Macrophage microvesicle-derived circ_YTHDF2 in methamphetamine-induced chronic lung injury.

Long-term abuse of methamphetamine (MA) can cause lung toxicity. Intercellular communication between macrophages and alveolar epithelial cells (AECs) is critical for maintaining lung homeostasis. Microvesicles (MVs) are an important medium of intercellular communication. However, the mechanism of macrophage MVs (MMVs) in MA-induced chronic lung injury remains unclear. This study aimed to investigate if MA can augment the activity of MMVs and if circ_YTHDF2 is a key factor in MMV-mediated macrophage-AEC communication, and to explore the mechanism of MMV-derived circ_YTHDF2 in MA-induced chronic lung injury. MA elevated peak velocity of the pulmonary artery and pulmonary artery accelerate time, reduced the number of alveolar sacs, thickened the alveolar septum, and accelerated the release of MMVs and the uptake of MMVs by AECs. Circ_YTHDF2 was downregulated in lung and MMVs induced by MA. The immune factors in MMVs were increased by si-circ_YTHDF. Circ_YTHDF2 knockdown in MMVs induced inflammation and remodelling in the internalised AECs by MMVs, which was reversed by circ_YTHDF2 overexpression in MMVs. Circ_YTHDF2 bound specifically to and sponged miRNA-145-5p. Runt-related transcription factor 3 (RUNX3) was identified as potential target of miR-145-5p. RUNX3 targeted zinc finger E-box-binding homeobox 1 (ZEB1)-related inflammation and EMT of AECs. In vivo, circ_YTHDF2 overexpression-MMVs attenuated MA-induced lung inflammation and remodelling by the circ_YTHDF2-miRNA-145-5p-RUNX3 axis. Therefore, MA abuse can induce pulmonary dysfunction and alveolus injury. The immunoactivity of MMVs is regulated by circ_YTHDF2. Circ_YTHDF2 in MMVs is the key to communication between macrophages and AECs. Circ_YTHDF2 sponges miR-145-5p targeting RUNX3 to participate in ZEB1-related inflammation and remodelling of AECs. MMV-derived circ_YTHDF2 would be an important therapeutic target for MA-induced chronic lung injury. KEY POINTS: Methamphetamine (MA) abuse induces pulmonary dysfunction and alveoli injury. The immunoactivity of macrophage microvesicles (MMVs) is regulated by circ_YTHDF2. Circ_YTHDF2 in MMVs is the key to MMV-mediated intercellular communication between macrophages and alveolar epithelial cells. Circ_YTHDF2 sponges miR-145-5p targeting runt-related transcription factor 3 (RUNX3) to participate in zinc finger E-box-binding homeobox 1 (ZEB1)-related inflammation and remodelling. MMV-derived circ_YTHDF2 would be an important therapeutic target for MA-induced chronic lung injury.

Cobalt-catalyzed Divergent Markovnikov and Anti-Markovnikov Hydroamination.

Catalytic hydroamination of the readily available alkenes is among the most straightforward means to construct diverse alkyl amines. To this end, the facile access to both regioselectivity, i.e., Markovnikov or anti-Markovnikov hydroamination, with minimum reaction-parameter alternation, remains challenging. Herein, we report a cobalt-catalyzed highly selective and divergent Markovnikov and anti-Markovnikov hydroamination of alkenes, in which the switch of regioselectivity is achieved simply by the variation of the addition sequence of 9-BBN.

Recent advances in cobalt-catalyzed allylic functionalization.

Unlike many other state-of-the-art transition-metal-catalyzed allylic substitutions, cobalt-catalyzed allylic substitution has received much less attention from synthetic chemists for a long time despite the fact that cobalt is an earth-abundant, low-cost and thus much more sustainable option as either a reagent or a catalyst in organic synthesis. Recently, there has been an upsurge in the use of cobalt catalysis in allylic functionalization reactions, including allylic substitution, nucleophilic allylation, and Heck-type allylic functionalization, to construct synthetically significant building blocks featuring a double bond available for diverse downstream synthetic manipulations. This review highlights the current development of cobalt catalysis in allylic functionalization with an in-depth discussion of the reaction scope and mechanistic insights.

Cobalt fluorides: preparation, reactivity and applications in catalytic fluorination and C-F functionalization.

Recent advances in the investigation of cobalt fluorides in organofluorine chemistry are highlighted. The preparation and reactivity of inorganic and organometallic cobalt fluorides are discussed. The in-depth understanding of the structures and reactivity of cobalt fluorides allows chemists to develop diverse innovative catalytic fluorination and C-F functionalization.

Redox Neutral Radical-Relay Cobalt Catalysis toward C-H Fluorination and Amination.

A redox neutral radical-relay cobalt-catalyzed intramolecular C-H fluorination of N-fluoroamides featuring the in situ formed cobalt fluorides as the latent radical fluorinating agents is reported. Moreover, the reactivity of such a cobalt catalysis could be diverted from C-H fluorination to amination by engineering substrates' conformational flexibility. Preliminary mechanistic studies (UV-vis spectroscopy, cyclic voltammetry studies and DFT calculations, etc.) support the reaction proceeding a redox neutral radical-relay mechanism.

[Molecular cloning and expression analysis of a SUPERMAN-like zinc finger protein gene in upland cotton].

The zinc finger proteins belong to the largest family of regulatory transcription factors, which play an important role in growth and development in animal and plant systems. SUPERMAN-like zinc finger protein gene has only one "finger like" motif. A pair of degenerate primers was designed according to the conserved regions, and 3 kinds of EST of this family were isolated from cotton through RT-PCR. The full length of one SUPERMAN-like zinc finger protein also has been acquired. The entire coding region is 744 bp and encodes a polypeptide of 248 amino acids with 40% homology to RBE protein of Arabidopsis deposited in the GenBank. This gene was designated as GZFP. It has the conserved zinc finger domain and the leucine rich region at the carboxyl terminus but no intron in the coding region. GZFP also has the plant nuclear localization signal. GZFP shows a more expression pattern in floral buds, ovaries, petals and roots than in phloem, xylem, fibers, leaves and seeds of cotton by RT-PCR, although it has a very low detection level and there is not any homologous ESTs found in the GenBank. Analysis of the 5' flanking sequence shows there are several regulatory elements responsible for pollen and root expression, four core sites required for binding of Dof proteins and four light-regulated elements.

[Therapeutical effects of esculentoside A on rats with MsPGN induced by anti-Thy1.1 antibody].

OBJECTIVE: To observe the therapeutical effects of esculentoside A (EsA) on rats with mesangial proliferative glomerulonephritis (MsPGN) induced by anti-Thy1.1 antibody and make a comparison of the effects between EsA and dexamethasone (DXM). METHODS: Wistar rats with MsPGN induced by anti-Thy1.1 serum (ATS) were randomly divided into 3 groups: EsA group, DXM group, and model group. Moreover, a normal group was used for comparison. The BUN, SCr, urinary protein and renal pathological changes were examined after 7 d treatment with EsA and DXM. RESULTS: The urinary protein, cell count and mesangium area of glomerulus were significantly higher in all modeled groups than in normal group (P<0.001-0.05), and they were significantly lower in the treated groups than in untreated group (P<0.001-0.01). CONCLUSION: The results suggest that EsA is effective for reducing the urinary protein excretion and inhibiting the proliferation process of glomerular mesangium and matrix in rats with MsPGN.

[Pathogenesis of rat mesangial proliferative glomerulonephritis induced by anti-Thy1 antibody].

OBJECTIVE: To probe into the pathogenesis of rat mesangial proliferative glomerulonephritis (MsPGN) induced by anti-Thy1 antibody. METHODS: Anti-Thy1 serum was produced, and then intravenously injected into Wistar rats for establishing an experimental model of MsPGN. The control group received intravenous injection of normal saline. Urinary volume and urinary protein were examined every other day. The IL-1, IL-6 and TNF contents of serum were detected by radioimmunoassay. Pathologic morphology of renal section was observed with micrscope and BI2000 Image Analysis System. The rats of model group were killed on the 1st, 3rd, 5th and 7th days. RESULTS: No significant difference was seen between the model group and control group in regard to the volume of urine and in-take water (P > 0.05). The levels of urinary protein, IL-1, IL-6 and TNF in model group were significantly higher than those in control group at all time points (P < 0.001-0.005). Glomerular mesangium cells and matrix in the model group were obviously proliferative, compared with those in control group. CONCLUSION: It is suggested that cytokine plays an important role in the onset of MsPGN.