Re-investigation of in vitro activity of acetohydroxyacid synthase I holoenzyme from Escherichia coli.

Acetohydroxyacid synthase (AHAS) is one of the key enzymes of the biosynthesis of branched-chain amino acids, it is also an effective target for the screening of herbicides and antibiotics. In this study we present a method for preparing Escherichia coli AHAS I holoenzyme (EcAHAS I) with exceptional stability, which provides a solid ground for us to re-investigate the in vitro catalytic properties of the protein. The results show EcAHAS I synthesized in this way exhibits similar function to Bacillus subtilis acetolactate synthase in its catalysis with pyruvate and 2-ketobutyrate (2-KB) as dual-substrate, producing four 2-hydroxy-3-ketoacids including (S)-2-acetolactate, (S)-2-aceto-2-hydroxybutyrate, (S)-2-propionyllactate, and (S)-2-propionyl-2-hydroxybutyrate. Quantification of the reaction indicates that the two substrates almost totally consume, and compound (S)-2-aceto-2- hydroxybutyrate forms in the highest yield among the four major products. Moreover, the protein also condenses two molecules of 2-KB to furnish (S)-2-propionyl-2-hydroxybutyrate. Further exploration manifests that EcAHAS I ligates pyruvate/2-KB and nitrosobenzene to generate two arylhydroxamic acids N-hydroxy-N-phenylacetamide and N-hydroxy-N-phenyl- propionamide. These findings enhance our comprehension of the catalytic characteristics of EcAHAS I. Furthermore, the application of this enzyme as a catalyst in construction of C-N bonds displays promising potential.

Spin-State Control in Dysprosium(III) Metallacrown Magnets via Thioacetal Modification.

Integrating controllable spin states into single-molecule magnets (SMMs) enables precise manipulation of magnetic interactions at a molecular level, but remains a synthetic challenge. Herein, we developed a 3d-4f metallacrown (MC) magnet [DyNi5(quinha)5(Clsal)2(py)8](ClO4) ⋅ 4H2O (H2quinha=quinaldichydroxamic acid, HClsal=5-chlorosalicylaldehyde) wherein a square planar NiII is stabilized by chemical stacking. Thioacetal modification was employed via post-synthetic ligand substitutions and yielded [DyNi5(quinha)5(Clsaldt)2(py)8](ClO4) ⋅ 3H2O (HClsaldt=4-chloro-2-(1,3-dithiolan-2-yl)phenol). Thanks to the additional ligations of thioacetal onto the NiII site, coordination-induced spin state switching (CISSS) took place with spin state altering from low-spin S=0 to high-spin S=1. The synergy of CISSS effect and magnetic interactions results in distinct energy splitting and magnetic dynamics. Magnetic studies indicate prominent enhancement of reversal barrier from 57 cm-1 to 423 cm-1, along with hysteresis opening and an over 200-fold increment in coercive field at 2 K. Ab initio calculations provide deeper insights into the exchange models and rationalize the relaxation/tunnelling pathways. These results demonstrate here provide a fire-new perspective in modulating the magnetization relaxation via the incorporation of controllable spin states and magnetic interactions facilitated by the CISSS approach.

"One-Pot" In Situ Tandem Reaction─Dy(III) Coordination-Catalyzed Multicomponent Condensation of Salicylaldehyde Derivatives to Obtain Ketals.

It is difficult to subject simple reaction starting materials to a "one-pot" in situ tandem reaction without post-treatment under mild reaction conditions to obtain multimers with complex structural linkages. In organic synthesis, acetal reactions are often used to protect derivatives containing carbonyl functional groups. Therefore, acetal products tend to have very low stability, and performing multi-step condensation to obtain complex multimeric products is difficult. Herein, we achieved the first efficient multiple condensation of o-vanillin derivatives using Dy(OAc)3·6H2O undergoing a "one-pot" in situ tandem reaction under mild solvothermal conditions to obtain a series of dimers (I and II, clusters 1 and 2) and trimers (I and II, clusters 3 and 4). When methanol or ethanol is used as the solvent, the alcoholic solvent participates in acetal and dehydration reactions to obtain dimers (I and II). Surprisingly, when using acetonitrile as the reaction solvent, the o-vanillin derivatives undergo acetal and dehydration reactions to obtain trimers (I and II). In addition, clusters 1-4 all showed distinct single-molecule magnetic behaviors under zero-field conditions. To the best of our knowledge, this is the first time that multiple acetal reactions catalyzed by coordination-directed catalysis under "one-pot" conditions have been realized, opening a new horizon for the development of fast, facile, green, and efficient synthetic methods for complex compounds.

Aggregation-Induced Emission via the Restriction of the Intramolecular Vibration Mechanism of Pinacol Lanthanide Complexes.

Pinacol lanthanide complexes PyraLn (Ln = Dy and Tb) with the restriction of intramolecular vibration were obtained for the first time via an in situ solvothermal coordination-catalyzed tandem reaction using cheap and simple starting materials, thereby avoiding complex, time-consuming, and expensive conventional organic synthesis strategies. A high-resolution electrospray ionization mass spectrometry (HRESI-MS) analysis confirmed the stability of PyraLn in an organic solution. The formation process of PyraLn was monitored in detail using time-dependent HRESI-MS, which allowed for proposing a mechanism for the formation of pinacol complexes via in situ tandem reactions under one-pot coordination-catalyzed conditions. The PyraLn complexes constructed using a pinacol ligand with a butterfly configuration exhibited distinct aggregation-induced emission (AIE) behavior, with the αAIE value as high as 60.42 according to the AIE titration curve. In addition, the PyraLn complexes in the aggregated state exhibit a rapid photoresponse to various 3d metal ions with low detection limits. These findings provide fast, facile, and high-yield access to dynamic, smart lanthanide complex emissions with bright emission and facilitate the rational construction of molecular machines for artificial intelligence.

Magnetic and Luminescent Dual Responses of Photochromic Hexaazamacrocyclic Lanthanide Complexes.

Herein, hexaazamacrocyclic ligand LN6 was employed to construct a series of photochromic rare-earth complexes, [Ln(LN6)(NO3)2](BPh4) [1-Ln, Ln = Dy, Tb, Eu, Gd, Y; LN6 = (3E,5E,10E,12E)-3,6,10,13-tetraaza-1,8(2,6)-dipyridinacyclotetradecaphane-3,5,10,12-tetraene]. The behavior of photogenerated radicals of hexaazamacrocyclic ligands was revealed for the first time. Upon 365 nm light irradiation, complexes 1-Ln exhibit photochromic behavior induced by photogenerated radicals according to EPR and UV-vis analyses. Static and dynamic magnetic studies of 1-Dy and irradiated product 1-Dy* indicate weak ferromagnetic interactions among DyIII ions and photogenerated LN6 radicals, as well as slow magnetization relaxation behavior under a 2 kOe applied field. Further fitting analyses show that the magnetization relaxation in 1-Dy* is markedly different from 1-Dy. Time-dependent fluorescence measurements reveal the characteristic luminescence quenching dynamics of lanthanide in the photochromic process. Especially for irradiated product 1-Eu*, the luminescence is almost completely quenched within 5 min with a quenching efficiency of 98.4%. The results reported here provide a prospect for the design of radical-induced photochromic lanthanide single-molecule magnets and will promote the further development of multiresponsive photomagnetic materials.

Giant Crown-Shaped Dy34 Nanocluster with High Acid-Base Stability Assembled by an out-to-in Growth Mechanism.

Lanthanoid metal ions have large ionic radii, complex coordination modes, and easy distortion of coordination spheres, but the design and synthesis of high-nucleation lanthanoid clusters with high stability in solution (especially aqueous solution) are challenging. Herein, a diacylhydrazone ligand (H2L1) with multidentate chelating coordination sites was used to react with Dy(OAc)3·4H2O under solvothermal conditions to obtain an example of a 34-nucleus crown-shaped dysprosium cluster [Dy34(L)8(µ2-OH)(µ3-OH)21(µ3-O)14(OAc)31(OCH3)2(H2O)15](OAc)3 (1). Structural analysis showed that the bisacylhydrazone ligand H2L1 with polydentate chelate coordination sites could rapidly capture DyIII ions, thereby forming 34-nucleus crown-shaped dysprosium cluster 1 following the out-to-in growth mechanism. Cluster 1 remained stable after immersion in solutions with different pH values (3-14) for 24 h. To the best of the authors' knowledge, high-nucleation lanthanoid clusters with excellent strong acid and base stability and water stability are very rare. Meanwhile, high-resolution electrospray mass spectrometry molecular ion peaks produced by cluster 1 were captured, which proved to be stable also in organic solvents. Magnetic research showed that cluster 1 exhibited frequency-dependent behavior. This work provides a new idea for designing and synthesizing high-nucleation lanthanoid clusters with high stability.

Series of the Largest Dish-Shaped Dysprosium Nanoclusters Formed by In Situ Reactions.

A three-dimensional supermolecule structure is easily formed due to the diverse coordination modes of high-oxidation-state lanthanide metal ions. However, the design and construction of zero-dimensional (0 D) dish-shaped high-nuclearity lanthanide clusters are difficult. Herein, for the first time, we synthesized a series of the largest dish-shaped high-nuclearity lanthanide nanoclusters (1-4) by in situ tandem reactions under solvothermal one-pot conditions. The formation of 1 and 2 involved an in situ reaction of aldehydes and amines, while the condensation reactions between aldehydes occurred in 3 and 4. Based on the structural characteristics of the dish-shaped lanthanide clusters, we proposed two possible assembly mechanisms involving Dy1 → Dy7 → Dy13 → Dy19 (planar epitaxial growth mechanism) and Dy1 → Dy12 → Dy18 → Dy19 (planar internal growth mechanism).

Manipulating Solvothermal Coordination-Catalyzed In Situ Tandem Reactions to Construct Dysprosium-Based Complexes with Different Shapes and Zero-Field SMM Behaviors.

By changing the coordination anions (OAc- and Cl-), reaction temperature, solvent, and ligand substituents, four Dy(III)-based complexes were obtained by directed synthesis, which are [Dy4(L1)2(L2)2(OAc)4]·4C2H5OH·3H2O (1, L1 = 1,3,4-thiadiazole-2,5-diamine, H4L2 = 6,6'-(((1,3,4-thiadiazole-2,5-diyl)bis(azanediyl))bis(((3-ethoxy-2-hydroxybenzyl)oxy)methylene))bis(2-ethoxyphen), [Dy4(L3)4(OAc)4]·C2H5OH·H2O (2, H3L3 = 2-(((5-amino-1,3,4-thiadiazol-2-yl)amino)((3-ethoxy-2-hydroxybenzyl)oxy)methyl)-6-ethoxyphenol)), [Dy6(L4)4(L5)2(µ3-OH)4(CH3O)4Cl4]Cl2 (3, H2L4 = 2-hydroxy-3-methoxybenzaldehyde, H2L5 = 2-(((5-amino-1,3,4-thiadiazol-2-yl)amino)(hydroxy)methyl)-6-methoxyphenol), and [Dy6(L6)4(L7)2(µ3-OH)4(CH3O)4Cl4]Cl2·2H3O (4, H2L6 = 2-hydroxy-3-ethoxybenzaldehyde, H2L7 = 2-(((5-amino-1,3,4-thiadiazol-2-yl)amino)(hydroxy)methyl)-6-ethoxyphenol). A series of acetal products (H4L2, H3L3, H2L5, and H2L7) were obtained through dehydration in situ tandem reactions. Magnetic studies show that complexes 1-4 exhibited different single-molecule magnet behavior under zero-field conditions. The best fitting results showed that under zero DC field, the effective energy barriers (Ueff) and magnetic relaxation times (τ0) of complexes 1-4 are Ueff = 117.0 (2.1) K and τ0 = 6.07 × 10-7 s; Ueff = 83.91 (1.5) K and τ0 = 4.28 × 10-7 s; Ueff = 1.28 (0.2) K and τ0 = 0.73 s, and Ueff = 104.43 (13.3) K and τ0 = 8.25 × 10-8 s, respectively.

Anion-Manipulated Hydrolysis Process Assembles of Giant High-Nucleation Lanthanide-Oxo Cluster.

Widespread concern has been raised over the synthesis of highly nucleated lanthanide clusters with special shapes and/or specific linkages. Construction of lanthanide clusters with specific shapes and/or linkages can be achieved by carefully regulating the hydrolysis of lanthanide metal ions and the resulting hydrolysis products. However, studies on the manipulation of lanthanide-ion hydrolysis to obtain giant lanthanide-oxo clusters have been few. In this study, we obtained a tetraicosa lanthanide cluster (3) by manipulating the hydrolysis of Dy(III) ions using an anion (OAc-). As far as we know, cluster 3 has the highest nucleation among all lanthanide-oxo clusters reported. In 3, two triangular Dy3O4 are oriented in opposite directions to form the central connecting axis Dy6(OH)8, which is in turn connected to six Dy3O4 that are oriented in different directions. Meanwhile, a sample of a chiral trinuclear dysprosium cluster (1) was obtained in a mixed CH3OH and CH3CN solvent and by replacing the anion in the reaction to Cl- ions. In this cluster, 1,3,4-thiadiazole-2,5-diamine (L2) is free on one side through π···π interactions and is parallel to the o-vanillin (L1)- ligand, thus resulting in a triangular arrangement. The arrangement of L2 affects the end group coordination in the cluster 1 structure through hydrogen bonding and induces the cluster to exhibit chirality. When the reaction solvent was changed to CH3OH, a sample of cluster 2, composed of two independent triangular Dy3 that have different end group arrangements, was obtained. Magnetic analysis showed that clusters 1 and 3 both exhibit distinctive single-molecule magnetic properties under zero-magnetic-field conditions. This study thus provides a method for the creation of chiral high-nucleation clusters from achiral ligands and potentially paves the way for the synthesis of high-nucleation lanthanide clusters with unique forms.

Awareness for Endoscopic Screening Among Accompanying Children of Hospitalized Esophageal Cancer Patients in Henan.

The free generalized endoscopic screening for diagnosis of early esophageal cancer and precancerous lesion could not be satisfactorily implemented in China. At present, the decision to accept endoscopic screening at their own expense may largely depend on the public awareness. This study was aimed to investigate the awareness and other influencing factors associated with the accompanying children of esophageal cancer patients after their hospitalization. In this cross-sectional study, from April to June 2016, 233 children of accompanying patients, who were admitted within the last 1 year due to esophageal cancer in three affiliated hospitals of Zhengzhou University and Anyang Tumor Hospital, were enrolled. In addition, telephone surveys were conducted to investigate their awareness about endoscopic screening. One child was corresponded to an esophageal cancer patient. About half (47.6%, 111/233) of the children were unaware that endoscopic screening could detect early esophageal cancer and precancerous lesion. There was no significant difference in their awareness rates between hospitals with different administration levels. Besides, the males who had a lower family income and lower education level showed a poor awareness rate (P < 0.05). The overall awareness rate among the accompanying children of patients on endoscopic screening was rather low in Henan province (China). Hence, the health education and awareness on the importance of endoscopic screening for early detection of esophageal cancer should be promoted among children accompanying the patients. More attention should be focused towards the subject group, particularly among those male children with lower educational level and family income.

Mfsd2a overexpression alleviates vascular dysfunction in diabetic retinopathy.

Diabetic retinopathy (DR) is one of the common complications in diabetic patients. Nowadays, VEGF pathway is subject to extensive research. However, about 27% of the patients have a poor visual outcome, with 50% still having edema after two years' treatment of diabetic macular edema (DME) with ranibizumab. Docosahexaenoic acid (DHA), the primary ω-3 long-chain polyunsaturated fatty acid (LC-PUFA), reduces abnormal neovascularization and alleviates neovascular eye diseases. A study reported that fish oil reduced the incidence of retinopathy of prematurity (ROP) by about 27.5% in preterm infants. Although ω-3 LC-PUFAs protects against pathological retinal neovascularization, the treatment effectiveness is low. It is interesting to investigate why DHA therapy fails in some patients. In human vitreous humor samples, we found that the ratio of DHA and DHA-derived metabolites to total fatty acids was higher in vitreous humor from DR patients than that from macular hole patients; however, the ratio of DHA metabolites to DHA and DHA-derived metabolites was lower in the diabetic vitreous humor. The expression of Mfsd2a, the LPC-DHA transporter, was reduced in the oxygen-induced retinopathy (OIR) model and streptozotocin (STZ) model. In vitro, Mfsd2a overexpression inhibited endothelial cell proliferation, migration and vesicular transcytosis. Moreover, Mfsd2a overexpression in combination with the DHA diet obviously reduced abnormal retinal neovascularization and vascular leakage, which is more effective than Mfsd2a overexpression alone. These results suggest that DHA therapy failure in some DR patients is linked to low expression of Mfsd2a, and the combination of Mfsd2a overexpression and DHA therapy may be an effective treatment.

A Series of High-Nuclear Gadolinium Cluster Aggregates with a Magnetocaloric Effect Constructed through Two-Component Manipulation.

The serialized expansion of high-nuclear clusters usually includes the controlled variable method and changes only a single variable. However, changing both variables will greatly increase the complexity of the reaction simultaneously. Therefore, the use of a two-component regulation reaction is rare. Herein, we used a diacylhydrazone ligand (H4L1) with multidentate chelating coordination sites for the reaction with Gd(NO3)3·6H2O under solvothermal conditions to obtain an example of 16-nucleus disc-shaped cluster 1 with a brucite structure. The overall structure of cluster 1 can be regarded as an equilateral triangle, which is formed by three (L1)4- ions that can be regarded as "sides" and wrap the four-layer metal center Gd(III) ions. Notably, upon simultaneous regulation of the substituent of the ligand and the coordination anion, heptanuclear gadolinium cluster 2 was obtained. Cluster 2 can be regarded as a butterfly structure, which was formed by connecting two Gd3L2 molecules that were not in the same plane and through the central Gd(III) ion as an intersection. Moreover, hexanuclear gadolinium cluster 3 was obtained by changing the ligand substituent and adding an auxiliary ligand. Cluster 3 can be regarded as a chair structure, which was composed of two molecules of diacylhydrazone ligand (L2)4- wrapping vacant cubane shared by four vertices. This study was the first to construct a series of high-nuclear gadolinium clusters through two-component regulation manipulation. The study of the magnetocaloric effect showed that the maximum values of -ΔSm for clusters 1-3 were 34.05, 29.04, and 24.32 J kg-1 K-1, respectively, when T = 2 K and ΔH = 7 T.

Two Decanuclear DyIIIxCoII10-x (x = 2, 4) Nanoclusters: Structure, Assembly Mechanism, and Magnetic Properties.

The aggregation and formation of heterometallic nanoclusters usually involves a variety of complex self-assembly processes; thus, the exploration of their assembly mechanisms through process tracking is more challenging than that for homometallic nanoclusters. We explored here the effect of solvent on the formation of heterometallic clusters, which gave two heterometallic nanoclusters, [Dy2Co8(µ3-OCH3)2(L)4(HL)2(OAc)2(NO3)2(CH3CN)2]·CH3CN·H2O (1) and [Dy4Co6(L)4(HL)2(OAc)6(OCH2CH2OH)2(HOCH2CH2OH)(H2O)]·9CH3CN (2), with the H3L ligand formed from the in situ condensation reaction of 3-amino-1,2-propanediol with 2-hydroxy-1-naphthaldehyde in the presence of Co(OAc)2·4H2O and Dy(NO)3·6H2O. It is worth noting that the skeleton of cluster 1 has a high stability under high-resolution electrospray ionization mass spectrometry (HRESI-MS) conditions with a gradually increasing energy of the ion source. Cluster 2 underwent a multistep fragmentation even under a zero ion-source voltage for the measurement of HRESI-MS. Further analysis showed that cluster 2 underwent a possible fragmentation mechanism of Dy4Co6L6 → Dy2Co6L5/DyL → DyCo2L3/DyCo2L → DyL/Co2L2. Most notably, the species emerging in the formation process of cluster 1 were tracked using time-dependent HRESI-MS, from which we proposed its possible formation mechanism of H2L → Co2L2 → Co2DyL2/Co3L2 → Co3DyL2 → Co4DyL2 → Co5Dy2L4 → Co8Dy2L6. As far as we know, it is the first time to track the formation process of Dy-Co heterometallic clusters through HRESI-MS with the proposed assembly mechanism. The magnetic properties of the two titled DyIIIxCoII10-x (x = 2, 4) clusters were studied. Both of them exhibit slow magnetic relaxation, and 1 is a single-molecule magnet at zero direct-current field.

The role of semaphorins in small vessels of the eye and brain.

Small vessel diseases, such as ischemic retinopathy and cerebral small vessel disease (CSVD), are increasingly recognized in patients with diabetes, dementia and cerebrovascular disease. The mechanisms of small vessel diseases are poorly understood, but the latest studies suggest a role for semaphorins. Initially identified as axon guidance cues, semaphorins are mainly studied in neuronal morphogenesis, neural circuit assembly, and synapse assembly and refinement. In recent years, semaphorins have been found to play important roles in regulating vascular growth and development and in many pathophysiological processes, including atherosclerosis, angiogenesis after stroke and retinopathy. Growing evidence indicates that semaphorins affect the occurrence, perfusion and regression of both the macrovasculature and microvasculature by regulating the proliferation, apoptosis, migration, barrier function and inflammatory response of endothelial cells, vascular smooth muscle cells (VSMCs) and pericytes. In this review, we concentrate on the regulatory effects of semaphorins on the cell components of the vessel wall and their potential roles in microvascular diseases, especially in the retina and cerebral small vessel. Finally, we discuss potential molecular approaches in targeting semaphorins as therapies for microvascular disorders in the eye and brain.

Multifunctional Binuclear Ln(III) Complexes Obtained via In Situ Tandem Reactions: Multiple Photoresponses to Volatile Organic Solvents and Anticounterfeiting and Magnetic Properties.

The design and synthesis of simple lanthanide complexes with multiple functions have been widely studied and have faced certain challenges. Herein, we successfully synthesized the series of binuclear lanthanide complexes [Ln2(L1)2(NO3)4] (HL1 = 2-amino-1,2-bis(pyridin-2-yl)ethanol; Ln = Dy (Dy2), Tb (Tb2), Ho (Ho2) Er (Er2)) via the in situ self-condensation of Ln(NO3)3·6H2O-catalyzed 2-aminomethylpyridine (16 steps) under solvothermal conditions. Dy2 was mixed with different volatile organic solvents, and photoluminescence tests demonstrated that it showed an excellent selective photoresponse to chloroform (CHCl3). Sensing Tb2 on different organic solvents under the same conditions showed that it exhibited excellent selective photoresponse to methanol (CH3OH). Even under EtOH conditions, Tb2 could selectively respond to small amounts of CH3OH. To the best of our knowledge, achieving a selective photoresponse to various volatile organic compounds by changing the metal center of the complex is difficult. Furthermore, we performed anticounterfeiting tests on Tb2, and the results showed significant differences between the anticounterfeiting marks under white light and ultraviolet light conditions. The alternating current susceptibilities of Dy2 suggested that it was a typical single-molecule magnet (SMM) (Ueff = 93.62 K, τ0 = 1.19 × 10-5 s) under a 0 Oe dc field. Ab initio calculations on Dy2 indicated that the high degrees of axiality of the constituent mononuclear Dy fragments are the main reasons for the existence of SMM behavior.

Substitution Effects Regulate the Formation of Butterfly-Shaped Tetranuclear Dy(III) Cluster and Dy-Based Hydrogen-Bonded Helix Frameworks: Structure and Magnetic Properties.

The generation of two types of complexes with different topological connections and completely different structural types merely via the substitution effect is extremely rare, especially for -CH3 and -C2H5 substituents with similar physical and chemical properties. Herein, we used 3-methoxysalicylaldehyde, 1,2-cyclohexanediamine, and Dy(NO3)3·6H2O to react under solvothermal conditions (CH3OH:CH3CN = 1:1) at 80 °C to obtain the butterfly-shaped tetranuclear DyIII cluster [Dy4(L1)4(µ3-O)2(NO3)2] (Dy4, H2L1 = 6,6'-((1E,1'E)-(cyclohexane-1,3-diylbis(azanylylidene))bis(methanylylidene))bis(2-methoxyphenol)). The ligand H2L1 was obtained by the Schiff base in situ reaction of 3-methoxysalicylaldehyde and 1,2-cyclohexanediamine. In the Dy4 structure, (L1)2- has two different coordination modes: µ2-η1:η2:η1:η1 and µ4-η1:η2:η1:η1:η2:η1. The four DyIII ions are in two coordination environments: N2O6 (Dy1) and O9 (Dy2). The magnetic testing of cluster Dy4 without the addition of an external field revealed that it exhibited a clear frequency-dependent behavior. We changed 3-methoxysalicylaldehyde to 3-ethoxysalicylaldehyde and obtained one case of a hydrogen-bonded helix framework, [DyL2(NO3)3]n·2CH3CN (Dy-HHFs, H2L2 = 6,6'-((1E,1'E)-(cyclohexane-1,3-diylbis(azanylylidene))bis(methanylylidene))bis(2-ethoxyphenol)), under the same reaction conditions. The ligand H2L2 was formed by the Schiff base in situ reaction of 3-ethoxysalicylaldehyde and 1,2-cyclohexanediamine. All DyIII ions in the Dy-HHFs structure are in the same coordination environment (O9). The twisted S-shaped (L2)2- ligand is linked by a Dy(III) ion to form a spiral chain. The spiral chain is one of the independent units that is interconnected to form Dy-HHFs through three strong hydrogen-bonding interactions. Magnetic studies show that Dy-HHFs exhibits single-ion-magnet behavior (Ueff = 68.59 K and τ0 = 1.10 × 10-7 s, 0 Oe DC field; Ueff = 131.5 K and τ0 = 1.22 × 10-7 s, 800 Oe DC field). Ab initio calculations were performed to interpret the dynamic magnetic performance of Dy-HHFs, and a satisfactory consistency between theory and experiment exists.

ATP6V0D2, a subunit associated with proton transport, serves an oncogenic role in esophagus cancer and is correlated with epithelial-mesenchymal transition.

BACKGROUND: The poor prognosis of esophagus cancer (EC) is mainly due to its high invasiveness and metastasis, so it is urgent to search effectively prognostic markers and explore their roles in the mechanism of metastasis. MATERIALS AND METHODS: Based on the TCGA database, we downloaded the RNA-Seq for analyzing the expression of ATP6V0D2. QRT-PCR was used to test the mRNA levels of ATP6V0D2 in cell lines. Chi-square tests were used to evaluate the correlation between ATP6V0D2 and clinical characteristics. Prognostic values were determined by Kaplan-Meier methods and cox's regression models. CCK-8 and clone formation assays were employed to evaluate the cell viability, and Transwell assay was implemented to determine the invasive and migratory abilities. Correlations between ATP6V0D2 and motion-related markers were analyzed by the GEPIA database and confirmed by western blot. Moreover, the relationship between ATP6V0D2 and molecules related to cell cycle and apoptosis was also determined by western blot. RESULTS: A significant increase was observed in 3 EC-related cell lines compared to the normal cell line. ATP6V0D2 has a connection with the poor prognosis and can be considered as an independent prognosticator for patients with EC. Besides, ATP6V0D2 can improve cells viability as well as invasive and migratory abilities. What's more, downregulation of ATP6V0D2 notably enhanced E-cadherin expression, while decreased N-cadherin, Vimentin, and MMP9 expression, whereas overexpression of ATP6V0D2 presented the opposite outcomes. Furthermore, we found that silencing ATP6V0D2 led to a significant reduction on the protein expression of Cyclin D1, CDK4, Bcl-2, whereas resulted in a notable enhancement on the Bax level. CONCLUSION: ATP6V0D2 might be an independent prognosticator for EC patients, and it possibly promotes tumorigenesis by regulating epithelial-mesenchymal transition, cell cycle and apoptosis-related markers, providing the possibility that ATP6V0D2 may be a novel biomarker for the therapeutic intervention of EC.

Metal-Helix Frameworks Formed by µ3 -NO3 - with Different Orientations and Connected to a Heterometallic CuII 10 DyIII 2 Folded Cluster.

Metal nanoclusters have a certain rigidity due to their specific coordination patterns and shapes; thus, they face extreme difficulty in folding into a specific direction to form a double-helix structure and in further interconnecting to form metal-helix frameworks (MHFs). To date, no MHFs have been produced by the formation of heterometallic clusters. Selecting the appropriate "bonding molecules" to bond metal nanoclusters in a specific multiple direction is one of the most effective strategies for designing synthetic MHFs. In this study, we realized for the first time the control of different orientations of µ3 -NO3 - to join heterometallic clusters (Cu10 Dy2 ) and subsequently form a left-handed double helix chain, which further joins to form MHFs. In the structure of the MHFs, four different directions of bridging µ3 -NO3 - exist, three of which are involved in the linkage of the double-helix chain. Each µ3 -NO3 - is connected to three adjacent Cu10 Dy2 . Herein, we extend a new method for designing synthetic double-helix structures and MHFs, thereby further laying the foundation for the development of similar DNA double-helix structures and nucleic acid secondary structures in vitro.

Tracking the Stepwise Formation of the Dysprosium Cluster (Dy10) with Multiple Relaxation Behavior.

High-nuclear lanthanide clusters are generally formed by the rapid accumulation of simple building units. Thus, tracking and observing the stepwise assembly process, which is vital for understanding the assembly mechanism, are extremely difficult. Herein, the decanuclear nanocluster [Dy10(L1)6(µ5-NO3)2(OAc)10(HOAc)2]·8H2O (Dy10, H3L1 = (E)-3-((3-ethoxy-2-hydroxybenzylidene)amino)propane-1,2-diol) was obtained from the reaction of Dy(NO3)3·6H2O, Dy(OAc)3·6H2O, 3-ethoxy-2-hydroxybenzaldehyde (L2), and 3-amino-1,2-propanediol (L3). The reaction process was further tracked by time-dependent high-resolution electrospray ionization mass spectrometry, and seven reaction intermediate fragments were screened. A stepwise assembly mechanism was observed based on these fragments, that is, L → Dy1 → Dy2 → Dy3 → Dy4 → Dy5 → Dy6 → Dy10. This study is the first to discover a stepwise assembly mechanism during the formation of high-nuclear lanthanide clusters (cluster nucleus > 3). Magnetic studies have shown the multiple relaxation behavior of Dy10.

Bifunctional Mononuclear Dysprosium Complexes: Single-Ion Magnet Behaviors and Antitumor Activities.

Two mononuclear dysprosium complexes (Et3NH)[Dy(BrMQ)4]·H2O·DMF(BrMQ-Dy) and (Et3NH)[Dy(ClMQ)4]·H2O·DMF (ClMQ-Dy) (H-BrMQ = 5,7-dibromo-2-methyl-8-quinolinol, H-ClMQ = 5,7-dichloro-2-methyl-8-quinolinol) were synthesized and characterized. The Dy(III) ions in complexes BrMQ-Dy and ClMQ-Dy have a pseudo-D4d local symmetry. Magnetic characterizations reveal that complex BrMQ-Dy is a single-ion magnet and complex ClMQ-Dy exhibits field-induced slow magnetic relaxation behaviors. The calculated effective barriers of BrMQ-Dy, BrMQ-Dya, ClMQ-Dy, and ClMQ-Dya are 47.8, 27.3, 96.0, and 65.5 cm-1, respectively (BrMQ-Dya and ClMQ-Dya represent the desolvated samples of BrMQ-Dy and ClMQ-Dy, respectively). Ab initio calculations confirmed that coordination symmetry of the Dy(III) ions, electron-withdrawing ligands, and the guest molecules is a key factor affecting the magnetic dynamics of the two complexes. The IC50 values of BrMQ-Dy and ClMQ-Dy against BEL-7404, HeLa, and Hep-G2 cancer cells were 1.01-22.06 µM. Interestingly, two Dy(III) complexes were less toxic to normal HL-7702 cells. BrMQ-Dy and ClMQ-Dy significantly induced cell arrest at G2 phase and down-regulated the G2 phase-related protein levels. Various experiments suggested that BrMQ-Dy and ClMQ-Dy also caused dysfunction of mitochondrial pathways in HeLa cells. Taken together, the different in vitro anticancer activity of complexes BrMQ-Dy and ClMQ-Dy in the order of 5,7-dichloro substitution > 5,7-dibromo substitution.