Low-Molecular-Weight Fe(III) Complexes for MRI Contrast Agents.

Fe(III) complexes have again attracted much attention for application as MRI contrast agents in recent years due to their high thermodynamic stability, low long-term toxicity, and large relaxivity at a higher magnetic field. This mini-review covers the recent progress on low-molecular-weight Fe(III) complexes, which have been considered as one of the promising alternatives to clinically used Gd(III)-based contrast agents. Two kinds of complexes including mononuclear Fe(III) complexes and multinuclear Fe(III) complexes are summarized in sequence, with a specific highlight of the structural relationships between the complexes and their relaxivity and thermodynamic stability. In additional, the future perspectives for the design of low-molecular-weight Fe(III) complexes for MRI contrast agents are suggested.

Photoswitchable Fluorescent Self-Assembled Metallacycles with High Photostability.

In this study, photoswitchable fluorescent supramolecular metallacycles with high fatigue-resistance have been constructed by coordination-driven self-assembly by using bithienylethene with dipyridyl units (BTE) as a coordination donor and a fluorescent di-platinum(II) (Pt-F) as a coordination acceptor. The photo-triggered reversible transformation between the ring-open and ring-closed form of the metallacycles was confirmed by 1 H NMR, 31 P NMR, and UV/Vis spectroscopy. This unique property enabled a reversible noninvasive "off-on" switching of fluorescence through efficient Förster resonance energy transfer (FRET). Importantly, the metallacycles remained structurally intact after up to 10 photoswitching cycles. The photoresponsive property and exceptional photostability of the metallacycles posit their potential promising application in optical switching, image storage, and super-resolution microscopy.

L-Carnitine Reduces Myocardial Oxidative Stress and Alleviates Myocardial Ischemia-Reperfusion Injury by Activating Nuclear Transcription-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) Signaling Pathway.

BACKGROUND Myocardial ischemia-reperfusion injury (IRI) is an important injury mechanism of myocardial infarction. The purpose of this study was to explore the effects of L-carnitine (LC) on myocardial IRI and its mechanism. MATERIAL AND METHODS The IRI model was made by ligating the left anterior descending coronary artery. Then, we injected LC intraperitoneally into the rats of the experimental group to assess the effect of LC on IRI rats by use of serum markers, Western blot, and qRT-PCR. H9c2 cells were cultured and then treated with hypoxia-reoxygenation. The effect of LC on oxidative stress, apoptosis, and nuclear transcription-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway of H9c2 cells were detected by Western blot, RT-PCR, and flow cytometry. RESULTS LC significantly reduced malondialdehyde (MDA), creatine kinase (CK), and lactate dehydrogenase (LDH) levels in rat myocardial tissue and increased superoxide dismutase (SOD) expression. LC also increased the expression of SOD1/2 and Bcl-2 in rat myocardial tissue and H9c2 cells and decreased the expression of caspase3/8 and Bax. In addition, LC increased the expression of Nrf2/HO-1 signaling pathway-related molecules in H9c2 cells and increased the activity of the Nrf2/HO-1 signaling pathway. Moreover, inhibition of the Nrf2/HO-1 signaling pathway attenuated the protective effect of LC on H9c2 cells. CONCLUSIONS LC can activate the Nrf2/HO-1 signaling pathway and reduce oxidative stress and apoptosis in cardiomyocytes, thereby reducing myocardial IRI.

Effect of single-nucleotide polymorphism in pri-microRNA-124 on poststroke motor function recovery.

BACKGROUND: Stroke is a leading cause of long-term disability and further one of the main causes of motor impairment. The current study aimed to investigate whether miR-124 polymorphism (rs531564) influences the motor function of patients after stroke. METHODS: In total, 56 patients with stroke-induced motor dysfunction were enrolled. Box and block test (BBT) and Fugl-Meyer assessment (FMA) were performed to evaluate the motor functions in all participants. Computation analysis, luciferase activity, PCR assays, and Western blot analysis were performed to reveal the molecular mechanism underlying the effect of miR-124 polymorphism on motor functions. RESULTS: The 56 participants were genotyped as CC, CG, and GG, respectively. The serum miR-124 was significantly upregulated in the CC group than that in the GC and GG groups. According to the result of FMA or BBT, there was no obvious difference in upper and lower limb motor functions between CC and CG/GG groups 1 week after the treatment. In addition, scores of BBT and FMA exhibited apparent improvement in both groups at 1 month and 3 months after the treatment. Furthermore, improvements in the CG/GG groups were more significant as compared with those in the CC group. CDK4 was a target of miR-124, and the effect of miR-124 on the motor function recovery might be mediated by CDK4. CONCLUSION: The presence of a minor allele, G, of miR-124 polymorphism (rs531564) reduced the expression of miRNA and upregulated the expression of CDK4, which may contribute to the effect of rs531564 on the motor function recovery in poststroke patients.

Multivariable analysis of anatomic risk factors for anterior cruciate ligament injury in active individuals.

OBJECTIVE: The aim of the present study was to compare the morphometric differences between patients with or without anterior cruciate ligament (ACL) injury, and identify the anatomic risk factors associated with ACL injury in active individuals. METHODS: The knee joint magnetic resonance images (MRI) of 100 subjects were included in this study. Data from the ACL-injured group (50 patients) and matched controls (50 subjects) were obtained from the same hospital. These data were analyzed by univariable analysis or multivariable conditional logistic regression analysis to examine the effects of the following variables on the risk of suffering ACL injury for the first time: TT-TG distance, medial and lateral tibial slope, intercondylar notch width and depth, femur condylar width, lateral femoral condylar depth, notch width index (NWI), notch shape index (NSI), notch depth index (NDI), and cross-sectional area (CSA). RESULTS: In the univariable analysis, the ACL-injured group had a larger TT-TG distance, increased medial and lateral tibial slope, narrower intercondylar notch width, deeper lateral femoral condylar depth, lesser NWI and NSI, and CSA when compared with the control group (P < 0.05). However, there were no significant between-group differences in intercondylar notch depth (P = 0.174), femur condylar width (P = 0.797), and NDI (P = 0.436). The multivariable analysis revealed that TT-TG distance [odds ratio (OR) = 1.37, 95% CI = 1.04-1.81, P = 0.028], medial tibial slope (OR = 1.30, 95% CI = 1.02-1.66, P = 0.036) and NWI (OR = 0.46, 95% CI = 0.24-0.91, P = 0.025) had significant multivariable associations with the sole independent risk of ACL injury. CONCLUSION: Larger TT-TG distance, increased MTS, and lesser NWI are independent anatomic risk factors for active individuals with ACL injury. LEVEL OF EVIDENCE: Case-control study; Level of Evidence, III.

Construction of Porphyrin-Containing Metallacycle with Improved Stability and Activity within Mesoporous Carbon.

The successful construction of porphyrin functionalized metallacycle in the confined cavity of mesoporous carbon FDU-16 (3⊂C) is presented in this study. Because of high dispersity of metallacycles within the mesoporous cavities, the stability and activity of porphyrin-containing metallacycles were obviously improved. For example, 1O2 generation efficiency of 3⊂C is ca. 6-fold faster than that of free metallaycles in solution. Thus, the resultant hybrid material has been successfully employed as a heterogeneous catalyst for photooxidation of sulfides.

Preoperative T1 Slope as a Predictor of Change in Cervical Alignment and Range of Motion After Cervical Disc Arthroplasty.

BACKGROUND This study analyzed the effect of preoperative T1 slope on cervical alignment and range of motion (ROM) after cervical disc arthroplasty (CDA) in patients with cervical degenerative disease. MATERIAL AND METHODS This retrospective study included 32 patients with single-level symptomatic cervical disc disease who underwent CDA with the Mobi-C cervical disc prosthesis and had a mean follow-up of 26.8±6.4 months. Standing lateral, flexion, and extension X-rays of the cervical spine were obtained preoperatively and postoperatively at 24-month follow-up. Simple linear regression analysis was used to assess the impact of preoperative T1 slope on changes from preoperative values in radiologic parameters. RESULTS Compared to preoperative values, at 24-month follow-up, there was a significant increase in mean functional spinal unit (FSU) angle (+7.4°), upper adjacent segment (UAS) angle (+3.1°), and overall cervical alignment (C2-C7 angle) (+6.3°), and a significant decrease in mean lower adjacent segment (LAS) angle (-2.4°). Mean ROM of the FSU (-3.6°), LAS (-3.0°), and overall cervical spine (-11.5°) significantly decreased, and mean ROM of the UAS (+1.6°) significantly increased. There were significant correlations between preoperative T1 slope and mean change from preoperative value in FSU angle, C2-C7 angle, and ROM of the overall cervical spine (C2-C7). CONCLUSIONS T1 slope is useful for evaluating changes in the FSU angle, C2-C7 angle, and ROM of the overall cervical spine following CDA with the Mobi-C disc. Patients with a large preoperative T1 slope may be good candidates for CDA with the Mobi-C prosthesis due its motion maintenance and the fact that it has little adverse impact on sagittal alignment. It also could be a good option in terms of sagittal alignment improvement or motion maintenance for patients with kyphosis.

Glioma-derived exosome Lncrna Agap2-As1 promotes glioma proliferation and metastasis by mediating Tgf-ß1 secretion of myeloid-derived suppressor cells.

Background: Glioma (GBM) is the most prevalent malignancy worldwide with high morbidity and mortality. Exosome-mediated transfer of long noncoding RNA (lncRNA) has been reported to be associated with human cancers, containing GBM. Meanwhile, myeloid-derived suppressor cells (MDSCs) play a vital role in mediating the immunosuppressive environments in GBM. Objectives: This study is designed to explore the role and mechanism of exosomal (Exo) lncRNA AGAP2-AS1 on the MDSC pathway in GBM. Methods: AGAP2-AS1, microRNA-486-3p (miR-486-3p), and Transforming growth factor beta-1 (TGF-ß1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, migration, and invasion were detected by 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, and Transwell assays. E-cadherin, Vimentin, CD9, CD81, and TGF-ß1 protein levels were examined using Western blot. Exosomes were detected by a transmission electron microscope (TEM). Binding between miR-486-3p and AGAP2-AS1 or TGF-ß1 was predicted by LncBase or TargetScan and then verified using a dual-luciferase reporter assay. Results: AGAP2-AS1 was highly expressed in GBM tissues and cells. Functionally, AGAP2-AS1 absence or TGF-ß1 knockdown repressed tumor cell growth and metastasis. Furthermore, Exo-AGAP2-AS1 from GBM cells regulated TGF-ß1 expression via sponging miR-486-3p in MDSCs. Exo-AGAP2-AS1 upregulation facilitated GBM cell growth and metastasis via the MDSC pathway. Conclusion: Exo-AGAP2-AS1 boosted GBM cell development partly by regulating the MDSC pathway, hinting at a promising therapeutic target for GBM treatment.

Light-triggered reversible supramolecular transformations of multi-bisthienylethene hexagons.

It is very challenging to realize well-controlled structural transformations in artificial supramolecules. Herein we report the construction of a novel family of multi-bisthienylethene hexagons with precise control of the shape and size as well as the specific number of photochromic units via coordination-driven self-assembly. These newly developed multi-bisthienylethene hexagons are highly sensitive and responsive to photostimuli, especially allowing for quantitative reversible supramolecular transformations triggered by light irradiation.

Palladium catalyzed radical relay for the oxidative cross-coupling of quinolines.

Traditional approaches for transition-metal catalyzed oxidative cross-coupling reactions rely on sp2-hybridized starting materials, such as aryl halides, and more specifically, homogeneous catalysts. We report a heterogeneous Pd-catalyzed radical relay method for the conversion of a heteroarene C(sp3)-H bond into ethers. Pd nanoparticles are supported on an ordered mesoporous composite which, when compared with microporous activated carbons, greatly increases the Pd d charge because of their strong interaction with N-doped anatase nanocrystals. Mechanistic studies provide evidence that electron-deficient Pd with Pd-O/N coordinations efficiently catalyzes the radical relay reaction to release diffusible methoxyl radicals, and highlight the difference between this surface reaction and C-H oxidation mediated by homogeneous catalysts that operate with cyclopalladated intermediates. The reactions proceed efficiently with a turn-over frequency of 84 h-1 and high selectivity toward ethers of >99%. Negligible Pd leaching and activity loss are observed after 7 catalytic runs.

Unleash electron transfer in C-H functionalization by mesoporous carbon-supported palladium interstitial catalysts.

The functionalization of otherwise unreactive C-H bonds adds a new dimension to synthetic chemistry, yielding useful molecules for a range of applications. Arylation has emerged as an increasingly viable strategy for functionalization of heteroarenes which constitute an important class of structural moieties for organic materials. However, direct bisarylation of heteroarenes to enable aryl-heteroaryl-aryl bond formation remains a formidable challenge, due to the strong coordination between heteroatom of N or S and transitional metals. Here we report Pd interstitial nanocatalysts supported on ordered mesoporous carbon as catalysts for a direct and highly efficient bisarylation method for five-membered heteroarenes that allows for green and mild reaction conditions. Notably, in the absence of any base, ligands and phase transfer agents, high activity (turn-over frequency, TOF, up to 107 h-1) and selectivity (>99%) for the 2,5-bisarylation of five-membered heteroarenes are achieved in water. A combination of characterization reveals that the remarkable catalytic reactivity here is attributable to the parallel adsorption of heteroarene over Pd clusters, which breaks the barrier to electron transfer in traditional homogenous catalysis and creates dual electrophilic sites for aryl radicals and adsorbate at C2 and C5 positions. The d-band filling at Pd sites shows a linear relationship with activation entropy and catalytic activity. The ordered mesopores facilitate the absence of a mass transfer effect. These findings suggest alternative synthesis pathways for the design, synthesis and understanding of a large number of organic chemicals by ordered mesoporous carbon supported palladium catalysts.

Gold catalysts containing interstitial carbon atoms boost hydrogenation activity.

Supported gold nanoparticles are emerging catalysts for heterogeneous catalytic reactions, including selective hydrogenation. The traditionally used supports such as silica do not favor the heterolytic dissociation of hydrogen on the surface of gold, thus limiting its hydrogenation activity. Here we use gold catalyst particles partially embedded in the pore walls of mesoporous carbon with carbon atoms occupying interstitial sites in the gold lattice. This catalyst allows improved electron transfer from carbon to gold and, when used for the chemoselective hydrogenation of 3-nitrostyrene, gives a three times higher turn-over frequency (TOF) than that for the well-established Au/TiO2 system. The d electron gain of Au is linearly related to the activation entropy and TOF. The catalyst is stable, and can be recycled ten times with negligible loss of both reaction rate and overall conversion. This strategy paves the way for optimizing noble metal catalysts to give an enhanced hydrogenation catalytic performance.

Two-isophorone fluorophore-based design of a ratiometric fluorescent probe and its application in the sensing of biothiols.

2,4-Dinitrobenzenesulfonyl (DNBS) has been widely used for the design of small fluorescent probes for biothiols due to its high reactivity. However, most DNBS-based fluorescent probes exhibit "off-on" fluorescence response towards biothiols due to the strong quenching effects of DBNS on the fluorophores. Herein, we present an alternative design of a ratiometric fluorescent probe based on DNBS for biothiols. A new fluorophore bearing two isophorone malononitrile structures was conjugated with DNBS to provide a target probe (CHT), which exhibited a ratiometric sensing behavior towards biothiols. The sensing process is rapid and highly selective. Most importantly, CHT has high stability in the quantitative detection of Cys compared to the control probe CHM, which performed an "off-on" sensing for biothiols. Endogenous biothiols were successfully monitored with CHT in live cells through the ratiometric fluorescence signal. This new fluorophore bearing two isophorone malononitrile moieties will pave a new avenue to design ratiometric fluorescent probes for imaging and quantitative detection.

Optimising surface d charge of AuPd nanoalloy catalysts for enhanced catalytic activity.

Understanding the catalytic mechanism of bimetallic nanocatalysts remains challenging. Here, we adopt an adsorbate mediated thermal reduction approach to yield monodispersed AuPd catalysts with continuous change of the Pd-Au coordination numbers embedded in a mesoporous carbonaceous matrix. The structure of nanoalloys is well-defined, allowing for a direct determination of the structure-property relationship. The results show that the Pd single atom and dimer are the active sites for the base-free oxidation of primary alcohols. Remarkably, the d-orbital charge on the surface of Pd serves as a descriptor to the adsorbate states and hence the catalytic performance. The maximum d-charge gain occurred in a composition with 33-50 at% Pd corresponds to up to 9 times enhancement in the reaction rate compared to the neat Pd. The findings not only open an avenue towards the rational design of catalysts but also enable the identification of key steps involved in the catalytic reactions.

Long noncoding RNA lncARSR promotes hepatic cholesterol biosynthesis via modulating Akt/SREBP-2/HMGCR pathway.

AIMS: Disruption of cholesterol homeostasis has been identified as a major factor in the pathogenesis of atherosclerosis, myocardial infarction, and strokes. Long noncoding RNAs (lncRNAs) have emerged as critical players in cellular cholesterol metabolism, but their functions are still largely unknown. MATERIALS AND METHODS: C57BL6/j mice were fed with high cholesterol diet (containing 4% cholesterol) or chow diet. Adenoviruses-lncARSR and lncARSR shRNA were used to overexpress or knockdown lncARSR expression. KEY FINDINGS: The expression of lncARSR were increased both in patients with hypercholesterolemia and mice with high cholesterol diet feeding. Overexpression of lncARSR in mice resulted in elevated lipid levels in both serum and liver fragments. However, knockdown of lncARSR in mice fed with high cholesterol diet showed decreased lipid levels in serum and liver fragments compared with control mice. Furthermore, we found that the expression of HMG-CoA reductase (HMGCR), the rate-limiting enzyme of cholesterol synthesis was increased with lncARSR overexpression, which was accompanied with the increase of hepatic de novo cholesterol synthesis rate. Mechanistically, we found that lncARSR increased the expression of mature SREBP-2, which is a primary transcription factor of HMGCR. And lncARSR activated the PI3K/Akt pathway. When PI3K/Akt pathway was blocked by LY294002, the inhibitor of PI3K, the effect of lncARSR on SREBP-2 and HMGCR disappeared. SIGNIFICANCE: Our data indicated upregulated lncARSR promotes hepatic cholesterol biosynthesis via modulating Akt/SREBP-2/HMGCR pathway, and implied that lncARSR may serve as a therapeutic target for cholesterol disorder.

Correcting pelvic obliquity in the lateral position to improve acetabular component orientation during total hip arthroplasty.

BACKGROUND: The acetabular component orientation during total hip arthroplasty (THA) impacts future hip function and early revision. Correcting pelvic obliquity may improve outcomes. OBJECTIVE: To correct pelvic obliquity in the lateral position by applying a gradienter and plumb during THA using fluoroscopy. METHODS: Fifty patients undergoing THA were randomized and divided into 2 groups. In controls, acetabular components were placed using traditional methods. In experimental patients, acetabular components were placed after correcting pelvic obliquity. We measured pelvic obliquity and recorded intra-operative and post-operative abduction angles, comparing abduction angle bias between post-operative measurements and intra-operation estimations. RESULTS: Before correction, the average pelvic obliquity was -1.647∘± 4.512∘ in experimental patients. The average abduction angle in experimental patients was 42.685∘± 3.355∘ postoperatively, differing by 1.962∘± 1.515∘ from intra-operative estimates, while in control patients, it was 44.534∘± 4.844∘ postoperatively, differing by 4.244∘± 3.042∘ from intra-operative estimates. The bias of the abduction angle was much greater in control than in experimental patients (P< 0.05). CONCLUSION: The pelvic obliquity in the lateral position affects surgeon judgment during THA. By correcting pelvic obliquity with a gradienter and plumb, the abduction angle bias can be reduced.

A multiaddressable photochromic bisthienylethene with sequence-dependent responses: construction of an INHIBIT logic gate and a keypad lock.

A photochromic bisthienylethene derivative (BIT) containing two imidazole units has been synthesized and fully characterized. When triggered by chemical ions (Ag(+)), protons, and light, BIT can behave as an absorbance switch, leading to a multiaddressable system. BIT exhibits sequence-dependent responses via efficient interaction of the specific imidazole unit with protons and Ag(+). Furthermore, an INHIBIT logic gate and a keypad lock with three inputs are constructed with the unimolecular platform by employing an absorption mode at different wavelengths as outputs on the basis of an appropriate combination of chemical and photonic stimuli.

A novel gated photochromic reactivity controlled by complexation/dissociation with BF3.

A photochemically active dithiazolethene BN was designed and synthesized, exhibiting a specific gated photochromism. That is, the photochromic reactivity of BN is prevented to a great extent by BF(3), showing a "Lock" gate.