The Role of MicroRNAs in Impaired Diabetic Wound Healing

Diabetes mellitus is a worldwide pandemic, affecting 29 million Americans, resulting in substantial morbidity and mortality, and accounting for an annual healthcare expenditure exceeding $176 billion in the US alone. This burden of disease is the result of a progressive disease associated with numerous complications and the development of chronic wounds, which remain the leading cause of hospital admissions and nontraumatic lower extremity amputations in diabetic patients. Despite clinical strategies aimed at prevention and early detection, patients with diabetes continue to remain at risk of developing chronic diabetic wounds due to poor patient compliance and progression of the diabetic phenotype. Development of the diabetic phenotype and wound healing impairment is associated with dysregulation of microRNAs that regulate inflammation, extracellular matrix composition, and angiogenesis; here we present evidence from the studies that demonstrate correction of microRNA dysregulation expedites wound healing and reverses the diabetic skin phenotype

Nearly 100% selective and visible-light-driven methane conversion to formaldehyde via. single-atom Cu and Wδ+

Direct solar-driven methane (CH4) reforming is highly desirable but challenging, particularly to achieve a value-added product with high selectivity. Here, we identify a synergistic ensemble effect of atomically dispersed copper (Cu) species and partially reduced tungsten (Wδ+), stabilised over an oxygen-vacancy-rich WO3, which enables exceptional photocatalytic CH4 conversion to formaldehyde (HCHO) under visible light, leading to nearly 100% selectivity, a very high yield of 4979.0 μmol·g-1 within 2 h, and the normalised mass activity of 8.5 × 106 μmol·g-1Cu·h-1 of HCHO at ambient temperature. In-situ EPR and XPS analyses indicate that the Cu species serve as the electron acceptor, promoting the photo-induced electron transfer from the conduction band to O2, generating reactive •OOH radicals. In parallel, the adjacent Wδ+ species act as the hole acceptor and the preferred adsorption and activation site of H2O to produce hydroxyl radicals (•OH), and thus activate CH4 to methyl radicals (•CH3). The synergy of the adjacent dual active sites boosts the overall efficiency and selectivity of the conversion process

Inhibition of stromal cell-derived factor-1α further impairs diabetic wound healing

ObjectiveImpaired diabetic wound healing is associated with abnormal stromal cell-derived factor (SDF)-1α production, decreased angiogenesis, and chronic inflammation. Lentiviral-mediated overexpression of SDF-1α can correct the impairments in angiogenesis and healing in diabetic wounds. We hypothesized that SDF-1α is a critical component of the normal wound-healing response and that inhibition of SDF-1α would further delay the wound-healing process.MethodsdB/Db diabetic mice and Db/+ nondiabetic mice were wounded with an 8-mm punch biopsy and the wounds treated with a lentiviral vector containing either the green fluorescent protein (GFP) or SDF-1α inhibitor transgene. The inhibitor transgene is a mutant form of SDF-1α that binds, but does not activate, the CXCR4 receptor. Computerized planimetry was used to measure wound size daily. Wounds were analyzed at 3 and 7 days by histology and for production of inflammatory markers using real-time polymerase chain reaction. The effect of the SDF-1α inhibitor on cellular migration was also assessed.ResultsInhibition of SDF-1α resulted in a significant decrease in the rate of diabetic wound healing, (3.8 vs 6.5 cm2/day in GFP-treated wounds; P = .04), and also impaired the early phase of nondiabetic wound healing. SDF-1α inhibition resulted in fewer small-caliber vessels, less granulation tissue formation, and increased proinflammatory gene expression of interleukin-6 and macrophage inflammatory protein-2 in the diabetic wounds.ConclusionsThe relative level of SDF-1α in the wound plays a key role in the wound-healing response. Alterations in the wound level of SDF-1α, as seen in diabetes or by SDF-1α inhibition, impair healing by decreasing cellular migration and angiogenesis, leading to increased production of inflammatory cytokines and inflammation. Inhibition of SDF-1α further impairs diabetic wound healing.Clinical RelevanceDiabetes results in a significant impairment in wound healing, leading to significant morbidity and health care expenditures. The pathophysiology that underlies this process is multifactorial, including abnormal growth factor production, cellular migration, and cellular function. Stromal cell-derived factor (SDF)-1α is a key chemokine involved in the wound-healing process and is involved in cellular recruitment and angiogenesis. SDF-1α is decreased in diabetic individuals. This study showed that inhibition of SDF-1α results in an even more dramatic delay in the diabetic wound-healing process and even results in a delay in the early phases of wound healing in normal mice, further supporting its role in wound healing. Inhibition of this chemokine promotes greater inflammatory cytokine production, inflammatory cell migration, and less vasculogenesis after dermal wounding. This study identifies SDF-1α as an essential component of normal wound healing and provides a potential therapeutic target to improve the diabetic wound-healing impairment

Synergy of Pd atoms and oxygen vacancies on In₂O₃ for methane conversion under visible light

Methane (CH4) oxidation to high value chemicals under mild conditions through photocatalysis is a sustainable and appealing pathway, nevertheless confronting the critical issues regarding both conversion and selectivity. Herein, under visible irradiation (420 nm), the synergy of palladium (Pd) atom cocatalyst and oxygen vacancies (OVs) on In2O3 nanorods enables superior photocatalytic CH4 activation by O2. The optimized catalyst reaches ca. 100 μmol h-1 of C1 oxygenates, with a selectivity of primary products (CH3OH and CH3OOH) up to 82.5%. Mechanism investigation elucidates that such superior photocatalysis is induced by the dedicated function of Pd single atoms and oxygen vacancies on boosting hole and electron transfer, respectively. O2 is proven to be the only oxygen source for CH3OH production, while H2O acts as the promoter for efficient CH4 activation through ·OH production and facilitates product desorption as indicated by DFT modeling. This work thus provides new understandings on simultaneous regulation of both activity and selectivity by the synergy of single atom cocatalysts and oxygen vacancies

PdCu nanoalloy decorated photocatalysts for efficient and selective oxidative coupling of methane in flow reactors

Methane activation by photocatalysis is one of the promising sustainable technologies for chemical synthesis. However, the current efficiency and stability of the process are moderate. Herein, a PdCu nanoalloy (~2.3 nm) was decorated on TiO2, which works for the efficient, stable, and selective photocatalytic oxidative coupling of methane at room temperature. A high methane conversion rate of 2480 μmol g-1 h-1 to C2 with an apparent quantum efficiency of ~8.4% has been achieved. More importantly, the photocatalyst exhibits the turnover frequency and turnover number of 116 h-1 and 12,642 with respect to PdCu, representing a record among all the photocatalytic processes (λ > 300 nm) operated at room temperature, together with a long stability of over 112 hours. The nanoalloy works as a hole acceptor, in which Pd softens and weakens C-H bond in methane and Cu decreases the adsorption energy of C2 products, leading to the high efficiency and long-time stability

Efficient hole abstraction for highly selective oxidative coupling of methane by Au-sputtered TiO2 photocatalysts

Photocatalytic oxidative coupling of methane (OCM) produces C2 molecules that can be used as building blocks for synthesis of fuels and chemicals. However, the yield rate and the selectivity of C2 products are still moderate due to the stable nature of methane molecules. Here we develop a Au nanocluster-loaded TiO2 photocatalyst by a sputtering approach, achieving a high methane conversion rate of 1.1 mmol h−1, C2 selectivity of ~90% and apparent quantum efficiency of 10.3 ± 0.6%. The high C2/C2+ yield rate is on the same order of magnitude as the benchmark thermal catalysts in OCM processes operated at high temperature (>680 °C). Au nanoparticles are shown to prolong TiO2 photoelectron lifetimes by a factor of 66 for O2 reduction, together with Au acting as a hole acceptor and catalytic centre to promote methane adsorption, C–H activation and C–C coupling. This work underscores the importance of multifunctional co-catalysts and mechanistic understanding to improve photocatalytic OCM

Unique hole-accepting carbon-dots promoting selective carbon dioxide reduction nearly 100% to methanol by pure water

X.L., M.K.B., J.T. acknowledge EPSRC (EP/S018204/2/1), Leverhulme Trust (Grant No: RPG-2017-122) and Newton Advanced Fellowship grant ((NA170422 and NAF\R1\191163).). X.H., Z.X.G. and S.A.S. acknowledge UCL Grace High-Performance Computing Facility (Grace@UCL) and EPSRC (EP/K021192/1, EP/L018330/1). R.G. thanks the FRQNT for postdoctoral funding and NSERC for operational funding. Y.W., J.C. and C.J., acknowledge CSC Scholarship. R.G., J.F.T. and J.R.D. acknowledge ERC AdG Intersolar grant (291482). J.F.T. acknowledges EPSRC CDT (EP/L015277/1). W.Z. thanks EPSRC for Titan Themis S/TEM microscope (EP/L017008/01). We also thank Dr. Jijia Xie for constructive comments on experimental design.Solar-driven CO2 reduction by abundant water to alcohols can supply sustainable liquid fuels and alleviate global warming. However, the sluggish water oxidation reaction has been hardly reported to be efficient and selective in CO2 conversion due to fast charge recombination. Here, using transient absorption spectroscopy, we demonstrate that microwave-synthesised carbon-dots (mCD) possess unique hole-accepting nature, prolonging the electron lifetime (t50%) of carbon nitride (CN) by six folds, favouring a six-electron product. mCD-decorated CN stably produces stoichiometric oxygen and methanol from water and CO2 with nearly 100% selectivity to methanol and internal quantum efficiency of 2.1% in the visible region, further confirmed by isotopic labelling. Such mCD rapidly extracts holes from CN and prevents the surface adsorption of methanol, favourably oxidising water over methanol and enhancing the selective CO2 reduction to alcohols. This work provides a unique strategy for efficient and highly selective CO2 reduction by water to high-value chemicals.Publisher PDFPeer reviewe

Internet addiction, loneliness, and academic burnout among Chinese college students: a mediation model

BackgroundThe dynamics of education and student life have changed since the COVID-19 pandemic. Our society, especially the education system, has become largely dependent on the Internet. This paradigm shifts largely took place in the last few decades. As such, there are various ways in which we cannot comprehend the impact that the Internet can have on student psychology, and how multiple other factors could influence that. Internet addiction and its relationship with academic burnout, along with the impact of loneliness, are all essential factors that must be discussed candidly in the post-COVID-19 era. Hence, the objective of this study was, therefore, to explore the relationship between Internet addiction, loneliness, and academic burnout among Chinese college students as well as the mediating role of loneliness.MethodsWe conducted a cross-sectional questionnaire survey at a Chinese university from October to November 2022. In total, 810 valid respondents were selected via random cluster sampling using the well-established Internet Addiction, Loneliness, and Academic Burnout Scale. The primary approach of mediation analysis and structural equation modeling testing examined the relationships among the three components.ResultsInternet addiction could be responsible for academic burnout among college students. Loneliness partially mediates the relationship between Internet addiction and academic burnout. In a mediated way, different types of loneliness contribute to different types of academic burnout.ConclusionPsychological interventions for loneliness, especially emotional loneliness prevention, are the critical aspects of the problem of Internet addiction accompanied with academic burnout. The causal relationship between Internet addiction and academic burnout, possibly of a two-way nature, needs to be further explored in the next future