Combined cardiac, lung, and diaphragm ultrasound for predicting weaning failure during spontaneous breathing trial.

BACKGROUND: Weaning from invasive mechanical ventilation (MV) is a complex and challenging process that involves multiple pathophysiological mechanisms. A combined ultrasound evaluation of the heart, lungs, and diaphragm during the weaning phase can help to identify risk factors and underlying mechanisms for weaning failure. This study aimed to investigate the accuracy of lung ultrasound (LUS), transthoracic echocardiography (TTE), and diaphragm ultrasound for predicting weaning failure in critically ill patients. METHODS: Patients undergoing invasive MV for > 48 h and who were readied for their first spontaneous breathing trial (SBT) were studied. Patients were scheduled for a 2-h SBT using low-level pressure support ventilation. LUS and TTE were performed prospectively before and 30 min after starting the SBT, and diaphragm ultrasound was only performed 30 min after starting the SBT. Weaning failure was defined as failure of SBT, re-intubation, or non-invasive ventilation within 48 h. RESULTS: Fifty-one patients were included, of whom 15 experienced weaning failure. During the SBT, the global, anterior, and antero-lateral LUS scores were higher in the failed group than in the successful group. Receiver operating characteristic curve analysis showed that the areas under the curves for diaphragm thickening fraction (DTF) and global and antero-lateral LUS scores during the SBT to predict weaning failure were 0.678, 0.719, and 0.721, respectively. There was no correlation between the LUS scores and the average E/e' ratio during the SBT. Multivariate analysis identified antero-lateral LUS score > 7 and DTF < 31% during the SBT as independent predictors of weaning failure. CONCLUSION: LUS and diaphragm ultrasound can help to predict weaning failure in patients undergoing an SBT with low-level pressure support. An antero-lateral LUS score > 7 and DTF < 31% during the SBT were associated with weaning failure.

Bis-Alkoxide Dysprosium(III) Crown Ether Complexes Exhibit Tunable Air Stability and Record Energy Barrier.

High-performance and air-stable single-molecule magnets (SMMs) can offer great convenience for the fabrication of information storage devices. However, the controversial requisition of high stability and magnetic axiality is hard to balance for lanthanide-based SMMs. Here, a family of dysprosium(III) crown ether complexes possessing hexagonal-bipyramidal (pseudo-D6h symmetry) local coordination geometry with tunable air stability and effective energy barrier for magnetization reversal (Ueff ) are shown. The three complexes share the common formula of [Dy(18-C-6)L2 ][I3 ] (18-C-6 = 1,4,7,10,13,16-hexaoxacyclooctadecane; L = I, 1; L = Ot Bu 2 and L = 1-AdO 3). 1 is highly unstable in the air. 2 can survive in the air for a few minutes, while 3 remains unchanged in the air for more than 1 week. This is roughly in accordance with the percentage of buried volumes of the axial ligands. More strikingly, 2 and 3 show progressive enhancement of Ueff and 3 exhibits a record high Ueff of 2427(19) K, which significantly contributes to the 100 s blocking temperature up to 11 K for Yttrium-diluted sample, setting a new benchmark for solid-state air-stable SMMs.

Thermally Stable Terbium(II) and Dysprosium(II) Bis-amidinate Complexes.

The thermostable four-coordinate divalent lanthanide (Ln) bis-amidinate complexes [Ln(Piso)2] (Ln = Tb, Dy; Piso = {(NDipp)2CtBu}, Dipp = C6H3iPr2-2,6) were prepared by the reduction of parent five-coordinate Ln(III) precursors [Ln(Piso)2I] (Ln = Tb, Dy) with KC8; halide abstraction of [Ln(Piso)2I] with [H(SiEt3)2][B(C6F5)] gave the respective Ln(III) complexes [Ln(Piso)2][B(C6F5)]. All complexes were characterized by X-ray diffraction, ICP-MS, elemental analysis, SQUID magnetometry, UV-vis-NIR, ATR-IR, NMR, and EPR spectroscopy and ab initio CASSCF-SO calculations. These data consistently show that [Ln(Piso)2] formally exhibit Ln(II) centers with 4fn5dz21 (Ln = Tb, n = 8; Dy, n = 9) valence electron configurations. We show that simple assignments of the f-d coupling to either L-S or J-s schemes are an oversimplification, especially in the presence of significant crystal field splitting. The coordination geometry of [Ln(Piso)2] is intermediate between square planar and tetrahedral. Projecting from the quaternary carbon atoms of the CN2 ligand backbones shows near-linear C···Ln···C arrangements. This results in strong axial ligand fields to give effective energy barriers to magnetic reversal of 1920(91) K for the Tb(II) analogue and 1964(48) K for Dy(II), the highest values observed for mononuclear Ln(II) single-molecule magnets, eclipsing 1738 K for [Tb(C5iPr5)2]. We tentatively attribute the fast zero-field magnetic relaxation for these complexes at low temperatures to transverse fields, resulting in considerable mixing of mJ states.

A Dynamic Triradical: Synthesis, Crystal Structure, and Spin Frustration.

Polyradicals, i.e., multispin organic molecules, are playing important roles in radical-based material applications for their spin-spin interaction. A dynamic covalently bonded multispin molecule may endow materials with added function such as memory and switching. However, such a species has yet to be reported. We here report the synthesis, characterization, and crystal structure of a dynamic triradical species. It is generated by the self-assembly of two molecules through a Lewis acid coupled electron transfer. The crystalline species is spin-frustrated without Jahn-Teller distortion at low temperature, while it dissociates back to diamagnetic starting material in solution at high temperature. The reversible process is tracked by variable-temperature NMR, EPR, and UV-vis-NIR spectroscopy. Isolation, property study, and dynamic bonding investigation on such a species lay the foundation for the design of functional polyradicals with potential application as memory or switching devices.

Two-dimensional semiconducting Cu(I)/Sb(III) bimetallic hybrid iodides with a double perovskite structure and photocurrent response.

Stable lead-free hybrid halide double perovskites have sparked widespread interest as a new kind of photoelectric material. Herein, for the first time, we successfully incorporated copper(I) and antimony(III) into two two-dimensional (2D) hybrid bimetallic double perovskite iodides, namely (NH3C6H11)4CuSbI8·H2O (CuSbI-1) and (NH3C6H10NH3)2CuSbI8·0.5H2O (CuSbI-2), using cyclohexylamine and 1,4-cyclohexanediamine as organic components. The band gaps for CuSbI-1 and CuSbI-2 were determined to be 2.22(2) eV and 2.21(2) eV, respectively. Furthermore, these two layered perovskites were readily dissolved in an organic solvent (1 mL DMF can dissolve 1 g sample for each compound) and could form smooth, pinhole-free, and uniform thin films through a facile spin-coating method. Photocurrent experiments with xenon lamp irradiation revealed the obvious photoelectric responses for both 2D double perovskites. The ratio of the photocurrent to the dark current (Ilight/Idark) for CuSbI-1 and CuSbI-2 is about 23 and 10, respectively, further suggesting their potential to be applied as light harvesters or light detectors. More importantly, these 2D double perovskite iodides show high moisture and thermal stabilities, indicating their potential for optoelectronic applications.

Radical-Bridged Heterometallic Single-Molecule Magnets Incorporating Four Lanthanoceniums.

The syntheses and magnetic properties of organometallic heterometallic compounds [K(THF)6 ]{CoI [(µ3 -HAN)RE2 Cp*4 ]2 } (1-RE) and [K(Crypt)]2 {CoI [(µ3 -HAN)RE2 Cp*4 ]2 } (2-RE) containing hexaazatrinaphthylene radicals (HAN⋅3- ) and four rare earth (RE) ions are reported. 1-RE shows isolable species with ligand-based mixed valency as revealed by cyclic voltammetry (CV) thus leading to the isolation of 2-RE via one-electron chemical reduction. Strong electronic communication in mixed-valency supports stronger overall ferromagnetic behaviors in 2-RE than 1-RE containing Gd and Dy ions. Ac magnetic susceptibility data reveal 1-Dy and 2-Dy both exhibit slow magnetic relaxation. Importantly, larger coercive field was observed in the hysteresis of 2-Dy at 2.0 K, indicating the enhanced SMM behavior compared with 1-Dy. Ligand-based mixed-valency strategy has been used for the first time to improve the magnetic coupling in lanthanide (Ln) SMMs, thus opening up new ways to construct strongly coupled Ln-SMMs.

A C,S bonded quasi-two-coordinate chromium(II) complex showing field-induced slow magnetic relaxation behaviour.

A C,S bonded quasi-two-coordinate Cr(II) complex, Cr(SAr*)2 (HSAr* = HSC6H3-2,6(C6H2-2,4,6-Pri3)2), has been synthesized according to literature precedent. Magnetic measurements, high-frequency/field electron paramagnetic resonance (HF-EPR) experiments and ab initio calculation studies show that the field-induced slow magnetic relaxation behaviour is caused by relatively weak axial magnetic anisotropy.

Photoinduced Phase Transition of Ce-UiO-66 to Ce-BDC-OH.

External stimuli-responsive phase transition of metal-organic frameworks (MOFs) introduces intriguing functions for diverse applications under practical settings. Herein, we reported a phase transition from cubic Ce-UiO-66 to triclinic Ce-BDC-OH under light irradiation. Such a phase transition underwent a ligand-to-metal charge transfer process, which was unambiguously revealed by Fourier transform infrared spectroscopy, nuclear magnetic resonance, electron paramagnetic resonance, etc. We proposed a phase transition mechanism through (1) the photoreduction of the metal core from Ce4+ into Ce3+; (2) the photogeneration of •OH and hydroxylation of BDC into BDC-OH; and (3) the carboxylate migration and lattice rearrangement for transitions. The phenomenon of the Ce4+-to-Ce3+ reduction also enables a diamagnetism-to-paramagnetism transition, suggesting its potential as a photostimulus-responsive magnetic switch.

MicroRNAs Promote the Progression of Sepsis-Induced Cardiomyopathy and Neurovascular Dysfunction Through Upregulation of NF-kappaB Signaling Pathway-Associated HDAC7/ACTN4.

Introduction: The objective of this study was to determine the NF-kappaB pathway, hub genes, and transcription factors (TFs) in monocytes implicated in the progression of neurovascular-related sepsis-induced cardiomyopathy (SIC) as well as potential miRNAs with regulatory functions. Methods: : Sepsis-induced cardiomyopathy-and heart failure (HF)-related differentially expressed genes (DEGs) between SIC and HF groups were identified separately by differential analysis. In addition, DEGs and differentially expressed miRNAs (DEmiRNAs) in monocytes between sepsis and the HC group were identified. Then, common DEGs in SIC, HF, and monocyte groups were identified by intersection analysis. Based on the functional pathways enriched by these DEGs, genes related to the NF-kB-inducing kinase (NIK)/NF-kappaB signaling pathway were selected for further intersection analysis to obtain hub genes. These common DEGs, together with sepsis-related DEmiRNAs, were used to construct a molecular interplay network and to identify core TFs in the network. Results: : A total of 153 upregulated genes and 25 downregulated genes were obtained from SIC-, HF-, and monocyte-related DEGs. Functional pathway analysis revealed that the upregulated genes were enriched in NF-κB signaling pathway. A total of eight genes associated with NF-κB signaling pathway were then further identified from the 178 DEGs. In combination with sepsis-related DEmiRNAs, HDAC7/ACTN4 was identified as a key transcriptional regulatory pair in the progression of SIC and in monocyte regulation. hsa-miR-23a-3p, hsa-miR-3175, and hsa-miR-23b-3p can regulate the progression of SIC through the regulation of HDAC7/ACTN4. Finally, gene set enrichment analysis (GSEA) suggested that HDAC7/ACTN4 may be associated with apoptosis in addition to the inflammatory response. Conclusion: : hsa-miR-23a-3p, hsa-miR-3175, and hsa-miR-23b-3p are involved in SIC progression by regulating NF-κB signaling signaling pathway-related HDAC7/ACTN4 in monocytes and cardiac tissue cells. These mechanisms may contribute to sepsis-induced neurovascular damage.

Ligand Fluorination to Mitigate the Raman Relaxation of DyIII Single-Molecule Magnets: A Combined Terahertz, Far-IR and Vibronic Barrier Model Study.

The fast Raman relaxation process via a virtual energy level has become a puzzle for how to chemically engineer single-molecule magnets (SMMs) with better performance. Here, we use the trifluoromethyl group to systematically substitute the methyl groups in the axial position of the parent bis-butoxide pentapyridyl dysprosium(III) SMM. The resulting complexes-[Dy(OLA )2 py5 ][BPh4 ] (LA =CH(CF3 )2 - 1, CH2 CF3 - 2, CMe2 CF3 - 3)-show progressively enhanced TB hys (@100 Oe s-1 ) from 17 K (for 3), 20 K (for 2) to 23 K (for 1). By experimentally identifying the varied under barrier relaxation energy in the 5-500 cm-1 regime, we are able to identify that the C-F bond related vibration energy of the axial ligand ranging from 200 to 350 cm-1 is the key variant for this improvement. Thus, this finding not only reveals a correlation between the structure and the Raman process but also provides a paradigm for how to apply the vibronic barrier model to analyze multi-phonon relaxation processes in lanthanide SMMs.

Tetraanionic arachno-Carboranyl Ligand Imparts Strong Axiality to Terbium(III) Single-Molecule Magnets.

A family of fully sandwiched arachno-lanthanacarborane complexes formulated as {η6 -[µ-1,2-[o-C6 H4 (CH2 )2 ]-1,2-C2 B10 H10 ]2 Ln}{Li5 (THF)10 } (Ln=Tb, Dy, Ho, Er, Y) is successfully synthesized, where the "carbons-adjacent" carboranyl ligand (arachno-R2 -C2 B10 H10 4- ) bears four negative charges and coordinates to the central lanthanide ions using the hexagonal η6 C2 B4 face. Thus, the central lanthanide cations are pseudo-twelve-coordinate and have an approximate pseudo-D6h symmetry or hexagonal-prismatic geometry. As the crystal field effect imparted by this geometry is still unknown, we thoroughly investigated the magnetic properties of this series of complexes and found that the crystal field imposed by this ligand causes a relation of Tb>Dy>Ho>Er for the energy gaps between the ground and the first excited states, which is of striking resemblance to the ferrocenophane and phthalocyanine ligands although the latter two ligands give disparate local coordination geometries. Moreover, the effective energy barrier to magnetization reversal of 445(10) K, the observable hysteresis loop up to 4 K and the relaxation time of the yttrium-diluted sample reaching 193(17) seconds at 2 K under an optimized field for the Tb analogue of this family of arachno-lanthanacarborane complexes, render a new benchmark for Tb3+ -based single-molecule magnets.

Exosomes from 3T3-J2 promote expansion of tracheal basal cells to facilitate rapid epithelization of 3D-printed double-layer tissue engineered trachea.

Functional epithelization plays a pivotal role in maintaining long-term lumen patency of tissue-engineered trachea (TET). Due to the slow migration of autologous epithelium, spontaneous epithelization process of transplanted TET is always tardive. Seeding tracheal basal cells (TBCs) on TET before transplantation might be favorable for accelerating epithelization, but rapid expansion of TBCs in vitro is still relatively intractable. In this study, we proposed a promising expansion strategy which enables the TBCs to proliferate rapidly in vitro. TBCs were isolated from the autologous tracheal mucosae of rabbit, and co-cultured with exosomes derived from 3T3-J2 cells. After co-culture with exosomal component, TBCs could vigorously proliferate in vitro and retained their multi-potency. It was in stark contrast to that the single-cultured TBCs could only be expand to passage 2 in about 30 days, moreover, the most majority of single-cultured cells entered late apoptotic stage. On the other hand, a bionic tubular double-layer scaffold with good mechanical property and bio-compatibility was designed and fabricated by 3D printing technology. Then TET with bi-lineage cell-type was constructed in vitro by implanting autologous chondrocytes on the outer-layer of scaffold, and TBCs on the inner-layer, respectively. And then TET was pre-vascularized in vivo, and pedicled transplanted to restore long-segmental defect in recipient rabbits. It was found that the chondrocytes and TBCs seeded on double-layer scaffolds developed well as expected. And almost complete coverage with ciliated epitheliums was observed on the lumen surface of TET 2-week after operation, in comparison with that the epithelization of TET without pre-seeding of TBCs accomplished nearly 2-month after operation. In conclusion, the promising expansion strategy of TBCs together with 3D-printed double-layer scaffolds facilitate the rapid epithelization process of transplanted TET, which might be of vital significance for clinical and translational medicine.

A study of cation-dependent inverse hydrogen bonds and magnetic exchange-couplings in lanthanacarborane complexes.

Ten lanthanacarborane complexes were synthesized to study the rare B-Hδ-∙∙∙Mn+ inverse hydrogen bonds (IHBs). The average bonding energy of B-Hδ-∙∙∙Ln3+ is theoretically determined to be larger than 24 kJ/mol, which is comparable to moderately strong hydrogen bonds (21-56 kJ/mol). In addition to NMR and IR, magnetometer was used to study the exchange-coupling interaction via such B-Hδ-∙∙∙Ln3+ IHBs in detail, and the coupling constant is determined to be -2.0 cm-1, which is strong enough to compare with single-atom bridged dysprosium(III) complexes. Two imidazolin-iminato incorporated complexes have shown energy barrier for magnetization reversal larger than 1000 K, and the exchange-biasing effects are evident. Moreover, the bonding strengths of B-Hδ-∙∙∙Mn+ IHBs are cation-dependent. If M = Na, the B-Hδ-∙∙∙Na+ bonding energy is reduced to 14 kJ/mol, and the dimerization process is no longer reversible. The exchange-biasing effect is also disappeared. We believe such a finding extends our knowledge of IHBs.

Cangrelor ameliorates CLP-induced pulmonary injury in sepsis by inhibiting GPR17.

BACKGROUND: Sepsis is a common complication of severe wound injury and infection, with a very high mortality rate. The P2Y12 receptor inhibitor, cangrelor, is an antagonist anti-platelet drug. METHODS: In our study, we investigated the protective mechanisms of cangrelor in CLP-induced pulmonary injury in sepsis, using C57BL/6 mouse models. RESULTS: TdT-mediated dUTP Nick-End Labeling (TUNEL) and Masson staining showed that apoptosis and fibrosis in lungs were alleviated by cangrelor treatment. Cangrelor significantly promoted surface expression of CD40L on platelets and inhibited CLP-induced neutrophils in Bronchoalveolar lavage fluid (BALF) (p < 0.001). We also found that cangrelor decreased the inflammatory response in the CLP mouse model and inhibited the expression of inflammatory cytokines, IL-1ß (p < 0.01), IL-6 (p < 0.05), and TNF-α (p < 0.001). Western blotting and RT-PCR showed that cangrelor inhibited the increased levels of G-protein-coupled receptor 17 (GPR17) induced by CLP (p < 0.001). CONCLUSION: Our study indicated that cangrelor repressed the levels of GPR17, followed by a decrease in the inflammatory response and a rise of neutrophils in BALF, potentially reversing CLP-mediated pulmonary injury during sepsis.

Preoperative Morphological Prediction of Early Reoperation Risk After Primary Repair in Tetralogy of Fallot: A Contemporary Analysis of 83 Cases.

This study was conducted to investigate the pulmonary artery (PA) variations in tetralogy of Fallot (TOF) and preoperative morphological predictors for early reoperation. Eighty-three TOF patients and 20 children with normal PA were included. The TOF group was divided into two subsets according to whether or not reoperation was performed within 3 years postoperatively. Clinical information was obtained, along with computed tomography (CT)-based three-dimensional geometry of the PA. Morphological measurements of the length of the main PA branches, the angles between them, and the cross-sectional area of each segment of the PAs were acquired using computer software. Logistic regression and receiver operating characteristic curves were applied to analysis. The TOF group showed a significantly smaller PA size and irregular PA shape, with lower Nakata and McGoon indices, than the control group. The median bifurcation angle (angle-γ) was greater than 100° in the TOF group, as compared to 66.70° in the control group (P < 0.000). Residual obstruction of the infundibulum or PAs was the main reason for early reoperation in this series. The development of the main PA and left PA was poorer in the reoperation subset than in the non-reoperation subset (P ≤ 0.01). The preoperative angle-γ in the reoperation subset was larger than that in the non-reoperation subset (median, 117.8° vs. 112.0°, P = 0.026). Higher weight (OR = 0.372) and McGoon index (OR = 0.122) were protective factors, while larger angle-γ (> 114.8°, OR = 5.040) and angle-γ normalized by body surface area (BSA) (γ/BSA > 297.9, OR = 18.860) were risk factors. This study provides an intuitive perspective of PA anatomical variations in TOF. Larger preoperative PA bifurcation angle and γ/BSA were morphological risk predictors of postoperative reoperation in patients with TOF.

Pulmonary Hypoplasia Resulting from Pulmonary Artery Banding in Infancy: A Neonatal Rat Model Study.

The aim of this study was to establish a neonatal rat model of decreased pulmonary blood flow (PBF) for studying pulmonary pathophysiological changes in newborn lung development with reduced PBF. Horizontal thoracotomy surgery with banding of the main pulmonary artery (PA) was performed on 30 rats in the PA banding (PAB) group and without banding on another 30 rats in the sham group within 6 h after birth. The body growth and mortality were recorded. Constriction of PA was checked by echocardiography on postnatal day 7 (P7). Lung morphology was assessed with computed tomography scanning and three-dimensional reconstruction. Histological differences of two groups were evaluated using hematoxylin and eosin (H&E) staining, Masson's trichrome staining, TdT-mediated dUTP nick-end labeling assay, and CD31 labeling with microscopic examination. PA ultrasound confirmed the establishment of constriction on P7. Relative to the sham group, the neonates' physical growth, survival fraction, and lung geometry volume were decreased in the PAB group over time (p < 0.05). Histologic appearance with reduced PBF characterized a markedly simplified alveolarization with noted lower radial alveolar count and alveolar septal thickness in the PAB group (p < 0.0001), pulmonary arteries with thinner/uneven membranous layers and smaller lumina. The deficient alveolar capillary bed, enhanced pulmonary collagen deposition, and increased apoptotic alveolar epithelium were significant in the PAB group compared to the sham group (p < 0.0001). A neonatal rat PAB model demonstrated that PBF reduction during early infancy impairs alveolarization and pulmonary microvasculature.

miR-381-abundant small extracellular vesicles derived from kartogenin-preconditioned mesenchymal stem cells promote chondrogenesis of MSCs by targeting TAOK1.

Small extracellular vesicles (sEVs) derived from mesenchymal stem cells have been shown to possess potent regenerative potential. In this study, we evaluated the chondrogenic effect of sEVs derived from kartogenin-preconditioned human umbilical cord mesenchymal stem cells (hUCMSCs). sEVs were isolated from the supernatants of KGN-preconditioned hUCMSCs (KGN-sEV) by gradient ultra-centrifugation, and internalized by native hUCMSCs, thereby inducing the chondrogenic differentiation. The underlying mechanism of KGN-sEV-induced chondrogenesis was explored by high-throughput sequencing and verified by transfection with the corresponding mimic and inhibitor. Sequencing identified the unique enrichment of a set of miRNAs in KGN-sEV compared with sEVs derived from unpreconditioned cells (un-sEV). Overexpression/inhibition in vitro and in vivo demonstrated that this chondrogenesis-inducing potential was primarily attributed to miR-381-3p, one of the most abundant miRNAs in KGN-sEV. Dual-luciferase reporter assays showed that miR-381-3p promoted chondrogenesis through direct suppression of TAOK1 by targeting its 3' untranslated region, thereby suppressing the Hippo signaling pathway. Collectively, our results highlight the regenerative potential of KGN-sEV to induce chondrogenic differentiation of MSCs, which is mainly achieved by delivering sEV-miR-381-3p, which targets TAOK1.

Circular RNA circPIP5K1A promotes non-small cell lung cancer proliferation and metastasis through miR-600/HIF-1α regulation.

Circular RNAs (circRNAs) have an important function in human diseases, especially in cancer. circRNA hsa_circ_0014130 (circPIP5K1A), a particularly abundant circRNA, participates in the tumorigenesis of non-small cell lung cancer (NSCLC), although the underlying regulatory mechanism remains unclear. Here, we investigated the circPIP5K1A role in NSCLC. Expression of circPIP5K1A in NSCLC cell lines was explored with quantitative real-time PCR. The effect of circPIP5K1A on NSCLC was evaluated with circPIP5K1A silencing, miR-600 mimic transfection, and hypoxia-inducible factor (HIF)-1α overexpression, followed by assessment of cell proliferation, metastasis, and tumorigenesis in nude mice. The subcellular localization of circPIP5K1A was evaluated via fluorescence in situ hybridization (FISH), and correlation between circPIP5K1A, miR-600, and HIF-1α was assessed by luciferase assay. The data demonstrated that circPIP5K1A expression was increased in NSCLC cells. FISH showed that circPIP5K1A localized to the cytoplasm. The circPIP5K1A knockdown suppressed NSCLC cell metastasis and proliferation by promoting expression of miR-600. Overexpression of miR-600 inhibited HIF-1α-mediated metastasis and proliferation of NSCLC cell by downregulating the endothelial mesenchymal transition-related proteins, Snail and vimentin, and upregulating E-cadherin. In vivo experiments illustrated that circPIP5K1A silence suppressed tumor growth and pulmonary metastasis. The circPIP5K1A may function as an miR-600 sponge to facilitate NSCLC proliferation and metastasis by promoting HIF-1α. A bifluorescein reporter experiment confirmed that miR-600 was the circPIP5K1A target, and miR-600 interacted with the 3' untranslated region of HIF-1α. These results show that circPIP5K1A acted as a tumor promoter through a novel circPIP5K1A/miR-600/HIF-1α axis, which provides candidate markers and therapeutic targets for NSCLC.

MicroRNA-106 attenuates hyperglycemia-induced vascular endothelial cell dysfunction by targeting HMGB1.

Chronic wounds are a common surgical problem exacerbated by diabetes. A hyperglycemic microenvironment induces inflammation and apoptosis, and plays an important role in vascular endothelial cell dysfunction in diabetes. Increasing evidence shows that high mobility group box 1 (HMGB1) expression is related to inflammation and apoptosis. The aim of this study was to determine the function of HMGB1 in hyperglycemia-induced vascular endothelial cell dysfunction. The results showed that the expression of HMGB1 was increased in human umbilical vein endothelial cells (HUVECs) after exposure to high glucose (25 mM). Downregulation of HMGB1 attenuated the high glucose-induced antiangiogenesis of HUVECs, and the decrease expression of HMGB1 inhibiting HUVEC apoptosis and inflammatory factor expression. In addition, miR-106 expression in HUVECs was decreased under high glucose conditions. Increased miR-106 significantly reversed the high glucose-induced vascular endothelial cell dysfunction by inhibition of HUVEC apoptosis and inflammatory factor expression. However, HMGB1 overexpression attenuated the protective effect of miR-106 on HUVECs in high glucose conditions. This suggested that miR-106 suppressed hyperglycemia-induced vascular endothelial cell dysfunction by targeting HMGB1. Double fluorescent reporter assays confirmed that miR-106 interacted with the 3'-UTR of HMGB1 and inhibited HMGB1 expression. Taken together, these data collectively suggested that miR-106 was a potential molecular target for inhibiting high glucose-induced inflammation and apoptosis by targeting HMGB1.