) increased from 83.03% to 98.74% within 12 h in the presence of nanoFe3O4, and the addition of nanoFe3O4 also promoted the accumulation of CO2. Reductive dechlorination mechanism was involved in anoxic biodegradation of TCP. Molecular approaches further revealed that nanoFe3O4 distinctly induced the shifts of bacterial community. The dominant genus Ochrobactrum was converted to genus Delftia in nanoFe3O4 treatment, and the relative abundance of Delftia increased from 10.26% to 44.62%. Meanwhile, the total relative abundance of bacteria related to TCP dechlorination and degradation significantly increased in the presence of nanoFe3O4. These results indicated that nanoFe3O4 induced the enrichment of TCP-degrading bacteria to promote the anoxic biodegradation of TCP.

Degradation of 3,5,6-trichloro-2-pyridinol by a microbial consortium in dryland soil with anaerobic incubation.

Biodegradation of 3,5,6-trichloro-2-pyridinol (TCP) in drylands is an important biological process of detoxification. Flooding in drylands can result in the formation of anaerobic habitats. However, little is known about the microbial metabolism of TCP in dryland soil under anaerobic conditions. Here, chlorpyrifos-contaminated dryland soil was incubated to enrich the TCP-degrading microbial consortium under anaerobic conditions. Chloridion and CO2 were released with TCP degradation, and the enrichment cultures of dryland soil could metabolize 97% of TCP (100 mg/L) within 20 h. Both reductive and hydrolysis dechlorination mechanisms were involved in TCP biodegradation under anaerobic conditions. Bacterial taxonomic analysis revealed that the aerobic TCP-degrading bacteria Ochrobactrum and dechlorination bacteria Delftia were the dominant genera. Anaerobic and facultative bacteria; i.e., Bacteroides, Bacillus, and Cupriavidus had lower relative abundances, but they were significantly enriched following treatment with TCP. These results indicate that the enrichment cultures of dryland soil dominated by aerobic bacteria could dechlorinate and degrade TCP under anaerobic conditions.

Sarcopenia is independently associated with diabetic foot disease.

The aim of this study was to investigate the association of sarcopenia and diabetic foot disease (DFD) in a cross-sectional study. Body composition was assessed using dual-energy X-ray-absorptiometry (DXA) among 1105 patients with type 2 diabetes (120 patients with newly diagnosed DFD [DFD duration less than 3 months]). Severity of DFD was assessed, referring to foot ulcers, Wagner grade and the percentage of amputation. Skeletal muscle index (SMI) was calculated, and sarcopenia was defined as SMI less than 7.0 kg/m2 (in men) or 5.4 kg/m2 (in women). SMI was significantly decreased in patients with DFD compared to patients without (6.79 ± 1.20 vs. 7.21 ± 1.05 kg/m2, P < 0.001). The percentage of sarcopenia in DFD patients was more than double than those without DFD (35.3% vs. 16.4%, P < 0.001). Multivariable logistic regression analysis showed that sarcopenia was independently associated with DFD (OR 2.05[95% CI 1.15,3.89], P = 0.027) after controlling confounders including age, diabetic duration and diabetic chronic complications. In DFD group, patients with sarcopenia exhibited more foot ulcers, higher Wagner grade and greater percentage of amputation compared to patients without sarcopenia. We conclude that sarcopenia is independently associated with DFD. Worse prognosis is seen in patients with DFD accompanied by sarcopenia.