Protein Crotonylation Promotes Osteogenic Differentiation of Periodontal Ligament Stem Cells via the PI3K-AKT Pathway.

Posttranslational modifications (PTMs) are crucial regulatory mechanisms for cellular differentiation and organismal development. Acylation modification is one of the main PTMs that plays a pivotal role in regulating the osteogenic differentiation of mesenchymal stem cells and is a focal point of research in bone tissue regeneration. However, its mechanism remains incompletely understood. This article aims to investigate the impact of protein crotonylation on osteogenic differentiation in periodontal ligament stem cells (PDLSCs) and elucidate its underlying mechanisms. Western blot analysis identified that the modification level of acetylation, crotonylation, and succinylation were significantly upregulated after osteogenic induction of PDLSCs. Subsequently, sodium crotonate (NaCr) was added to the medium and acyl-CoA synthetase short-chain family member 2 (ACSS2) was knocked down by short hairpin RNA plasmids to regulate the total level of protein crotonylation. The results indicated that treatment with NaCr promoted the expression of osteogenic differentiation-related factors in PDLSCs, whereas silencing ACSS2 had the opposite effect. In addition, mass spectrometry analysis was used to investigate the comprehensive analysis of proteome-wide crotonylation in PDLSCs under osteogenic differentiation. The analysis revealed that the level of protein crotonylation related to the PI3K-AKT signaling pathway was significantly upregulated in PDLSCs after osteogenic induction. Treatment with NaCr and silencing ACSS2 affected the activation of the PI3K-AKT signaling pathway. Collectively, our study demonstrates that protein crotonylation promotes osteogenic differentiation of PDLSCs via the PI3K-AKT pathway, providing a novel targeting therapeutic approach for bone tissue regeneration.

Tuning Multiple Counter-Anions in Porous Coordination Polymers with lcy Topology for Acetylene/Ethylene Separation.

The efficient separation of acetylene (C2H2) and ethylene (C2H4) is an important and complex process in the industry. Herein, we report a new family of lcy-topologic coordination frameworks (termed NTU-90 to NTU-92) with Cu3MF6 (M = Si, Ti, and Zr) nodes. These charged frameworks are compensated by different counterbalanced ions (MF62-, BF4-, and Cl-), yielding changes in the size of the window apertures. Among these frameworks, NTU-92-a (activated NTU-92) shows good adsorption selectivity of C2H2/C2H4 and also significant ability in recovering both highly pure C2H4 (99.95%) and C2H2 (99.98%). Our work not only presents a potential alternative for energy-saving purification of C2 hydrocarbons but also provides a new approach for tuning the function of charged porous materials.

Fine Tuning Metal-Organic Frameworks with Halogen Functional Groups for Ethylene Purification.

One-step C2H4 purification from a mixture of C2H2/C2H4/C2H6 could be achieved by metal-organic framework (MOF) NTUniv-70 with an F-functional group. The selectivities of C2H4/C2H6 and C2H4/C2H2 of NTUnvi-70 based on ideal adsorbed solution theory were at least twice that of the original MOF platform, which was in line with the enthalpy of adsorption (Qst) and breakthrough testing. Grand canonical Monte Carlo simulations indicated that the C-H···F interactions played an important role in enhanced C2H4/C2H6 and C2H4/C2H2 adsorption selectivities.

Fine-Tuning MOFs with Amino Group for One-Step Ethylene Purification from the C2 Hydrocarbon Mixture.

Due to the similar kinetic diameters of C2H2, C2H4, and C2H6, one-step purification of C2H4 from a ternary C2H2/C2H4/C2H6 mixture by adsorption separation is still a challenge. Based on a C2H6-trapping platform and crystal engineering strategy, the N atom and amino group were introduced into NTUniv-58 and NTUniv-59, respectively. Gas adsorption testing of NTUniv-58 showed that both the C2H2 and C2H4 uptake capacities and the C2H2/C2H4 separation ability were boosted compared with the original platform. However, the C2H4 uptake value exceeds the C2H6 adsorption data. For NTUniv-59, the C2H2 uptake at low pressure increased and the C2H4 uptake decreased; thus, the C2H2/C2H4 selectivity was enhanced and the one-step purification of C2H4 from a ternary C2H2/C2H4/C2H6 mixture was realized, which was supported by the enthalpy of adsorption (Qst) and breakthrough testing. Grand canonical monte carlo (GCMC) simulation indicated that the preference for C2H2 over C2H4 originates from multiple hydrogen-bonding interactions between amino groups and C2H2 molecules.

Expanding MOF with Unexpanded Channel via Ketone Decorated Ligand for Ethylene Purification and Stability Enhancement.

The concept of an expanding MOF with unexpanded channel size was realized in MOF NTUniv-61 by the utilization of a ketone-functional-group-decorated semirigid ligand and pillar-layer platform. After this unusual expansion, the preferential C2H6 adsorption was preserved via the unchanged pore size, and the functional group was inserted into the MOF. Interestingly, the C2H2 uptake ability, C2H4 selective adsorption ability, and structural stability were obviously enhanced due to the incorporation of the ketone functional group, which were further verified by isosteric heats of adsorption (Qst), GCMC modeling, and breakthrough experiments.

Creating an Ethane Trap in a Ketone-Decorated MOF for One-Step Ethylene Separation from C2 Hydrocarbons.

One-step C2H4 purification from a mixture of C2H2/C2H4/C2H6 by physical adsorption separation was realized via creating an ethane trap in MOF NTUniv-63 by the utilization of a ketone-decorated semirigid ligand, which has further been verified by the breakthrough experiment, isosteric heats of adsorption (Qst), and Grand Canonical Monte Carlo (GCMC) modeling.

Metabolism, pharmacokinetics, and bioavailability of yuanhuacine in rat using LC-MS.

Yuanhuacine is a Daphne-type diterpene ortho-ester and is one of the main active ingredients of genkwa flos. Anticancer activity of yuanhuacine has been well investigated in various tumor cells and animal models, but information on metabolism and pharmacokinetics is limited. The aims of the present study were to investigate the metabolic and pharmacokinetic profiles of yuanhuacine in rat. The metabolic profile of yuanhuacine was obtained from rat plasma, urine, and feces using ultra-high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. A total of seven metabolites were detected, and the proposed metabolic pathways involved oxidation and glucuronidation. A simple and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry method was developed for the determination of yuanhuacine in rat plasma. The linear range of yuanhuacine was 1-1000 ng/ml (R2  = 0.998). The intra- and inter-precision (coefficient of variation %) of the assay was 3.86-6.18% and 2.65-5.75%, respectively, and the intra- and inter-accuracy (relative error %) was -3.83-4.77% and -3.03-5.11%, respectively. The extraction recovery, matrix effect, stability, and incurred sample reanalysis of yuanhuacine were within acceptable levels. The established method was validated and successfully applied to the preclinical pharmacokinetic study of yuanhuacine. The absolute oral bioavailability of yuanhuacine was calculated as 1.14%, and it reached the maximum plasma concentration of 28.21 ± 2.79 ng/ml in rat plasma at 2 h in the oral dosing group. The apparent volume of distribution of intravenous and intragastric administrations was 26.07 ± 6.45 and 21.83 ± 3.54 L/kg, respectively. The half-life of elimination of yuanhuacine was 9.64 ± 1.53 h in the intravenous dosing group.

Significantly Enhanced Carbon Dioxide Selective Adsorption via Gradual Acylamide Truncation in MOFs: Experimental and Theoretical Research.

A gradual amide truncation strategy was presented to tune the pore chemistry and CO2 capture performance of a series of tetracarboxylate-based Cu-MOFs. These MOFs exhibited a high density of Lewis basic sites (LBSs) and open metal sites and were prepared with the goal to enhance CO2 selective adsorption capacity. [Cu2(L1)(H2O)2]n (NJU-Bai42: NJU-Bai for Nanjing University Bai's group), [Cu2(L2) (H2O)2]n (NJU-Bai17), and [Cu2(L3)(H2O)2]n (NTUniv-60: NTUniv for Nantong University) were synthesized, and we observed that the CO2 adsorption capacities and MOF structures were impacted by subtle changes in ligands. Interestingly, although the NTUniv-60 was decorated with the least LBSs in these three MOFs, its CO2 adsorption capacity reached 270 (53.0 wt %) and 164 (32.2 wt %) cm3 g-1 at 273 and 296 K under 1 bar, respectively, which is the highest data reported for MOFs under similar conditions. From the grand canonical Monte Carlo (GCMC) simulation, the cooperative interactions between the CO2 molecules within the shuttle-shaped cages of NTUniv-60 could potentially explain why the CO2 uptake is high in this material.

MOF Pillaring Method: Ligand-to-Ligand and Axial-to-Axial Cross-Linking of "Paddlewheels".

By shortening the previous shortest tetracarboxylate ligand, the first ligand-to-ligand and axial-to-axial pillaring method was realized in the prototype MOF NTUniv-56 (NTUniv = Nantong University), which exhibit a rare (2,4,6)-connected net with a new topology and interesting gas adsorption performance.

Formation of a Polar Flow Channel with Embedded Gas Recognition Pockets in a Yttrium-Based MOF for Enhanced C2H2/C2H4 and CO2 Selective Adsorptions.

A polar flow channel with embedded gas recognition pockets was made in a 10-connected hexanuclear yttrium-based metal-organic frameworks (MOF) NTUniv-57 (NTUniv = Nantong University) by lowering the symmetry of the ligand, which showed high chemical stability and obviously enhanced gas adsorption selectivities.

Lighting quantity indexes for lighting traditional Chinese paintings based on pigments protection and substrates protection in museums.

In museum lighting, traditional Chinese paintings are the artworks with the highest light sensitivity. They are vulnerable to the color damage to pigments and the mechanical damage to substrates after the irradiation from light sources. As the basis of effective preventive protection, the research on the two lighting quantity indexes of illuminance and annual exposure (illuminance × time) is currently missing. In this study, the halogen lamp was used as the experimental light source to conduct a 1440 h irradiation experiment on the samples of paper and silk substrates under 4 illuminance levels, respectively, and the test of infrared spectrum was carried out on the samples every 240 h. The oxidation index of paper and crystallinity degree of silk were calculated then. Three-dimensional visual curved surface plots of mechanical damage to samples with the change of illuminance and time were established and then fitted into damage evaluation equations, which revealed and described mathematically the mechanical damage law of samples. Through the equations, the recommended values of illuminance and annual exposure for samples could be calculated. Combining the previous researches on pigments, the lighting quantity indexes of traditional Chinese paintings with different combinations of substrates and pigments were proposed.

Finely Tuning Tridentate Carboxylic Acids for the Construction of Rod Scandium Metal-Organic Frameworks with High Chemical Stability and Selective Gas Adsorption.

By systematic ligand tuning for control of the secondary building units, the use of tridentate carboxylic acid to construct the rod scandium metal-organic framework NTUniv-55 (NTUniv = Nantong University) with high chemical stability and interesting selective gas adsorption was reported.

Epigenetic modifier trichostatin A enhanced osteogenic differentiation of mesenchymal stem cells by inhibiting NF-κB (p65) DNA binding and promoted periodontal repair in rats.

We wished to evaluate whether epigenetic modifiers have a beneficial effect on treating experimental periodontitis and mechanisms for regulating the cell fate of mesenchymal stem cells (MSCs) in inflammatory microenvironments. We isolated MSCs from healthy and inflamed gingival tissues to investigate whether trichostatin A (TSA) could improve osteogenic differentiation and resolve inflammation in vitro. The tissue regenerative potentials were evaluated when treated with a temperature-dependent, chitosan-scaffold-encapsulated TSA, in a rat model of periodontitis. After induction with the conditioned medium, TSA treatment increased the osteogenic differentiation potential of inflamed MSCs and healthy MSCs. In addition, interleukin-6 and interleukin-8 levels in supernatants were significantly decreased after TSA treatment. Moreover, TSA promoted osteogenic differentiation by inhibiting nuclear factor-κB (p65) DNA binding in MSCs. In rats with experimental periodontitis, 7 weeks after local injections of chitosan-scaffold-encapsulated TSA, histology and microcomputed tomography showed a significant increase in alveolar bone volume and less inflammatory infiltration compared with vehicle-treated rats. The concentrations of interferon-γ and interleukin-6 were significantly decreased in the gingival crevicular fluid after TSA treatment. This study demonstrated that TSA had anti-inflammatory properties and could promote periodontal tissue repair, which indicated that epigenetic modifiers hold promise as a potential therapeutic option for periodontal tissue repair.

Raman spectroscopy-based method for evaluating LED illumination-induced damage to pigments in high-light-sensitivity art.

Because commonly used organic pigments are highly responsive to visible light, high-light-sensitivity art is vulnerable to irreversible illumination-induced damage caused by radiation from light sources. With application of the four primary white light-emitting diodes (fp-WLEDs) in museums, it is urgent to evaluate the illumination-induced damage to high-light-sensitivity art caused by the fp-WLEDs. Four narrowband LEDs with different peak wavelengths of 450, 510, 583, and 650 nm that constitute the spectra of the fp-WLEDs were used to irradiate three commonly used organic pigments: safflower, gamboge, and indigo. Based on the fundamental reason for the illumination-induced damage, that is, photochemical reactions, Raman spectroscopy was introduced into the study. The Raman spectra of pigments were measured before and after illumination. The characteristic Raman peaks corresponding to the functional groups that determine color and structure of pigments were selected, and the variations in their peak intensities were calculated. The illumination-induced damage coefficients of four narrowband LEDs on three organic pigments were obtained, providing a data basis for illumination-induced damage evaluation equation proposed in this study, which was expected to further realize museum admission evaluation of the new fp-WLEDs.

Exploring genotype-phenotype relationships of the CRABP2 gene on growth traits in beef cattle.

Cellular retinoic acid binding protein 2 (CRABP2) is essential to myoblast differentiation. However, there was no report about the function of CRABP2 gene in cattle. This study explored the association of CRABP2 gene polymorphisms with growth traits in cattle breeds by several methods, such as DNA sequencing, PCR, PCR-RFLP and forced PCR-RFLP. Two sequence variants were determined. There were 621 individuals in six cattle breeds from China for the experiment, and three breeds were used to test validation of polymorphisms and extent of linkage disequilibrium (LD). The results showed that both SNPs (SNP1, g.2458 G > T, SNP2, g.3878 G > A) were in intron1. Two SNPs were in low linkage disequilibrium. Association analysis suggested that SNP1 had the significant difference on growth traits with body height, height at hip cross and body slanting length (P < .05), while SNP2 showed a significant difference in growth traits with body height, height at hip cross and body slanting length(P < .05). The results of this investigation displayed that the CRABP2 gene is an available candidate gene and may be used for breed selection and conservation.

Determination of genetic effects of SERPINA3 on important growth traits in beef cattle.

Serine protease inhibitor protein 3 (serpin peptidase inhibitor, clade A, member 3, SERPINA3) is a member of the serpin superfamily, probably related to the yield and quality of muscle. This study focuses on the relationship between SERPINA3 gene polymorphism and growth traits in beef cattle. The study first uses sequencing pooled DNA samples (Pool-Seq), PCR-RFLP and Tetra-primer ARMS-PCR techniques to determine the genetic polymorphisms of SERPINA3 in 765 beef cattle. Then, the polymorphic loci were correlated with the growth characters of cattle. Five SNPs (SNP1:A-648G, SNP2:T6496A, SNP3:G2495A, SNP4:T2595A, SNP5:A2615G) were found, located in the promoter, introns 5 and SNP 3, 4, 5 were in exons 2, respectively. The observed He was from 0.44 to 0.5, Ne were approaching 2 (1.78 to 2.00). The maximum and minimum PIC (polymorphism information content) values were 0.37 and 0.34, respectively. The association analysis results showed that the SNPs had a significant height in the chest girth and body length. (p < 0.05 or p < 0.01). This will provide important information for the rapid breeding of Chinese yellow cattle and the establishment of a molecular genetic marker database.

Circular RNA hsa_circ_0010729 regulates vascular endothelial cell proliferation and apoptosis by targeting the miR-186/HIF-1α axis.

Circular RNAs (circRNAs) are a group of non-protein-coding RNAs generated from back splicing. Emerging evidence has demonstrated its vital regulation on angiogenesis. However, the underlying mechanism responsible for circRNAs effects on vascular endothelial cells is still unclear. In the present study, we screened the expression profiles and investigated the physiological role of circRNAs in hypoxia-induced human umbilical vein endothelial cells (HUVECs). Using circRNA microarray analysis, we identified 36 circRNAs that were significantly dysregulated including 14 down-regulated circRNAs and 22 up-regulated with 2-fold change (P < 0.05). From the over-expressed circRNAs, hsa_circ_0010729 was selected as candidate circRNA and which was validated to be significantly up-regulated using RT-PCR. In loss-of-function experiments of HUVECs, hsa_circ_0010729 knockdown suppressed the proliferation and migration ability and enhanced apoptosis. Bioinformatic prediction and luciferase assay revealed that hsa_circ_0010729 and hypoxia inducible factor 1 alpha (HIF-1α) were targeted by miR-186. Validation experiments verified that hsa_circ_0010729 was co-expressed with HIF-1α, being negatively correlated with miR-186. Moreover, rescue experiments demonstrated that miR-186 inhibitor could reverse the role of hsa_circ_0010729 knockdown on HUVECs progression. Overall, the present study identifies the crucial regulation of hsa_circ_0010729 on vascular endothelial cell proliferation and apoptosis via targeting miR-186/HIF-1α axis.

A20 plays a critical role in the immunoregulatory function of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) possess an immunoregulatory capacity and are a therapeutic target for many inflammation-related diseases. However, the detailed mechanisms of MSC-mediated immunosuppression remain unclear. In this study, we provide new information to partly explain the molecular mechanisms of immunoregulation by MSCs. Specifically, we found that A20 expression was induced in MSCs by inflammatory cytokines. Knockdown of A20 in MSCs resulted in increased proliferation and reduced adipogenesis, and partly reversed the suppressive effect of MSCs on T cell proliferation in vitro and inhibited tumour growth in vivo. Mechanistic studies indicated that knockdown of A20 in MSCs inhibited activation of the p38 mitogen-activated protein kinase (MAPK) pathway, which potently promoted the production of tumour necrosis factor (TNF)-α and inhibited the production of interleukin (IL)-10. Collectively, these data reveal a crucial role of A20 in regulating the immunomodulatory activities of MSCs by controlling the expression of TNF-α and IL-10 in an inflammatory environment. These findings provide novel insights into the pathogenesis of various inflammatory-associated diseases, and are a new reference for the future development of treatments for such afflictions.

Architectural properties of the neuromuscular compartments in selected forearm skeletal muscles.

The purposes f this study were to (i) explore the possibility of splitting the selected forearm muscles into separate compartments in human subjects; (ii) quantify the architectural properties of each neuromuscular compartment; and (iii) discuss the implication of these properties in split tendon transfer procedures. Twenty upper limbs from 10 fresh human cadavers were used in this study. Ten limbs of five cadavers were used for intramuscular nerve study by modified Sihler's staining technique, which confirmed the neuromuscular compartments. The other 10 limbs were included for architectural analysis of neuromuscular compartments. The architectural features of the compartments including muscle weight, muscle length, fiber length, pennation angle, and sarcomere length were determined. Physiological cross-sectional area and fiber length/muscle length ratio were calculated. Five of the selected forearm muscles were ideal candidates for splitting, including flexor carpi ulnaris, flexor carpi radials, extensor carpi radialis brevis, extensor carpi ulnaris and pronator teres. The humeral head of pronator teres contained the longest fiber length (6.23 ± 0.31 cm), and the radial compartment of extensor carpi ulnaris contained the shortest (2.90 ± 0.28 cm). The ulnar compartment of flexor carpi ulnaris had the largest physiological cross-sectional area (5.17 ± 0.59 cm(2)), and the ulnar head of pronator teres had the smallest (0.67 ± 0.06 cm(2)). Fiber length/muscle length ratios of the neuromuscular compartments were relatively low (average 0.27 ± 0.09, range 0.18-0.39) except for the ulnar head of pronator teres, which had the highest one (0.72 ± 0.05). Using modified Sihler's technique, this research demonstrated that each compartment of these selected forearm muscles has its own neurovascular supply after being split along its central tendon. Data of the architectural properties of each neuromuscular compartment provide insight into the 'design' of their functional capability. In addition to improving our understanding of muscle anatomy and function, elucidation of forearm neuromuscular compartments architecture may ultimately provide information useful for selection of muscle subdivisions used in tendon transfer.

[Study on early intervention of compound nutrition for cognitive dysfunction in Alzheimer's disease].

OBJECTIVE: To observe the early prevention effect of the compound nutrients recipe for cognitive dysfunction of Alzheimer' s disease model-APP-PSN transgenic mouse. METHODS: 36 APP-PSN transgenic mice aged two months randomly were divided into the intervention group supplied with compound recipe in the diet and the control group fed based feed, the former had high dose and low dose, 12 APP-PSN transgenic negative mice aged two months as the negative control were fed based feed. After 3 months' intervention, four groups' cognitive functions were evaluated using the Morris water maze, active avoidance experiment and jumping stair experiment. RESULTS: There was not statistically different between all the four groups for the weight and food intake. Compared with the control group, Morris water maze's incubation period of the intervention group was lower obviously, and jumping stair experiment's incubation period of the intervention group was higher obviously. In the active avoidance experiment, the high and low dose intervention group' s conditioned response accounted about 46.67% and 45.00% respectively, and the control group's conditioned response accounted about 20.83%. The differences of the three behavioral experiments between control group and intervention group had the statistical significance (P < 0.05), so the same as between control group and negative control group (P < 0.05). And there was no difference between intervention group and negative control group for the three behavioral experiments. CONCLUSION: The early supplementation with compound nutrition could postpone the occurrence and development of Alzheimer' s disease mice model's cognitive dysfunction.