The association of three vaccination doses with reduced gastrointestinal symptoms after severe acute respiratory syndrome coronavirus 2 infections in patients with inflammatory bowel disease

BackgroundThe protective efficacy of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination against the new-onset gastrointestinal (GI) symptoms following COVID-19 infection is critical among patients with inflammatory bowel disease (IBD); however, the optimal protective vaccine dose remains unknown. Therefore, this study aimed to clarify whether there is a correlation between SARS-CoV-2 vaccinations and GI symptoms following Omicron infection in patients with IBD.MethodsWe conducted a multicenter cross-sectional study of IBD patients among three tertiary hospitals in eastern China. Professional physicians collected all data using online questionnaires. The patients were stratified into four groups: patients who were unvaccinated and patients who received one, two, or three vaccination doses. The primary outcome was the presence of any new-onset GI symptoms after SARS-CoV-2 infection before a negative SARS-CoV-2 nucleic acid test or a negative self-testing for antigens.ResultsIn total, 536 patients with IBD (175 unvaccinated, 31 vaccinated, 166 vaccinated with two doses, and 164 vaccinated with three doses) reported having COVID-19 infection. Compared with the unvaccinated, the three vaccination doses group was associated with reduced GI symptoms after infection (adjusted odds ratio = 0.56, 95% confidence interval 0.34–0.90, P < 0.05). Reduced diarrhea (adjusted odds ratio = 0.54, 95% confidence interval 0.31–0.92, P < 0.05) and nausea or vomiting (adjusted odds ratio = 0.45, 95% confidence interval 0.21–0.92, P < 0.05) were observed in the three vaccination doses group compared with the unvaccinated group.ConclusionsIn conclusion, in the 536 patients with IBD who reported COVID-19 infection, we found that the three vaccination doses, but not the one or two doses group, were associated with reduced GI symptoms after infection compared with the unvaccinated group

Nonheme Iron-Mediated Amination of C(sp³)–H Bonds. Quinquepyridine-Supported Iron-Imide/Nitrene Intermediates by Experimental Studies and DFT Calculations

The 7-coordinate complex [Fe­(qpy)­(MeCN)₂]­(ClO₄)₂ (<b>1</b>, qpy = 2,2′:6′,2″:6″,2′′′:6′′′,2′′′′-quinquepyridine) is a highly active nonheme iron catalyst for intra- and intermolecular amination of C­(sp³)–H bonds. This complex effectively catalyzes the amination of limiting amounts of not only benzylic and allylic C­(sp³)–H bonds of hydrocarbons but also the C­(sp³)–H bonds of cyclic alkanes and cycloalkane/linear alkane moieties in sulfamate esters, such as those derived from menthane and steroids cholane and androstane, using PhINR or “PhI­(OAc)₂ + H₂NR” [R = Ts (<i>p</i>-toluenesulfonyl), Ns (<i>p</i>-nitrobenzenesulfonyl)] as nitrogen source, with the amination products isolated in up to 93% yield. Iron imide/nitrene intermediates [Fe­(qpy)­(NR)­(X)]^<i>n</i>+ (<b>C</b>_<b>X</b>, X = NR, solvent, or anion) are proposed in these amination reactions on the basis of experimental studies including ESI-MS analysis, crossover experiments, Hammett plots, and correlation with C–H bond dissociation energies and with support by DFT calculations. Species consistent with the formulations of [Fe­(qpy)­(NTs)₂]²⁺ (<b>C</b>_<b>NTs</b>) and [Fe­(qpy)­(NTs)]²⁺ (<b>C</b>) were detected by high-resolution ESI-MS analysis of the reaction mixture of <b>1</b> with PhINTs (4 equiv). DFT calculations revealed that the reaction barriers for H-atom abstraction of cyclohexane by the ground state of 7-coordinate <b>C</b>_<b>NTs</b> and ground state of <b>C</b> are 15.3 and 14.2 kcal/mol, respectively, in line with the observed high activity of <b>1</b> in catalyzing the C–H amination of alkanes under mild conditions

Cbfβ Is a Novel Modulator against Osteoarthritis by Maintaining Articular Cartilage Homeostasis through TGF-β Signaling

TGF-β signaling is a vital regulator for maintaining articular cartilage homeostasis. Runx transcription factors, downstream targets of TGF-β signaling, have been studied in the context of osteoarthritis (OA). Although Runx partner core binding factor β (Cbfβ) is known to play a pivotal role in chondrocyte and osteoblast differentiation, the role of Cbfβ in maintaining articular cartilage integrity remains obscure. This study investigated Cbfβ as a novel anabolic modulator of TGF-β signaling and determined its role in articular cartilage homeostasis. Cbfβ significantly decreased in aged mouse articular cartilage and human OA cartilage. Articular chondrocyte-specific Cbfb-deficient mice (Cbfb△ac/△ac) exhibited early cartilage degeneration at 20 weeks of age and developed OA at 12 months. Cbfb△ac/△ac mice showed enhanced OA progression under the surgically induced OA model in mice. Mechanistically, forced expression of Cbfβ rescued Type II collagen (Col2α1) and Runx1 expression in Cbfβ-deficient chondrocytes. TGF-β1-mediated Col2α1 expression failed despite the p-Smad3 activation under TGF-β1 treatment in Cbfβ-deficient chondrocytes. Cbfβ protected Runx1 from proteasomal degradation through Cbfβ/Runx1 complex formation. These results indicate that Cbfβ is a novel anabolic regulator for cartilage homeostasis, suggesting that Cbfβ could protect OA development by maintaining the integrity of the TGF-β signaling pathway in articular cartilage

Structurally robust phosphorescent [Pt(O^N^C^N)] emitters for high performance organic light-emitting devices with power efficiency up to 126 lm W-1 and external quantum efficiency over 20%

© the Partner Organisations 2014. A series of robust, bulky and strongly emissive platinum(ii) complexes supported by tetradentate O^N^C^N ligands with tert-butyl groups (1-4), a bridging tertiary amine (5) or a biphenyl group with a spiro linkage (6) at the periphery of the [O^N^C^N] ligand scaffold have been prepared. Their photophysical properties were examined by absorption and emission spectroscopy, density functional theory calculations, and ultra-fast time-resolved emission measurements. These complexes display emission quantum yields of up to 95%, with emission maxima λmax in the range of 522 to 570 nm, and have a good thermal stability of up to Td > 423 °C. Notably, the kq values of 4-6 are in the range of 8.5 × 106 to 2.0 × 107 mol-1 dm3 s-1, smaller than those (∼108 to 109 mol-1 dm3 s-1) of other reported Pt(ii) complexes. The bulky groups at the periphery of the [O^N^C^N] ligand disfavour intermolecular interactions and hence excimer formation in solutions. These complexes are good light-emitting materials (dopants) for OLEDs, since the triplet-triplet annihilation (TTA) and concentration quenching effect arising from intermolecular interactions can be minimized even at a high dopant concentration. The efficiency of the devices fabricated with 4-6 increased with dopant concentration up to a high level of 10% with no extra emitting component or significant shift in the CIE observed. The maximum power efficiency (PE) values achieved for the 5 (yellow-emitting) and 6 (green-emitting) based devices were 118 and 126 lm W-1, respectively. These PE values are the highest among the reported Pt(ii)-OLEDs and comparable to those of the best reported Ir(iii)-OLEDs without the out-coupling technique. Complex 7 is structurally analogous to, but less bulky than 3-6 and is prone to giving excimer emission in the solid state. A high PE of up to 55.5 lm W-1 and external quantum efficiency of up to 25.1% have been realized in the white OLEDs fabricated with 7 as a single emitting material. These values are comparable with those of the best reported WOLEDs based on a single emitting material. This journal isLink_to_subscribed_fulltex

<i>cis</i>-Dioxorhenium(V/VI) Complexes Supported by Neutral Tetradentate N₄ Ligands. Synthesis, Characterization, and Spectroscopy

A series of <i>cis</i>-dioxorhenium­(V) complexes containing chiral tetradentate N₄ ligands, including <i>cis</i>-[Re^V(O)₂(pyxn)]⁺ (<b>1</b>; pyxn = <i>N,N</i>′<i>-</i>dimethyl-<i>N,N</i>′-bis­(2-pyridylmethyl)­cyclohexane-1,2-diamine), <i>cis</i>-[Re^V(O)₂(6-Me₂pyxn)]⁺ (<i><b>cis</b></i><b>-2</b>), <i>cis</i>-[Re^V(O)₂(<i>R,R</i>-pdp)]⁺ (<b>3</b>; <i>R,R</i>-pdp = 1,1′-bis­((<i>R,R</i>)-2-pyridinylmethyl)-2,2′-bipyrrolidine), <i>cis</i>-[Re^V(O)₂(<i>R,R</i>-6-Me₂pdp)]⁺ (<b>4</b>), and <i>cis</i>-[Re^V(O)₂(bqcn)]⁺ (<b>5</b>; bqcn = <i>N,N</i>′-dimethyl-<i>N,N</i>′-di­(quinolin-8-yl)­cyclohexane-1,2-diamine), were synthesized. Their structures were established by X-ray crystallography, showing Re–O distances in the range of 1.740(3)–1.769(8) Å and O–Re–O angles of 121.4(2)–124.8(4)°. Their cyclic voltammograms in MeCN (0.1 M [NBu₄]­PF₆) display a reversible Re^VI/V couple at <i>E</i>_1/2 = 0.39–0.49 V vs SCE. In aqueous media, three proton-coupled electron transfer reactions corresponding to Re^VI/V, Re^V/III, and Re^III/II couples were observed at pH 1. The Pourbaix diagrams of <b>1</b>·OTf, <b>3</b>·OTf, and <b>5</b>·OTf have been examined. The electronic absorption spectra of the <i>cis</i>-dioxorhenium­(V) complexes show three absorption bands at around 800 nm (600–1730 dm³ mol^–1 cm^–1), 580 nm (1700–5580 dm³ mol^–1 cm^–1), and 462–523 nm (3170–6000 dm³ mol^–1 cm^–1). Reaction of <b>1</b> with Lewis acids (or protic acids) gave <i>cis</i>-[Re^V(O)­(OH)­(pyxn)]²⁺ (<b>1</b>·<b>H</b>^<b>+</b>), in which the Re–O distances are lengthened to 1.788(5) Å. Complex <i><b>cis</b></i><b>-2</b> resulted from isomerization of <i><b>trans</b></i>-<b>2</b> at elevated temperature. <i>cis</i>-[Re^VI(O)₂(pyxn)]­(PF₆)₂ (<b>1′</b>·(PF₆)₂) was obtained by constant-potential electrolysis of <b>1</b>·PF₆ in MeCN (0.1 M [NBu₄]­PF₆) at 0.56 V vs SCE; it displays shorter Re–O distances (1.722(4), 1.726(4) Å) and a smaller O–Re–O angle (114.88(18)°) relative to <b>1</b> and shows a d–d transition absorption band at 591 nm (ε = 77 dm³ mol^–1 cm^–1). With a driving force of ca. 75 kcal mol^–1, <b>1′</b> oxidizes hydrocarbons with weak C–H bonds (75.5–76.3 kcal mol^–1) via hydrogen atom abstraction. DFT and TDDFT calculations on the electronic structures and spectroscopic properties of the <i>cis</i>-dioxorhenium­(V/VI) complexes were performed

Functional Cooperation between Vitamin D Receptor and Runx2 in Vitamin D-Induced Vascular Calcification

<div><p>The transdifferentiation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells has been implicated in the context of vascular calcification. We investigated the roles of vitamin D receptor (Vdr) and <i>runt-related transcription</i> factor <i>2</i> (<i>Runx2</i>) in the osteoblastic differentiation of VSMCs in response to vitamin D₃ using <i>in vitro</i> VSMCs cultures and <i>in vivo</i> in <i>Vdr</i> knockout (<i>Vdr</i>^<i>-/-</i>) and <i>Runx2 carboxy-terminus</i> truncated heterozygous (<i>Runx2</i>^<i>+/ΔC</i>) mice. Treatment of VSMCs with active vitamin D₃ promoted matrix mineral deposition, and increased the expressions of Vdr, Runx2, and of osteoblastic genes but decreased the expression of smooth muscle myosin heavy chain in primary VSMCs cultures. Immunoprecipitation experiments suggested an interaction between Vdr and Runx2. Furthermore, silencing <i>Vdr</i> or <i>Runx2</i> attenuated the procalcific effects of vitamin D₃. Functional cooperation between Vdr and Runx2 in vascular calcification was also confirmed in <i>in vivo</i> mouse models. Vascular calcification induced by high-dose vitamin D₃ was completely inhibited in <i>Vdr</i>^<i>-/-</i> or <i>Runx2</i>^<i>+/ΔC</i> mice, despite elevated levels of serum calcium or alkaline phosphatase. Collectively, these findings suggest that functional cooperation between Vdr and Runx2 is necessary for vascular calcification in response to vitamin D₃.</p> </div

Protection from vitamin D₃-induced VC in <i>Runx2</i>^+/ΔC mice.

<p>Eight-week-old Runx2^+/+ and <i>Runx2</i>^+/ΔC mice were injected with vitamin D₃ (6 x 10⁵ IU/kg of body weight). (A) Calcified regions were detected by von Kossa staining. The protein levels of Vdr, Runx2, Mgp, and Smmhc in these regions were assessed by immunohistochemical staining. Original magnification, X400 (Scale bar=10 μm). Experimental groups (n=5-8). N.IgG was used as an internal control. (B) Serum calcium, phosphate, and Alp levels were also measured. Data are group means ± SDs (n=5-8/group). Statistical analysis was analyzed using the unpaired Student’s <i>t</i>-test. *P<0.05; **P<0.01.</p

Effects of 1,25(OH)₂D₃on the expressions of Vdr and Runx2.

<p>(A) Primary cultured mouse VSMCs were treated with 1,25(OH)₂D₃ (0, 10^-10,10^-9,10^-8, or 10^-7 mol/l) for 24 hours. Relative mRNA levels of <i>Vdr</i>, Runx2, and Smmhc were measured by real-time RT-PCR. (B) Protein levels of Vdr, Runx2, Smmhc, and Sm-α-actin were measured in total cell lysates by immunoblotting after treatment with 1,25(OH)₂D₃for 24 hours. β-Actin was used as an internal control. Statistical analysis was performed using the unpaired Student’s <i>t</i>-test. *P<0.05 or **P<0.01 versus the untreated condition.</p

Reciprocal regulation of Vdr and Runx2 by 1,25(OH)₂D₃.

<p>(A) Rat VSMCs were infected with adenovirus expressing LacZ (Ad-LacZ) or Runx2 (Ad-Runx2) vectors (50 moi) for 4 hours and then treated with or without 1,25(OH)₂D₃ (1x10^-7 mol/l) for 42 hours. The expression levels of Vdr and Runx2 were detected by immunoblotting. (B) Sub-confluent mouse VSMCs were seeded in 6-well plates, cultured overnight, and transfected with siRNAs (25 and 50 nmol/l) for <i>Vdr</i> or Runx2 mRNAs and then treated with 1,25(OH)₂D₃ (except the control) for 24 hours. Total RNAs were subjected to real-time RT PCR. (C) Mouse VSMCs cultured for 48 hours were analyzed for Vdr and Runx2 protein levels. Lamin B1 was used as internal control. Results are the means ± SD of three independent experiments. Statistical analysis was analyzed using the unpaired Student’s <i>t</i>-test. *P<0.05; **P<0.01.</p