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Masquelet technique demonstrated superiority in reconstructing long bone defect after trauma or infection. However, reports in foot tumor were rare. A 24-year-old male diagnosed with calcaneal chondroblastoma who had a defect of calcaneal after intralesional curettage. We reconstructed the defect by Masquelet technique. This is the first case as far as we know that reported Masquelet technique for calcaneal tumor. The technique to treat irregular bone defects after operation can be considered in other similar situations. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no cure. Huge efforts have been made to develop anti‐AD drugs in the past decades. However, all drug development programs for disease‐modifying therapies have failed. Possible reasons for the high failure rate include incomplete understanding of complex pathophysiology of AD, especially sporadic AD (sAD), and species difference between humans and animal models used in preclinical studies. In this study, sAD is modeled using human induced pluripotent stem cell (hiPSC)‐derived 3D brain organoids. Because the blood–brain barrier (BBB) leakage is a well‐known risk factor for AD, brain organoids are exposed to human serum to mimic the serum exposure consequence of BBB breakdown in AD patient brains. The serum‐exposed brain organoids are able to recapitulate AD‐like pathologies, including increased amyloid beta (Aβ) aggregates and phosphorylated microtubule‐associated tau protein (p‐Tau) level, synaptic loss, and impaired neural network. Serum exposure increases Aβ and p‐Tau levels through inducing beta‐secretase 1 (BACE) and glycogen synthase kinase‐3 alpha / beta (GSK3α/β) levels, respectively. In addition, single‐cell transcriptomic analysis of brain organoids reveals that serum exposure reduced synaptic function in both neurons and astrocytes and induced immune response in astrocytes. The human brain organoid‐based sAD model established in this study can provide a powerful platform for both mechanistic study and therapeutic development in the future. [ABSTRACT FROM AUTHOR]

Gum arabic (GA) is the most widely used natural emulsifier in food industry. However, due to its high price and unstable market supply, the search for substitutes of gum arabic has attracted the attention of researchers. Recent studies have shown that sugar beet pectin (SBP) has great potential as a natural emulsifier. However, the mechanisms and differences of GA- and SBP-stabilized emulsions are still unclear. In this study, the interfacial behavior of GA and SBP on the oil-water interface was studied and compared through dissipative quartz crystal microbalance and interfacial dilatational rheology. Then, droplet size, zeta-potential and viscosity of the emulsion stabilized by GA and SBP were measured. Meanwhile, the long-term stability of GA- and SBP-stabilized emulsions was evaluated and compared through a LUMiSizer stability analyzer. The study showed that at the same concentration, SBP-stabilized emulsion had significant advantages of a smaller droplet size, a larger viscosity, a thicker and more elastic interfacial layer, and better long-term stability. A comparison of the long-term stability of SBP2.0%- and GA15.0%-stabilized emulsions, evidenced that the elasticity of the interfacial layer plays a crucial role in the long-term stability of emulsions. This research may provide useful information for finding alternatives to GA. [Display omitted] • SBP and GA forms different interfacial layers at oil-in-water interface. • Elasticity of interfacial layer is crucial to long-term stability of emulsion. • SBP may be a good alternative to GA. [ABSTRACT FROM AUTHOR]

The epidermal growth factor (EGF) receptor (EGFR) pathway is one of the most dysregulated and extensively investigated signaling pathways in human cancers and plays important roles in the regulation of nuclear functions through both cytoplasmic and nuclear EGFR pathways. However, the current understanding of the nuclear phosphorylation responses to activated EGFR pathways remains limited. In the present study, phosphoproteomics analysis revealed the increased phosphorylation of 90 nuclear proteins, primarily involved in RNA processing, pre-mRNA splicing and cell cycle regulation, upon EGF stimulation in MDA-MB-468 cells. Cellular splicing assays of the β-globin (HBB) minigene confirmed that EGF induced constitutive pre-mRNA splicing. Further analysis of phosphoproteomics data identified multiple CDK1/2 substrates in pre-mRNA splicing-related proteins, and both CDK1/2 inhibitors and CDK1/2 knockdowns reduced EGF-regulated pre-mRNA splicing. In conclusion, the results of the present study provide evidence that CDK1/2 participate in the regulation of constitutive pre-mRNA splicing by EGF stimulation in MDA-MB-468 cells. Significance In this study, we successfully carried out a survey of nuclear phosphorylation changes in response to EGF stimulation. The results from the functional category analysis and pre-mRNA splicing assay strongly indicated that EGFR activation increased constitutive pre-mRNA splicing in MDA-MB-468 cells, revealing additional role of EGFR on regulation of mRNA maturation beyond alternative pre-mRNA splicing reported by previous studies. Furthermore, we found that CDK1/2 participated in constitutive pre-mRNA splicing regulation by EGF in MDA-MB-468 cells. Our study provides new knowledge for understanding the regulation of constitutive pre-mRNA splicing by EGF stimulation. [ABSTRACT FROM AUTHOR]

Mammalian target of rapamycin complex 1 (mTORC1) plays important roles in regulating cell growth and proliferation, and the aberrant activation of mTORC1 has been observed in many human diseases. However, the proteins regulated by mTORC1 activation and their roles in mTORC1 downstream functions are still poorly understood. Using proteomic analysis, we found that proteins regulated by mTORC1 in MEFs could be categorized into eight functional groups including protein nuclear import and glycolysis. The positive regulation of Karyopherin subunit alpha-2 (KPNA2), an importer protein involved in protein nuclear import, by mTORC1 was verified in several other mouse and human cell lines. The regulation occurred at the transcriptional level, rather than at the level of S6K1- and 4E-BP1-dependent protein synthesis. KPNA2 knockdown partially blocked upregulation of glycolytic genes by mTORC1 activation, indicating that mTORC1 activation enhanced expression of glycolytic genes by increasing KPNA2 abundances. Furthermore, KPNA2 knockdown had no effects on the expression and subcellular localization of HIF1α, a transcription factor involved in regulating glycolytic genes downstream of mTORC1. In conclusion, our results proved that KPNA2 regulated the expression of glycolytic genes downstream of mTORC1 in a HIF1α-independent manner. Significance Identifying mTORC1-regulated proteins through proteomic method is a feasible way to study the downstream functions of mTORC1. In this study, we identified many mTORC1-regulated proteins using proteomic analysis by overlapping two different high vs low/no mTORC1 activity comparisons, TSC2 −/− vs WT MEFs and TSC2 −/− with/without rapamycin treatment. We found the abundances of many enzymes in glycolysis pathway and several proteins involved in protein nuclear import were positively regulated by mTORC1. More importantly, we first discovered that mTORC1 positively regulated the importer protein KPNA2, which participated in glycolysis regulation downstream of mTORC1 in a HIF1α-independent manner, indicating that mTORC1 regulates glycolysis through multiple ways. [ABSTRACT FROM AUTHOR]

In this paper, the discrete-time mathematical model for tissue inflammation obtained by Euler is investigated in detail. Conditions of the existence for fold bifurcation, flip bifurcation and Hopf bifurcation are derived by using center manifold theorem and bifurcation theory, and chaos in the sense of Marotto is proved by analytical method. Numerical simulations, including bifurcation diagrams, Lyapunov exponents, fractal dimensions, and phase portraits are plotted to perfectly show the consistence with the theoretical analysis. [ABSTRACT FROM AUTHOR]

In this study, structural characterization and chemical compositions of three pectins from different sources were studied, which showed that compared with apple pectin (AP) and citrus peel pectin (CPP), sugar beet pectin (SBP) has higher protein contents, feruloylated groups, acetyl groups and more hairy regions. Molecular dynamics simulations showed that HG domain was tiled on the oil-water interface, while RG-Ⅰ and RG-Ⅱ domains were adsorbed on the oil-water interface in a folded form, resulting in a thick viscoelastic film. Dissipative quartz crystal microbalance (QCM-D) and dilatational rheology studies showed that under high-concentration and acidic conditions, pectin molecules were adsorbed in multiple layers at the oil-water interface, forming a thicker viscoelastic film, which was crucial for the long-term stability of pectin-stabilized emulsions. [Display omitted] • HG domain was tiled on the oil-water interface. • RG-Ⅰ and RG-Ⅱ domains adsorbed on the oil-water interface in a folded form. • Pectin molecules adsorbed in multiple layers under acidic conditions. [ABSTRACT FROM AUTHOR]

Pendulum equation with a phase shift, parametric and external excitations is investigated in detail. By applying Melnikov's method, we prove the criteria of existence of chaos under periodic perturbation. Numerical simulations, including bifurcation diagrams of fixed points, bifurcation diagrams of the system in three- and two-dimensional spaces, homoclinic and heteroclinic bifurcation surfaces, Maximum Lyapunov exponents (ML), Fractal Dimension (FD), phase portraits, Poincaré maps are plotted to illustrate the theoretical analysis, and to expose the complex dynamical behaviors including the onset of chaos, sudden conversion of chaos to period orbits, interior crisis, periodic orbits, the symmetry-breaking of periodic orbits, jumping behaviors of periodic orbits, new chaotic attractors including two-three-four-five-six-eight-band chaotic attractors, nonchaotic attractors, period-doubling bifurcations from period-1, 2, 3 and 5 to chaos, reverse period-doubling bifurcations from period-3 and 5 to chaos, and so on. By applying the second-order averaging method and Melnikov's method, we obtain the criteria of existence of chaos in an averaged system under quasi-periodic perturbation for Ω = nω + ϵν, n = 1, 2, 4, but cannot prove the criteria of existence of chaos in the averaged system under quasi-periodic perturbation for Ω = nω + ϵν, n = 3, 5 - 15, by Melnikov's method, where ν is not rational to ω. By using numerical simulation, we have verified our theoretical analysis and studied the effect of parameters of the original system on the dynamical behaviors generated under quasi-periodic perturbations, such as the onset of chaos, jumping behaviors of quasi-periodic orbits, interleaving occurrence of chaotic behaviors and nonchaotic behaviors, interior crisis, quasi-periodic orbits to chaotic attractors, sudden conversion of chaos to quasi-periodic behaviors, nonchaotic attractors, and so on. However, we did not find period-doubling and reverse period-doubling bifurcations. We found that the dynamical behaviors under quasi-periodic perturbations are different from that under periodic perturbations, and the dynamics with a phase shift are different from the dynamics without phase shift. [ABSTRACT FROM AUTHOR]

Abstract In recent years, RG-I pectin isolated by low-temperature alkaline extraction methods has attracted the attention of a large number of researchers due to its huge health benefits. However, studies on other applications of RG-I pectin are still lacking. In this study, we summarized the sources (e.g. potato pulp, sugar beet pulp, okra, apple pomace, citrus peel, pumpkin, grapefruit, ginseng, etc.), extraction methods, fine structure and applications of RG-I pectin in physiological activities (e.g. anti-cancer, anti-inflammatory, anti-obesity, anti-oxidation, immune regulation, prebiotics, etc.), emulsions, gels, etc. These neutral sugar side chains not only endow RG-I pectin with various physiological activities but the entanglement and cross-linking of these side chains also endow RG-I pectin with excellent emulsifying and gelling properties. We believe that this review can not only provide a comprehensive reading for new workers interested in RG-I pectin, but also provide a valuable reference for future research directions of RG-I pectin. [ABSTRACT FROM AUTHOR]

Pin1, a peptide prolyl cis-trans isomerase, is overexpressed and/or overactivated in many human malignancies. However, whether Pin1 regulates the immunosuppressive TME has not been well defined. In this study, we detected the effect of Pin1 on immune cells and immune checkpoint PD-L1 in the TME of CRC and explored the anti-tumor efficacy of Pin1 inhibitor ATRA combined with PD-1 antibody. We found that Pin1 facilitated the immunosuppressive TME by raising the proportion of myeloid-derived suppressor cells (MDSCs) and declining the percentage of CD8+ T cells and CD4+ T cells. Pin1 restrained PD-L1 protein expression in CRC cells and the effect was tempered by endoplasmic reticulum (ER) stress inducers. Mechanically, Pin1 overexpression decreased the stability of PD-L1 and promoted its degradation by mitigating ER stress. Silencing or inhibiting Pin1 promoted PD-L1 protein expression by inducing ER stress. Hence, Pin1 inhibitor ATRA enhanced the anti-tumor efficacy of PD-1 antibody in the CRC allograft by upregulating PD-L1. Our results reveal the critical and pleiotropic effects of Pin1 on managing the immune cells and immune checkpoint PD-L1 in the TME of CRC, providing a new promising candidate for combination with immunotherapy. [Display omitted] • Pin1 facilitates immunosuppressive TME by managing immune cells in CRC. • Pin1 promotes PD-L1 degradation by mitigating ER stress. • Inhibition of Pin1 enhances the therapeutic efficacy of the PD-1 antibody. [ABSTRACT FROM AUTHOR]

Previous studies have shown that Mesona chinensis Benth polysaccharide (MP) has a variety of physiological activities, including anti-inflammation, anti-oxidation, immune regulation, etc. In addition, MP can also enhance the gel properties of starch. However, there are few reports about the interfacial properties and long-term emulsion stability of MP. In this study, we measured adsorption kinetics of MP molecules on the oil-water interface, interfacial viscoelasticity and adsorption mass, interfacial film thickness, the resistance of the interfacial film to external perturbations, and droplet size, zeta-potential, viscosity and long-term stability of MP-stabilized emulsion under different pH values. The results represented that MP could form much thicker and more elastic interfacial films on the oil-water interface under pH7 and pH9 conditions than that under pH5 condition. Besides, this interfacial film has stronger resistance to external perturbations, which is very significant for the long-term emulsion stability. This study explores the stability mechanism and application of MP in emulsion, which has a positive effect on expanding the application scene and scope of MP. [Display omitted] • Highly elastic interfacial films have greater resistance to external perturbations. • PH influences the stability and rheological behavior of MP-stabilized emulsion. • Elasticity of interfacial layer is crucial to long-term stability of emulsion. • MP-stabilized emulsion at pH7 and pH9 has better stability than that at pH5. [ABSTRACT FROM AUTHOR]

[Display omitted] • The Pueraria lobata polysaccharide (PLP) was degraded by ultrasound irradiation. • The degradation process of PLP followed to the midpoint fracture model. • The degraded PLP fractions with lower Mw exhibited better bioactivities. • PLPs may protect against oxidative stress through the Nrf2/Keap1 pathway. In this study, a high-molecular-weight Pueraria lobata polysaccharide (PLP) with a molecular weight of 273.54 kDa was degraded by ultrasound, and the ultrasonic degradation kinetics, structural characteristics and hepatoprotective activity of ultrasonic degraded PLP fractions (PLPs) were evaluated. The results showed that the ultrasonic treatment significantly reduced the Mw and particle size of PLP, and the kinetic equation of ultrasonic degradation of PLP followed to the midpoint fracture model (the fist-order model). The monosaccharide composition analysis, FT-IR, triple helix structure and XRD analysis all indicated that the ultrasound degradation did not destroy the primary structure of PLP, but the thermal stability of degraded fractions improved. Additionally, the scanning electron microscopy analysis demonstrated that the surface morphology of PLP was altered from smooth, flat, compact large flaky structure to a sparse rod-like structure with sparse crosslinking (PLP-7). The degraded PLP fractions (0.5 mg/mL) with lower Mw exhibited better antioxidant activities and protective effects against palmitic acid-induced hepatic lipotoxicity, which may be due to the increased exposure of active groups such as hydroxyl groups of PLP after ultrasound. Further investigation showed that PLPs not only increased Nrf2 phosphorylation and its nuclear translocation, thereby activating Nrf2/Keap1 signaling pathway, but also enhanced HO-1, NQO-1, γ-GCL gene expressions and promoted superoxide dismutase and catalase activities, which protected hepatocytes against PA-induced oxidative stress and lipotoxicity. Overall, our research might provide an in-depth insight into P. Lobata polysaccharide in ameliorating lipid metabolic disorders, and the results revealed that ultrasonic irradiation could be a promising degradation method to produce value-added polysaccharide for use in functional food. [ABSTRACT FROM AUTHOR]

Canavan disease (CD) is a fatal leukodystrophy caused by mutation of the aspartoacylase (ASPA) gene, which leads to deficiency in ASPA activity, accumulation of the substrate N‐acetyl‐L‐aspartate (NAA), demyelination, and spongy degeneration of the brain. There is neither a cure nor a standard treatment for this disease. In this study, human induced pluripotent stem cell (iPSC)‐based cell therapy is developed for CD. A functional ASPA gene is introduced into patient iPSC‐derived neural progenitor cells (iNPCs) or oligodendrocyte progenitor cells (iOPCs) via lentiviral transduction or TALEN‐mediated genetic engineering to generate ASPA iNPC or ASPA iOPC. After stereotactic transplantation into a CD (Nur7) mouse model, the engrafted cells are able to rescue major pathological features of CD, including deficient ASPA activity, elevated NAA levels, extensive vacuolation, defective myelination, and motor function deficits, in a robust and sustainable manner. Moreover, the transplanted mice exhibit much prolonged survival. These genetically engineered patient iPSC‐derived cellular products are promising cell therapies for CD. This study has the potential to bring effective cell therapies, for the first time, to Canavan disease children who have no treatment options. The approach established in this study can also benefit many other children who have deadly genetic diseases that have no cure. [ABSTRACT FROM AUTHOR]

Emulsions are multiscale and thermodynamically unstable systems which will undergo various unstable processes over time. The behavior of emulsifier molecules at the oil-water interface and the properties of the interfacial film are very important to the stability of the emulsion. In this paper, we mainly discussed the instability phenomena and mechanisms of emulsions, the effects of interfacial films on the long-term stability of emulsions and summarized a set of systematic multiscale combined methods for studying emulsion stability, including droplet size and distribution, zeta-potential, the continuous phase viscosity, adsorption mass and thickness of the interfacial film, interfacial dilatational rheology, interfacial shear rheology, particle tracking microrheology, visualization technologies of the interfacial film, molecular dynamics simulation and the quantitative evaluation methods of emulsion stability. This review provides the latest research progress and a set of systematic multiscale combined techniques and methods for researchers who are committed to the study of oil-water interface and emulsion stability. In addition, this review has important guiding significances for designing and customizing interfacial films with different properties, so as to obtain emulsion-based delivery systems with varying stability, oil digestibility and bioactive substance utilization. [Display omitted] • A set of systematic techniques and methods for the study of oil-water interface were presented. • Structure-induced self-assembly of emulsifier molecules at the oil-water interface is critical for the long-term stability of emulsions. • Emulsion-based delivery systems with varying stability, oil digestibility and bioactive substance utilization can be obtained based on the design and customization of the interfacial film. [ABSTRACT FROM AUTHOR]

Autophagy has been referred to as a double-edged sword in tumorigenesis and tumor progression. Emerging evidence suggests that pharmacological modulation of autophagy is a promising therapeutic strategy for cancer. However, few autophagy-modulating compounds are currently approved for clinical use in humans. Matrine is a natural compound extracted from traditional Chinese medicine that is widely used for treatment of a variety of diseases without any obvious side effects. Recently, matrine has been reported to induce autophagy and autophagic cell death in cancer cells, although the underlying mechanisms have yet to be elucidated. Here, we systematically examined the autophagic events induced by matrine in SGC7901 cells. The accumulation of autophagic vacuoles in matrine-treated cells was verified by the conversion of microtubule-associated protein light chain 3 as well as confocal and transmission electron microscopy. Furthermore, we demonstrated that matrine blocked autophagic degradation by impairing the activities of lysosomal proteases. Moreover, confocal microscopy and gradient ultracentrifugation revealed that the trafficking processes and proteolytic activation of cathepsins were inhibited by matrine. Using a pH sensor probe, we found elevated pH values in endosomes/lysosomes in response to matrine treatment. Therefore, matrine seems to be a novel autophagy inhibitor that can modulate the maturation process of lysosomal proteases. [ABSTRACT FROM PUBLISHER]