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We report two novel three‐dimensional copper‐benzoquinoid metal–organic frameworks (MOFs), [Cu4L3]n and [Cu4L3 ⋅ Cu(iq)3]n (LH4=1,4‐dicyano‐2,3,5,6‐tetrahydroxybenzene, iq=isoquinoline). Spectroscopic techniques and computational studies reveal the unprecedented mixed valency in MOFs, formal Cu(I)/Cu(III). This is the first time that formally Cu(III) species are witnessed in metal–organic extended solids. The coordination between the mixed‐valence metal and redox‐non‐innocent ligand L, which promotes through‐bond charge transfer between Cu metal sites, allows better metal‐ligand orbital overlap of the d‐π conjugation, leading to strong long‐range delocalization and semiconducting behavior. Our findings highlight the significance of the unique mixed valency between formal Cu(I) and highly‐covalent Cu(III), non‐innocent ligand, and pore environments of these bench stable Cu(III)‐containing frameworks on multielectron transfer and electrochemical properties. [ABSTRACT FROM AUTHOR]

Background and Purpose: Renal fibrosis is the final common outcome in most forms of chronic kidney disease (CKD). However, the underlying causal mechanisms remain obscure. The present study examined whether transmembrane member 16A (TMEM16A), a Ca2+‐activated chloride channel, contributes to the progression of renal fibrosis. Experimental Approach Masson staining, western blot and immunohistochemistry were used to measure renal fibrosis and related proteins expression. MQAE was used to evaluate the intracellular Cl− concentration. Key Results: TMEM16A expression was significantly up‐regulated in fibrotic kidneys of unilateral ureteral obstruction (UUO) and high‐fat diet murine models and in renal samples of IgA nephropathy patients. In vivo knockdown of TMEM16A with adenovirus harbouring TMEM16A‐shRNA or inhibition of TMEM16A channel activity with inhibitors CaCCinh‐A01 or T16Ainh‐A01 effectively prevented UUO‐induced renal fibrosis and decreased protein expression of fibronectin, α‐SMA and collagen in the obstructed kidneys. In cultured HK2 cells, knockdown or inhibition of TMEM16A suppressed TGF‐β1‐induced epithelial–mesenchymal transition, reduced snail1 expression and phosphorylation of Smad2/3 and ERK1/2, whereas overexpression of TMEM16A showed the opposite effects. TGF‐β1 increased [Cl−]i in HK2 cells, which was inhibited by knockdown or inhibition of TMEM16A. Reducing [Cl−]i significantly blunted TGF‐β1‐induced Smad2/3 phosphorylation and profibrotic factors expression. The profibrotic effects of TGF‐β1 were also reduced by inhibition of serum‐ and glucocorticoid‐inducible protein kinase 1 (SGK1). SGK1 was also suppressed by reducing [Cl−]i. Conclusion and Implications: Blockade of TMEM16A prevented the progression of kidney fibrosis, likely by suppressing [Cl−]i/SGK1/TGF‐β1 signalling pathway. TMEM16A may be a potential new therapeutic target against renal fibrosis. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a complex condition and serious health problem, with growing occurrence of DM-associated complications occurring globally. Persistent hyperglycemia is confirmed as promoting neurovascular dysfunction leading to irreversible endothelial cell dysfunction, increased neuronal cell apoptosis, oxidative stress and inflammation. These collaboratively and individually result in micro- and macroangiopathy as well as neuropathy demonstrated by progressive neuronal loss. Recently, major efforts have been pursued to select not only useful diagnostic and prognostic biomarkers, but also novel therapeutic approaches. Both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) belong to a class of non-coding RNAs identified in most of the body fluids i.e., peripheral blood, cerebrospinal fluid, brain tissue and neurons. Numerous miRNAs, lncRNAs and their target genes are able to modulate signaling pathways known to play a role in the pathophysiology of progressive neuronal dysfunction. Therefore, they pose as promising biomarkers and treatment for the vast majority of neurodegenerative disorders. This review provides an overall assessment of both miRNAs' and lncRNAs' utility in decelerating progressive nervous system impairment, including neurodegeneration in diabetic pathways. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) is an essential endogenous signaling molecule regulating multifaceted physiological functions in the (cardio)vascular, neuronal, and immune systems. Due to the short half-life and location-/concentration-dependent physiological function of NO, translational application of NO as a novel therapeutic approach, however, awaits a strategy for spatiotemporal control on the delivery of NO. Inspired by the magnetic hyperthermia and magneto-triggered drug release featured by Fe 3 O 4 conjugates, in this study, we aim to develop a magnetic responsive NO-release material (MagNORM) featuring dual NO-release phases, namely, burst and steady release, for the selective activation of NO-related physiology and treatment of bacteria-infected cutaneous wound. After conjugation of NO-delivery [Fe(μ- S -thioglycerol)(NO) 2 ] 2 with a metal-organic framework (MOF)-derived porous Fe 3 O 4 @C, encapsulation of obtained conjugates within the thermo-responsive poly(lactic- co -glycolic acid) (PLGA) microsphere completes the assembly of MagNORM. Through continuous/pulsatile/no application of the alternating magnetic field (AMF) to MagNORM, moreover, burst/intermittent/slow release of NO from MagNORM demonstrates the AMF as an ON/OFF switch for temporal control on the delivery of NO. Under continuous application of the AMF, in particular, burst release of NO from MagNORM triggers an effective anti-bacterial activity against both Gram-positive Staphylococcus aureus ( S. aureus ) and Gram-negative Escherichia coli ( E. coli ). In addition to the magneto-triggered bactericidal effect of MagNORM against E. coli -infected cutaneous wound in mice, of importance, steady release of NO from MagNORM without the AMF promotes the subsequent collagen formation and wound healing in mice.

During our screening programme for agrochemicals from Chinese medicinal herbs, the root bark essential oil of Periploca sepium was found to possess strong contact toxicity against the fruit flies, Drosophila melanogaster with a LD(50) value of 1.22 µg/adult. The main component of the essential oil was identified to be 2-hydroxy-4-methoxy-benzaldehyde (78.8%), followed by linalool (2.8%) and (-)-α-terpineol (2.7%). The 2-hydroxy-4-methoxy-benzaldehyde was further isolated and identified by bioassay-directed fractionation. The compound showed strong contact toxicity against D. melanogaster and the maize weevil (Sitophilus zeamais) with LD(50) values of 1.47 and 6.99 µg/adult, respectively.