Gate-opening Induced by C8 Aromatics in a Double Diamondoid Coordination Network.

Coordination networks (CNs) that undergo guest-induced structural transformations are of topical interest thanks to their potential utility in separations and storage applications. Herein, we report a double diamondoid (ddi) topology CN, [Ni2(bimpz)2(bdc)2(H2O)] n or X-ddi-2-Ni (H2bdc = 1,4-benzenedicarboxylic acid, bimpz = 3,6-bis(imidazol-1-yl)pyridazine), that undergoes structural transformations induced by C8 isomers, i.e., xylenes (o-xylene, OX; m-xylene, MX; p-xylene, PX) and ethylbenzene (EB). X-ddi-2-Ni was characterized by single-crystal to single-crystal transformations from a nonporous phase, X-ddi-2-Ni-ß, to isostructural C8-loaded phases, namely X-ddi-2-Ni-OX, X-ddi-2-Ni-MX, X-ddi-2-Ni-PX and X-ddi-2-Ni-EB. X-ddi-2-Ni accommodates two C8 isomers per Ni unit, resulting in relatively high uptake (ca. 50 wt %), but with low selectivity toward C8 isomers as found using nuclear magnetic resonance (NMR) and gas chromatography (GC). In addition, a narrow range of gate-opening pressures for each isomer was determined from dynamic vapor sorption, consistent with the nonadaptable nature of the C8-loaded phase determined crystallographically, also supported by modeling.

Effect of Polymorphism on the Sorption Properties of a Flexible Square-Lattice Topology Coordination Network.

The stimulus-responsive behavior of coordination networks (CNs), which switch between closed (nonporous) and open (porous) phases, is of interest because of its potential utility in gas storage and separation. Herein, we report two polymorphs of a new square-lattice (sql) topology CN, X-sql-1-Cu, of formula [Cu(Imibz)2]n (HImibz = {[4-(1H-imidazol-1-yl)phenylimino]methyl}benzoic acid), isolated from the as-synthesized CN X-sql-1-Cu-(MeOH)2·2MeOH, which subsequently transformed to a narrow pore solvate, X-sql-1-Cu-A·MeOH, upon mild activation (drying in air or heating at 333 K under nitrogen). X-sql-1-Cu-A·MeOH contains MeOH in cavities, which was removed through exposure to vacuum for 2 h, yielding the nonporous (closed) phase X-sql-1-Cu-A. In contrast, a more dense polymorph, X-sql-1-Cu-B, was obtained by exposing X-sql-1-Cu-(MeOH)2·2MeOH directly to vacuum for 2 h. Gas sorption studies conducted on X-sql-1-Cu-A and X-sql-1-Cu-B revealed different switching behaviors to two open phases (X-sql-1-Cu·CO2 and X-sql-1-Cu·C2H2), with different gate-opening threshold pressures for CO2 at 195 K and C2H2 at 278 K. Coincident CO2 sorption and in situ powder X-ray diffraction studies at 195 K revealed that X-sql-1-Cu-A transformed to X-sql-1-Cu-B after the first sorption cycle and that the CO2-induced switching transformation was thereafter reversible. The results presented herein provide insights into the relationship between two polymorphs of a CN and the effect of polymorphism upon gas sorption properties. To the best of our knowledge, whereas sql networks such as X-sql-1-Cu are widely studied in terms of their structural and sorption properties, this study represents only the second example of an in-depth study of the sorption properties of polymorphic sql networks.

Exercise preconditioning inhibits doxorubicin-induced cardiotoxicity via YAP/STAT3 signaling.

Doxorubicin (DOX) possesses strong anti-tumor effects but is limited by its irreversible cardiac toxicity. The relationship between exercise, a known enhancer of cardiovascular health, and DOX-induced cardiotoxicity has been a focus of recent research. Exercise has been suggested to mitigate DOX's cardiac harm by modulating the Yes-associated protein (YAP) and Signal transducer and activator of transcription 3 (STAT3) pathways, which are crucial in regulating cardiac cell functions and responses to damage. This study aimed to assess the protective role of exercise preconditioning against DOX-induced cardiac injury. We used Sprague-Dawley rats, divided into five groups (control, DOX, exercise preconditioning (EP), EP-DOX, and verteporfin + EP + DOX), to investigate the potential mechanisms. Our findings, including echocardiography, histological staining, Western blot, and q-PCR analysis, demonstrated that exercise preconditioning could alleviate DOX-induced cardiac dysfunction and structural damage. Notably, exercise preconditioning enhanced the nuclear localization and co-localization of YAP and STAT3. Our study suggests that exercise preconditioning may counteract DOX-induced cardiotoxicity by activating the YAP/STAT3 pathway, highlighting a potential therapeutic approach for reducing DOX's cardiac side effects.

Insight into the Gas-Induced Phase Transformations in a 2D Switching Coordination Network via Coincident Gas Sorption and In Situ PXRD.

Switching coordination networks (CNs) that reversibly transform between narrow or closed pore (cp) and large pore (lp) phases, though fewer than their rigid counterparts, offer opportunities for sorption-related applications. However, their structural transformations and switching mechanisms remain underexplored at the molecular level. In this study, we conducted a systematic investigation into a 2D switching CN, [Ni(bpy)2(NCS)2]n, sql-1-Ni-NCS (1 = bpy = 4,4'-bipyridine), using coincident gas sorption and in situ powder X-ray diffraction (PXRD) under low-temperature conditions. Gas adsorption measurements revealed that C2H4 (169 K) and C2H6 (185 K) exhibited single-step type F-IVs sorption isotherms with sorption uptakes of around 180-185 cm3 g-1, equivalent to four sorbate molecules per formula unit. Furthermore, parallel in situ PXRD experiments provided insight into sorbate-dependent phase switching during the sorption process. Specifically, CO2 sorption induced single-step phase switching (path I) solely between cp and lp phases consistent with the observed single-step type F-IVs sorption isotherm. By contrast, intermediate pore (ip) phases emerged during C2H4 and C2H6 desorption as well as C3H6 adsorption, although they remained undetectable in the sorption isotherms. To our knowledge, such a cp-lp-ip-cp transformation (path II) induced by C2H4/6 and accompanied by single-step type F-IVs sorption isotherms represents a novel type of phase transition mechanism in switching CNs. By virtue of Rietveld refinements and molecular simulations, we elucidated that the phase transformations are governed by cooperative local and global structural changes involving NCS- ligand reorientation, bpy ligand twist and rotation, cavity edge (Ni-bpy-Ni) deformation, and interlayer expansion and sliding.

Robust small molecule-aided cardiac reprogramming systems selective to cardiac fibroblasts.

Direct cardiac reprogramming to induce cardiomyocyte-like cells, e.g., by GMT (Gata4, Mef2c and Tbx5), is a promising route for regenerating damaged heart in vivo and disease modeling in vitro. Supplementation with additional factors and chemical agents can enhance efficiency but raises concerns regarding selectivity to cardiac fibroblasts and complicates delivery for in situ cardiac reprogramming. Here, we screened 2000 chemicals with known biological activities and found that a combination of 2C (SB431542 and Baricitinib) significantly enhances cardiac reprogramming by GMT. Without Gata4, MT (Mef2c and Tbx5) plus 2C could selectively reprogram cardiac fibroblasts with enhanced efficiency, kinetics, and cardiomyocyte function. Moreover, 2C significantly enhanced cardiac reprogramming in human cardiac fibroblasts. 2C synergistically enhances cardiac reprogramming by inhibiting Alk5, Tyk2 and downregulating Oas2, Oas3, Serpina3n and Tgfbi. 2C enables selective and robust cardiac reprogramming that can greatly facilitate disease modeling in vitro and advance clinical therapeutic heart regeneration in vivo.

Highly Selective p-Xylene Separation from Mixtures of C8 Aromatics by a Nonporous Molecular Apohost.

High and increasing production of separation of C8 aromatic isomers demands the development of purification methods that are efficient, scalable, and inexpensive, especially for p-xylene, PX, the largest volume C8 commodity. Herein, we report that 4-(1H-1,2,4-triazol-1-yl)-phenyl-1H-benzo[de]isoquinoline-1,3(2H)-dione (TPBD), a molecular compound that can be prepared and scaled up via solid-state synthesis, exhibits exceptional PX selectivity over each of the other C8 isomers, o-xylene (OX), m-xylene (MX), and ethylbenzene (EB). The apohost or α form of TPBD was found to exhibit conformational polymorphism in the solid state enabled by rotation of its triazole and benzene rings. TPBD-αI and TPBD-αII are nonporous polymorphs that transformed to the same PX inclusion compound, TPBD-PX, upon contact with liquid PX. TPBD enabled highly selective capture of PX, as established by competitive slurry experiments involving various molar ratios in binary, ternary, and quaternary mixtures of C8 aromatics. Binary selectivity values for PX as determined by 1H NMR spectroscopy and gas chromatography ranged from 22.4 to 108.4, setting new benchmarks for both PX/MX (70.3) and PX/EB (59.9) selectivity as well as close to benchmark selectivity for PX/OX (108.4). To our knowledge, TPBD is the first material of any class to exhibit such high across-the-board PX selectivity from quaternary mixtures of C8 aromatics under ambient conditions. Crystallographic and computational studies provide structural insight into the PX binding site in TPBD-PX, whereas thermal stability and capture kinetics were determined by variable-temperature powder X-ray diffraction and slurry tests, respectively. That TPBD offers benchmark PX selectivity and facile recyclability makes it a prototypal molecular compound for PX purification or capture under ambient conditions.

Switching Adsorbent Layered Material that Enables Stepwise Capture of C8 Aromatics via Single-Crystal-to-Single-Crystal Transformations.

Separation of the C8 aromatic isomers, xylenes (PX, MX, and OX) and ethylbenzene (EB), is important to the petrochemical industry. Whereas physisorptive separation is an energy-efficient alternative to current processes, such as distillation, physisorbents do not generally exhibit strong C8 selectivity. Herein, we report the mixed-linker square lattice (sql) coordination network [Zn2(sba)2(bis)]n·mDMF (sql-4,5-Zn, H2sba or 4 = 4,4'-sulfonyldibenzoic acid, bis or 5 = trans-4,4'-bis(1-imidazolyl)stilbene) and its C8 sorption properties. sql-4,5-Zn was found to exhibit high uptake capacity for liquid C8 aromatics (∼20.2 wt %), and to the best of our knowledge, it is the first sorbent to exhibit selectivity for PX, EB, and MX over OX for binary, ternary, and quaternary mixtures from gas chromatography. Single-crystal structures of narrow-pore, intermediate-pore, and large-pore phases provided insight into the phase transformations, which were enabled by flexibility of the linker ligands and changes in the square grid geometry and interlayer distances. This work adds to the library of two-dimensional coordination networks that exhibit high uptake, thanks to clay-like expansion, and strong selectivity, thanks to shape-selective binding sites, for C8 isomers.

Shape-Memory Effect Enabled by Ligand Substitution and CO2 Affinity in a Flexible SIFSIX Coordination Network.

We report that linker ligand substitution involving just one atom induces a shape-memory effect in a flexible coordination network. Specifically, whereas SIFSIX-23-Cu, [Cu(SiF6 )(L)2 ]n , (L=1,4-bis(1-imidazolyl)benzene, SiF6 2- =SIFSIX) has been previously reported to exhibit reversible switching between closed and open phases, the activated phase of SIFSIX-23-CuN , [Cu(SiF6 )(LN )2 ]n (LN =2,5-bis(1-imidazolyl)pyridine), transformed to a kinetically stable porous phase with strong affinity for CO2 . As-synthesized SIFSIX-23-CuN , α, transformed to less open, γ, and closed, ß, phases during activation. ß did not adsorb N2 (77 K), rather it reverted to α induced by CO2 at 195, 273 and 298 K. CO2 desorption resulted in α', a shape-memory phase which subsequently exhibited type-I isotherms for N2 (77 K) and CO2 as well as strong performance for separation of CO2 /N2 (15/85) at 298 K and 1 bar driven by strong binding (Qst =45-51 kJ/mol) and excellent CO2 /N2 selectivity (up to 700). Interestingly, α' reverted to ß after re-solvation/desolvation. Molecular simulations and density functional theory (DFT) calculations provide insight into the properties of SIFSIX-23-CuN .

A live-cell image-based machine learning strategy for reducing variability in PSC differentiation systems.

The differentiation of pluripotent stem cells (PSCs) into diverse functional cell types provides a promising solution to support drug discovery, disease modeling, and regenerative medicine. However, functional cell differentiation is currently limited by the substantial line-to-line and batch-to-batch variabilities, which severely impede the progress of scientific research and the manufacturing of cell products. For instance, PSC-to-cardiomyocyte (CM) differentiation is vulnerable to inappropriate doses of CHIR99021 (CHIR) that are applied in the initial stage of mesoderm differentiation. Here, by harnessing live-cell bright-field imaging and machine learning (ML), we realize real-time cell recognition in the entire differentiation process, e.g., CMs, cardiac progenitor cells (CPCs), PSC clones, and even misdifferentiated cells. This enables non-invasive prediction of differentiation efficiency, purification of ML-recognized CMs and CPCs for reducing cell contamination, early assessment of the CHIR dose for correcting the misdifferentiation trajectory, and evaluation of initial PSC colonies for controlling the start point of differentiation, all of which provide a more invulnerable differentiation method with resistance to variability. Moreover, with the established ML models as a readout for the chemical screen, we identify a CDK8 inhibitor that can further improve the cell resistance to the overdose of CHIR. Together, this study indicates that artificial intelligence is able to guide and iteratively optimize PSC differentiation to achieve consistently high efficiency across cell lines and batches, providing a better understanding and rational modulation of the differentiation process for functional cell manufacturing in biomedical applications.

Water vapour and gas induced phase transformations in an 8-fold interpenetrated diamondoid metal-organic framework.

In this work, we report the synthesis, structural characterisation and sorption properties of an 8-fold interpenetrated diamondoid (dia) metal-organic framework (MOF) that is sustained by a new extended linker ligand, [Cd(Imibz)2], X-dia-2-Cd, HImibz or 2 = 4-((4-(1H-imidazol-1-yl)phenylimino)methyl)benzoic acid. X-dia-2-Cd was found to exhibit reversible single-crystal-to-single-crystal (SC-SC) transformations between four distinct phases: an as-synthesised (from N,N-dimethylformamide) wide-pore phase, X-dia-2-Cd-α; a narrow-pore phase, X-dia-2-Cd-ß, formed upon exposure to water; a narrow-pore phase obtained by activation, X-dia-2-Cd-γ; a medium-pore CO2-loaded phase X-dia-2-Cd-δ. While the space group remained constant in the four phases, the cell volumes and calculated void space ranged from 4988.7 Å3 and 47% (X-dia-2-Cd-α), respectively, to 3200.8 Å3 and 9.1% (X-dia-2-Cd-γ), respectively. X-dia-2-Cd-γ also exhibited a water vapour-induced structural transformation to the water-loaded X-dia-2-Cd-ß phase, resulting in an S-shaped sorption isotherm. The inflection point occurred at 18% RH with negligible hysteresis on the desorption profile. Water vapour temperature-humidity swing cycling (60% RH, 300 K to 0% RH, 333 K) indicated hydrolytic stability of X-dia-2-Cd and working capacity was retained after 128 cycles of sorbent regeneration. CO2 (at 195 K) was also observed to induce a structural transformation in X-dia-2-Cd-γ and in situ PXRD studies at 1 bar of CO2, 195 K revealed the formation of X-dia-2-Cd-δ, which exhibited 31% larger unit cell volume than X-dia-2-Cd-γ.

Control over Phase Transformations in a Family of Flexible Double Diamondoid Coordination Networks through Linker Ligand Substitution.

In this work, we present the first metal-organic framework (MOF) platform with a self-penetrated double diamondoid (ddi) topology that exhibits switching between closed (nonporous) and open (porous) phases induced by exposure to gases. A crystal engineering strategy, linker ligand substitution, was used to control gas sorption properties for CO2 and C3 gases. Specifically, bimbz (1,4-bis(imidazol-1-yl)benzene) in the coordination network X-ddi-1-Ni ([Ni2(bimbz)2(bdc)2(H2O)]n, H2bdc = 1,4-benzenedicarboxylic acid) was replaced by bimpz (3,6-bis(imidazol-1-yl)pyridazine) in X-ddi-2-Ni ([Ni2(bimpz)2(bdc)2(H2O)]n). In addition, the 1:1 mixed crystal X-ddi-1,2-Ni ([Ni2(bimbz)(bimpz)(bdc)2(H2O)]n) was prepared and studied. All three variants form isostructural closed (ß) phases upon activation which each exhibited different reversible properties upon exposure to CO2 at 195 K and C3 gases at 273 K. For CO2, X-ddi-1-Ni revealed incomplete gate-opening, X-ddi-2-Ni exhibited a stepped isotherm with saturation uptake of 3.92 mol·mol-1, and X-ddi-1,2-Ni achieved up to 62% more gas uptake and a distinct isotherm shape vs the parent materials. Single-crystal X-ray diffraction (SCXRD) and in situ powder X-ray diffraction (PXRD) experiments provided insight into the mechanisms of phase transformation and revealed that the ß phases are nonporous with unit cell volumes 39.9, 40.8, and 41.0% lower than the corresponding as-synthesized α phases, X-ddi-1-Ni-α, X-ddi-2-Ni-α, and X-ddi-1,2-Ni-α, respectively. The results presented herein represent the first report of reversible switching between closed and open phases in ddi topology coordination networks and further highlight how ligand substitution can profoundly impact the gas sorption properties of switching sorbents.

Highly Productive C3H4/C3H6 Trace Separation by a Packing Polymorph of a Layered Hybrid Ultramicroporous Material.

Ultramicroporous materials can be highly effective at trace gas separations when they offer a high density of selective binding sites. Herein, we report that sql-NbOFFIVE-bpe-Cu, a new variant of a previously reported ultramicroporous square lattice, sql, topology material, sql-SIFSIX-bpe-Zn, can exist in two polymorphs. These polymorphs, sql-NbOFFIVE-bpe-Cu-AA (AA) and sql-NbOFFIVE-bpe-Cu-AB (AB), exhibit AAAA and ABAB packing of the sql layers, respectively. Whereas NbOFFIVE-bpe-Cu-AA (AA) is isostructural with sql-SIFSIX-bpe-Zn, each exhibiting intrinsic 1D channels, sql-NbOFFIVE-bpe-Cu-AB (AB) has two types of channels, the intrinsic channels and extrinsic channels between the sql networks. Gas and temperature induced transformations of the two polymorphs of sql-NbOFFIVE-bpe-Cu were investigated by pure gas sorption, single-crystal X-ray diffraction (SCXRD), variable temperature powder X-ray diffraction (VT-PXRD), and synchrotron PXRD. We observed that the extrinsic pore structure of AB resulted in properties with potential for selective C3H4/C3H6 separation. Subsequent dynamic gas breakthrough measurements revealed exceptional experimental C3H4/C3H6 selectivity (270) and a new benchmark for productivity (118 mmol g-1) of polymer grade C3H6 (purity >99.99%) from a 1:99 C3H4/C3H6 mixture. Structural analysis, gas sorption studies, and gas adsorption kinetics enabled us to determine that a binding "sweet spot" for C3H4 in the extrinsic pores is behind the benchmark separation performance. Density-functional theory (DFT) calculations and Canonical Monte Carlo (CMC) simulations provided further insight into the binding sites of C3H4 and C3H6 molecules within these two hybrid ultramicroporous materials, HUMs. These results highlight, to our knowledge for the first time, how pore engineering through the study of packing polymorphism in layered materials can dramatically change the separation performance of a physisorbent.

Pressure-Induced Structural Effects in the Square Lattice (sql) Topology Coordination Network Sql-1-Co-NCS·4OX.

A high-pressure study of a switching coordination network of square lattice topology (sql) loaded with o-xylene (OX), [Co(4,4'-bipyridine)2(NCS)2] n ·4nC8H10 (sql-1-Co-NCS·4OX), was conducted up to approximately 1 GPa to investigate pressure-induced structural changes. Previous reports revealed that sql-1-Co-NCS exhibits multiple phases thanks to its ability to switch between closed (nonporous) and several open (porous) phases in the presence of various gases, vapors, and liquids. Networks of such properties are of topical interest because they can offer high working capacity and improved recyclability for gas adsorption. The monoclinic crystal structure of sql-1-Co-NCS·4OX at 100 K was previously reported to show an increase in interlayer separation of more than 100% compared to the corresponding closed phase, sql-1-Co-NCS, when exposed to gases or vapors under ambient conditions. Herein, a tetragonal crystal form of sql-1-Co-NCS·4OX (space group I4/mmm, Phase I) that exists at 0.1 MPa/303 K is reported. Exposure of Phase I to high pressure using penetrable pressure transmitting media (OX and 1:1 vol MeOH/EtOH) did not result in further separation of the sql networks. Rather, compression of the crystals and release of adsorbed OX molecules occurred. These pressure-induced changes are discussed in terms of structural voids, framework conformation, and molecular packing of the sql layers. Although Phase I retained tetragonal symmetry throughout the investigated pressure range, the interlayer voids occupied by OX molecules were significantly reduced between 0.3 and 0.5 GPa; further compression above 0.5 GPa induced structural disorder. Additionally, analysis of the electron count present in the pores of sql-1-Co-NCS confirmed the multistep evacuation of OX molecules from the crystal, and two intermediate phases, Ia and Ib, differing in the OX loading level, are postulated.

Engineering of NEMO as calcium indicators with large dynamics and high sensitivity.

Genetically encoded calcium indicators (GECIs) are indispensable tools for real-time monitoring of intracellular calcium signals and cellular activities in living organisms. Current GECIs face the challenge of suboptimal peak signal-to-baseline ratio (SBR) with limited resolution for reporting subtle calcium transients. We report herein the development of a suite of calcium sensors, designated NEMO, with fast kinetics and wide dynamic ranges (>100-fold). NEMO indicators report Ca2+ transients with peak SBRs around 20-fold larger than the top-of-the-range GCaMP6 series. NEMO sensors further enable the quantification of absolution calcium concentration with ratiometric or photochromic imaging. Compared with GCaMP6s, NEMOs could detect single action potentials in neurons with a peak SBR two times higher and a median peak SBR four times larger in vivo, thereby outperforming most existing state-of-the-art GECIs. Given their high sensitivity and resolution to report intracellular Ca2+ signals, NEMO sensors may find broad applications in monitoring neuronal activities and other Ca2+-modulated physiological processes in both mammals and plants.

Dosimetry comparison with helical tomotherapy, volumetric modulated arc therapy, and intensity-modulated radiotherapy for grade II gliomas: A single­institution case series.

Radiotherapy is an essential postoperative treatment for grade II gliomas. However, comparative dosimetric studies of different radiotherapy plans for grade II gliomas are still lacking. Therefore, we conducted this case series analysis to compare the dosimetric differences among helical tomotherapy (TOMO), volumetric modulated arc therapy (VMAT), and intensity-modulated radiotherapy (IMRT) for grade II gliomas. To achieve that, seven diagnosed postoperative patients with grade II gliomas were analyzed by computed tomography and then planned with TOMO, VMAT, and IMRT. The plan target volume (PTV) prescribed dose was 50 Gy (daily fraction of 2.0 Gy, 5 days/week). The expected treatment efficiency was measured by monitor units (MUs) scoring. Treatment plans of the patients were compared in the quality of target volumes dosage coverage, the efficiency of dosage delivery, and the dosage exposure of normal adjacent organs at risk (OAR). Differences in each method were measured by utilizing the Nonparametric ANOVA. The study shows that TOMO achieved a significantly higher PTV-D98% (doses received by 98% of the PTV volume) than VMAT and IMRT (50.30 ± 0.13 vs 49.21 ± 0.19, p = 0.006; 50.30 ± 0.13 vs 49.78 ± 0.18, p = 0.014), while there was no difference in PTV-D2% (doses received by 2% of the PTV volume). IMRT achieved a conformity index (CI) preferably, and TOMO generated a favorable homogeneity index (HI) (p < 0.05 for both). The MUs were fewer for VMAT than IMRT and TOMO (294 ± 19, 572 ± 24, 317 ± 97, respectively). IMRT achieved better protection for the lens and brain stems. Our case series study indicated that TOMO, VMAT, and IMRT achieved a comparatively good target dosimetric coverage, and most OARs were protected well. IMRT is not inferior to TOMO and VMAT and is still very suitable for treating most grade II glioma patients.

Adsorbate-dependent phase switching in the square lattice topology coordination network [Ni(4,4'-bipyridine)2(NCS)2]n.

Switching coordination networks (CNs) featuring stepped sorption isotherms that are accompanied by phase changes offer promise for gas storage and separation applications. However, their responsiveness to different adsorbates remains largely understudied. Herein, we report the variable switching behaviour of a previously known square lattice (sql) topology CN, [Ni(4,4'-bipyridine)2(NCS)2] (sql-1-Ni-NCS), with respect to nine gaseous adsorbates.

Magnetic 3d-4f Chiral Clusters Showing Multimetal Site Magneto-Chiral Dichroism.

Here, we report the molecular self-assembly of hydroxido-bridged {Ln5Ni6} ((Ln3+ = Dy3+, Y3+) metal clusters by the reaction of enantiopure chiral ligands, namely, (R/S)-(2-hydroxy-3-methoxybenzyl)-serine), with NiII and LnIII precursors. Single-crystal diffraction analysis reveals that these compounds are isostructural sandwich-like 3d-4f heterometallic clusters showing helical chirality. Direct current magnetic measurements on {Dy5Ni6} indicates ferromagnetic coupling between DyIII and NiII centers, whereas those on {Y5Ni6} denote that the NiII centers are antiferromagnetically coupled and/or magnetically anisotropic. Magneto-chiral dichroism (MChD) measurements on {Dy5Ni6} and its comparison to that of {Y5Ni6} provide the first experimental observation of intense multimetal site MChD signals in the visible-near-infrared region. Moreover, the comparison of MChD with natural and magnetic circular dichroism spectra unambiguously demonstrate for the first time that the MChD signals associated with the NiII d-d transitions are mostly driven by natural optical activity and those associated with the DyIII f-f transitions are driven by magnetic optical activity.

Novel CaMKII-δ Inhibitor Hesperadin Exerts Dual Functions to Ameliorate Cardiac Ischemia/Reperfusion Injury and Inhibit Tumor Growth.

BACKGROUND: Cardiac ischemia/reperfusion (I/R) injury has emerged as an important therapeutic target for ischemic heart disease, the leading cause of morbidity and mortality worldwide. At present, there is no effective therapy for reducing cardiac I/R injury. CaMKII (Ca2+/calmodulin-dependent kinase II) plays a pivotal role in the pathogenesis of severe heart conditions, including I/R injury. Pharmacological inhibition of CaMKII is an important strategy in the protection against myocardial damage and cardiac diseases. To date, there is no drug targeting CaMKII for the clinical therapy of heart disease. Furthermore, at present, there is no selective inhibitor of CaMKII-δ, the major CaMKII isoform in the heart. METHODS: A small-molecule kinase inhibitor library and a high-throughput screening system for the kinase activity assay of CaMKII-δ9 (the most abundant CaMKII-δ splice variant in human heart) were used to screen for CaMKII-δ inhibitors. Using cultured neonatal rat ventricular myocytes, human embryonic stem cell-derived cardiomyocytes, and in vivo mouse models, in conjunction with myocardial injury induced by I/R (or hypoxia/reoxygenation) and CaMKII-δ9 overexpression, we sought to investigate the protection of hesperadin against cardiomyocyte death and cardiac diseases. BALB/c nude mice with xenografted tumors of human cancer cells were used to evaluate the in vivo antitumor effect of hesperadin. RESULTS: Based on the small-molecule kinase inhibitor library and screening system, we found that hesperadin, an Aurora B kinase inhibitor with antitumor activity in vitro, directly bound to CaMKII-δ and specifically blocked its activation in an ATP-competitive manner. Hesperadin functionally ameliorated both I/R- and overexpressed CaMKII-δ9-induced cardiomyocyte death, myocardial damage, and heart failure in both rodents and human embryonic stem cell-derived cardiomyocytes. In addition, in an in vivo BALB/c nude mouse model with xenografted tumors of human cancer cells, hesperadin delayed tumor growth without inducing cardiomyocyte death or cardiac injury. CONCLUSIONS: Here, we identified hesperadin as a specific small-molecule inhibitor of CaMKII-δ with dual functions of cardioprotective and antitumor effects. These findings not only suggest that hesperadin is a promising leading compound for clinical therapy of cardiac I/R injury and heart failure, but also provide a strategy for the joint therapy of cancer and cardiovascular disease caused by anticancer treatment.

Predicting potential distribution of Ziziphus spinosa (Bunge) H.H. Hu ex F.H. Chen in China under climate change scenarios.

Ziziphus spinosa (Bunge) H.H. Hu ex F.H. Chen is a woody plant species of the family Rhamnaceae (order Rhamnales) that possesses high nutritional and medicinal value. Predicting the effects of climate change on the distribution of Z. spinosa is of great significance for the investigation, protection, and exploitation of this germplasm resource. For this study, optimized maximum entropy models were employed to predict the distribution patterns and changes of its present (1970-2000) and future (2050s, 2070s, and 2090s) potential suitable regions in China under multiple climate scenarios (SSP1-2.6, SSP2-4.5, SSP3-7.0 & SSP5-8.5). The results revealed that the total area of the present potential suitable region for Z. spinosa is 162.60 × 104 km2, which accounts for 16.94% of China's territory. Within this area, the regions having low, medium, and high suitability were 80.14 × 104 km2, 81.50 × 104 km2, and 0.96 × 104 km2, respectively, with the high suitability regions being distributed primarily in Shanxi, Hebei, and Beijing Provinces. Except for SSP-1-2.6-2070s, SSP-5-8.5-2070s, and SSP-5-8.5-2090s, the suitable areas for Z. spinosa in the future increased to different degrees. Meanwhile, considering the distribution of Z. spinosa during different periods and under different climate scenarios, our study predicted that the low impact areas of Z. spinosa were mainly restricted to Shanxi, Shaanxi, Ningxia, Gansu, Liaoning, Inner Mongolia, and Jilin Provinces. The results of core distributional shifts showed that, except for SSP1-2.6, the center of the potential suitable region of Z. spinosa exhibited a trend of gradually shifting to the northwest.

Acetylene storage performance of [Ni(4,4'-bipyridine)2(NCS)2]n, a switching square lattice coordination network.

We report that the previously reported square lattice coordination network [Ni(4,4'-bipyridine)2(NCS)2]n, sql-1-Ni-NCS, undergoes acetylene induced switching between closed (nonporous) and open (porous) phases. The resulting stepped sorption isotherms exhibit temperature controlled steps, consistent high uptake and benchmark working capacity (185 cm-3 g-1 or 189 cm-3, 1-3.2 bar, 288 K) for acetylene storage.