CO2-induced gate-opening structural transition process of a porous coordination polymer revealed by solid-state 13C NMR.

This study investigates the gate-opening closed-to-open-pore structural transition of a porous coordination polymer induced by CO2 adsorption. Solid-state 13C NMR examination of adsorbed CO2 and framework dynamics reveals the surface adsorption state of the closed structure below the transition pressure and an intermediate structure during the transition process.

Iguratimod suppresses sclerostin and receptor activator of NF-κB ligand production via the extracellular signal-regulated kinase/early growth response protein 1/tumor necrosis factor alpha pathway in osteocytes and ameliorates disuse osteoporosis in mice.

Disuse osteoporosis is a prevalent complication among patients afflicted with rheumatoid arthritis (RA). Although reports have shown that the antirheumatic drug iguratimod (IGU) ameliorates osteoporosis in RA patients, details regarding its effects on osteocytes remain unclear. The current study examined the effects of IGU on osteocytes using a mouse model of disuse-induced osteoporosis, the pathology of which crucially involves osteocytes. A reduction in distal femur bone mass was achieved after 3 weeks of hindlimb unloading in mice, which was subsequently reversed by intraperitoneal IGU treatment (30 mg/kg; five times per week). Histology revealed that hindlimb-unloaded (HLU) mice had significantly increased osteoclast number and sclerostin-positive osteocyte rates, which were suppressed by IGU treatment. Moreover, HLU mice exhibited a significant decrease in osteocalcin-positive cells, which was attenuated by IGU treatment. In vitro, IGU suppressed the gene expression of receptor activator of NF-κB ligand (RANKL) and sclerostin in MLO-Y4 and Saos-2 cells, which inhibited osteoclast differentiation of mouse bone marrow cells in cocultures. Although IGU did not affect the nuclear translocation or transcriptional activity of NF-κB, RNA sequencing revealed that IGU downregulated the expression of early growth response protein 1 (EGR1) in osteocytes. HLU mice showed significantly increased EGR1- and tumor necrosis factor alpha (TNFα)-positive osteocyte rates, which were decreased by IGU treatment. EGR1 overexpression enhanced the gene expression of TNFα, RANKL, and sclerostin in osteocytes, which was suppressed by IGU. Contrarily, small interfering RNA-mediated suppression of EGR1 downregulated RANKL and sclerostin gene expression. These findings indicate that IGU inhibits the expression of EGR1, which may downregulate TNFα and consequently RANKL and sclerostin in osteocytes. These mechanisms suggest that IGU could potentially be used as a treatment option for disuse osteoporosis by targeting osteocytes.

Enhanced Orientation of Liquid Crystals Inside Micropores of Metal-Organic Frameworks Having Thermoresponsivity.

With the aim of controlling the orientation of liquid crystals (LCs) toward realizing external stimuli-responsive materials with tunable functionalities, we synthesized a composite of LCs and metal-organic frameworks (MOFs) by filling LCs into the pores of MOFs (LC@MOFs) for the first time. The included LCs interact with the MOFs through coordination bonds between the cyano groups of the LCs and the metal ions of the MOFs, enabling the orientation of the LC molecules inside the pores of the MOFs and the realization of birefringence of LC@MOFs. The three-dimensional nanometer interstice frameworks maintained the LC orientation even at temperatures much higher than the isotropic phase transition temperature of bulk LCs. Furthermore, the orientational state changed upon heating or cooling, inducing temperature-dependent birefringence. This study provides a new approach to the development of stimuli-responsive optical materials and stimuli-responsive MOFs.

An investigation of the differential therapeutic effects of romosozumab on postmenopausal osteoporosis patients with or without rheumatoid arthritis complications: a case-control study.

The impact of ROMO on the width of anabolic windows and the increase in BMD was reduced in the RA group compared to the non-RA group, and this reduction was associated with correlations to RA-related factors. PURPOSE: To investigate the effects of romosozumab (ROMO) in postmenopausal osteoporosis, with and without comorbid rheumatoid arthritis (RA). METHODS: In this retrospective, case-controlled, multicenter study, 171 postmenopausal patients who did not receive oral glucocorticoid, comprising 59 in the RA group and 121 in the non-RA group, received uninterrupted ROMO treatment for 12 months. Propensity score matching was employed to ensure comparability in clinical backgrounds, resulting in 41 patients in each group. Baseline characteristics were as follows: overall (mean age, 76.3 years; T-score of lumbar spine (LS), - 3.0; 45.1% were treatment-naive for osteoporosis); RA group (anti-cyclic citrullinated peptide antibody (ACPA) positivity, 80.5%; titer, 206.2 U/ml; clinical disease activity index (CDAI), 13.6; health assessment questionnaire disability index (HAQ-DI), 0.9). Bone mineral density (BMD) and serum bone turnover markers were monitored over a 12-month period. RESULTS: The rate of increase in the bone formation marker, PINP, and the rates of decrease in the bone resorption marker, TRACP-5b, exhibited a trend toward smaller changes in the RA group compared to the non-RA group, implying a smaller anabolic window. After 12 months, the RA group displayed lower BMD increases in the LS (9.1% vs. 12.6%; P = 0.013) and total hip (2.4% vs. 4.8%; P = 0.025) compared to the non-RA group. Multiple regression analysis in the all RA group (n = 59) for the association between RA-specific factors and 12-month BMD changes revealed negative correlations between ACPA titer and LS BMD and between HAQ-DI and femoral neck BMD. CONCLUSIONS: The efficacy of ROMO may be attenuated by RA-related factors.

Anti-NF-κB peptide derived from nuclear acidic protein attenuates ovariectomy-induced osteoporosis in mice.

NF-κB is a transcription factor that is activated with aging. It plays a key role in the development of osteoporosis by promoting osteoclast differentiation and inhibiting osteoblast differentiation. In this study, we developed a small anti-NF-κB peptide called 6A-8R from a nuclear acidic protein (also known as macromolecular translocation inhibitor II, Zn2+-binding protein, or parathymosin) that inhibits transcriptional activity of NF-κB without altering its nuclear translocation and binding to DNA. Intraperitoneal injection of 6A-8R attenuated ovariectomy-induced osteoporosis in mice by inhibiting osteoclast differentiation, promoting osteoblast differentiation, and inhibiting sclerostin production by osteocytes in vivo with no apparent side effects. Conversely, in vitro, 6A-8R inhibited osteoclast differentiation by inhibiting NF-κB transcriptional activity, promoted osteoblast differentiation by promoting Smad1 phosphorylation, and inhibited sclerostin expression in osteocytes by inhibiting myocyte enhancer factors 2C and 2D. These findings suggest that 6A-8R has the potential to be an antiosteoporotic therapeutic agent with uncoupling properties.

Basic fibroblast growth factor promotes meniscus regeneration through the cultivation of synovial mesenchymal stem cells via the CXCL6-CXCR2 pathway.

OBJECTIVE: To investigate the efficacy of basic fibroblast growth factor (bFGF) in promoting meniscus regeneration by cultivating synovial mesenchymal stem cells (SMSCs) and to validate the underlying mechanisms. METHODS: Human SMSCs were collected from patients with osteoarthritis. Eight-week-old nude rats underwent hemi-meniscectomy, and SMSCs in pellet form, either with or without bFGF (1.0 × 106 cells per pellet), were implanted at the site of meniscus defects. Rats were divided into the control (no transplantation), FGF (-) (pellet without bFGF), and FGF (+) (pellet with bFGF) groups. Different examinations, including assessment of the regenerated meniscus area, histological scoring of the regenerated meniscus and cartilage, meniscus indentation test, and immunohistochemistry analysis, were performed at 4 and 8 weeks after surgery. RESULTS: Transplanted SMSCs adhered to the regenerative meniscus. Compared with the control group, the FGF (+) group had larger regenerated meniscus areas, superior histological scores of the meniscus and cartilage, and better meniscus mechanical properties. RNA sequencing of SMSCs revealed that the gene expression of chemokines that bind to CXCR2 was upregulated by bFGF. Furthermore, conditioned medium derived from SMSCs cultivated with bFGF exhibited enhanced cell migration, proliferation, and chondrogenic differentiation, which were specifically inhibited by CXCR2 or CXCL6 inhibitors. CONCLUSION: SMSCs cultured with bFGF promoted the expression of CXCL6. This mechanism may enhance cell migration, proliferation, and chondrogenic differentiation, thereby resulting in superior meniscus regeneration and cartilage preservation.

Isolation and physiological properties of methanogenic archaea that degrade tetramethylammonium hydroxide.

Tetramethylammonium hydroxide (TMAH) is a known toxic chemical used in the photolithography process of semiconductor photoelectronic processes. Significant amounts of wastewater containing TMAH are discharged from electronic industries. It is therefore attractive to apply anaerobic treatment to industrial wastewater containing TMAH. In this study, a novel TMAH-degrading methanogenic archaeon was isolated from the granular sludge of a psychrophilic upflow anaerobic sludge blanket (UASB) reactor treating synthetic wastewater containing TMAH. Although the isolate (strain NY-STAYD) was phylogenetically related to Methanomethylovorans uponensis, it was the only isolated Methanomethylovorans strain capable of TMAH degradation. Strain NY-STAYD was capable of degrading methylamine compounds, similar to the previously isolated Methanomethylovorans spp. While the strain was able to grow at temperatures ranging from 15 to 37°C, the cell yield was higher at lower temperatures. The distribution of archaeal cells affiliated with the genus Methanomethylovorans in the original granular sludge was investigated by fluorescence in situ hybridization (FISH) using specific oligonucleotide probe targeting 16S rRNA. The results demonstrated that the TMAH-degrading cells associated with the genus Methanomethylovorans were not intermingled with other microorganisms but rather isolated on the granule's surface as a lone dominant archaeon. KEY POINTS: • A TMAH-degrading methanogenic Methanomethylovorans strain was isolated • This strain was the only known Methanomethylovorans isolate that can degrade TMAH • The highest cell yield of the isolate was obtained at psychrophilic conditions.

Coordination polymer-forming liquid Cu(2-isopropylimidazolate).

The structure of the melt state of one-dimensional (1D) coordination polymer crystal Cu(isopropylimidazolate) (melting temperature T m = 143 °C) was characterized by DSC, variable temperature PXRD, solid-state NMR (SSNMR), viscoelastic measurements, XAS, and DFT-AIMD calculations. These analyses suggested "coordination polymer-forming liquid" formation with preserved coordination bonds above T m. Variable chain configurations and moderate cohesive interaction in adjacent chains are the keys to the rarely observed polymer-forming liquid. The melt structure is reminiscent of the common 1D organic polymer melts such as entanglement or random coil structures.

Three-Dimensional Metal-Organic Network Glasses from Bridging MF62- Anions and Their Dynamic Insights by Solid-State NMR.

Glassy-state coordination polymers (CPs) are a new class of network-forming glasses. In this work, we constructed glass-forming CPs composed of both anionic and neutral ligands as network formers. With the use of hexafluoro anions (MF62-) and 1,3-bis(4-pyridyl)propane (bpp), two isostructural CP crystals, [Zn(SiF6)(bpp)2] (ZnSi) and [Zn(TiF6)(bpp)2] (ZnTi), were synthesized. Solid-state 19F NMR revealed rotational motion of MF62- with dissociation and re-formation of the Zn-F coordination bonds in both CP crystals, which reflects the thermodynamic parameters related to the glass formability. The mobility of SiF62- is larger than that of TiF62-, suggesting a higher glass formability of ZnSi. When mechanical ball milling was conducted, ZnSi completely changed into a glassy state, whereas ZnTi showed incomplete glass formation. Examination of the amorphous structures elucidated retention and partial destruction of the Zn-F coordination bonds in ball-milled ZnSi and ZnTi, respectively. These results provide the relationship between the ligand dynamics and glass formability of CPs.

Slow CO2 Diffusion Governed by Steric Hindrance of Rotatory Ligands in Small Pores of a Metal-Organic Framework.

Understanding the adsorption and diffusional dynamics of CO2 in metal-organic frameworks (MOFs) is essential in the application of these materials to CO2 capture and separation. We show that the dynamics of adsorbed CO2 is related to the rotational motion of ligands located in the narrow pore windows of a MOF using solid-state nuclear magnetic resonance (NMR) spectroscopy. NMR analyses of local dynamics reveal that CO2 adsorbed in the pore hinders the rotation of the ligands. The rate of diffusion of adsorbed CO2 monitored by 13C NMR is much less than that in the larger pores of MOFs and decreases cooperatively with ligand mobility, which indicates that the rate of diffusion is influenced by the steric hindrance of the rotatory ligands. Adsorbed CH4 also showed slow diffusion in the MOF, suggesting molecular size-selective effect of the mobile steric hindrance on the rate of adsorbate diffusion.

Polyoxocationic antimony oxide cluster with acidic protons.

The success and continued expansion of research on metal-oxo clusters owe largely to their structural richness and wide range of functions. However, while most of them known to date are negatively charged polyoxometalates, there is only a handful of cationic ones, much less functional ones. Here, we show an all-inorganic hydroxyiodide [H10.7Sb32.1O44][H2.1Sb2.1I8O6][Sb0.76I6]2·25H2O (HSbOI), forming a face-centered cubic structure with cationic Sb32O44 clusters and two types of anionic clusters in its interstitial spaces. Although it is submicrometer in size, electron diffraction tomography of HSbOI allowed the construction of the initial structural model, followed by powder Rietveld refinement to reach the final structure. The cationic cluster is characterized by the presence of acidic protons on its surface due to substantial Sb3+ deficiencies, which enables HSbOI to serve as an excellent solid acid catalyst. These results open up a frontier for the exploration and functionalization of cationic metal-oxo clusters containing heavy main group elements.

Neuronal DAF-16-to-intestinal DAF-16 communication underlies organismal lifespan extension in C. elegans.

Previous studies have revealed the importance of inter-tissue communications for lifespan regulation. However, the inter-tissue network responsible for lifespan regulation is not well understood, even in a simple organism Caenorhabditis elegans. To understand the mechanisms underlying systemic lifespan regulation, we focused on lifespan regulation by the insulin/insulin-like growth factor-1 signaling (IIS) pathway; IIS reduction activates the DAF-16/FOXO transcription factor, which results in lifespan extension. Our tissue-specific knockdown and knockout analyses demonstrated that IIS reduction in neurons and the intestine markedly extended lifespan. DAF-16 activation in neurons resulted in DAF-16 activation in the intestine and vice versa. Our dual gene manipulation method revealed that intestinal and neuronal DAF-16 mediate longevity induced by daf-2 knockout in neurons and the intestine, respectively. In addition, the systemic regulation of intestinal DAF-16 required the IIS pathway in intestinal and neurons. Collectively, these results highlight the importance of the neuronal DAF-16-to-intestinal DAF-16 communication for organismal lifespan regulation.

Probing dynamics of carbon dioxide in a metal-organic framework under high pressure by high-resolution solid-state NMR.

The application of high-resolution NMR analysis for CO2 adsorbed in a MOF under high pressure is reported for the first time. The results showed that CO2 adsorbed in MOF-74 had an unusually slow mobility (τ ∼ 10-8 s). CO2-CO2 interactions suppressed the mobility of CO2 under high pressure, which, in turn, would have contributed to the stability of CO2 at the adsorption sites.

Capping Structure of Ligand-Cysteine on CdSe Magic-Sized Clusters.

Ligand molecules capping on clusters largely affect the formation and stabilization mechanism and the property of clusters. In semiconductor CdSe clusters, cysteine is used as one of the ligands and allows the formation of ultrastable (CdSe)34 magic-sized clusters. Cysteine has sulfhydryl, amine, and carboxylate groups, all of which have coordination ability to the CdSe surface, and the bonding states of the three functional groups of ligand-cysteine on the CdSe core have not been determined. In this work, the capping structure of ligand-cysteine is examined by performing Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and multinuclear solid-state nuclear magnetic resonance (NMR) spectroscopy. FT-IR, XPS, and 1H, 13C, and 23Na magic-angle spinning NMR show that the sulfhydryl group of ligand-cysteine forms a sulfur-cadmium bond with a cadmium atom at the CdSe surface, while the carboxylate group does not contribute to the protection of the CdSe core and binds to a sodium ion contained as a counterion. 15N-{77Se} through-bond J-single quantum filtered NMR experiment reveals that the amine group of ligand-cysteine has no coordination to selenium atoms. By considering the N-Cd bond forming ratio (∼43%) revealed in our previous work, which is confirmed in this work by analyzing 13Cα signal intensity (∼42%), we concluded that cysteine capping on (CdSe)34 occurs in two ways: one involves both the sulfur-cadmium and nitrogen-cadmium bonds, and the other bears only the sulfur-cadmium bond.

Synthesis and Atomic Structure of the Yb-Ga-Au 1/1 Quasicrystal Approximant.

The Yb-Ga-Au 1/1 quasicrystal approximant (AP) composition ranges from Yb14.0Ga20.6Au65.4 to Yb14.8Ga46.3Au38.9, and single crystals of the 1/1 AP having the composition Yb13.8Ga26.1Au60.1 were obtained by the self-flux technique. X-ray structural analysis demonstrated that the atomic structure [space group Im3; a = 14.6889(9) Å] can be described by the body-centered packing of Tsai-type rhombic triacontahedron (RTH) clusters. The positional disorder in these clusters, interpreted as the average of an orientationally disordered tetrahedron and triangle, results in positional disorder in the outer shells. The elemental distributions and positions of mixtures of Au and Ga atoms in the RTH clusters correspond to those in the isostructural Yb15Al36Au49 1/1 AP.

Precision imaging of 4.4 MeV gamma rays using a 3-D position sensitive Compton camera.

Imaging of nuclear gamma-ray lines in the 1-10 MeV range is far from being established in both medical and physical applications. In proton therapy, 4.4 MeV gamma rays are emitted from the excited nucleus of either 12C* or 11B* and are considered good indicators of dose delivery and/or range verification. Further, in gamma-ray astronomy, 4.4 MeV gamma rays are produced by cosmic ray interactions in the interstellar medium, and can thus be used to probe nucleothynthesis in the universe. In this paper, we present a high-precision image of 4.4 MeV gamma rays taken by newly developed 3-D position sensitive Compton camera (3D-PSCC). To mimic the situation in proton therapy, we first irradiated water, PMMA and Ca(OH)2 with a 70 MeV proton beam, then we identified various nuclear lines with the HPGe detector. The 4.4 MeV gamma rays constitute a broad peak, including single and double escape peaks. Thus, by setting an energy window of 3D-PSCC from 3 to 5 MeV, we show that a gamma ray image sharply concentrates near the Bragg peak, as expected from the minimum energy threshold and sharp peak profile in the cross section of 12C(p,p)12C*.

Quantitative Solid-State NMR Study on Ligand-Surface Interaction in Cysteine-Capped CdSe Magic-Sized Clusters.

Ligand-surface interaction of semiconductor nanoparticles (NPs) controls their optoelectronic properties, and thus examination of the interaction is essential for the nanoelectronic applications of NPs. Herein, solid-state nuclear magnetic resonance (NMR) is performed to unravel the ligand-surface interaction in cysteine-capped CdSe magic-sized clusters. 15N-113Cd through-bond J-filtered NMR directly shows the presence of the nitrogen-cadmium chemical bond for the first time and indicates that ∼43% of the amines form the chemical bond. 15N-113Cd through-space dipolar-correlated NMR reveals that ∼54% of the amines locate nearby the surface cadmium with the average nitrogen-cadmium distance of 0.247 nm. The average distance is comparable with that estimated by J-filtered NMR. The difference of the two ratios (∼11%) proposes that some amines locate on the surface without forming the chemical bond, and these amines affect the relatively long observed distance in the dipolar-based experiment. Our study shows effectiveness of solid-state NMR for investigation of the ligand-surface interactions of NPs.