Hyperbranched Polylysine Exhibits a Collaborative Enhancement of the Antibiotic Capacity to Kill Gram-Negative Pathogens.

In recent years, traditional antibiotic efficacy outcomes have rapidly diminished due to the advent of drug resistance, and the dose limitation value has increased due to the severe side effect of globalized healthcare. Therefore, novel strategies are required to resensitize resistant pathogens to antibiotics existing in the field and prevent the emergence of drug resistance. In this study, cationic hyperbranched polylysine (HBPL-6) was synthesized using the one-pot polymerization method. HBPL-6 exhibited excellent non-cytotoxicity and bio-solubility properties. The present study also showed that HBPL-6 altered the outer membrane (OM) integrity of Escherichia coli O157:H7, Salmonella typhimurium, and Pseudomonas aeruginosa PAO1 by improving their permeability levels. When administered at a safe dosage, HBPL-6 enhanced the accumulation of rifampicin (RIF) and erythromycin (ERY) in bacteria to restore the efficacy of the antibiotics used. Moreover, the combination of HBPL-6 with colistin (COL) reduced the antibiotic dosage, which was helpful in preventing further drug-resistance outcomes. Therefore, this research provides a new strategy for reducing the dosage of drugs used to combat Gram-negative (G-) bacteria through their synergistic effects.

Insights into Recent Nickel-Catalyzed Reductive and Redox C-C Coupling of Electrophiles, C(sp3)-H Bonds and Alkenes.

ConspectusTransition metal-catalyzed reductive cross-coupling of two carbon electrophiles, also known as cross-electrophile coupling (XEC), has transformed the landscape of C-C coupling chemistry. Nickel catalysts, in particular, have demonstrated exceptional performance in facilitating XEC reactions, allowing for diverse elegant transformations by employing various electrophiles to forge C-C bonds. Nevertheless, several crucial challenges remain to be addressed. First, the intrinsic chemoselectivity between two structurally similar electrophiles in Ni-catalyzed C(sp3)-C(sp3) and C(sp2)-C(sp2) cross-coupling has not been well understood; this necessitates an excess of one of the coupling partners to achieve synthetically useful outcomes. Second, the substitution of economically and environmentally benign nonmetal reductants for Zn/Mn can help scale up XEC reactions and avoid trace metals in pharmaceutical products, but research in this direction has progressed slowly. Finally, it is highly warranted to leverage mechanistic insights from Ni-catalyzed XEC to develop innovative thermoredox coupling protocols, specifically designed to tackle challenges associated with difficult substrates such as C(sp3)-H bonds and unactivated alkenes.In this Account, we address the aforementioned issues by reviewing our recent work on the reductive coupling of C-X and C-O electrophiles, the thermoredox strategy for coupling associated with C(sp3)-H bonds and unactivated alkenes, and the use of diboron esters as nonmetal reductants to achieve reductive coupling. We focus on the mechanistic perspectives of the transformations, particularly how the key C-NiIII-C intermediates are generated, in order to explain the chemoselective and regioselective coupling results. The Account consists of four sections. First, we discuss the Zn/Mn-mediated chemoselective C(sp2)-C(sp2) and C(sp3)-C(sp3) bond formations based on the coupling of selected alkyl/aryl, allyl/benzyl, and other electrophiles. Second, we describe the use of diboron esters as versatile reductants to achieve C(sp3)-C(sp3) and C(sp3)-C(sp2) couplings, with an emphasis on the mechanistic consideration for the construction of C(sp3)-C(sp2) bonds. Third, we discuss leveraging C(sp3)-O bonds for effective C(sp3)-C bond formation via in situ halogenation of alcohols as well as the reductive preparation of α-vinylated and -arylated unusual amino esters. In the final section, we illustrate the thermoredox functionalization of challenging C(sp3)-H bonds with aryl and alkyl halides to afford C(sp3)-C bonds by taking advantage of the compatibility of Zn with the oxidant di-tert-butylperoxide (DTBP). Furthermore, we discuss a Ni-catalyzed and SiH/DTBP-mediated hydrodimerization of terminal alkenes to selectively forge head-to-head and methyl branched C(sp3)-C(sp3) bonds. This process, conducted in the presence or absence of catalytic CuBr2, provides a solution to a long-standing challenge: site-selective hydrocoupling of unactivated alkenes to produce challenging C(sp3)-C(sp3) bonds.

Modified halloysite nanotubes as GRAS nanocarrier for intelligent monitoring and food preservation.

Conventional "all-in-one" methods for multi-component active packaging systems are not wholly adequate for fresh food. Given the need for multifunctional properties, introducing halloysite nanotubes (HNTs) could be a promising way to achieve controllable release of active ingredients while endowing with pH-sensitive performance. Here, we pioneered a GRAS composite with multifunctional properties, employing natural HNTs as a nanocarrier, citral (Cit) as an active antimicrobial agent, and myricetin (Myr) for monitoring freshness. The Cit-HNTs-Myr had excellent DPPH, ABTS and ·OH radical scavenging capacity, dual-model (contact and fumigant) antibacterial properties, and pH-sensitive performance. Subsequently, a smart tag prepared by dipping cellulose fibers into Cit-HNTs-Myr, which extended the shelf life of shrimp and blueberries, and provided freshness information for the shrimp. These results demonstrate the applicability of Cit-HNTs-Myr in the preservation of perishable goods and freshness monitoring.

Dapagliflozin Suppresses Isoprenaline-Induced Cardiac Hypertrophy Through Inhibition of Mitochondrial Fission.

ABSTRACT: Dapagliflozin (DAPA) is a novel oral hypoglycemic agent, and there is increasing evidence that DAPA has a protective effect against cardiovascular disease. The study aimed to investigate how DAPA inhibits cardiac hypertrophy and explore its potential mechanisms. By continuously infusing isoprenaline (ISO) for 2 weeks using a subcutaneous osmotic pump, a cardiac hypertrophic model was established in male C57BL/6 mice. On day 14 after surgery, echocardiography showed that left ventricle mass (LV mass), interventricular septum, left ventricle posterior wall diastole, and left ventricular posterior wall systole were significantly increased, and ejection fraction was decreased compared with control mice. Masson and Wheat Germ Agglutinin staining indicated enhanced myocardial fibrosis and cell morphology compared with control mice. Importantly, these effects were inhibited by DAPA treatment in ISO-induced mice. In H9c2 cells and neonatal rat cardiomyocytes, we found that mitochondrial fragmentation and mitochondrial oxidative stress were significantly augmented in the ISO-induced group. However, DAPA rescued the cardiac hypertrophy in ISO-induced H9c2 cells and neonatal rat cardiomyocytes. Mechanistically, we found that DAPA restored the PIM1 activity in ISO-induced H9c2 cells and subsequent increase in dynamin-associated protein 1 (Drp1) phosphorylation at S616 and decrease in Drp1 phosphorylation at S637 in ISO-induced cells. We found that DAPA mitigated ISO-induced cardiac hypertrophy by suppressing Drp1-mediated mitochondrial fission in a PIM1-dependent fashion.

A Poly-D-Mannose Synthesized by a One-Pot Method Exhibits Anti-Biofilm, Antioxidant, and Anti-Inflammatory Properties In Vitro.

In this study, D-mannose was used to synthesize poly-D-mannose using a one-pot method. The molecular weight, degree of branching, monosaccharide composition, total sugar content, and infrared spectrum were determined. In addition, we evaluated the safety and bioactivity of poly-D-mannose including anti-pathogen biofilm, antioxidant, and anti-inflammatory activity. The results showed that poly-D-mannose was a mixture of four components with different molecular weights. The molecular weight of the first three components was larger than 410,000 Da, and that of the fourth was 3884 Da. The branching degree of poly-D-mannose was 0.53. The total sugar content was 97.70%, and the monosaccharide was composed only of mannose. The infrared spectra showed that poly-D-mannose possessed characteristic groups of polysaccharides. Poly-D-mannose showed no cytotoxicity or hemolytic activity at the concentration range from 0.125 mg/mL to 8 mg/mL. In addition, poly-D-mannose had the best inhibition effect on Salmonella typhimurium at the concentration of 2 mg/mL (68.0% ± 3.9%). The inhibition effect on Escherichia coli O157:H7 was not obvious, and the biofilm was reduced by 37.6% ± 2.9% at 2 mg/mL. For Staphylococcus aureus and Bacillus cereus, poly-D-mannose had no effect on biofilms at low concentration; however, 2 mg/mL of poly-D-mannose showed inhibition rates of 33.7% ± 6.4% and 47.5% ± 4%, respectively. Poly-D-mannose showed different scavenging ability on free radicals. It showed the best scavenging effect on DPPH, with the highest scavenging rate of 74.0% ± 2.8%, followed by hydroxyl radicals, with the scavenging rate of 36.5% ± 1.6%; the scavenging rates of superoxide anion radicals and ABTS radicals were the lowest, at only 10.1% ± 2.1% and 16.3% ± 0.9%, respectively. In lipopolysaccharide (LPS)-stimulated macrophages, poly-D-mannose decreased the secretion of nitric oxide (NO) and reactive oxygen species (ROS), and down-regulated the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Therefore, it can be concluded that poly-D-mannose prepared in this research is safe and has certain biological activity. Meanwhile, it provides a new idea for the development of novel prebiotics for food and feed industries or active ingredients used for pharmaceutical production in the future.

Physiological and Transcriptomic Analyses of Escherichia coli Serotype O157:H7 in Response to Rhamnolipid Treatment.

Rhamnolipid (RL) can inhibit biofilm formation of Escherichia coli O157:H7, but the associated mechanism remains unknown. We here conducted comparative physiological and transcriptomic analyses of cultures treated with RL and untreated cultures to elucidate a potential mechanism by which RL may inhibit biofilm formation in E. coli O157:H7. Anti-biofilm assays showed that over 70% of the E. coli O157:H7 biofilm formation capacity was inhibited by treatment with 0.25-1 mg/mL of RL. Cellular-level physiological analysis revealed that a high concentration of RL significantly reduced outer membrane hydrophobicity. E. coli cell membrane integrity and permeability were also significantly affected by RL due to an increase in the release of lipopolysaccharide (LPS) from the cell membrane. Furthermore, transcriptomic profiling showed 2601 differentially expressed genes (1344 up-regulated and 1257 down-regulated) in cells treated with RL compared to untreated cells. Functional enrichment analysis indicated that RL treatment up-regulated biosynthetic genes responsible for LPS synthesis, outer membrane protein synthesis, and flagellar assembly, and down-regulated genes required for poly-N-acetyl-glucosamine biosynthesis and genes present in the locus of enterocyte effacement pathogenicity island. In summary, RL treatment inhibited E. coli O157:H7 biofilm formation by modifying key outer membrane surface properties and expression levels of adhesion genes.

Hydra gasdermin-gated pyroptosis signalling regulates tissue regeneration.

Pyroptosis, an inflammatory form of programmed cell death, is directly executed by gasdermin (GSDM) depending on its N-terminal pore-forming fragment-mediated membrane-disrupting, triggering intracellular contents release, which plays important roles in mammalian anti-infection and anti-tumor immune responses. However, whether pyroptosis engages in the regulation of tissue regeneration remains largely unknown. Here, utilizing Hydra vulgaris as the research model, we found that an HyCARD2-HyGSDME-mediated pyroptosis signalling is activated in both head and foot regenerated tips after amputation. Impeding pyroptosis by knocking down the expression of either HyGSDME or HyCARD2 significantly hampered both head and foot regeneration in Hydra. Mechanistically, the activation of HyCARD2-HyGSDME axis at wound sites is dependent of intracellular mitochondrial reactive oxygen species (mtROS), the removing of which hindered Hydra head regeneration. Moreover, the HyCARD2-HyGSDME axis-gated pyroptosis was found to enhance the initial secretion and upregulated expression of Wnt3. Collectively, these findings indicate that gasdermin-gated pyroptosis is critical for the evoking of Wnt signalling to facilitate Hydra tissue regeneration, which provides insights into functional diversification within the gasdermin family in the animal kingdom.

Recent Advances in Structural Optimization and Surface Modification on Current Collectors for High-Performance Zinc Anode: Principles, Strategies, and Challenges.

The last several years have witnessed the prosperous development of zinc-ion batteries (ZIBs), which are considered as a promising competitor of energy storage systems thanks to their low cost and high safety. However, the reversibility and availability of this system are blighted by problems such as uncontrollable dendritic growth, hydrogen evolution, and corrosion passivation on anode side. A functionally and structurally well-designed anode current collectors (CCs) is believed as a viable solution for those problems, with a lack of summarization according to its working mechanisms. Herein, this review focuses on the challenges of zinc anode and the mechanisms of modified anode CCs, which can be divided into zincophilic modification, structural design, and steering the preferred crystal facet orientation. The possible prospects and directions on zinc anode research and design are proposed at the end to hopefully promote the practical application of ZIBs.

Retraction: Deoxygenative cross-electrophile coupling of benzyl chloroformates with aryl iodides.

Retraction of 'Deoxygenative cross-electrophile coupling of benzyl chloroformates with aryl iodides' by Yingying Pan et al., Org. Biomol. Chem., 2019, 17, 4230-4233, https://doi.org/10.1039/C9OB00628A.

Caspase-mediated LPS sensing and pyroptosis signaling in Hydra.

Inflammatory caspases sensing lipopolysaccharide (LPS) to drive gasdermin (GSDM)-mediated pyroptosis is an important immune response mechanism for anti-infection defense in mammals. In this work, we resolved an LPS-induced and GSDM-gated pyroptosis signaling cascade in Cnidarians. Initially, we identified a functional GSDM protein, HyGSDME, in Hydra, executing cytosolic LPS-induced pyroptosis in a caspase-dependent manner. Further, we identified a proinflammatory caspase, HyCaspA, capable of sensing cytosolic LPS by an uncharacterized N-terminal domain relying on its unique hydrophobic property, thereby triggering its oligomerization and self-activation. Subsequently, the LPS-activated HyCaspA cleaved an apoptotic caspase, HyCARD2, to trigger HyGSDME-gated pyroptosis. Last, HyGSDME exhibited an enriched distribution on the ectodermal layer of Hydra polyps, exerting a canonical immune defense function against surface-invading bacteria. Collectively, our work resolved an ancient pyroptosis signaling cascade in Hydra, suggesting that inflammatory caspases sensing cytosolic LPS to initiate GSDM-gated pyroptosis are a conserved immune defense mechanism from Cnidarians to mammals.

Correction to: Effective transport network driven by tortuosity gradient enables high-electrochem-active solid-state batteries.

[This corrects the article DOI: 10.1093/nsr/nwac272.].

Bioinformatics analysis and reveal potential crosstalk genetic and immune relationships between atherosclerosis and periodontitis.

Periodontitis is an inflammatory and immune-related disease with links to several systemic diseases, and the pathological process of atherosclerosis also involves inflammatory and immune involvement. The aim of this study was to investigate the common immune cells and potential crosstalk genes between periodontitis (PD) and atherosclerosis (AS). By analyzing the weighted gene co-expression network of differentially immune infiltrating cells in two diseases to obtain important module genes, and taking the intersection of the module genes, we obtained 14 co-expressed immune-related genes, and evaluated the predictive value of 14 immune-related genes using three machine learning models.Two potential immune-related crosstalk genes (BTK and ITGAL) were finally obtained by taking intersections of WGCNA intersection genes, DEGs and IRGs.Then, the diagnostic column line graphs were constructed based on the 2 crosstalk genes, and the calibration curves, DCA curves and clinical impact curves indicated that the two genes had strong disease prediction ability, and we further validated the accuracy of the two potential crosstalk genes for disease diagnosis in the validation dataset.Single gene GSEA analysis showed that both genes are jointly involved in biological processes such as antigen presentation and immune regulation, and single sample GSEA analysis showed that macrophages and T cells play an important role in periodontitis in atherosclerosis.This study explored the genetic correlation between atherosclerosis and periodontitis using bioinformatics tools. BTK and ITGAL were found to be the most important crosstalk genes between the two diseases and may have an important role in the diagnosis and treatment of the diseases. Macrophage and T cell mediated inflammatory and immune responses may play an important role in periodontitis and atherosclerosis.

Effects of dexmedetomidine on oxidative stress, programmed cell death, liver function, and expression of peripheral immune cells in patients with primary liver cancer undergoing hepatectomy.

Study background: Primary liver cancer is a severe health issue that imposes a significant health burden on families. Oxidation and subsequent cell death impair liver function and provoke an immune response. The present article investigates the effect of Dexmedetomidine on oxidation, cell death, the expression of peripheral immune cells, and liver function. The clinical data will represent the facts and evidence of the effects of this intervention. Methods: We analyzed clinical data reporting various accounts of the effects of Dexmedetomidine on oxidation, cell death, the expression of peripheral immune cells, and liver function among patients who underwent hepatectomy. The surgical procedure reported the differences in cell death as procedural outcomes among pre- and post-treatment records were compared and contrasted. Results: We found decreased cell apoptosis in the treatment group: the number of incisions to remove dead cells was lower in the treatment group than in the pre-treatment group. Likewise, lower oxidation was reported in pre-treatment than in post-treatment records. The expression of peripheral immune cells was higher in the pre-treatment clinical data than in post-treatment, suggesting a reduction in oxidation following dexmedetomidine treatment. Liver function was a function of oxidation and cell death outcomes. In the pre-treatment clinical data, liver function was poor, whereas improved functions were reported in the post-treatment clinical data. Discussion: We found compelling evidence of Dexmedetomidine's effects on oxidative stress and programmed cell death. The intervention suppresses the production of reactive oxygen species and the consequential apoptosis. Additionally, liver functions improve due to the decrease in hepatocyte apoptosis. Since the peripheral immune cells are expressed against tumors, a decrease in the progression of primary liver cancer decreased the expression of the peripheral immune cells. Conclusion: Dexmedetomidine's positive effects stood out in the present research article. The intervention reduced oxidation by balancing the production of reactive oxygen species and the detoxification processes. Reduced oxidation induced reduced cell death through apoptosis, resulting in a low expression of peripheral immune cells and improved liver functions.

Effective transport network driven by tortuosity gradient enables high-electrochem-active solid-state batteries.

Simultaneously achieving high electrochemical activity and high loading for solid-state batteries has been hindered by slow ion transport within solid electrodes, in particular with an increase in electrode thickness. Ion transport governed by 'point-to-point' diffusion inside a solid-state electrode is challenging, but still remains elusive. Herein, synchronized electrochemical analysis using X-ray tomography and ptychography reveals new insights into the nature of slow ion transport in solid-state electrodes. Thickness-dependent delithiation kinetics are spatially probed to identify that low-delithiation kinetics originate from the high tortuous and slow longitudinal transport pathways. By fabricating a tortuosity-gradient electrode to create an effective ion-percolation network, the tortuosity-gradient electrode architecture promotes fast charge transport, migrates the heterogeneous solid-state reaction, enhances electrochemical activity and extends cycle life in thick solid-state electrodes. These findings establish effective transport pathways as key design principles for realizing the promise of solid-state high-loading cathodes.

SCCNet: Self-correction boundary preservation with a dynamic class prior filter for high-variability ultrasound image segmentation.

The highly ambiguous nature of boundaries and similar objects is difficult to address in some ultrasound image segmentation tasks, such as neck muscle segmentation, leading to unsatisfactory performance. Thus, this paper proposes a two-stage network called SCCNet (self-correction context network) using a self-correction boundary preservation module and class-context filter to alleviate these problems. The proposed self-correction boundary preservation module uses a dynamic key boundary point (KBP) map to increase the capability of iteratively discriminating ambiguous boundary points segments, and the predicted segmentation map from one stage is used to obtain a dynamic class prior filter to improve the segmentation performance at Stage 2. Finally, three datasets, Neck Muscle, CAMUS and Thyroid, are used to demonstrate that our proposed SCCNet outperforms other state-of-the art methods, such as BPBnet, DSNnet, and RAGCnet. Our proposed network shows at least a 1.2-3.7% improvement on the three datasets, Neck Muscle, Thyroid, and CAMUS. The source code is available at https://github.com/lijixing0425/SCCNet.

A combined analysis of TyG index, SII index, and SIRI index: positive association with CHD risk and coronary atherosclerosis severity in patients with NAFLD.

Background: Insulin resistance(IR) and inflammation have been regarded as common potential mechanisms in coronary heart disease (CHD) and non-alcoholic fatty liver disease (NAFLD). Triglyceride-glucose (TyG) index is a novel biomarker of insulin resistance, System immune-inflammation index(SII) and Systemic inflammation response index(SIRI) are novel biomarkers of inflammation, these biomarkers have not been studied in CHD with NAFLD patients. This study investigated the correlation between the TyG index, SII index, and SIRI index and CHD risk among NAFLD patients. Methods: This cross-sectional study included 407 patients with NAFLD in the Department of Cardiology, The Second Hospital of Shanxi Medical University. Of these, 250 patients with CHD were enrolled in the NAFLD+CHD group and 157 patients without CHD were enrolled as NAFLD control. To balance covariates between groups, 144 patients were selected from each group in a 1:1 ratio based on propensity score matching (PSM). Potential influences were screened using Lasso regression analysis. Univariate and multivariate logistic regression analyses and the Least Absolute Shrinkage and Selection Operator (LASSO) regression were used to assess independent risk and protective factors for CHD. Construction of nomogram using independent risk factors screened by machine learning. The receiver operating characteristic(ROC) curve was used to assess the ability of these independent risk factors to predict coronary heart disease. The relationship between the Gensini score and independent risk factors was reflected using the Sankey diagram. Results: The LASSO logistic regression analysis and Logistic regression analyses suggest that TyG index (OR, 2.193; 95% CI, 1.242-3.873; P = 0.007), SII index (OR, 1.002; 95% CI, 1.001-29 1.003; P <0.001), and SIRI index (OR,1.483;95%CI,1.058-2.079,P=0.022) are independent risk factors for CHD. At the same time, Neutrophils, TG, and LDL-C were also found to be independent risk factors in patients, HDL-C was a protective factor for CHD in patients with NAFLD. Further analysis using three machine learning algorithms found these independent risk factors to have good predictive value for disease diagnosis, SII index shows the highest predictive value. ROC curve analysis demonstrated that combining the SII index, SIRI index, and TyG index can improve the diagnostic ability of non-alcoholic liver cirrhosis patients with CHD.ROC curve analysis showed that the combined analysis of these independent risk factors improved the predictive value of CHD(AUC: 0.751; 95% CI: 0.704-0.798; P <0.001). Conclusion: TyG index, SII index, and SIRI index are all independent risk factors for CHD in patients with NAFLD and are strongly associated with prediction and the severity of CHD.

Methyltransferase-like 3 upregulation is involved in the chemoresistance of non-small cell lung cancer.

Background: Treatments for non-small cell lung cancer (NSCLC) have improved tremendously, but therapeutic resistance is a common and major clinical challenge in treatment. Methyltransferase-like 3 (METTL3) is a ribonucleic acid (RNA) methyltransferase that has crucial functions in the development and progression of cancers, including drug resistance, by regulating N6-methyladenosine (m6A) modification. However, the role of METTL3 in the progression and drug resistance of NSCLC is poorly understood. Methods: The expression levels of METTL3 and AKT serine/threonine kinase 1 (AKT1) in NSCLC tissues were detected using quantitative real-time PCR (RT-qPCR), Western blots, and immunohistochemical assays. The m6A levels of AKT1 messenger RNA (mRNA) in NSCLC tissues were detected using m6A methylated RNA immunoprecipitation-quantitative polymerase chain reaction. Results: The expression levels of METTL3 and the AKT1 protein were significantly increased in NSCLC tissues, and m6A expression levels of AKT1 mRNA were dramatically upregulated in NSCLC tissues. Additionally, METTL3, AKT1 protein, and m6A levels of AKT1 mRNA were overexpressed in chemoresistant NSCLC samples, and high expression levels of METTL3 and AKT1 were correlated with poor patient survival, especially in chemoresistant NSCLC patients. Further, AKT1 protein expression and m6A levels of AKT1 mRNA were positively correlated with METTL3 expression, and AKT1 protein expression was positively correlated with m6A levels of AKT1 mRNA. Moreover, METTL3 and AKT1 protein expression levels were significantly associated with cisplatin susceptibility, tumor, node, metastasis stage, and lymph node metastasis. Conclusions: Taken together, our results indicate that METTL3 contributes to the progression and chemoresistance of NSCLC by promoting AKT1 protein expression through regulating AKT1 mRNA m6A levels, and may provide an efficient therapeutic intervention target for overcoming chemoresistance in NSCLC.

Nickel-Catalyzed Thermal Redox Functionalization of C(sp3 )-H Bonds with Carbon Electrophiles.

C(sp3 )-H bond coupling with carbon electrophiles remains rarely explored under thermo-driven hydrogen atom transfer (HAT) conditions due to the challenge of integrating oxidation and reduction in a single operation. We report here a Ni-catalyzed arylation and alkylation of C(sp3 )-H bonds with organohalides to forge C(sp3 )-C bonds by merging economical Zn and tBuOOtBu (DTBP) as the external reductant and oxidant. The mild and easy-to-operate protocol enables facile carbofunctionalization of N-/O-α- and cyclohexane C-H bonds, and preparation of a few intermediates of bioactive compounds and drug derivatives. Preliminary mechanistic studies implied addition of an alkyl radical to a NiII salt.

Improving selenium accumulation in broilers using Escherichia coli Nissle 1917 with surface-displayed selenite reductase SerV01.

Selenium levels have a critical impact on livestock and poultry, and selenium nanoparticles (SeNPs) have shown significant efficiency in supplementation. This study identified a high-efficiency selenite reductase, SerV01, in Staphylococcus aureus LZ-01, which can convert Se2O32- to SeNPs. Subsequently, SerV01 was introduced into the intestines of the broilers using the surface display-engineered E. coli Nissle 1917 (EcN). The results showed that the engineered bacteria (EcN-IS) significantly increased the selenium content by 0.87 mg kg-1, 0.52 mg kg-1, and 6.10 mg L-1 in the liver, breast muscle, and serum, respectively. With SeNPs + EcN-IS treatment, glutathione peroxidase and thioredoxin reductase levels reached 0.7536 ± 0.03176 U µL-1 protein and 2.463 ± 0.1685 U µL-1 protein, respectively. With the modified probiotics, the proportion of beneficial intestinal flora increased, with Lactobacillus and Propionibacterium accounting for 75.85% and 0.19%. This technology provides a novel idea to facilitate the exploitation of selenium in broiler diets and improve antioxidant capability.

Hydrogen Sulfide Diminishes Activation of Adventitial Fibroblasts Through the Inhibition of Mitochondrial Fission.

ABSTRACT: Activation of adventitial fibroblasts (AFs) on vascular injury contributes to vascular remodeling. Hydrogen sulfide (H2S), a gaseous signal molecule, modulates various cardiovascular functions. The aim of this study was to explore whether exogenous H2S ameliorates transforming growth factor-ß1 (TGF-ß1)-induced activation of AFs and, if so, to determine the underlying molecular mechanisms. Immunofluorescent staining and western blot were used to determine the expression of collagen I and α-smooth muscle actin. The proliferation and migration of AFs were performed by using cell counting Kit-8 and transwell assay, respectively. The mitochondrial morphology was assessed by using MitoTracker Red staining. The activation of signaling pathway was evaluated by western blot. The mitochondrial reactive oxygen species and mitochondrial membrane potential were determined by MitoSOX and JC-1 (5,5',6,6'-tetrachloro-1,1,3,3'-tetraethylbenzimidazolyl carbocyanine iodide) staining. Our study demonstrated exogenous H2S treatment dramatically suppressed TGF-ß1-induced AF proliferation, migration, and phenotypic transition by blockage of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and regulated mitochondrial reactive oxygen species generation. Moreover, exogenous H2S reversed TGF-ß1-induced mitochondrial fission and AF activation by modulating Rho-associated protein kinase 1-dependent phosphorylation of Drp1. In conclusion, our results suggested that exogenous H2S attenuates TGF-ß1-induced AF activation through suppression of Drp1-mediated mitochondrial fission in a Rho-associated protein kinase 1-dependent fashion.