Reductive dechlorination of 2,4-dichlorophenol by using MWCNTs-Pd/Fe nanocomposites prepared in the presence of ultrasonic irradiation.

The research on developing a purification technology for 2,4-dichlorophenol (2,4-DCP) polluted water with high efficiency and the low energy consumption is crucial for achieving several Sustainable Development Goals (SDGs). In order to achieve these goals, MWCNTs-Pd/Fe nanocomposites were prepared by Fe nanoparticles modified with multi-walled carbon nanotubes (MWCNTs) and palladium (Pd) in the presence of ultrasonic irradiation. The MWCNTs-Pd/Fe nanocomposites were characterized by using Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and X-Ray Diffraction (XRD), and others. Characterization results confirmed that the MWCNTs-Pd/Fe was successfully prepared, with the particle size of 80 nm and the specific surface area of 89.5 m2/g confirmed. We studied the reductive dechlorination of 2,4-Dichlorophenol (2,4-DCP) by MWCNTs-Pd/Fe nanocomposites under different conditions, and the optimized experimental results were found when the Pd loading was 0.4 %, the pH was 3, and the temperature was 30 °C. The phenol yield increased from 76.5 % (without ultrasonic irradiation) to 92.3 % (with ultrasonic irradiation) in 300 min and the 2,4-DCP removal rate reached 98.7 % under the optimal conditions. Therefore, ultrasonic irradiation enhanced the performance of MWCNTs-Pd/Fe nanocomposites for 2,4-DCP removal. We also established the degradation mechanism of chlorophenol by analyzing the intermediates, and proposed the degradation kinetics model. The degradation of 2,4-DCP followed the pseudo-first-order kinetics with the rate constant of 0.05988 min-1. Also, this study demonstrated the potential of using ultrasonic irradiation to improve the properties and recovery of MWCNTs-Pd/Fe nanocomposites, contributing to achievement of the Sustainable Development Goals (SDGs), including SDG-3, SDG-6.

Biotin-conjugated Ru(II) complexes with AIE characteristics as mitochondria-targeted photosensitizers for enhancing photodynamic therapy by disrupting cellular redox balance.

The potential use of Ru(II) complexes as photosensitizers (PSs) in photodynamic therapy (PDT) has gained significant attention. In comparison with fluorophores with aggregation-caused quenching (ACQ), fluorophores with aggregation-induced emission (AIE) characteristics exhibit sustained fluorescence and dispersibility in aqueous solutions. PSs with AIE characteristics have received much attention in recent years. Herein, we reported two novel biotin-conjugated Ru(II) polypyridyl complexes (Ru1 and Ru2) with AIE characteristics. When exposed to 460 nm (10 mW cm-2) light, Ru1 and Ru2 exhibited outstanding photostability and photocatalytic activity. Ru1 and Ru2 could efficiently generate singlet oxygen and induce pUC19 DNA photolysis when exposed to 460 nm light. Interestingly, both Ru1 and Ru2 also functioned as catalysts for NADH oxidation when exposed to 460 nm light. The presence of biotin fragments in Ru1 and Ru2 enhanced the specific uptake of these complexes by tumor cells. Both complexes showed minimal toxicity to selected cells in the dark. Nevertheless, the phototoxicity of both complexes significantly increased upon 460 nm light irradiation for 15 min. Further experiments revealed that Ru2 primarily accumulated in mitochondria and might bind to mitochondrial DNA. Under 460 nm light irradiation, Ru2 induced the generation of reactive oxygen species (ROS) and NADH depletion disrupting intracellular redox homeostasis in A549 cells, activating the mitochondrial apoptosis pathway resulting in up-regulation of apoptotic marker caspase-3, effectively damaged A549 cell DNA and arrested A549 cell cycle in the S phase. In vivo anti-tumor experiments were conducted to assess the effects of Ru2 on tumor growth in A549 tumor-bearing mice. The results showed that Ru2 effectively inhibited tumor growth under 460 nm light irradiation conditions. These findings indicate that Ru2 has great potential as a targeted photosensitizer for mitochondrial targeting imaging and photodynamic therapy of tumors.

Synergetic impact of combined navoximod with cisplatin mitigates chemo-immune resistance via blockading IDO1+ CAFs-secreted Kyn/AhR/IL-6 and pol ζ-prevented CIN in human oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is the most prevalent aggressive form of HNSC and treated with platinum-based chemotherapy as initial therapy. However, the development of acquired resistance and neurotoxicity to platinum agents poses a significant challenge to treat locally advanced OSCC. Notably, IDO1+ CAFs could promote immunosuppressive TME for OSCC progression. Therefore, we developed a potent IDO1 inhibitor navoximod to overcome chemo-immune resistance via an antitumor immune effect synergized with cisplatin in SCC-9 co-cultured IDO1+/IDO1- CAFs and SCC-7/IDO1+ CAFs-inoculated mice. The in vitro biological assays on IDO1+ CAFs co-cultured OSCC cancer cells supported that combined navoximod with cisplatin could mitigate chemo-immune resistance through blockading IDO1+ CAFs-secreted kynurenine (Kyn)-aryl hydrocarbon receptor (AhR)-IL-6 via suppressing p-STAT3/NF-κB signals and ceasing AhR-induced loss of pol ζ-caused chromosomal instability (CIN). Moreover, the combination elicited antitumor immunity via reducing IDO1+ CAFs-secreted Kyn/AhR and conferring pol ζ in SCC-7/IDO1+ CAFs-inoculated BALB/c mice. Meanwhile, the combination could block cisplatin-induced neurotoxicity and not interfere with chemotherapy. Taken together, the study investigated the promising therapeutic potential of combined navoximod with cisplatin to mitigate tumoral immune resistance via alleviating IDO1+ CAFs-secreted immune-suppression and CIN-caused cisplatin resistance, providing a paradigm for combined chemo-immunotherapy to prolong survival in patients with OSCC.

NLG-919 combined with cisplatin to enhance inhibitory effect on cell migration and invasion via IDO1-Kyn-AhR pathway in human nasopharyngeal carcinoma cell.

As a common aggressive head and neck cancer, nasopharyngeal carcinoma (NPC) received cisplatin treatment as a first-line chemotherapy. Platinum-induced resistance is a major limitation of current treatment strategy in the advanced NPC. Increased indoleamine 2,3-dioxygenase (IDO1) activities are found in cisplatin-resistant NPC cells versus cisplatin-sensitive NPC cells. As an IDO1 immunosuppressant, NLG-919 has entered clinical phase I to treat advanced solid tumors. To reverse cisplatin resistance, we investigated the combinatory application of cisplatin and NLG-919 in NPC treatment. In vitro biological studies on cisplatin-resistant and cisplatin-sensitive NPC cells were taken to imply that the combination of NLG-919 and cisplatin got a stronger impact on the induction of cell apoptosis and the inhibition of cell migration, exploring superior effect of antitumor over single drug. We proved that the mechanism of the combined therapy could inhibit the activity of IDO1, blocking amino acid tryptophan conversion to kynurenine through the kynurenine pathway, which further inhibited the aryl hydrocarbon receptor expression. Our study underscored the combination of cisplatin and NLG-919 as a potent therapeutic way for the reversal of cisplatin resistance.

Cardiolipin externalization mediates prion protein (PrP) peptide 106-126-associated mitophagy and mitochondrial dysfunction.

Proper mitochondrial performance is imperative for the maintenance of normal neuronal function to prevent the development of neurodegenerative diseases. Persistent accumulation of damaged mitochondria plays a role in prion disease pathogenesis, which involves a chain of events that culminate in the generation of reactive oxygen species and neuronal death. Our previous studies have demonstrated that PINK1/Parkin-mediated mitophagy induced by PrP106-126 is defective and leads to an accumulation of damaged mitochondria after PrP106-126 treatment. Externalized cardiolipin (CL), a mitochondria-specific phospholipid, has been reported to play a role in mitophagy by directly interacting with LC3II at the outer mitochondrial membrane. The involvement of CL externalization in PrP106-126-induced mitophagy and its significance in other physiological processes of N2a cells treated with PrP106-126 remain unknown. We demonstrate that the PrP106-126 peptide caused a temporal course of mitophagy in N2a cells, which gradually increased and subsequently decreased. A similar trend in CL externalization to the mitochondrial surface was seen, resulting in a gradual decrease in CL content at the cellular level. Inhibition of CL externalization by knockdown of CL synthase, responsible for de novo synthesis of CL, or phospholipid scramblase-3 and NDPK-D, responsible for CL translocation to the mitochondrial surface, significantly decreased PrP106-126-induced mitophagy in N2a cells. Meanwhile, the inhibition of CL redistribution significantly decreased PINK1 and DRP1 recruitment in PrP106-126 treatment but had no significant decrease in Parkin recruitment. Furthermore, the inhibition of CL externalization resulted in impaired oxidative phosphorylation and severe oxidative stress, which led to mitochondrial dysfunction. Our results indicate that CL externalization induced by PrP106-126 on N2a cells plays a positive role in the initiation of mitophagy, leading to the stabilization of mitochondrial function.

Adsorption of Cr(â ¥) polluted water by Fe3O4@SiO2-APTMS nanocomposites prepared in the presence of ultrasonic irradiation for sustainable water resources utilization.

The research on developing a purification technology for Cr(Ⅵ) polluted water with high efficiency and the low energy consumption is crucial for achieving several Sustainable Development Goals (SDGs). In order to achieve these goals, Fe3O4@SiO2-APTMS nanocomposites were prepared by Fe3O4 nanoparticles modified with silica and 3-aminopropyltrimethoxysilane in the presence of ultrasonic irradiation. The nanocomposites were characterized by TEM, FT-IR, VSM, TGA, BET, XRD, XPS and these analytic results proved that the nanocomposites were successfully prepared. The influential factors of Fe3O4@SiO2-APTMS on Cr(Ⅵ) adsorption have been explored and better experimental conditions have been obtained. The adsorption isotherm conformed to the Freundlich model. Pseudo-second-order kinetic model provided a better correlation for the experimental data compared to other kinetic models. Thermodynamic parameters for adsorption indicated that the adsorption of Cr(Ⅵ) was a spontaneous process. It was speculated that the adsorption mechanism of this adsorbent includes redox, electrostatic adsorption and physical adsorption. In summary, the Fe3O4@SiO2-APTMS nanocomposites were of great significance to human health and the remediation of heavy ion pollution, contributing to achievement of the Sustainable Development Goals (SDGs), including SDG-3, SDG-6.

PINK1/Parkin-mediated mitophagy in neurodegenerative diseases.

Mitochondria play key roles in bioenergetics, metabolism, and signaling; therefore, stable mitochondrial function is essential for cell survival, particularly in energy-intensive neuronal cells. In neurodegenerative diseases, damaged mitochondria accumulate in neurons causing associated bioenergetics deficiency, impaired cell signaling, defective cytoplasmic calcium buffering, and other pathological changes. Mitochondrial quality control is an important mechanism to ensure the maintenance of mitochondrial health, homeostasis, and mitophagy, the latter of which is a pathway that delivers defective mitochondria to the lysosome for degradation. Defective mitophagy is thought to be responsible for the accumulation of damaged mitochondria, which leads to cellular dysfunction and/or death in neurodegenerative diseases. PINK1/Parkin mainly regulates ubiquitin-dependent mitophagy, which is crucial for many aspects of mitochondrial physiology, particularly the initiation of autophagic mechanisms. Therefore, in the present review, we summarize the current knowledge of the conventional mitophagy pathway, focusing on the molecular mechanisms underlying mitophagy dysregulation in prion disease and other age-related neurodegenerative diseases, especially in relation to the PINK1/Parkin pathway. Moreover, we list the inducers of mitophagy that possess neuroprotective effects, in addition to their mechanisms related to the PINK1/Parkin pathway. These mechanisms may provide potential interventions centered on the regulation of mitophagy and offer therapeutic strategies for the treatment of neurodegenerative diseases.

RAB7A GTPase Is Involved in Mitophagosome Formation and Autophagosome-Lysosome Fusion in N2a Cells Treated with the Prion Protein Fragment 106-126.

Failed communication between mitochondria and lysosomes causes dysfunctional mitochondria, which may induce mitochondria-related neurodegenerative diseases. Here, we show that RAB7A, a small GTPase of the Rab family, mediates the crosstalk between these two important organelles to maintain homeostasis in N2a cells treated with PrP106-126. Specifically, we demonstrate that mitophagy deficiency in N2a cells caused by PrP106-126 is associated with dysregulated RAB7A localization in mitochondria. Cells lacking RAB7A display decreased mitochondrial colocalization with lysosomes and significantly increased mitochondrial protein expression, resulting in inhibited mitophagy. In contrast, overexpression of GTP-bound RAB7A directly induces lysosome colocalization with mitochondria. Further study revealed that GTP-bound RAB7A protects mitochondrial homeostasis by supporting autophagosome biogenesis. Moreover, we suggest that depletion of RAB7A leads to gross morphological changes in lysosomes, which prevents autophagosome-lysosome fusion and interferes with the breakdown of autophagic cargo within lysosomes. Overexpression of GTP-bound RAB7A can also alleviate PrP106-126-induced morphological damage and dysfunction of mitochondria, reducing neuronal apoptosis. Collectively, our data demonstrate that RAB7A successfully drives mitochondria to the autophagosomal lumen for degradation, suggesting that the communication of proteotoxic stress from mitochondria to lysosomes requires RAB7A, as a signaling molecule, to establish a link between the disturbed mitochondrial network and its remodeling. These findings indicate that small molecules regulating mitophagy have the potential to modulate cellular homeostasis and the clinical course of neurodegenerative diseases. Proposed model of mitophagy regulated by RAB7A. (1) Accumulating PrP106-126 induced mitophagy. (2) RAB7A is recruited to mitochondria. (3) ATG5-12 and ATG9A (5) vesicles are recruited to the autophagosome formation sites in a RAB7A-dependent manner. The ATG5-12 complex recruits and anchors LC3-I to form active LC3-II (4), accelerating mitophagosomal formation. The ATG9A vesicles are thought to be a source of membranes for autophagosome assembly. The recruitment of proteins and lipids induces membrane expansion and subsequent closure to form the mitophagosome. (6) Maintenance of the normal low lysosomal PH depends on active (GTP-bound) RAB7A. (7) RAB7A recruits effector molecules responsible for tight membrane interactions, and directly or indirectly, the subsequent autophagosome merges with the lysosome, and the cargo is completely degraded.

SARM1 participates in axonal degeneration and mitochondrial dysfunction in prion disease.

Prion disease represents a group of fatal neurogenerative diseases in humans and animals that are associated with energy loss, axonal degeneration, and mitochondrial dysfunction. Axonal degeneration is an early hallmark of neurodegeneration and is triggered by SARM1. We found that depletion or dysfunctional mutation of SARM1 protected against NAD+ loss, axonal degeneration, and mitochondrial functional disorder induced by the neurotoxic peptide PrP106-126. NAD+ supplementation rescued prion-triggered axonal degeneration and mitochondrial dysfunction and SARM1 overexpression suppressed this protective effect. NAD+ supplementation in PrP106-126-incubated N2a cells, SARM1 depletion, and SARM1 dysfunctional mutation each blocked neuronal apoptosis and increased cell survival. Our results indicate that the axonal degeneration and mitochondrial dysfunction triggered by PrP106-126 are partially dependent on SARM1 NADase activity. This pathway has potential as a therapeutic target in the early stages of prion disease.

PINK1-parkin-mediated neuronal mitophagy deficiency in prion disease.

A persistent accumulation of damaged mitochondria is part of prion disease pathogenesis. Normally, damaged mitochondria are cleared via a major pathway that involves the E3 ubiquitin ligase parkin and PTEN-induced kinase 1 (PINK1) that together initiate mitophagy, recognize and eliminate damaged mitochondria. However, the precise mechanisms underlying mitophagy in prion disease remain largely unknown. Using prion disease cell models, we observed PINK1-parkin-mediated mitophagy deficiency in which parkin depletion aggravated blocked mitochondrial colocalization with LC3-II-labeled autophagosomes, and significantly increased mitochondrial protein levels, which led to inhibited mitophagy. Parkin overexpression directly induced LC3-II colocalization with mitochondria and alleviated defective mitophagy. Moreover, parkin-mediated mitophagy was dependent on PINK1, since PINK1 depletion blocked mitochondrial Parkin recruitment and reduced optineurin and LC3-II proteins levels, thus inhibiting mitophagy. PINK1 overexpression induced parkin recruitment to the mitochondria, which then stimulated mitophagy. In addition, overexpressed parkin and PINK1 also protected neurons from apoptosis. Furthermore, we found that supplementation with two mitophagy-inducing agents, nicotinamide mononucleotide (NMN) and urolithin A (UA), significantly stimulated PINK1-parkin-mediated mitophagy. However, compared with NMN, UA could not alleviate prion-induced mitochondrial fragmentation and dysfunction, and neuronal apoptosis. These findings show that PINK1-parkin-mediated mitophagy defects lead to an accumulation of damaged mitochondria, thus suggesting that interventions that stimulate mitophagy may be potential therapeutic targets for prion diseases.

In Silico Functional Prediction and Expression Analysis of C2H2 Zinc-Finger Family Transcription Factor Revealed Regulatory Role of ZmZFP126 in Maize Growth.

The C2H2-zinc finger proteins (ZFP) comprise a large family of transcription factors with various functions in biological processes. In maize, the function regulation of C2H2- zine finger (ZF) genes are poorly understood. We conducted an evolution analysis and functional prediction of the maize C2H2-ZF gene family. Furthermore, the ZmZFP126 gene has been cloned and sequenced for further favorable allelic variation discovery. The phylogenetic analysis of the C2H2-ZF domain indicated that the position and sequence of the C2H2-ZF domain of the poly-zinc finger gene are relatively conserved during evolution, and the C2H2-ZF domain with the same position is highly conserved. The expression analysis of the C2H2-ZF gene family in 11 tissues at different growth stages of B73 inbred lines showed that genes with multiple transcripts were endowed with more functions. The expression analysis of the C2H2-ZF gene in P1 and P2 inbred lines under drought conditions showed that the C2H2-ZF genes were mainly subjected to negative regulation under drought stress. Functional prediction indicated that the maize C2H2-ZF gene is mainly involved in reproduction and development, especially concerning the formation of important agronomic traits in maize yield. Furthermore, sequencing and correlation analysis of the ZmZFP126 gene indicated that this gene was significantly associated with the SDW-NAP and TDW-NAP. The analysis of the relationship between maize C2H2-ZF genes and C2H2-ZF genes with known functions indicated that the functions of some C2H2-ZF genes are relatively conservative, and the functions of homologous genes in different species are similar.

Koumiss promotes Mycobacterium bovis infection by disturbing intestinal flora and inhibiting endoplasmic reticulum stress.

Mycobacterium bovis is the causative agent of bovine tuberculosis and also responsible for serious threat to public health. Koumiss is a fermented mare's milk product, used as traditional drink. Here, we explored the effect of koumiss on gut microbiota and the host immune response against M bovis infection. Therefore, mice were treated with koumiss and fresh mare milk for 14 days before M bovis infection and continue for 5 weeks after infection. The results showed a clear change in the intestinal flora of mice treated with koumiss, and the lungs of mice treated with koumiss showed severe edema, inflammatory infiltration, and pulmonary nodules in M bovis-infected mice. Notably, we found that the content of short-chain fatty acids was significantly lower in the koumiss-treated group compared with the control group. However, the expression of endoplasmic reticulum stress and apoptosis-related proteins in the lungs of koumiss-treated mice were significantly decreased. Collectively, these findings suggest that koumiss treatment disturb the intestinal flora of, which is associated with disease severity and the possible mechanism that induces lungs pathology. Our current findings can be exploited further to establish the "gut-lung" axis which might be a novel strategy for the control of tuberculosis.

Caspase-1 inhibits IFN-ß production via cleavage of cGAS during M. bovis infection.

Mycobacterium bovis (M. bovis) infection triggers cytokine production via pattern recognition receptors. These cytokines include type I interferons (IFNs) and interleukin-1ß (IL-1ß). Excessive type I IFN levels impair host resistance to M. bovis infection. Therefore, strict control of type I IFN production is helpful to reduce pathological damage and bacterial burden. Here, we found that a deficiency in caspase-1, which is the critical component of the inflammasome responsible for IL-1ß production, resulted in increased IFN-ß production upon M. bovis infection. Subsequent experiments demonstrated that caspase-1 activation reduced cyclic GMP-AMP synthase (cGAS) expression, thereby inhibiting downstream TANK-binding kinase 1 (TBK1)- interferon regulatory factor 3 (IRF3) signaling and ultimately reducing IFN production. A deficiency in caspase-1 activation enhanced the bacterial burden during M. bovis infection in vitro and in vivo and aggravated pathological lesion formation. Thus, caspase-1 activation reduced IFN-ß production upon M. bovis infection by dampening cGAS-TBK1-IRF3 signaling, suggesting that the inflammasome protects hosts by negatively regulating harmful cytokines.

Deformation modeling based on mechanical properties of liver tissue for virtuanormal vectors of trianglesl surgical simulation.

PURPOSE: In this paper, a method for rapidly constructing a virtual surgical simulation system is proposed. A deformation model based on the mechanical properties of the liver and a rapid collision detection between the surgical micro-instruments and the liver tissue are included in this method. The purpose of this work is to improve the accuracy and real time of particle model deformation interaction in virtual surgery system. METHODS: Firstly, a finite element model is established based on the constitutive model parameters of liver tissue. According to the simulation results, a mathematical model of node displacement is established. Secondly, the virtual liver is established based on the fast model reconstruction method, and the virtual manipulator is controlled by Geomagic Touch manipulator. Based on the hybrid bounding box, a rapid collision detection process between the instrument and liver is realized and the proposed deformation method is used to simulate the deformation of liver tissue. RESULTS: The simulation and experiment results show that the proposed deformation model can achieve high deformation interaction accuracy. The collision detection algorithm based on the hybrid bounding boxes can realize the collision between the liver and the instrument, and the established virtual surgical simulation system can simulate the liver tissue deformation in the case of small loading displacement. CONCLUSIONS: The effectiveness of the collision detection algorithm and deformation model was verified by an established virtual surgery simulation system. The proposed rapid construction method of virtual surgical simulation is feasible.

Association of MDM4 Gene rs4245739 Polymorphism with the Risk and Clinical Characteristics of Colorectal Cancer in a Chinese Han Population.

BACKGROUND: Studies show that MDM4 may play a pivotal role in colorectal cancer (CRC). Recently, a host of studies suggest that MDM4 gene rs4245739 polymorphism may modify the risk of different cancers. METHODS: In this study, we were interested whether MDM4 gene rs4245739 polymorphism correlated with the risk and clinical characteristics of CRC. Logistic regression was adopted to estimate the association of rs4245739 polymorphism and CRC risk. RESULTS: We enrolled 444 CRC patients and 530 controls and found MDM4 gene rs4245739 polymorphism may decrease the risk of CRC. Stratified analyses uncovered that this variant was connected to a less risk of CRC in females, non-drinkers, non-smokers, and people under 60 years old. Additionally, rs4245739 polymorphism was related to TNM staging, pathological type, tumor size, and location of CRC. Furthermore, this polymorphism was significantly linked with the survival of CRC. CONCLUSION: Totally, this study suggests that MDM4 rs4245739 polymorphism is linked with the risk and clinical characteristics of CRC.

Melatonin regulates mitochondrial dynamics and alleviates neuron damage in prion diseases.

Prion diseases are neurodegenerative diseases associated with neuron damage and behavioral disorders in animals and humans. Melatonin is a potent antioxidant and is used to treat a variety of diseases. We investigated the neuroprotective effect of melatonin on prion-induced damage in N2a cells. N2a cells were pretreated with 10 µM melatonin for 1 hour followed by incubation with 100 µM PrP106-126 for 24 hours. Melatonin markedly alleviated PrP106-126-induced apoptosis of N2a cells, and inhibited PrP106-126-induced mitochondrial abnormality and dysfunction, including mitochondrial fragmentation and overproduction of reactive oxygen species (ROS), suppression of ATP, reduced mitochondrial membrane potential (MMP), and altered mitochondrial dynamic proteins dynamin-related protein 1 (DRP1) and optic atrophy protein 1 (OPA1). Our findings identify that pretreatment with melatonin prevents the deleterious effects of PrPSc on mitochondrial function and dynamics, protects synapses and alleviates neuron damage. Melatonin could be a novel and effective medication in the therapy of prion diseases.

Complementary Oxidative Generation of Iminyl Radicals from α-Imino-oxy Acids: Silver-Catalyzed C-H Cyanoalkylation of Heterocycles and Quinones.

A complementary and general strategy for the oxidative generation of iminyl radicals from the readily available α-imino-oxy acids has been established through silver-catalyzed decarboxylation. To demonstrate its synthesis utility, the direct C-H cyanoalkylation of heterocycles and quinones with cyclic α-imino-oxy acids via the iminyl radical-mediated C-C bond cleavage is developed. This cost-effective method takes place under mild reaction conditions and exhibits a broad substrate scope.

Mitochondrial Transcription Factor A Regulates Mycobacterium bovis-Induced IFN-ß Production by Modulating Mitochondrial DNA Replication in Macrophages.

BACKGROUND: Mycobacterium bovis persistently survives in macrophages by developing multiple strategies to evade host immune responses, and the early induction of interferon-ß (IFN-ß) is one of these critical strategies. The mitochondrial transcription factor A (TFAM) plays a vital role in mitochondrial DNA (mtDNA) metabolism and has been suggested to influence IFN-ß production in response to viral infection. However, its role in the production of IFN-ß by M. bovis has not been elucidated. METHODS: In the current study, we investigated the role of TFAM in the production of IFN-ß in M. bovis-infected macrophages. RESULTS: We found that knockdown of TFAM expression significantly reduced M. bovis-induced IFN-ß production, mtDNA copy numbers and cytosolic mtDNA were increased in murine macrophages with M. bovis infection, cytosolic mtDNA contributed to IFN-ß production, and TFAM was required for the increase in mtDNA copy numbers induced by M. bovis. We also observed that TFAM affected the intracellular survival of M. bovis. CONCLUSIONS: Our results suggest that TFAM plays an essential role in M. bovis-induced IFN-ß production by regulating mtDNA copy numbers. This might be a new strategy adopted by M. bovis for its intracellular survival.