Solid/liquid interfaces are ubiquitous in nature and knowledge of their atomic-level structure is essential in elucidating many phenomena in chemistry, physics, materials science and Earth science
. ...In electrochemistry, in particular, the detailed structure of interfacial water, such as the orientation and hydrogen-bonding network in electric double layers under bias potentials, has a significant impact on the electrochemical performances of electrode materials
. To elucidate the structures of electric double layers at electrochemical interfaces, we combine in situ Raman spectroscopy and ab initio molecular dynamics and distinguish two structural transitions of interfacial water at electrified Au single-crystal electrode surfaces. Towards negative potentials, the interfacial water molecules evolve from structurally 'parallel' to 'one-H-down' and then to 'two-H-down'. Concurrently, the number of hydrogen bonds in the interfacial water also undergoes two transitions. Our findings shed light on the fundamental understanding of electric double layers and electrochemical processes at the interfaces.
Diabetic nephropathy (DN) is one of the most common complications in diabetes mellitus and the leading cause of end-stage renal disease. TGF-β is a pleiotropic cytokine and has been recognized as a ...key mediator of DN. However, anti-TGF-β treatment for DN remains controversial due to the diverse role of TGF-β1 in DN. Thus, understanding the regulatory role and mechanisms of TGF-β in the pathogenesis of DN is the initial step towards the development of anti-TGF-β treatment for DN. In this review, we first discuss the diverse roles and signaling mechanisms of TGF-β in DN by focusing on the latent versus active TGF-β1, the TGF-β receptors, and the downstream individual Smad signaling molecules including Smad2, Smad3, Smad4, and Smad7. Then, we dissect the regulatory mechanisms of TGF-β/Smad signaling in the development of DN by emphasizing Smad-dependent non-coding RNAs including microRNAs and long-non-coding RNAs. Finally, the potential therapeutic strategies for DN by targeting TGF-β signaling with various therapeutic approaches are discussed.
Elucidating hydrogen oxidation reaction (HOR) mechanisms in alkaline conditions is vital for understanding and improving the efficiency of anion‐exchange‐membrane fuel cells. However, uncertainty ...remains around the alkaline HOR mechanism owing to a lack of direct in situ evidence of intermediates. In this study, in situ electrochemical surface‐enhanced Raman spectroscopy (SERS) and DFT were used to study HOR processes on PtNi alloy and Pt surfaces, respectively. Spectroscopic evidence indicates that adsorbed hydroxy species (OHad) were directly involved in HOR processes in alkaline conditions on the PtNi alloy surface. However, OHad species were not observed on the Pt surface during the HOR. We show that Ni doping promoted hydroxy adsorption on the platinum‐alloy catalytic surface, improving the HOR activity. DFT calculations also suggest that the free energy was decreased by hydroxy adsorption. Consequently, tuning OH adsorption by designing bifunctional catalysts is an efficient method for promoting HOR activity.
HOR on Au@PtNi surfaces in alkaline media has been investigated by in situ surface‐enhanced Raman spectroscopy (see picture). Direct spectroscopic evidence for OHad species was observed and further confirmed by deuterium isotopic experiments and DFT.
Acute kidney injury (AKI) with high incidence and mortality is the main cause of chronic kidney disease. Previous studies have indicated that quercetin, an abundant flavonoid in plants, exhibited ...renoprotective role in AKI. However, the underlying mechanism is largely unknown. In this study, we try to explore whether quercetin protects against AKI by inhibiting macrophage inflammation via regulation of Mincle/Syk/NF‐κB signaling. The results demonstrated that quercetin can significantly inhibit expression and secretion of IL‐1β, IL‐6, and TNF‐α in LPS‐induced bone marrow‐derived macrophages (BMDMs) and reduce activity of Mincle/Syk/NF‐κB signaling in vitro. We also found that quercetin can strongly reduce the concentration of serum creatinine, BUN, IL‐1β, IL‐6, and TNF‐α in cisplatin‐induced AKI model. Furthermore, quercetin down‐regulated protein levels of Mincle, phosphorylated Syk and NF‐κB in kidney macrophages of AKI, as well as inhibited M1, up‐regulated M2 macrophage activity. Notably, the down‐regulation of LPS‐induced inflammation by quercetin was reversed after adding TDB (an agonist of Mincle) in BMDMs, suggesting that quercetin suppresses macrophage inflammation may mainly through inhibiting Mincle and its downstream signaling. In summary, these findings clarified a new mechanism of quercetin improving AKI‐induced kidney inflammation and injury, which provides a new drug option for the clinical treatment of AKI.
Proliferating cells often have increased glucose consumption and lactate excretion relative to the same cells in the quiescent state, a phenomenon known as the Warburg effect. Despite an increase in ...glycolysis, however, here we show that non-transformed mouse fibroblasts also increase oxidative phosphorylation (OXPHOS) by nearly two-fold and mitochondrial coupling efficiency by ~30% during proliferation. Both increases are supported by mitochondrial fusion. Impairing mitochondrial fusion by knocking down mitofusion-2 (Mfn2) was sufficient to attenuate proliferation, while overexpressing Mfn2 increased proliferation. Interestingly, impairing mitochondrial fusion decreased OXPHOS but did not deplete ATP levels. Instead, inhibition caused cells to transition from excreting aspartate to consuming it. Transforming fibroblasts with the
oncogene induced mitochondrial biogenesis, which further elevated OXPHOS. Notably, transformed fibroblasts continued to have elongated mitochondria and their proliferation remained sensitive to inhibition of Mfn2. Our results suggest that cell proliferation requires increased OXPHOS as supported by mitochondrial fusion.
Interstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells ...contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast (
-smooth muscle actin
-SMA) markers. CD68
/
-SMA
cells accounted for approximately 50% of the myofibroblast population, and the number of these cells correlated with allograft function and the severity of interstitial fibrosis. Similarly, in C57BL/6J mice with a BALB/c renal allograft, cells coexpressing macrophage markers (CD68 or F4/80) and
-SMA composed a significant population in the interstitium of allografts undergoing chronic rejection. Fate-mapping in Lyz2-Cre/Rosa26-Tomato mice showed that approximately half of
-SMA
myofibroblasts in renal allografts originated from recipient bone marrow-derived macrophages. Knockout of
protected against interstitial fibrosis in renal allografts and substantially reduced the number of macrophage-to-myofibroblast transition cells. Furthermore, the majority of macrophage-to-myofibroblast transition cells in human and experimental renal allograft rejection coexpressed the M2-type macrophage marker CD206, and this expression was considerably reduced in
-knockout recipients. In conclusion, our studies indicate that macrophage-to-myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury. Moreover, the transition of bone marrow-derived M2-type macrophages to myofibroblasts in the renal allograft is regulated
a Smad3-dependent mechanism.
Esophageal cancer (EC) is a type of aggressive cancer without clinically relevant molecular subtypes, hindering the development of effective strategies for treatment. To define molecular subtypes of ...EC, we perform mass spectrometry-based proteomic and phosphoproteomics profiling of EC tumors and adjacent non-tumor tissues, revealing a catalog of proteins and phosphosites that are dysregulated in ECs. The EC cohort is stratified into two molecular subtypes-S1 and S2-based on proteomic analysis, with the S2 subtype characterized by the upregulation of spliceosomal and ribosomal proteins, and being more aggressive. Moreover, we identify a subtype signature composed of ELOA and SCAF4, and construct a subtype diagnostic and prognostic model. Potential drugs are predicted for treating patients of S2 subtype, and three candidate drugs are validated to inhibit EC. Taken together, our proteomic analysis define molecular subtypes of EC, thus providing a potential therapeutic outlook for improving disease outcomes in patients with EC.
The expression pattern and role of circular RNAs (circRNAs) in the pathogenesis of gastric cancer (GC) and their underlying mechanisms remain unresolved. In this study, we identified differentially ...expressed circRNAs by a circRNA microarray and verified the results by quantitative reverse transcription‐polymerase chain reaction using 117 clinical samples. Cell Counting Kit‐8, wound healing, Transwell, and tumorsphere formation assays were conducted to assess the effects of circ‐CEP85L on cell proliferation and invasion in vitro. Mouse intraperitoneal injection models were used to assess the functions of circ‐CEP85L in vivo. Luciferase reporter assays, fluorescence in situ hybridization, and rescue experiments were performed to elucidate the underlying mechanism of circ‐CEP85L. We found that circ‐CEP85L, which has not been studied in GC, was significantly downregulated in GC tissues and that decreased circ‐CEP85L expression correlated significantly with a worse prognosis. The knockdown of circ‐CEP85L promoted the proliferation and invasion of GC cells, which was reversed by overexpression of circ‐CEP85L. Furthermore, inhibition of circ‐CEP85L promoted tumor growth in vivo. Mechanistically, circ‐CEP85L was confirmed to be a direct target of miR‐942‐5p. In addition, rescue experiments indicated that circ‐CEP85L is able to inhibit the proliferation and invasion of GC cells by sponging miR‐942‐5p. Finally, western blot assays verified that the downregulation of miR‐942‐5p efficiently reversed the inhibition of NFKBIA induced by circ‐CEP85L overexpression. Therefore, we conclude that circ‐CEP85L promotes NFKBIA expression by acting as a sponge of miR‐942‐5p; thus, inhibiting GC proliferation and invasion. circ‐CEP85L is a potential target in the treatment of GC.
The role of circular RNAs in gastric cancer (GC) and their underlying mechanisms remain unresolved. In this study, we demonstrated that circ‐CEP85L promotes NFKBIA expression by acting as a sponge of miR‐942‐5p, thus inhibiting GC proliferation and invasion. Targeting circ‐CEP85L may have promising prospects in GC therapy.
Abstract
Ruthenium exhibits comparable or even better alkaline hydrogen evolution reaction activity than platinum, however, the mechanistic aspects are yet to be settled, which are elucidated by ...combining in situ Raman spectroscopy and theoretical calculations herein. We simultaneously capture dynamic spectral evidence of Ru surfaces, interfacial water, *H and *OH intermediates. Ru surfaces exist in different valence states in the reaction potential range, dissociating interfacial water differently and generating two distinct *H, resulting in different activities. The local cation tuning effect of hydrated Na
+
ion water and the large work function of high-valence Ru(n+) surfaces promote interfacial water dissociation. Moreover, compared to low-valence Ru(0) surfaces, high-valence Ru(n+) surfaces have more moderate adsorption energies for interfacial water, *H, and *OH. They, therefore, facilitate the activity. Our findings demonstrate the regulation of valence state on interfacial water, intermediates, and finally the catalytic activity, which provide guidelines for the rational design of high-efficiency catalysts.
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