piSTING: A Pocket-Independent Agonist Based on Multivalency-Driven STING Oligomerization.

The stimulator of interferon genes (STING) pathway is a potent therapeutic target for innate immunity. Despite the efforts to develop pocket-dependent small-molecule STING agonists that mimic the endogenous STING ligand, cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), most of these agonists showed disappointing results in clinical trials owing to the limitations of the STING pocket. In this study, we developed novel pocket-independent STING-activating agonists (piSTINGs), which act through multivalency-driven oligomerization to activate STING. Additionally, a piSTING-adjuvanted vaccine elicited a significant antibody response and inhibited tumour growth in therapeutic models. Moreover, a piSTING-based vaccine combination with aPD-1 showed remarkable potential to enhance the effectiveness of immune checkpoint blockade (ICB) immunotherapy. In particular, piSTING can strengthen the impact of STING pathway in immunotherapy and accelerate the clinical translation of STING agonists.

The prognostic predictive value of the components of the PR interval in hospitalized patients with heart failure.

OBJECTIVE: Previous reports on the epidemiology, influencing factors, and the prognostic value of the components of PR interval in hospitalized heart failure patients were limited. METHODS: This study retrospectively enrolled 1182 patients hospitalized with heart failure from 2014 to 2017. Multiple linear regression analysis was used to explore the association between the components of PR interval and the baseline parameters. The primary outcome was all-cause death or heart transplantation. Multivariable-adjusted Cox proportional hazard regression models were constructed to explore the predictive value of the components of PR interval for the primary outcome. RESULTS: In multiple linear regression analysis, higher height (for every 10 cm increase in height: regression coefficient 4.83, P < 0.001) as well as larger atrial and ventricular size were associated with larger P wave duration but not with PR segment. The primary outcome occurred in 310 patients after an average follow-up of 2.39 years. Cox regression analyses revealed that the increase in PR segment was an independent predictor of the primary outcome (every 10 ms increase: hazard ratio 1.041, 95% confidence interval [CI] 1.010-1.083, P = 0.023), whereas the P wave duration did not show significant correlation. When adding the PR segment to an initial prognostic prediction model, the likelihood ratio test and categorical net reclassification index (NRI) showed a significant improvement, but the increase in C-index was not significant. In subgroup analysis, increased PR segment was an independent predictor of the primary endpoint in patients taller than 170 cm (each 10 ms increase: hazard ratio 1.153, 95% CI 1.085-1.225, P < 0.001) but not the shorter group (P for interaction = 0.006). CONCLUSIONS: In hospitalized patients with heart failure, longer PR segment was an independent predictor of the composite endpoint of all-cause death and heart transplantation, especially in the taller group, but it had limited significance in improving the prognostic risk stratification of this population.

Structure and function characterization of the α-L-arabinofuranosidase from the white-rot fungus Trametes hirsuta.

α-L-Arabinofuranosidases (Abfs) play a crucial role in the degradation of hemicelluloses, especially arabinoxylans (AX). Most of the available characterized Abfs are from bacteria, while fungi, as natural decomposers, contain Abfs with little attention given. An arabinofuranosidase (ThAbf1), belonging to the glycoside hydrolase 51 (GH51) family, from the genome of the white-rot fungus Trametes hirsuta, was recombinantly expressed, characterized, and functionally determined. The general biochemical properties showed that the optimal conditions for ThAbf1 were pH 6.0 and 50°C. In substrate kinetics assays, ThAbf1 preferred small fragment arabinoxylo-oligosaccharides (AXOS) and could surprisingly hydrolyze di-substituted 23,33-di-L-arabinofuranosyl-xylotriose (A2,3XX). It also synergized with commercial xylanase (XYL) and increased the saccharification efficiency of arabinoxylan. The crystal structure of ThAbf1 indicated the presence of an adjacent cavity next to the catalytic pocket which led to the ability of ThAbf1 to degrade di-substituted AXOS. The narrow binding pocket prevents ThAbf1 from binding larger substrates. These findings have strengthened our understanding of the catalytic mechanism of GH51 family Abfs and provided a theoretical foundation for the development of more efficient and versatile Abfs to accelerate the degradation and biotransformation of hemicellulose in biomass. KEY POINTS: • ThAbf1 from Trametes hirsuta degraded di-substituted arabinoxylo-oligosaccharide. • ThAbf1 performed detailed biochemical characterization and kinetics. • ThAbf1 structure has been obtained to illustrate the substrate specificity.

Organocatalytic Allylic Alkylation of α-(Alkylideneamino)nitriles and Its Application in the Preparation of Multisubstituted 1-Pyrrolines.

A synthetic approach for the construction of functionalized diverse 1-pyrrolines incorporating ß-quaternary carbon centers under mild reaction conditions has been reported, in which α-allyl α-(alkylideneamino)nitriles generated from a Lewis base-catalyzed allylic alkylation reaction engaged in a Lewis base-mediated tandem intramolecular cyclization to deliver the targeted molecules in a catalytically atom-economic fashion.

Prognostic utility of the prognostic nutritional index combined with serum sodium level in patients with heart failure.

BACKGROUND AND AIMS: Both malnutrition and hyponatremia (serum sodium <135 mmol/L) can be induced by the impaired absorption function of the edematous intestinal wall caused by heart failure (HF) and are prognostic factors of mortality in HF. However, little is known about the interrelationship of nutritional status and hyponatremia in mortality risk prediction in HF. METHODS AND RESULTS: This study enrolled 2882 HF patients admitted to the HF care unit of Fuwai Hospital, Beijing, China from 2008 to 2018; 71.3% were male and the mean age was 56.64 ± 15.96 years. Nutritional status was assessed by prognostic nutritional index (PNI), calculated as serum albumin (g/L) + 5 × total lymphocyte count (109/L). Lower PNI indicates worse nutritional status. Patients were divided into 8 groups based on baseline PNI quartiles (Q1: <43.6, Q2: 43.6-48.55, Q3: 48.55-63.25, Q4: >63.25) and sodium level (normal sodium and hyponatremia). After adjustment, patients in the PNI Q1 associated with hyponatremia had a 2.12-fold higher risk of all-cause death (95% confidence interval [CI]: 1.67-2.70) compared with those in the PNI Q4 with normal sodium. A refinement in risk prediction was observed after adding PNI quartile and serum sodium category to the original model (ΔC-statistic = 0.018, 95% CI: 0.007-0.025; net re-classification index = 0.459, 95% CI: 0.371-0.548; integrated discrimination improvement = 0.025, 95% CI: 0.018-0.032). CONCLUSION: HF patients with both the lowest PNI quartile and hyponatremia are at higher risk of all-cause mortality. The combination of PNI and serum sodium level enhanced the predictive value for all-cause mortality in hospitalized HF patients. CLINICAL TRIAL REGISTRATION: URL: ClinicalTrials.gov; Unique Identifier: NCT02664818.

Agonists and inhibitors of the STING pathway: Potential agents for immunotherapy.

Since being discovered in 2008, the STING (stimulator of interferon genes) pathway has gradually been recognized as a central and promising target for immunotherapy. The STING pathway can be stimulated by cyclic dinucleotides (CDNs), leading to the type I interferons (IFN) production for immunotherapy for cancer or other diseases. However, the negative charges, hydrophilicity, and instability of CDNs have hindered their further applications. In addition, chronic activation of the STING pathway has been found to be involved in autoimmune diseases as IFN overproduction. Thus, research and development of STING agonists and inhibitors has been a hot field for the treatment of several diseases. The past several years, especially 2018, has seen increasingly rapid advances in this field. Here, this review summarizes the synthesis and modification of CDNs, the identification of nonnucleotide agonists, the recent progress in delivery systems and the medical applications, such as personalized vaccine adjuvants, in detail. In addition, in this review, we summarize the STING inhibitors' advances from two aspects, covalent, and noncovalent inhibitors.

Aldehyde dehydrogenase 2 protects cardiomyocytes against lipotoxicity via the AKT/glycogen synthase kinase 3 beta pathways.

Aldehyde dehydrogenase 2, a mitochondrial matrix enzyme, plays a crucial role in protecting the heart against stress, such as ischemia reperfusion and alcohol injury. The present study aimed to investigate the effect of aldehyde dehydrogenase 2 on lipotoxic cardiomyopathy and to explore the possible mechanisms in vitro. Primary cardiomyocytes in the lipotoxic group were treated with oxidatively modified low-density lipoprotein (50 mg/L) for 24 h. Overexpression of aldehyde dehydrogenase 2 was achieved using the aldehyde dehydrogenase 2 activator, Alda-1 (20 µM). We found that cardiomyocyte apoptosis was attenuated by aldehyde dehydrogenase 2 overexpression. In addition, aldehyde dehydrogenase 2 overexpression inhibited the expression of BCL2 associated X, apoptosis regulator (BAX) and caspase 3, while it enhanced protein kinase B (AKT) and glycogen synthase kinase 3 beta (GSK-3ß) phosphorylation. The results suggested that aldehyde dehydrogenase 2 is cardioprotective against lipotoxic cardiomyopathy, probably by reducing apoptosis through the AKT/glycogen synthase kinase 3 beta (GSK-3ß) pathway. Our findings partially revealed the molecular mechanism of aldehyde dehydrogenase 2's cardioprotective effect against lipotoxic injury, and suggest a new therapeutic strategy to treat lipotoxic cardiomyopathy.

Influence of Magnetic Interactions and Single-Ion Anisotropy on Magnetic Relaxation within a Family of Tetranuclear Dysprosium Complexes.

Six tetranuclear DyIII complexes [Dy4(L)2(CH3OH)3(NO3)3]·3NO3·2H2O (1a), [Dy4(L)2(CH3OH)2(SCN)4(OCH3)2]·2CH3OH·2H2O (1b), {[Dy4(L)2(CH3OH)(SCN)6(CH3CN)]·3CH3OH·4CH3CN}2 (2a), [Dy4(L)2(CH3OH)2(SCN)6]·6CH3OH·2H2O (2b), [Dy4(L)2(CH3OH)2(SCN)4(OCH3)2]·5CH3OH·2H2O (3a), and [Dy4(L)2(CH3OH)(SCN)5(H2O)2]·SCN·4CH3OH·2H2O (3b) were structurally and magnetically characterized. The Dy1/Dy2 centers in these complexes are eight-coordinate and submitted to pseudo- D4d symmetry environments. It is noteworthy that the modulation of coordination terminal around Dy1/Dy2 centers induces distinct magnetic relaxation processes, switching from single relaxation (1b) to two-step relaxation (2b). All complexes show significant zero-field single-molecule magnet (SMM) properties with the exception of 3b, which only features the slow magnetic relaxation behavior under a zero dc field. Ab initio calculations substantiate that the excellent SMM property of complex 1b should mainly profit from strong ferromagnetic interactions between the individual DyIII ions, while different single-ion magnetism results in better SMM property of complex 3a than that of 3b.

Lanthanide(III) Hexanuclear Circular Helicates: Slow Magnetic Relaxation, Toroidal Arrangement of Magnetic Moments, and Magnetocaloric Effects.

Four hexanuclear circular helicates, {[Dy6L6(DMF)12]·6CF3SO3·12DMF}2 (1Dy), {[Gd6L6(DMF)12]·6CF3SO3·12DMF}2 (1Gd), [Dy6L6(DMF)10(H2O)2]·6ClO4·4H2O·10DMF (2Dy), and [Gd6L6(DMF)12]·6ClO4·2H2O·10DMF (2Gd), where DMF = N,N-dimethylformamide, were synthesized by employing a glutaratedihydrazide-bridged bis(3-methoxysalicylaldehyde) ligand (H2L) and characterized structurally and magnetically. Direct-current magnetic susceptibility studies indicated predominant weak antiferromagnetic exchange interactions among gadolinium analogues, which were quantified using the PHI software, giving J = -0.003 cm-1 with g = 2.00 for 1Gd and J = -0.001 cm-1 with g = 2.02 for 2Gd. Alternating-current magnetic susceptibility measurements indicated that complexes 1Dy and 2Dy show slow relaxation of magnetization behavior, further supported by theoretical calculations that also highlighted the toroidal arrangement of the magnetic moments.

Thiophene Derivatives as Anticancer Agents and Their Delivery to Tumor Cells Using Albumin Nanoparticles.

A series of thiophene derivatives (TPs) were synthesized and evaluated for cytotoxicity in HepG2 and SMMC-7721 cell lines by MTT assay. TP 5 was identified as a potential anticancer agent based on its ability to inhibit tumor cell growth. Drawbacks of TPs, including poor solubility and high toxicity, were overcome through delivery using self-assembling HSA nanoparticles (NPs). The optimum conditions for TP 5-NPs synthesis obtained by adjusting the temperature and concentration of TP 5. The NPs had an encapsulation efficiency of 99.59% and drug-loading capacity of 3.70%. TP 5 was slowly released from TP 5-NPs in vitro over 120 h. HepG2 and SMMC-7721 cell lines were employed to study cytotoxicity of TP 5-NPs, which exhibited high potency. ROS levels were elevated and mitochondrial membrane potentials reversed when the two cell lines were treated with TP 5-NPs for 12 h. Cellular uptake of fluorescence-labeled TP 5-NPs in vitro was analyzed by flow cytometry and laser confocal scanning microscopy. Fluorescence intensity increased over time, suggesting that TP 5-NPs were efficiently taken up by tumor cells. In conclusion, TP 5-NPs showed great promise as an anticancer therapeutic agent.

Aldehyde Dehydrogenase-2 Attenuates Myocardial Remodeling and Contractile Dysfunction Induced by a High-Fat Diet.

BACKGROUND/AIMS: Consumption of a high-fat (HF) diet exacerbates metabolic cardiomyopathy through lipotoxic mechanisms. In this study, we explored the role of aldehyde dehydrogenase-2 (ALDH2) in myocardial damage induced by a HF diet. METHODS: Wild-type C57 BL/6J mice were fed a HF diet or control diet for 16 weeks. ALDH2 overexpression was achieved by injecting a lentiviral ALDH2 expression vector into the left ventricle. RESULTS: Consumption of a HF diet induced metabolic syndrome and myocardial remodeling, and these deleterious effects were attenuated by ALDH2 overexpression. In addition, ALDH2 overexpression attenuated the cellular apoptosis and insulin resistance associated with a HF diet. Mechanistically, ALDH2 overexpression inhibited the expression of c-Jun N-terminal kinase (JNK)-1, activated protein 1 (AP-1), insulin receptor substrate 1 (IRS-1), 4- hydroxynonenal, caspase 3, transforming growth factor ß1, and collagen I and III, and enhanced Akt phosphorylation. CONCLUSION: ALDH2 may effectively attenuate myocardial remodeling and contractile defects induced by a HF diet through the regulation of the JNK/AP-1 and IRS-1/Akt signaling pathways. Our study demonstrates that ALDH2 plays an essential role in protecting cardiac function from lipotoxic cardiomyopathy.

Exchange Interactions Switch Tunneling: A Comparative Experimental and Theoretical Study on Relaxation Dynamics by Targeted Metal Ion Replacement.

The magnetic relaxation and magnetization blocking barriers of tailor-made homo- and heterodinuclear compounds [Dy2 (opch)2 (OAc)2 (H2 O)2 ]⋅MeOH (1) and [DyMn(opch)2 (OAc)(MeOH)(H2 O)2 ] (2), where H2 opch is (E)-N'-(2-hydroxy-3-methoxybenzylidene)pyrazine-2-carbohydrazide, were systematically investigated and the change in single-molecule magnet behavior originating from targeted replacement of one dysprosium site in the Dy2 compound with manganese was elucidated through a combination of experimental and theoretical studies. A detailed comparative study on these closely related model compounds revealed remarkable changes of the crystal-field splitting and anisotropy of the Dy site and the total exchange spectrum due to the replacement of Dy by Mn. The blocking barriers of these two compounds, which explain their different relaxation behaviors, were analyzed. The two Ising doublets arising from the magnetic interaction in the case of 1 are strongly uniaxial, with tunneling splittings smaller than 10-6  cm-1 , and this leads to magnetic relaxation at temperatures exceeding the exchange energy (2.14 cm-1 ), which involves transition via the excited states corresponding to local transitions on the excited doublet at the Dy site. The third and fourth exchange doublets in 2 (located at 2.16 and 3.25 cm-1 , respectively) show much larger tunneling splittings (of 10-4 and 10-3  cm-1 , respectively), and thus open an important path for magnetic relaxation.

Enhancement of Magnetocaloric Effect through Fixation of Carbon Dioxide: Molecular Assembly from Ln4 to Ln4 Cluster Pairs.

A series 1.Ln of tetranuclear lanthanide clusters [Ln4(µ4-O)L2(PhCOO)6]·solvent (Ln = Gd (1.Gd), Dy (1.Dy), Ho (1.Ho)) and octanuclear lanthanide Ln4 cluster pairs 2.Ln [Ln8(µ3-OH)4(CO3)2L4(PhCOO)8]·solvent (Ln = Gd (2.Gd), Dy (2.Dy), Tb (2.Tb)) were assembled by using a bi-Schiff-based ligand H2L and characterized structurally and magnetically. Interestingly, the octanuclear Ln4 cluster pairs 2.Ln are proposed to be assembled from the tetranuclear clusters 1.Ln through the uptake of CO2 from air in a more basic media. X-ray structural analyses approved the possible evolution mechanism. Magnetic studies reveal the coexistence of ferro- and anti-ferromagnetic interaction in 1.Gd and 2.Gd by simulating the direct-current magnetic susceptibility and indicate the CO32- bridges produce weak ferromagnetic interaction in 2.Gd rather than anti-ferromagnetic interaction by benzoate bridges in 1.Gd. The magnitude of the magnetocaloric effect has been examined and shows that complex 2.Gd exhibits larger magnetocaloric effect than 1.Gd, which could be probably ascribed to the weak ferromagnetic interaction produced by the CO32- bridges.

Axial Ligand Field in D4d Coordination Symmetry: Magnetic Relaxation of Dy SMMs Perturbed by Counteranions.

A series of mononuclear DyIII complexes with the general formula [DyLz2(salicylaldehyde)2]·X·solvent (Lz = 6-pyridin-2-yl[1,3,5]triazine-2,4-diamine; X = OH- (1·OH), Cl- (2·Cl), Br- (3·Br)) have been synthesized using mixed salicylaldehyde/pyridinyl-triazine ligands and discriminative counteranions. The DyIII ion in these three complexes resides in a similar D4d coordination geometry with counteranions perturbing the coordination environment and bond lengths and angles in the lattice. Magnetostructural studies reveal that the asymmetric distribution of salicylaldehyde/pyridinyl-triazine ligands and the presence of discriminative counteranions result in the coexistence of large anisotropy and quantum tunneling of magnetization. The magnetic anisotropy is dominated by the axial ligand field with short Dy-Osali distances and large ∠Osali-Dy-Osali angles, while the quantum tunneling relaxation is probably dictated by the π-π stacking of the Lz ligands, which induces an axial constriction of the coordinating plane. Ab initio calculations substantiate the diversity of the magnetic behaviors in these complexes and highlight the importance of axial ligand field with short Dy-Osali distances, large ∠Osali-Dy-Osali angles and less ligand stacking in these pseudo-D4d-symmetrical single-molecule magnets.

Single-Molecule Magnet Behavior Enhanced by Synergic Effect of Single-Ion Anisotropy and Magnetic Interactions.

As the simplest entity carrying intramolecular magnetic interactions, a dinuclear lanthanide complex serves as a model to investigate the effects of magnetic interactions on relaxation of magnetization, and importantly, it proves to be an efficient method to obtain robust single-molecule magnets via improving the communication between lanthanide centers. Here, three Dy2 complexes (1, 2, 3) with a similar structural motif, namely, [Dy2(HL)2(NO3)2(CH3CN)2]·2CH3CN (1), [Dy2(HL)2(NO3)2(DMF)2]·2H2O (2), and Dy2(HL)2(NO3)2(DMF)4 (3), were successfully assembled. One critical difference found in this series of complexes is that the Dy center in complex 3 is coordinated by one more solvent molecule. Surprisingly, complex 3 exhibits the best magnet-like behavior, as evidenced by the high effective barrier and butterfly-type hysteresis, although the crystal field effect around Dy ions is weakened heavily. Ab initio calculations revealed the crucial reason is the significant synergic effect between single-ion anisotropy and magnetic interactions, i.e., not only the axiality of the Dy ion is improved efficiently but also the exchange magnetic interactions increased to the same order of magnitude to the dipolar interaction in 3. This effect mainly benefits from the elaborate modification of the local coordinate environment around the Dy ion, which results in a special arrangement of anisotropy axes different from the other two complexes. It demonstrates that the magnetic interactions could be effectively enhanced by means of deliberate local structural modulation.

Site-Resolved Two-Step Relaxation Process in an Asymmetric Dy2 Single-Molecule Magnet.

Elaborate chemical design is of utmost importance in order to slow down the relaxation dynamics in single-molecule magnets (SMMs) and hence improve their potential applications. Much interest was devoted to the study of distinct relaxation processes related to the different crystal fields of crystallographically independent lanthanide ions. However, the assignment of the relaxation processes to specific metal sites remains a challenging task. To address this challenge, a new asymmetric Dy2 SMM displaying a well-separated two-step relaxation process with the anisotropic centers in fine-tuned local environments was elaborately designed. For the first time a one-to-one relationship between the metal sites and the relaxation processes was evidenced. This work sheds light on complex multiple relaxation and may direct the rational design of lanthanide SMMs with enhanced magnetic properties.

Metallosupramolecular Coordination Complexes: The Design of Heterometallic 3d-4f Gridlike Structures.

A series of mixed metal 3d-4f gridlike structures, [Dy4(H2L')4Zn4(SCN)4] (1) and [Dy4(H2L')4Mx(SCN)8] (Mx = Co3 (2); Mx = Cu5 (3)), showing Chinese hieroglyph like [2 × 2], [3 × 2], and [3 × 3] matrixes, were assembled and magnetically characterized. Remarkably, the empty cage constructed by the oblique organic ligands and SCN(-) ions in complex 1 were filled with the large inorganic ions [Co3(SCN)4](2+) and [Cu5(SCN)4](6+) in complexes 2 and 3, respectively, forming the first [3 × 2] and [3 × 3] 3d-4f gridlike structures. Additionally, magnetic studies show that complex 1 exhibits field-induced SMM behavior and double magnetic relaxation, while complexes 2 and 3 display typical SMM behavior at zero applied field.

Macroscopic Hexagonal Tubes of 3 d-4 f Metallocycles.

The self-assembly of three giant hexagonal 3d-4f metallocycles with inner diameters of 16.4, 16.5, and 16.4 Å, is described. Hexagonal metallocycles were stacked along the crystallographic c axis, producing unique hexagonal macroscopic tubular single crystals. The assembly mechanism of the tubular crystals was investigated. Remarkably, all three hexagonal metallocycles show typical single-molecule magnet behavior, benefiting from the ferromagnetic couplings between the 3d and 4f ions.

Nanoscale {LnIII(24)ZnII(6)} Triangular Metalloring with Magnetic Refrigerant, Slow Magnetic Relaxation, and Fluorescent Properties.

The self-assembly of Ln(ClO4)3 · 6H2O and Zn(OAc)2 · 2H2O with pyrazine-2-carboxylic acid (HL) results in the formation of three novel nanosized {LnIII(24)ZnII(6)} triangular metallorings, [Gd24Zn6L24(OAc)22(µ3-OH)30(H2O)14](ClO4)7(OAc) · 2CH3OH · 26H2O (1), [Tb24Zn6L24(OAc)22(µ3-OH)30(CH3O)2(CH3OH)2(H2O)10](ClO4)5(OH) · 6CH3OH · 12H2O (2), and (H3O)[Dy24Zn6L24(OAc)22(µ3-OH)30(H2O)14](ClO4)7(OAc)2 · 4CH3OH · 22H2O (3), having the largest nuclearity among any known Ln/Zn clusters. Magnetic and luminescent studies reveal the special prowess for each lanthanide complex. Magnetic studies reveal that 1 exhibits a significant cryogenic magnetocaloric effect with a maximum -ΔSm (isothermal magnetic entropy change) value of 30.0 J kg(-1) K(-1) at 2.5 K and 7 T and that a slow magnetization relaxation is observed for the dysprosium analogue. In addition, the solid-state photophysical properties of 2 display strong characteristic Tb(III) photoluminescent emission in the visible region, suggesting that Tb(III)-based luminescence is sensitized by the effective energy transfer from the ligand HL to the metal centers.

Anions Influence the Relaxation Dynamics of Mono-µ3-OH-Capped Triangular Dysprosium Aggregates.

A family of four Dy3 triangular circular helicates, namely, [Dy3(HL)3(µ3-OH)(CH3OH)2(H2O)4]Cl1.5(OH)0.5·0.5H2O (1), [Dy3(HL)3(µ3-OH)(CH3OH)3(H2O)2Cl]Cl·CH3OH (2), [Dy3(HL)3(µ3-OH)(CH3OH)3(H2O)2(NO3)](NO3) (3), and [Dy3(HL)3(µ3-OH)(CH3OH)4(ClO4)](ClO4) (4), were assembled by the reaction of a new acylhydrazone ligand H3L [(3-hydroxy)-N'-((8-hydroxyquinolin-2-yl)methylene)picolinohydrazide] with different dysprosium(III) salts. These compounds represent the first examples of µ-Oacylhydrazone-bridged triangular Dy3 SMMs reported to date. Alternating-current magnetic susceptibility measurements revealed that compounds 1 and 2 show typical SMM behavior with the occurrence of multiple relaxation processes, whereas frequency-dependent relaxation signals without χ″ peaks were observed in 3 and 4 under zero dc field. Such distinct dynamic behaviors are attributed to the different sizes of the terminal coordination solvent/anions (H2O, Cl(-), NO3(-), and ClO4(-) for 1-4, respectively) at the Dy3 site. Here, similar deviations from the ideal monocapped square-antiprismatic (C4v) geometry defined by SHAPE software were observed around local Dy centers in 1 and 2, whereas the situation was completely different in 3 and 4 as a result of the presence of relatively large anions in the limited space defined by three intercrossing rigid hydrazone ligands.