Ligand-Dominated Activation of CO2 and CS2 by the Putative Nickel Phosphiniminato Intermediates.

Room-temperature photoactivation of the first- and second-generation PN3P-pincer nickel azido complexes 1a and 1b in the presence of CO2 or CS2 afforded N-bound carbamates, dithiocarbamates, and isothiocyanates, providing insights into CO2 and CS2 activation and demonstrating how a seemingly small difference in the ligand structure significantly influences the reactivity. Theoretical calculations disclosed that the charge of the phosphorus atom plays a critical role in determining the nitrogen atom transfer to form a plausible nickel phosphiniminato intermediate.

Soil's Hidden Power: The Stable Soil Organic Carbon Pool Controls the Burden of Persistent Organic Pollutants in Background Soils.

Persistent organic pollutants (POPs) tend to accumulate in cold regions by cold condensation and global distillation. Soil organic matter is the main storage compartment for POPs in terrestrial ecosystems due to deposition and repeated air-surface exchange processes. Here, physicochemical properties and environmental factors were investigated for their role in influencing POPs accumulation in soils of the Tibetan Plateau and Antarctic and Arctic regions. The results showed that the soil burden of most POPs was closely coupled to stable mineral-associated organic carbon (MAOC). Combining the proportion of MAOC and physicochemical properties can explain much of the soil distribution characteristics of the POPs. The background levels of POPs were estimated in conjunction with the global soil database. It led to the proposition that the stable soil carbon pools are key controlling factors affecting the ultimate global distribution of POPs, so that the dynamic cycling of soil carbon acts to counteract the cold-trapping effects. In the future, soil carbon pool composition should be fully considered in a multimedia environmental model of POPs, and the risk of secondary release of POPs in soils under conditions such as climate change can be further assessed with soil organic carbon models.

Amino-Functionalized Metal-Organic Framework as Fluorescence Probe for Cell Imaging and Doxorubicin Detection.

In this study, an NH2-Cu-MOF was synthesized using the one-pot method and employed as a fluorescence probe for doxorubicin (DOX) detection. The synthesized NH2-Cu-MOF exhibited remarkable fluorescence recognition capabilities for detecting DOX. Within the concentration range of 1-100 µmol/L, a linear relationship was observed between the fluorescence intensity of the NH2-Cu-MOF and the DOX concentration. Furthermore, the synthesized NH2-Cu-MOF was effectively utilized for highly selective fluorescence quenching recognition and quantitative detection of DOX in the presence of multiple metal ions and other antibiotics. Despite interference from multiple metal ions and antibiotics, DOX was identified and quantified by highly selective fluorescence quenching with a detection limit of 2.1654 µmol/L. These findings underscore the potential of NH2-Cu-MOF as a class of "on-off" fluorescent probes for the rapid detection of DOX.

Hepatocyte mitochondrial DNA mediates macrophage immune response in liver injury induced by trichloroethylene.

We have previously shown that excessive activation of macrophage proinflammatory activity plays a key role in TCE-induced immune liver injury, but the mechanism of polarization is unclear. Recent studies have shown that TLR9 activation plays an important regulatory role in macrophage polarization. In the present study, we demonstrated that elevated levels of oxidative stress in hepatocytes mediate the release of mtDNA into the bloodstream, leading to the activation of TLR9 in macrophages to regulate macrophage polarization. In vivo experiments revealed that pretreatment with SS-31, a mitochondria-targeting antioxidant peptide, reduced the level of oxidative stress in hepatocytes, leading to a decrease in mtDNA release. Importantly, SS-31 pretreatment inhibited TLR9 activation in macrophages, suggesting that hepatocyte mtDNA may activate TLR9 in macrophages. Further studies revealed that pharmacological inhibition of TLR9 by ODN2088 partially blocked macrophage activation, suggesting that the level of macrophage activation is dependent on TLR9 activation. In vitro experiments involving the extraction of mtDNA from TCE-sensitized mice treated with RAW264.7 cells further confirmed that hepatocyte mtDNA can activate TLR9 in mouse peritoneal macrophages, leading to macrophage polarization. In summary, our study comprehensively confirmed that TLR9 activation in macrophages is dependent on mtDNA released by elevated levels of oxidative stress in hepatocytes and that TLR9 activation in macrophages plays a key role in regulating macrophage polarization. These findings reveal the mechanism of macrophage activation in TCE-induced immune liver injury and provide new perspectives and therapeutic targets for the treatment of OMDT-induced immune liver injury.

A field incubation approach to evaluate the depth dependence of soil biogeochemical responses to climate change.

Soil biogeochemical processes may present depth-dependent responses to climate change, due to vertical environmental gradients (e.g., thermal and moisture regimes, and the quantity and quality of soil organic matter) along soil profile. However, it is a grand challenge to distinguish such depth dependence under field conditions. Here we present an innovative, cost-effective and simple approach of field incubation of intact soil cores to explore such depth dependence. The approach adopts field incubation of two sets of intact soil cores: one incubated right-side up (i.e., non-inverted), and another upside down (i.e., inverted). This inversion keeps soil intact but changes the depth of the soil layer of same depth origin. Combining reciprocal translocation experiments to generate natural climate shift, we applied this incubation approach along a 2200 m elevational mountainous transect in southeast Tibetan Plateau. We measured soil respiration (Rs) from non-inverted and inverted cores of 1 m deep, respectively, which were exchanged among and incubated at different elevations. The results indicated that Rs responds significantly (p < .05) to translocation-induced climate shifts, but this response is depth-independent. As the incubation proceeds, Rs from both non-inverted and inverted cores become more sensitive to climate shifts, indicating higher vulnerability of persistent soil organic matter (SOM) to climate change than labile components, if labile substrates are assumed to be depleted with the proceeding of incubation. These results show in situ evidence that whole-profile SOM mineralization is sensitive to climate change regardless of the depth location. Together with measurements of vertical physiochemical conditions, the inversion experiment can serve as an experimental platform to elucidate the depth dependence of the response of soil biogeochemical processes to climate change.

Percutaneous transluminal angioplasty for radial artery graft stenosis after high-flow superficial temporal artery trunk to middle cerebral artery interposition bypass.

Due to its higher patency rate, a radial artery graft (RAG) is used as an interposition graft for internal-external high-flow bypass more frequently than a saphenous vein graft (SAG). Nevertheless, there are still a few cases of RAG stenosis after bypass surgery. Unfortunately, these reports do not elaborate on the treatment for RAG stenosis. Here, we report the first case of severe RAG stenosis after high-flow STAt-RA-MCA bypass, which was successfully treated with PTA. We speculated that RAG stenosis is associated with the over-length and kinking of the intracranial segment of the RAG instead of vasospasm. We elaborated on the surgical procedure and treatment experience in this particular case in detail. According to our experience, PTA is a type of surgical procedure that can be considered for treating RAG stenosis after high-flow bypass. As long as the surgical procedure can be performed well according to the distance between the stenosis and the anastomosis and the characteristics of the RA tissue, PTA is able to achieve satisfactory long-term results.

Clinical Characteristics and Prognostic Analysis of Osteolytic and Hyperostosis Sphenoid Orbital Meningiomas: A Single-Center Experience.

Reactive hyperostosis of spheno-orbital meningiomas (SOMs) often occurred in the sphenoid wing, while osteolytic SOMs (O-SOMs) were rarely discussed. This study preliminarily evaluated the clinical characteristics of O-SOMs and analyzed prognostic factors affecting the recurrence of SOMs. We retrospectively analyzed the medical records of consecutive patients who underwent surgery for a SOM between 2015 and 2020. According to the bone changes of sphenoid wing, SOMs were divided into O-SOMs and hyperostosis SOMs (H-SOMs). A total of 31 procedures were performed in 28 patients. All cases were treated by pterional-orbital approach. It was confirmed that 8 cases were O-SOMs and the other 20 cases were H-SOMs. Total tumor resection was performed in 21 cases. There were 19 cases with Ki 67 ≥3%. The patients were followed up for 3 to 87 months. Proptosis improved in all patients. All O-SOMs had no visual deterioration, while 4 H-SOMs cases had visual deterioration. There was no significant difference in clinical outcomes between the two types of SOM. The recurrence of SOM was related to the degree of resection, but not to the type of bone lesions, invasion of cavernous sinus and Ki 67.

Multimodal Recanalization for Subacute Symptomatic Internal Carotid Artery Occlusion Due to Atherosclerosis: Outcomes and Notes on Hybrid Techniques.

BACKGROUND: Subacute internal carotid artery occlusion (ICAO) is associated with ipsilateral recurrent stroke, and successful recanalization of ICAO can improve cerebral blood perfusion (CBP) and prevent stroke. However, the optimal treatment remains controversial. METHODS: We conducted a retrospective analysis of patients with subacute symptomatic ICAO due to atherosclerosis treated at our center. The hybrid surgical procedures included carotid endarterectomy, Fogarty balloon catheter embolectomy, aspiration thrombectomy, and percutaneous transluminal angioplasty/stenting. Recanalization rates, CBP improvement, stroke recurrence, and restenosis/reocclusion were investigated. RESULTS: Fourteen symptomatic atherosclerotic ICAO patients (type A, 4; type C, 10; men, 11; women, 3; average age, 68.1 ± 7.9 years) in the subacute phase were treated with a multimodal recanalization technique. Symptoms included mild cerebral infarction, transient ischemic attack (TIA), and amaurosis fugax. The average onset-to-treatment time was 18.1 ± 4.8 days. The successful recanalization (thrombolysis in cerebral ischemia grade 2 or 3) rate was 100%. The ipsilateral-to-contralateral mean transit time ratio was significantly lower at the 1-year follow-up than preoperatively (1.01 ± 0.05 vs. 1.26 ± 0.09, P < 0.0001). There was one case of restenosis detected 1 year after surgery and no cases of reocclusion. During the 28.3 ± 10.0 months of follow-up, only two cases of TIA occurred. The average modified Rankin Scale score and National Institute of Health Stroke Scale score were significantly lower at the most recent follow-up than before recanalization (1.21 ± 0.89 vs. 1.86 ± 0.66, P = 0.0003; 1.36 ± 1.55 vs. 2.00 ± 1.88, P = 0.0066). CONCLUSIONS: Multimodal recanalization techniques performed in a hybrid operation theater can safely achieve high recanalization rates in atherosclerotic ICAO patients in the subacute phase, which can be beneficial for recovering CBP and preventing stroke.

Trans-eyebrow supraorbital keyhole approach for suprasellar and intra-suprasellar Rathke cleft cysts: the experience of 16 cases and a literature review.

BACKGROUND: Purely suprasellar and some complex intra-suprasellar Rathke cleft cysts (RCCs) are commonly treated via extended endonasal endoscopic approach or traditional transcranial approach. The feasibility of the trans-eyebrow supraorbital keyhole approach (TSKA) for RCCs was evaluated in this retrospective study. METHODS: A cohort of 16 patients (11 females and 5 males) with RCC was surgically treated via TSKA between January 2013 and November 2021. The medical data and follow-up results were analyzed. RESULTS: Eight patients had a purely suprasellar RCC, and 8 patients had an intra-suprasellar RCC with most of pituitary gland occupying the sellar floor. The mean maximal size of the cysts was 15.4 (range 7-29) mm. Postoperatively, complete cyst drainage was achieved in 15 (93.7%) patients. Preoperative headache, visual dysfunction, and hypopituitarism improved in 12 (100.0%), 3 (75.0%) and 3 (75.0%) patients, respectively, and hyperprolactinemia normalized in all patients. Except 2 (12.5%) cases of transient diabetes insipidus (TDI), no other complications were observed. During the mean follow-up period of 41.0 (range 4-102) months, 1 (6.3%) radiological recurrence was found. CONCLUSIONS: For the treatment of purely suprasellar and some intra-suprasellar RCCs with most of the pituitary occupying the sellar floor, the endoscopic TSKA has the advantage of the minimal invasiveness, excellent visualization of the intrasellar compartment, no additional damage to the underlying pituitary gland, and no risk of CSF leakage. TDI or DI is relative commonly found in treatment of these RCCs. During surgery, care should be taken to avoid damage to the surrounding structures, including the pituitary stalk.

Influencing factors of life satisfaction among medical staff of rehabilitation departments based on a structural equation model.

Life satisfaction (LS) exhibited gender differences and was associated with age, income, and negative emotions. There is no research on the relationship between professional values and LS, although professional values are essential for medical staff and correlate with negative emotions. This study aimed to explore the relationship between professional values and LS, the action mechanism of influencing factors of LS, and gender differences among medical staff of rehabilitation departments in China. A total of 284 participants (108 men and 176 women) completed the questionnaires. Data were analyzed using SPSS19.0 and Amos21.0. Age, length of service, and anxiety differed significantly between genders. Professional values had a direct effect on LS and an indirect effect on LS via anxiety and depression. Therefore, enhancing professional values and reducing anxiety and depression could increase the medical staff's LS. Moreover, the LS of female medical staff improved with age.

Silencing of Long Non-Coding RNA (LncRNA) Non-Coding RNA Activated by DNA Damage (NORAD) Inhibits Proliferation, Invasion, Migration, and Promotes Apoptosis of Glioma Cells via Downregulating the Expression of AKR1B1.

BACKGROUND We aimed to investigate the functions of long non-coding RNA (lncRNA) non-coding RNA activated by DNA damage (NORAD) in glioma and identify the potential mechanisms. MATERIAL AND METHODS The expression of NORAD and AKR1B1 in human glioma cell lines were examined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Then, cell proliferation, invasion, and migration were tested by Cell Counting Kit-8 (CCK-8), colony formation assay, Transwell, and scratch wound healing assay after NORAD silencing. Meanwhile, western blotting was utilized to measure the expression of migration-related proteins. Apoptosis of glioma cells was detected using flow cytometry and apoptosis-related proteins expression was determined. Moreover, the correlation between NORAD and AKR1B1 was verified by RNA-binding protein immunoprecipitation (RIP assay). After co-transfection with AKR1B1 overexpressed plasmid and NORAD siRNA, cell proliferation, invasion, migration, and apoptosis were examined again. Furthermore, the expression of proteins in extracellular signal-regulated kinase (ERK) signaling was tested using western blotting. RESULTS The results revealed that NORAD and AKR1B1 were highly expressed in glioma cells. NORAD silencing inhibited proliferation, invasion and migration but promoted apoptosis of glioma cells, accompanied by the expression changes of migration- and apoptosis-related proteins. However, after co-transfection with AKR1B1 pcDNA3.1 in NORAD silencing cells, the effects of NORAD silencing on proliferation, invasion, migration, and apoptosis were attenuated. Consistently, the expression of phosphorylated ERK (p-ERK) was decreased after NORAD silencing, which were reversed following AKR1B1 overexpression. CONCLUSIONS These findings demonstrated that NORAD silencing suppressed proliferation, invasion, and migration and boosted apoptosis of glioma cells via downregulating the AKR1B1 expression, which may provide a potential therapeutic target for glioma treatment.

Comparison of the Effectiveness of Ring-Stripping Retrograde Endarterectomy and Carotid Artery Crossover Bypass in the Treatment of Patients with Symptomatic Riles Type 1A Common Carotid Artery Occlusion.

OBJECTIVE: The surgical procedure most appropriate for treating symptomatic Riles type 1A common carotid artery occlusion (CCAO) is unclear. This study compares the effects of ring-stripping retrograde endarterectomy (RSRE) and carotid artery crossover bypass (CACB) on cerebral perfusion improvement in patients with symptomatic Riles type 1A CCAO. METHODS: We conducted a retrospective analysis of symptomatic Riles type 1A CCAO patients treated at our centre. Postoperative improvements in the ipsilateral internal carotid artery (ICA) flow rate, ipsilateral cerebral blood perfusion (CBP) and the stroke recurrence rate were compared between patients who underwent RSRE and those who underwent CACB. RESULTS: A total of 20 CCAO patients were surgically treated at our centre from 2011 to 2018. Nine of these patients underwent RSRE, and eleven underwent CACB. No significant differences were identified between the groups in the ipsilateral blood flow rate of the ICA immediately after surgery and the ipsilateral-to-contralateral mean transit time ratios 1 day after surgery. However, the flow rate in the ICA was significantly higher in the RSRE group than in the CACB group 1 year after surgery (135.44 ± 19.22 ml/min vs. 116.36 ± 17.70 ml/min, p = 0.033). For CBP, the ipsilateral-to-contralateral mean transit time ratios were significantly lower in RSRE patients than in CACB patients 1 year after surgery (1.005 ± 0.052 vs. 1.064 ± 0.066, p = 0.044). In addition, the postoperative modified Rankin scale (mRS) score at the latest follow-up point (p = 0.884) and the stroke recurrence rate during the follow-up (88.9% vs. 90.9%, p > 0.999) were not significantly different between the two groups. CONCLUSIONS: Although the postoperative mRS score and the stroke recurrence rate were not significantly different between RSRE and CACB patients, compared to CACB, RSRE was better for improving the ipsilateral ICA flow rate and cerebral perfusion in symptomatic Riles type 1A CCAO patients.

Trans-eyebrow supraorbital keyhole approach to tuberculum sellae meningiomas: a series of 30 cases with long-term visual outcomes and recurrence rates.

BACKGROUND: Approach selection paradigm for tuberculum sellae meningiomas (TSMs) is still a point of discussion. The trans-eyebrow supraorbital keyhole approach (TSKA) is a minimally invasive transcranial approach and has been used for the treatment of TSMs during recent years. In this study, we presented a series of 30 cases of TSMs treated via TSKA with a long-term follow-up. METHOD: Thirty patients with TSMs underwent surgery via TSKA between December 2006 and August 2018. The medical data and follow-up results were retrospectively analyzed. RESULTS: A total of 5 males and 25 females were included in this study. Three patients presented with recurrent TSMs. The mean tumor size was 25.3 ± 7.3 mm (range, 10-48 mm). The mean follow-up period was 58.0 months (interquartile range, 33.5-86.3 months). Gross total resection (GTR) was achieved in 27 patients (90.0%). One recurrence (3.3%) occurred 9 years after surgery. Out of 29 patients with preoperative visual impairment, 17 (58.6%) improved, eight (27.6%) remained stable, and four (13.8%) deteriorated. No peri-operative death, CSF rhinorrhea, or permanent endocrine dysfunction occurred. All patients exhibited satisfactory cosmetic results. At the last follow-up, the glasgow outcome scale score was five in 27 patients (90.0%). CONCLUSION: The TSKA is characterized by minimal invasion with a satisfactory cosmetic outcome. Based on the tumor characteristics and surgeon's experience, this approach can be employed as an alternative minimally invasive approach for the treatment of TSMs.

Contralateral Approach Based on a Preoperative 3-Dimensional Virtual Osteotomy Technique for Anterior Circulation Aneurysms.

OBJECTIVE: Our objective was to review 15 consecutive patients with anterior circulation aneurysms managed through a contralateral approach. Individualized surgical simulation using three-dimensional (3D) imaging was adopted to enable safe performance of clipping surgery. METHODS: Five patients had multiple intracranial aneurysms, and 10 patients had a single aneurysm on the contralateral side of the craniotomy. Preoperatively, the unique architecture of aneurysms was fully understood in their 3-dimensionality reconstructed by Mimics software. The location of the cranial bone window and the patient's head position was individually optimized using a preoperative simulation system. RESULTS: In this cohort, 17 contralateral aneurysms showed no wall calcifications. Projections of the aneurysms were superomedial (3/17, 17.6%), medial (8/17, 47.1%), posterior (3/17, 17.6%), and superior (3/17, 17.6%). The visual similarity between the simulating scene and the operative view was excellent in 100% of the cases. Four patients were treated with a contralateral pterional approach, and the remaining 11 patients were treated with a contralateral supraorbital keyhole approach. All of them were well-clipped, except 1 blister-like aneurysm being wrapped. All 15 patients had good outcomes (mRS ≤ 3) after a mean 13 months follow-up. There were no recurrences after surgical treatment. CONCLUSIONS: The contralateral approach for the selected anterior circulation aneurysms is feasible in experienced hands with acceptable morbidity. This approach should be the choice only under judicious case-to-case planning based on a preoperative 3D virtual osteotomy technique.

An NHC-Silyl-NHC Pincer Ligand for the Oxidative Addition of C-H, N-H, and O-H Bonds to Cobalt(I) Complexes.

N-Heterocyclic carbene based pincer ligands bearing a central silyl donor, [CSiC]- , have been envisioned as a class of strongly σ-donating ligands that can be used for synthesizing electron-rich transition-metal complexes for the activation of inert bonds. However, this type of pincer ligand and complexes thereof have remained elusive owing to their challenging synthesis. We herein describe the first synthesis of a CSiC pincer ligand scaffold through the coupling of a silyl-NHC chelate with a benzyl-NHC chelate induced by one-electron oxidation in the coordination sphere of a cobalt complex. The monoanionic CSiC ligand stabilizes the CoI dinitrogen complex [(CSiC)Co(N2 )] with an unusual coordination geometry and enables the challenging oxidative addition of E-H bonds (E=C, N, O) to CoI to form CoIII complexes. The structure and reactivity of the cobalt(I) complex are ascribed to the unique electronic properties of the CSiC pincer ligand, which provides a strong trans effect and pronounced σ-donation.

Light-Induced Bidirectional Metal-to-Metal Charge Transfer in a Linear Fe2 Co Complex.

It is a challenge to reversibly switch both magnetism and polarity using light irradiation. Herein we report a linear Fe2 Co complex, whereby interconversion between FeIIILS (µ-CN)CoIIHS (µ-NC)FeIIILS (LS=low-spin, HS=high-spin) and FeIIILS (µ-CN)CoIIILS (µ-NC)FeIILS linkages could be achieved upon heating and cooling, or alternating laser irradiation at 808 and 532 nm. The electron spin arrangement and charge distribution were simultaneously tuned accompanying bidirectional metal-to-metal charge transfer, providing switchable polarity and magnetism in the complex.

Mechanistic Insights into Ring Cleavage and Contraction of Benzene over a Titanium Hydride Cluster.

Carbon-carbon bond cleavage of benzene by transition metals is of great fundamental interest and practical importance, as this transformation is involved in the production of fuels and other important chemicals in the industrial hydrocracking of naphtha on solid catalysts. Although this transformation is thought to rely on cooperation of multiple metal sites, molecular-level information on the reaction mechanism has remained scarce to date. Here, we report the DFT studies of the ring cleavage and contraction of benzene by a molecular trinuclear titanium hydride cluster. Our studies suggest that the reaction is initiated by benzene coordination, followed by H2 release, C6H6 hydrometalation, repeated C-C and C-H bond cleavage and formation to give a MeC5H4 unit, and insertion of a Ti atom into the MeC5H4 unit with release of H2 to give a metallacycle product. The C-C bond cleavage and ring contraction of toluene can also occur in a similar fashion, though some details are different due to the presence of the methyl substituent. Obviously, the facile release of H2 from the metal hydride cluster to provide electrons and to alter the charge population at the metal centers, in combination with the flexible metal-hydride connections and dynamic redox behavior of the trimetallic framework, has enabled this unusual transformation to occur. This work has not only provided unprecedented insights into the activation and transformation of benzene over a multimetallic framework but it may also offer help in the design of new molecular catalysts for the activation and transformation of inactive aromatics.

Fluorescent Gold Nanoclusters with Interlocked Staples and a Fully Thiolate-Bound Kernel.

The structural features that render gold nanoclusters intrinsically fluorescent are currently not well understood. To address this issue, highly fluorescent gold nanoclusters have to be synthesized, and their structures must be determined. We herein report the synthesis of three fluorescent Au24 (SR)20 nanoclusters (R=C2 H4 Ph, CH2 Ph, or CH2 C6 H4 (t) Bu). According to UV/Vis/NIR, differential pulse voltammetry (DPV), and X-ray absorption fine structure (XAFS) analysis, these three nanoclusters adopt similar structures that feature a bi-tetrahedral Au8 kernel protected by four tetrameric Au4 (SR)5 motifs. At least two structural features are responsible for the unusual fluorescence of the Au24 (SR)20 nanoclusters: Two pairs of interlocked Au4 (SR)5 staples reduce the vibration loss, and the interactions between the kernel and the thiolate motifs enhance electron transfer from the ligand to the kernel moiety through the Au-S bonds, thereby enhancing the fluorescence. This work provides some clarification of the structure-fluorescence relationship of such clusters.

NF-κB induces miR-148a to sustain TGF-ß/Smad signaling activation in glioblastoma.

BACKGROUND: Inflammatory cytokines and transforming growth factor-ß (TGF-ß) are mutually inhibitory. However, hyperactivation of nuclear factor-κB (NF-κB) and TGF-ß signaling both emerge in glioblastoma. Here, we report microRNA-148a (miR-148a) overexpression in glioblastoma and that miR-148a directly suppressed Quaking (QKI), a negative regulator of TGF-ß signaling. METHODS: We determined NF-κB and TGF-ß/Smad signaling activity using pNF-κB-luc, pSMAD-luc, and control plasmids. The association between an RNA-induced silencing complex and QKI, mitogen-inducible gene 6 (MIG6), S-phase kinase-associated protein 1 (SKP1), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA was tested with microribonucleoprotein immunoprecipitation and real-time PCR. Xenograft tumors were established in the brains of nude mice. RESULTS: QKI suppression induced an aggressive phenotype of glioblastoma cells both in vitro and in vivo. Interestingly, we found that NF-κB induced miR-148a expression, leading to enhanced-strength and prolonged-duration TGF-ß/Smad signaling. Notably, these findings were consistent with the significant correlation between miR-148a levels with NF-κB hyperactivation and activated TGF-ß/Smad signaling in a cohort of human glioblastoma specimens. CONCLUSIONS: These findings uncover a plausible mechanism for NF-κB-sustained TGF-ß/Smad activation via miR-148a in glioblastoma, and may suggest a new target for clinical intervention in human cancer.

Four-Coordinate Iron(II) Diaryl Compounds with Monodentate N-Heterocyclic Carbene Ligation: Synthesis, Characterization, and Their Tetrahedral-Square Planar Isomerization in Solution.

The salt elimination reactions of (IPr2Me2)2FeCl2 (IPr2Me2 = 1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene) with the corresponding aryl Grignard reagents afford [(IPr2Me2)2FeAr2] (Ar = Ph, 3; C6H4-p-Me, 4; C6H4-p-(t)Bu, 5; C6H3-3,5-(CF3)2, 6) in good yields. X-ray crystallographic studies revealed the presence of both tetrahedral and trans square planar isomers for 3 and 6 and the tetrahedral structures for 4 and 5. Magnetic susceptibility and (57)Fe Mössbauer spectrum measurements on the solid samples indicated the high-spin (S = 2) and intermediate-spin (S = 1) nature of the tetrahedral and square planar structures, respectively. Solution property studies, including solution magnetic susceptibility measurement, variable-temperature (1)H and (19)F NMR, and absorption spectroscopy, on 3-6, as well as an (57)Fe Mössbauer spectrum study on a frozen tetrahydrofuran solution of tetrahedral [(IPr2Me2)2(57)FePh2] suggest the coexistence of tetrahedral and trans square planar structures in solution phase. Density functional theory calculations on (IPr2Me2)2FePh2 disclosed that the tetrahedral and trans square planar isomers are close in energy and that the geometry isomerization can occur by spin-change-coupled geometric transformation on four-coordinate iron(II) center.