Thymosin ß4 Regulates the Differentiation of Thymocytes by Controlling the Cytoskeletal Rearrangement and Mitochondrial Transfer of Thymus Epithelial Cells.

The thymus is one of the most crucial immunological organs, undergoing visible age-related shrinkage. Thymic epithelial cells (TECs) play a vital role in maintaining the normal function of the thymus, and their degeneration is the primary cause of age-induced thymic devolution. Thymosin ß4 (Tß4) serves as a significant important G-actin sequestering peptide. The objective of this study was to explore whether Tß4 influences thymocyte differentiation by regulating the cytoskeletal rearrangement and mitochondrial transfer of TECs. A combination of H&E staining, immunofluorescence, transmission electron microscopy, RT-qPCR, flow cytometry, cytoskeletal immunolabeling, and mitochondrial immunolabeling were employed to observe the effects of Tß4 on TECs' skeleton rearrangement, mitochondrial transfer, and thymocyte differentiation. The study revealed that the Tß4 primarily regulates the formation of microfilaments and the mitochondrial transfer of TECs, along with the formation and maturation of double-negative cells (CD4-CD8-) and CD4 single-positive cells (CD3+TCRß+CD4+CD8-) thymocytes. This study suggests that Tß4 plays a crucial role in thymocyte differentiation by influencing the cytoskeletal rearrangement and mitochondrial transfer of TECs. These effects may be associated with Tß4's impact on the aggregation of F-actin. This finding opens up new avenues for research in the field of immune aging.

The effects of impurities in carbide slag on the morphological evolution of CaCO3 during carbonation.

Carbide slag (CS) is a kind of solid waste generated by the hydrolysis of calcium carbide for acetylene production. Its major component is Ca(OH)2, which shows great potential in CO2 mineralization to produce CaCO3. However, the types of impurities in CS and their mechanisms for inducing the morphological evolution of CaCO3 are still unclear. In this work, the influence of impurities in CS on the morphology evolution of CaCO3 was investigated. The following impurities were identified in the CS: Al2O3, MgO, Fe2O3, SiO2 and CaCO3. Ca(OH)2 was used to study the influence of impurities (Al2O3 and Fe2O3) on the evolution of CaCO3 morphology during CS carbonation. Calcite (CaCO3) was the carbonation product produced during CS carbonation under varying conditions. The morphology of calcite was changed from cubic to rod-shaped, with increasing solid-liquid ratios. Moreover, rod-shaped calcite was converted into irregular particles with increasing CO2 flow rate and stirring speed. Rod-shaped calcite (CaCO3) was formed by CS carbonation at a solid-liquid ratio of 10:100 under a stirring speed of 600 rpm and a CO2 flow rate of 200 ml/min; and spherical calcite was generated during Ca(OH)2 carbonation under the same conditions. Al2O3 impurities had negligible effects on spherical CaCO3 during Ca(OH)2 carbonation. In contrast, rod-shaped CaCO3 was generated by adding 0.13 wt% Fe2O3 particles, similar to the content of Fe2O3 in CS. Rod-shaped calcite was converted into particulate calcite with increasing Fe2O3 content. The surface wettability and surface negative charge of Fe2O3 appeared to be responsible for the formation of rod-shaped CaCO3. This study enhances our understanding and utilization of CS and CO2 reduction and the fabrication of high-value rod-shaped CaCO3.

Metagenomic analysis of the relationship between the microorganisms and the volatiles' development in the wines during spontaneous fermentation from the eastern foothills of the Ningxia Helan mountains in China.

BACKGROUND: The natural fermentation of multispecies microbial communities is responsible for unique flavors of winery regions of the eastern foothills of the Ningxia Helan Mountains in China. However, the participation of different microorganisms in the metabolic network for the development of important flavor substances is not clearly defined. Microbial population and diversity on different fermentation phases of Ningxia wine were analyzed by metagenomic sequencing approach. RESULTS: Gas chromatography-mass spectrometry and ion chromatography were used to identify flavor components, and 13 esters, 13 alcohols, nine aldehydes and seven ketones were detected in volatile substances with odor activity values > 1, and eight organic acids were detected as important flavor components in young wine. Thus, 52 238 predicted protein-coding genes from 24 genera were identified in the Kyoto Encyclopedia of Genes and Genomes level 2 pathways of global and overview maps, and the genes were primarily involved in amino acid metabolism and carbohydrate metabolism. Major microbial genera (Saccharomyces, Tatumella, Hanseniaspora, Lactobacillus, and Lachancea) were closely related to self-characteristic compound metabolism and further contributed to wine flavor. CONCLUSION: This study clarifies the different metabolic roles of microorganisms in flavor formation during Ningxia wine spontaneous fermentation. Saccharomyces, dominant fungi involved in glycolysis and pyruvate metabolism, produces not only ethanol but also two important precursors, pyruvate and acetyl-CoA, which are necessary for the tricarboxylic acid cycle, fatty acid metabolism, amino acid metabolism, and flavor formation. Lactobacillus and Lachancea, dominant bacteria involved in lactic acid metabolism. Tatumella, dominant bacteria involved in amino acid metabolism, fatty acid metabolism, and acetic acid metabolism to produce esters in the Shizuishan City region samples. These findings provide insights into the use of local functional strains to generate unique flavor formation, as well as improved stability and quality, in wine production. © 2023 Society of Chemical Industry.

Cobalt(II)-Based Metal-Organic Framework as Bifunctional Materials for Ag(I) Detection and Proton Reduction Catalysis for Hydrogen Production.

A novel cobalt(II)-based metal-organic framework, Co-MB, was prepared by hydrothermal reaction of Co(NO3)2·6H2O, 3,3'-methylenediphthalic acid (H4mda), and 1,4-bis(imidazol-1-ylmethyl)-benzene in sodium hydroxide aqueous solution and structurally characterized. It shows a high stability in water within the pH range from 2.2 to 11.6, which could be used as a highly selective and sensitive luminescent sensor for Ag(I) detection in a luminescent enhancement manner, with LOD about 23 nM. Importantly, such stable Co-MB could also work as proton reduction catalyst for photodriven hydrogen production coupled with visible-light organic dyes as photosensitizer. The influence factors of hydrogen production including pH, TEA (triethylamine) contents, and kinds of organic dyes are studied in detail. Under optimal condition, the TON value was up to 5133 per cycle, and this Co-MB could also be reused at least 3 times.

Enhanced Hematopoietic Stem Cell Self-Renewal-Promoting Ability of Clonal Primary Mesenchymal Stromal/Stem cells Versus Their Osteogenic Progeny.

Long-term self-renewing hematopoietic stem cell (LT-HSC) homeostasis within the bone marrow (BM) of adult mammals is regulated by complex interactions between LT-HSC and a number of niche-associated cell types including mesenchymal stromal/stem cells (MSC), osteoblasts (OB), macrophage, and neuronal cells in close proximity with the vasculature. Here, we cloned and functionally characterized a murine BM MSC subpopulation that was uniformly Nestin+ Lepr + Sca-1+ CD146+ and could be stably propagated with high colony-forming unit fibroblast re-cloning efficiency. MSC synergized with SCF and IL-11 to support a 20-fold expansion in true LT-HSC after 10-days of in vitro coculture. Optimal stimulation of LT-HSC expansion was minimally dependent on Notch signaling but was significantly enhanced by global inhibition of Wnt signaling. The self-renewal-promoting activity of MSC was progressively lost when MSC clones were differentiated into mature OB. This suggests that the stage of osteoblast development may significantly impact the ability of osteolineage cells to support LT-HSC homeostasis in vivo. Stem Cells 2017;35:473-484.

Genome-wide identification and evolutionary analyses of bZIP transcription factors in wheat and its relatives and expression profiles of anther development related TabZIP genes.

BACKGROUND: Among the largest and most diverse transcription factor families in plants, basic leucine zipper (bZIP) family participate in regulating various processes, including floral induction and development, stress and hormone signaling, photomorphogenesis, seed maturation and germination, and pathogen defense. Although common wheat (Triticum aestivum L.) is one of the most widely cultivated and consumed food crops in the world, there is no comprehensive analysis of bZIPs in wheat, especially those involved in anther development. Previous studies have demonstrated wheat, T. urartu, Ae. tauschii, barley and Brachypodium are evolutionarily close in Gramineae family, however, the real evolutionary relationship still remains mysterious. RESULTS: In this study, 187 bZIP family genes were comprehensively identified from current wheat genome. 98, 96 and 107 members of bZIP family were also identified from the genomes of T.urartu, Ae.tauschii and barley, respectively. Orthology analyses suggested 69.4 % of TubZIPs were orthologous to 68.8 % of AetbZIPs and wheat had many more in-paralogs in the bZIP family than its relatives. It was deduced wheat had a closer phylogenetic relationship with barley and Brachypodium than T.urartu and Ae.tauschii. bZIP proteins in wheat, T.urartu and Ae.tauschii were divided into 14 subgroups based on phylogenetic analyses. Using Affymetrix microarray data, 48 differentially expressed TabZIP genes were identified to be related to anther development from comparison between the male sterility line and the restorer line. Genes with close evolutionary relationship tended to share similar gene structures. 15 of 23 selected TabZIP genes contained LTR elements in their promoter regions. Expression of 21 among these 23 TabZIP genes were obviously responsive to low temperature. These 23 TabZIP genes all exhibited distinct tissue-specific expression pattern. Among them, 11 TabZIP genes were predominantly expressed in anther and most of them showed over-dominance expression mode in the cross combination TY806 × BS366. CONCLUSIONS: The genome-wide identification provided an overall insight of bZIP gene family in wheat and its relatives. The evolutionary relationship of wheat and its relatives was proposed based on orthology analyses. Microarray and expression analyses suggested the potential involvement of bZIP genes in anther development and facilitated selection of anther development related gene for further functional characterization.

Deciphering the effect of the different N-glycosylation sites on the secretion, activity, and stability of cellobiohydrolase I from Trichoderma reesei.

N-linked glycosylation modulates and diversifies the structures and functions of the eukaryotic proteome through both intrinsic and extrinsic effects on proteins. We investigated the significance of the three N-linked glycans on the catalytic domain of cellobiohydrolase I (CBH1) from the filamentous fungus Trichoderma reesei in its secretion and activity. While the removal of one or two N-glycosylation sites hardly affected the extracellular secretion of CBH1, eliminating all of the glycosylation sites did induce expression of the unfolded protein response (UPR) target genes, and secretion of this CBH1 variant was severely compromised in a calnexin gene deletion strain. Further characterization of the purified CBH1 variants showed that, compared to Asn270, the thermal reactivity of CBH1 was significantly decreased by removal of either Asn45 or Asn384 glycosylation site during the catalyzed hydrolysis of soluble substrate. Combinatorial loss of these two N-linked glycans further exacerbated the temperature-dependent inactivation. In contrast, this thermal labile property was less severe when hydrolyzing insoluble cellulose. Analysis of the structural integrity of CBH1 variants revealed that removal of N-glycosylation at Asn384 had a more pronounced effect on the integrity of regular secondary structure compared to the loss of Asn45 or Asn270. These data implicate differential roles of N-glycosylation modifications in contributing to the stability of specific functional regions of CBH1 and highlight the potential of improving the thermostability of CBH1 by tuning proper interactions between glycans and functional residues.

Dandelion polysaccharides improve the emulsifying properties and antioxidant capacities of emulsions stabilized by whey protein isolate.

In this study, the effects of dandelion polysaccharide (DP) and its carboxymethylated derivative (CMDP) on the emulsifying characteristics and antioxidant capacities of emulsions stabilized by whey protein isolate (WPI) were determined. The addition of both DP and CMDP reduced the particle size and zeta potential of the emulsions. Using 1.0 % WPI and 1.0 % CMDP as emulsifier, the emulsifying activity index (EAI) and emulsifying stability index (ESI) were 32.61 ± 0.11 m2/g and 42.58 ± 0.13 min, respectively, which were higher than the corresponding values of 27.19 ± 0.18 m2/g and 36.17 ± 0.15 min with 1.0 % WPI and 1.0 % DP. Fourier-transform infrared spectroscopy (FT-IR), far-ultraviolet circular dichroism (Far-UV CD), and fluorescence (FS) spectra analyses confirmed that the α-helix and ß-sheet structures in WPI-polysaccharide complexes were reduced compared with those in pure WPI, whereas the random-coil content was enhanced by the addition of polysaccharides. Moreover, DP and CMDP effectively improved the antioxidant capacity and inhibited oxidation of the emulsions during storage. Therefore, DP and its carboxymethylated derivative exhibit great potential to be applied in the emulsion-based delivery system.

Preparation, stability, and antibacterial activity of carboxymethylated Anemarrhena asphodeloides polysaccharide-chitosan nanoparticles loaded curcumin.

In present study, polysaccharide polyelectrolyte nanoparticles (CMAAP-CS NPs) were constructed by mixing carboxymethylated Anemarrhena asphodeloides polysaccharide (CMAAP) and chitosan (CS). CMAAP-CS NPs were applied as carrier to improve the bioavailability and stability of curcumin (Cur). The average particle size of CMAAP-CS NPs was 216.60 ± 4.21 nm and the entrapment efficiency of Cur reached 82.50 ± 2.09 %. The simulated digestion experiments in vitro confirmed that the bioavailability of Cur loaded in CMAAP-CS NPs was 59.84 ± 0.03 % after saliva, gastric and intestinal digestion, which was obvious higher than 21.57 ± 0.07 % of free Cur under the same conditions. The results of stability testing revealed that CMAAP-CS NPs could markedly reduce the degradation of Cur against storage, heating, UV light treatment, and neutral pH. This study provided promising polyelectrolyte complex loaded hydrophobic nutrients in medicine industry.

Advances in fruit aroma volatile research.

Fruits produce a range of volatile compounds that make up their characteristic aromas and contribute to their flavor. Fruit volatile compounds are mainly comprised of esters, alcohols, aldehydes, ketones, lactones, terpenoids and apocarotenoids. Many factors affect volatile composition, including the genetic makeup, degree of maturity, environmental conditions, postharvest handling and storage. There are several pathways involved in volatile biosynthesis starting from lipids, amino acids, terpenoids and carotenoids. Once the basic skeletons are produced via these pathways, the diversity of volatiles is achieved via additional modification reactions such as acylation, methylation, oxidation/reduction and cyclic ring closure. In this paper, we review the composition of fruit aroma, the characteristic aroma compounds of several representative fruits, the factors affecting aroma volatile, and the biosynthetic pathways of volatile aroma compounds. We anticipate that this review would provide some critical information for profound research on fruit aroma components and their manipulation during development and storage.

Gas Dispersion Coefficient Test System and Dimensionless Inversion Method for Porous Media.

Due to the complex porous media structure of the longwall gob area, it has been difficult to determine the gas dispersion coefficient of oxygen when studying spontaneous coal combustion in the gob area. In this work, we first designed an experimental device for testing the gas diffusion coefficient of porous media. Then, the distribution law of gas concentration in porous media under different particle size conditions was obtained by experiments. Subsequently, we established a dimensionless mathematical model of gas dispersion in porous media and developed a corresponding numerical simulator based on the finite volume method (FVM). The influence of the dimensionless gas dispersion coefficient on the gas concentration distribution was analyzed, and then a dimensionless inversion method of the gas dispersion coefficient was summarized and put forward. Finally, we obtained the values of the gas dispersion coefficient in the experimental device under different particle size conditions by inversion and discussed its effect on the gas dispersion behavior in porous media. The results show that (1) the distribution of gas concentration obtained from the experimental test and numerical simulation is consistent, which verifies the reliability of our work; (2) the dimensionless gas concentration is the highest near the injection point and gradually decreases along the depth and both sides of the test container; (3) with the increase of the dimensionless gas dispersion coefficient, the distance required for uniform gas mixing in the test container is gradually shortened and the gas dispersion coverage is wider; and (4) the larger pore space facilitates the dispersion behavior of the gas, and the gas dispersion coefficient shows a parabolic trend with the increase of porous medium particle size.

Nondimensional analysis and application of gas desorption and diffusion driven by density gradient in coal particles.

An in-depth understanding of gas diffusion characteristics in coal is of great value to coalbed methane (CBM) production planning and coal mine safety management. However, the mechanism and model of gas diffusion is still unclear, and some methods for determining diffusion coefficients are not accurate enough. Accordingly, a free gas density gradient (FGDG)-driven coal particle gas desorption and diffusion model was established in this work, and numerical solutions were performed via finite difference method (FDM) and dimensionless method. The variation rules of dimensionless gas pressure, gas content, desorption capacity, and desorption rate were obtained. Finally, the application of the dimensionless method in diffusion modeling and diffusion coefficient inversion was discussed. The results show that the dimensionless method can simplify mathematical equation processing and analyze the common phenomena of desorption and diffusion under different parameters. The gas desorption diffusion in coal particles is from the surface to the inside, and there is obvious desorption hysteresis effect. The larger the dimensionless radius or dimensionless time, the smaller the dimensionless gas pressure, gas content, and dimensionless desorption rate. The dimensionless cumulative gas desorption amount increased rapidly first and then tended to flat with dimensionless time. The simulated curve can be easily converted into the variation curves of several different measured parameters, and the diffusion coefficient can be calculated accurately. The prediction curve of the FGDG diffusion model is in good agreement with the experimentally measured data, which verifies its reasonableness. The research content aims to provide some ideas for modeling gas desorption and diffusion behavior.

Carboxymethylation modification, characterization of dandelion root polysaccharide and its effects on gel properties and microstructure of whey protein isolate.

In the present study, a native polysaccharide (DP) with sugar content of 87.54 ± 2.01 % was isolated from dandelion roots. DP was chemically modified to obtain a carboxymethylated polysaccharide (CMDP) with DS of 0.42 ± 0.07. DP and CMDP were composed of the same six monosaccharides including mannose, rhamnose, galacturonic acid, glucose, galactose, and arabinose. The molecular weights of DP and CMDP were 108,200 and 69,800 Da, respectively. CMDP exhibited more stable thermal performance and better gelling properties than DP. The effects of DP and CMDP on the strength, water holding capacity (WHC), microstructure, and rheological properties of whey protein isolate (WPI) gels were investigated. Results showed that CMDP-WPI gels had higher strength and WHC than DP-WPI gels. With the addition of 1.5 % CMDP, WPI gel had a good three-dimensional network structure. The apparent viscosities, loss modulus (G"), and storage modulus (G') of WPI gels were increased with the polysaccharide addition, the influence of CMDP was remarkable compared to DP at the same concentration. These findings suggest that CMDP may be used as a functional ingredient in protein-containing food products.

Numerical simulation and investigation of methane gas distribution and extraction in goaf with U-type ventilation of working face.

The accumulated methane in goaf during coal mining may leak into the working face under the airflow influence, which is possibly causing disasters such as methane gas excessive at the working face and seriously threatening the mine safety. This paper first established a three-dimensional numerical model of the mining area under U-shaped ventilation, introducing the gas state equation, continuity equation, momentum equation, porosity evolution equation, and permeability evolution equation to simulate the airflow field and gas concentration field in the mining area under the natural state. The reliability of the numerical simulations is then verified by the measured air volumes at the working face. The areas in the mining area where gas is likely to accumulate are also delineated. Subsequently, the gas concentration field in goaf under the gas extraction state was theoretically simulated for different locations of large-diameter borehole. The maximum gas concentration in goaf and the gas concentration trend in the upper corner were analyzed in detail, and the critical borehole location (17.8 m from the working face) was determined as the optimum location for gas extraction from the upper corner. Finally, a gas extraction test was carried out on-site to evaluate the application effect. The results show that the measured airflow rate has a small error with the simulated results. The gas concentration in the area without gas extraction is high, with the gas concentration in the upper corner being over 1.2%, which is greater than the critical value of 0.5%. The maximum reduction in gas concentration was 43.9%, effectively reducing the gas concentration in the extraction area after employing a large borehole to extract methane gas. The gas concentration in the upper corner and the distance of the borehole from the working face are expressed as a positive exponential function. The field engineering results show that the implementation of the large borehole at a distance of less than 17.8 m from the working face can control the gas in the upper corner to less than 0.5%, effectively reducing the risk of gas in the upper corner. The numerical simulation work in this paper can provide some basic support for the design of an on-site borehole to extract gas from the mining void and reduce the gas hazard in coal mines.

Two-step phase demodulation algorithm based on the extreme value of interference.

Using the maximum and the minimum of interference, a novel two-step phase demodulation algorithm is proposed to perform the phase extraction in phase-shifting interferometry. By means of the simulation calculation and the experimental research, it is proved that both the measured phase and the phase shift with high precision can be obtained in the proposed algorithm.

Selenium Application Enhances the Accumulation of Flavones and Anthocyanins in Bread Wheat (Triticum aestivum L.) Grains.

Selenium (Se) biofortification in wheat reduces the risk of Se deficiency in humans. Se biofortification increases the concentration of Se and anthocyanins in wheat grains. However, it is unknown whether Se biofortification can enhance flavonoids other than anthocyanins and the mechanism underlying flavonoid accumulation in wheat grains. Here, foliar application of selenite solution in wheat was conducted 10 days after flowering. Metabolite profiling and transcriptome sequencing were performed in Se-treated grains. A significant increase in the total contents of Se, anthocyanins, and flavonoids was observed in Se-treated mature grains. Twenty-seven significantly increased flavonoids were identified in Se-treated immature grains. The significant accumulation of flavones (tricin, tricin derivatives, and chrysoeriol derivatives) was detected, and six anthocyanins, dihydroquercetin (the precursor for anthocyanin biosynthesis) and catechins were also increased. Integrated analysis of metabolites and transcriptome revealed that Se application enhanced the biosynthesis of flavones, dihydroquercetin, anthocyanins, and catechins by increasing the expression levels of seven key structural genes in flavonoid biosynthesis (two TaF3Hs, two TaDFRs, one TaF3'5'H, one TaOMT, and one TaANR). Our findings shed new light on the molecular mechanism underlying the enhancement in flavonoid accumulation by Se supplementation and pave the way for further enhancing the nutritional value of wheat grains.

The effects of biogenic amines in Chinese Huangjiu on the behavior of mice and hangover headache-related indices.

Huangjiu (Chinese rice wine) is a popular and traditional alcoholic beverage in China; however, the consumption of Huangjiu readily results in hangover symptoms. The aim of this study was to identify the main components associated with behavioral inhibition, headache, and the relevant mechanisms by using a mice hangover model. The results of an open-field experiment revealed that the key biogenic amine associated with mice behavior was histamine, which inhibited the behavior activity of mice in a dose-dependent manner. Moreover, histamine treatment decreased the levels of serotonin (5-HT) and 5-hydroxyindole acetic acid. In addition, the levels of dopamine and nitric oxide, which are associated with migraine, increased in the brain tissue of mice. In addition, the expression of receptor genes of 5-HT, including Htr1a, Htr1f, and Htr2c, is essential in regulating various behaviors and mental activities. In conclusion, the present study demonstrated that histamine is a key component in Huangjiu, and it is related to hangover symptoms by affecting the level of 5-HT and its receptors.

TM9SF4 is a novel regulator in lineage commitment of bone marrow mesenchymal stem cells to either osteoblasts or adipocytes.

BACKGROUND: Osteoporosis is a common bone disease in elderly population caused by imbalanced bone formation and bone resorption. Mesenchymal stem cells (MSCs) are responsible for maintaining this bone homeostasis. The phenotype of transmembrane 9 superfamily 4 (TM9SF4) knockout mice suggests a relationship between TM9SF4 proteins and bone homeostasis. But the effect of TM9SF4 in osteology has never been reported. In the present study, we investigated the function of TM9SF4 in MSC differentiation commitment, as well as its role in osteoporosis. METHODS: Primary bone marrow MSCs, isolated from TM9SF4 wildtype (TM9SF4+/+) and knockout (TM9SF4-/-) mice, were induced to differentiate into osteoblasts or adipocytes, respectively. The osteogenesis was examined by qRT-PCR detection of osteogenic markers, ALP staining and Alizarin Red S staining. The adipogenesis was tested by qRT-PCR quantification of adipogenic markers and Oil Red O staining. The cytoskeletal organization of MSCs was observed under confocal microscope. The osteoporotic model was induced by ovariectomy in TM9SF4+/+ and TM9SF4-/- mice, followed by Toluidine blue and H&E staining to assess lipid accumulation in trabecular bones, as well as micro-computed tomography scanning and immunohistochemistry staining for bone mass density assessment. The experiments on signaling pathways were conducted using qRT-PCR, Western blot and Alizarin Red S staining. RESULTS: We determined the role of TM9SF4 in MSC differentiation and found that TM9SF4-/- MSCs had higher potential to differentiate into osteoblasts and lower capability into adipocytes, without affecting osteoclastogenesis in vitro. In ovariectomy-induced osteoporotic model, TM9SF4-/- mice retained higher bone mass and less lipid accumulation in trabecular bones, indicating an important role of TM9SF4 in the regulation of osteoporosis. Mechanistically, TM9SF4-depleted cells showed elongated actin fibers, which may act through mTORC2/Akt/ß-catenin pathway to promote their commitment into osteoblasts. Furthermore, TM9SF4-depleted cells showed higher activity of canonical Wnt pathway, suggesting the participation of Wnt/ß-catenin during TM9SF4-regulated osteogenesis. CONCLUSIONS: Our study demonstrates TM9SF4 as a novel regulator for MSC lineage commitment. Depletion of TM9SF4 preferentially drives MSCs into osteoblasts instead of adipocytes. Furthermore, TM9SF4-/- mice show delayed bone loss and reduced lipid accumulation during ovariectomy-induced osteoporosis. Our results indicate TM9SF4 as a promising target for the future clinical osteoporotic treatment.

Histone Modifications and Chondrocyte Fate: Regulation and Therapeutic Implications.

The involvement of histone modifications in cartilage development, pathology and regeneration is becoming increasingly evident. Understanding the molecular mechanisms and consequences of histone modification enzymes in cartilage development, homeostasis and pathology provides fundamental and precise perspectives to interpret the biological behavior of chondrocytes during skeletal development and the pathogenesis of various cartilage related diseases. Candidate molecules or drugs that target histone modifying proteins have shown promising therapeutic potential in the treatment of cartilage lesions associated with joint degeneration and other chondropathies. In this review, we summarized the advances in the understanding of histone modifications in the regulation of chondrocyte fate, cartilage development and pathology, particularly the molecular writers, erasers and readers involved. In addition, we have highlighted recent studies on the use of small molecules and drugs to manipulate histone signals to regulate chondrocyte functions or treat cartilage lesions, in particular osteoarthritis (OA), and discussed their potential therapeutic benefits and limitations in preventing articular cartilage degeneration or promoting its repair or regeneration.

Degradation of Axial Ultimate Load-Bearing Capacity of Circular Thin-Walled Concrete-Filled Steel Tubular Stub Columns after Corrosion.

This work aimed to investigate the effects of steel tube corrosion on the axial ultimate load-bearing capacity (AULC) of circular thin-walled concrete-filled steel tubular (CFST) members. Circular thin-walled CFST stub column specimens were made of steel tubes with various wall-thicknesses. These CFST column specimens were subjected to an accelerated corrosion test, where the steel tubes were corroded to different degrees of corrosion. Then, these CFST specimens with corroded steel tubes experienced an axial static loading test. Results show that the failure patterns of circular thin-walled CFST stub columns with corroded steel tubes are different from those of the counterpart CFST columns with ordinary wall-thickness steel tubes, which is a typical failure mode of shear bulging with slight local outward buckling. The ultimate strength and plastic deformation capacity of the CFST specimens decreased with the increasing degree of steel corrosion. The failure modes of the specimens still belonged to ductile failure because of the confinement of outer steel tube. The degree of steel tube corrosion, diameter-to-thickness ratio, and confinement coefficient had substantial influences on the AULC and the ultimate compressive strength of circular thin-walled CFST stub columns. A simple AULC prediction model for corroded circular thin-walled CFST stub columns was presented through the regression of the experimental data and parameter analysis.