The Effect of Type 2 Resistant Starch and Indole-3-Propionic Acid on Ameliorating High-Fat-Diet-Induced Hepatic Steatosis and Gut Dysbiosis.

Owing to the interplay of genetic and environmental factors, obesity has emerged as a significant global public health concern. To gain enhanced control over obesity, we examined the effects of type 2 resistant starch (RS2) and its promoted microbial-derived metabolite, indole-3-propionic acid (IPA), on hepatic steatosis, antioxidant activity, and gut microbiota in obese mice. Neither RS2 nor low-dose IPA (20 mg kg-1) exhibited a reduction in body weight or improved glucose and lipid metabolism in post-obesity state mice continuously fed the high-fat diet (HFD). However, both interventions improved hepatic steatosis, with RS2 being more effective in all measured parameters, potentially due to changes in gut microbiota and metabolites not solely attributed to IPA. LC-MS/MS analysis revealed increased serum IPA levels in both RS2 and IPA groups, which positively correlated with Bifidobacterium and Clostridium. Moreover, RS2 exhibited a more significant restoration of gut dysbiosis by promoting the abundance of health-promoting bacteria including Faecalibaculum and Bifidobacterium. These findings suggest that the regulatory role of RS2 on tryptophan metabolism only partially explains its prebiotic activity. Future studies should consider increasing the dose of IPA and combining RS2 and IPA to explore their potential interventions in obesity.

Insight into the promoted recrystallization and water distribution of bread by removing starch granule - surface and - associated proteins during storage.

The influence of starch granule surface proteins (SGSPs) and starch granule-associated proteins (SGAPs) on bread retrogradation was investigated in a reconstituted dough system. The removal of both SGSPs and SGAPs resulted in poor bread qualities, decreasing specific volume and crumb porosity, leading to more baking loss and compact crumb structure. Particularly, removing SGSPs was effective in promoting the bread retrogradation. After 7 days of storage, the hardness of bread without SGSPs showed an increase of 353.34 g than the bread without SGAPs. Proton population and relaxation times exhibited that the absence of SGSPs significantly decreased the content of bound water from 11.51 % to 7.03 %, indicating lower water-holding capacity due to the loosen gelling structure. Compared to the control group, bread without SGSPs accelerated the starch recrystallinity by a reduction in soluble starch content, thereby increasing the retrogradation enthalpy and relative crystallinity through promoting the molecular reassociation in starch.

Retrogradation behaviors of damaged wheat starch with different water contents.

The retrogradation behaviors of five damaged wheat starches (DS) after milling 0, 30, 60, 90, and 120 min with different water contents (33, 50, 60 %) were evaluated. Milling treatment increased DS content and developed an agglomeration of small particles. After 7 days of storage, the recrystallinity and long-range ordered structure of starch pastes were increased with the contents of DS and water. This process led to a lower setback viscosity and poor leaching of amylose. LF-NMR indicated a conversion from tightly bound water and free water to weakly bound water. During storage, DS12 with 60 % water content had the highest retrogradation tendency where the retrogradation enthalpy increased by 1.5 J/g and 2.2 J/g compared with DS0 with 60 % and DS12 with 33 % water content. DS with higher water content promoted the water mobility and made the starch molecular chains migrated conveniently. These changes facilitated the recrystallinity process during retrogradation period.

Anisotropic Friction in a Ligand-Protein Complex.

The effect of an externally applied directional force on molecular friction is so far poorly understood. Here, we study the force-driven dissociation of the ligand-protein complex biotin-streptavidin and identify anisotropic friction as a not yet described type of molecular friction. Using AFM-based stereographic single molecule force spectroscopy and targeted molecular dynamics simulations, we find that the rupture force and friction for biotin-streptavidin vary with the pulling angle. This observation holds true for friction extracted from Kramers' rate expression and by dissipation-corrected targeted molecular dynamics simulations based on Jarzynski's identity. We rule out ligand solvation and protein-internal friction as sources of the angle-dependent friction. Instead, we observe a heterogeneity in free energy barriers along an experimentally uncontrolled orientation parameter, which increases the rupture force variance and therefore the overall friction. We anticipate that anisotropic friction needs to be accounted for in a complete understanding of friction in biomolecular dynamics and anisotropic mechanical environments.

Emulating Titin by a Multidomain DNA Structure.

Titin, a giant protein containing multiple tandem domains, is essential in maintaining the superior mechanical performance of muscle. The consecutive and reversible unfolding and refolding of the domains are crucial for titin to serve as a modular spring. Since the discovery of the mechanical features of a single titin molecule, the exploration of biomimetic materials with titin-emulating modular structures has been an active field. However, it remains a challenge to prepare these modular polymers on a large scale due to the complex synthesis process. In this study, we propose modular DNA with multiple hairpins (MH-DNA) as the fundamental block for the bottom-up design of advanced materials. By analyzing the unfolding and refolding dynamics of modular hairpins by atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS), we find that MH-DNA shows comparable stability to those of polyproteins like titin. The unique low hysteresis of modular hairpin makes it an ideal molecular spring with remarkable mechanical efficiency. On the basis of the well-established DNA synthesis techniques, we anticipate that MH-DNA can be used as a promising building block for advanced materials with a combination of superior structural stability, considerable extensibility, and high mechanical efficiency.

Angle-dependent strength of a single chemical bond by stereographic force spectroscopy.

A wealth of chemical bonds and polymers have been studied with single-molecule force spectroscopy, usually by applying a force perpendicular to the anchoring surface. However, the direction-dependence of the bond strength lacks fundamental understanding. Here we establish stereographic force spectroscopy to study the single-bond strength for various pulling angles. Surprisingly, we find that the apparent bond strength increases with increasing pulling angle relative to the anchoring surface normal, indicating a sturdy mechanical anisotropy of a chemical bond. This finding can be rationalized by a fixed pathway for the rupture of the bond, resulting in an effective projection of the applied pulling force onto a nearly fixed rupture direction. Our study is fundamental for the molecular understanding of the role of the direction of force application in molecular adhesion and friction. It is also a prerequisite for the nanoscale tailoring of the anisotropic strength of bottom-up designed materials.

Sulfur-Mediated Polycarbonate Polyurethane for Potential Application of Blood-Contacting Materials.

In this study, a sulfur-mediated polycarbonate polyurethane (PCU-SS) is developed by mimicking the catalyzing ability of glutathione peroxidase (GPx) on nitric oxide (NO) in the human body. The PCU-SS is endowed with the capability to produce NO based on disulfide bonds, which could strongly improve the biocompatibility of the materials. The characterization results indicate that PCU-SS could not only decrease the adhesion of platelets but also enhance the capability of anti-thrombus. Moreover, it is shown that PCU-SS has a good compatibility with endothelial cells (ECs), while has a marked inhibition capacity of the proliferation of smooth muscle cells (SMCs) and macrophages (MA). Meanwhile, the result of animal implantation experiments further demonstrates the good abilities of PCU-SS on anti-inflammation, anti-thrombus, and anti-hyperplasia. Our results offer a novel strategy for the modification of blood-contacting materials based on disulfide bonds. It is expected that the PCU-SS could shed new light on biocompatibility improvement of cardiovascular stents.

Multivalent non-covalent interactions lead to strongest polymer adhesion.

Multivalent interactions play a leading role in biological processes such as the inhibition of inflammation or virus internalization. The multivalent interactions show enhanced strength and better selectivity compared to monovalent interactions, but they are much less understood due to their complexity. Here, we detect molecular interactions in the range of a few piconewtons to several nanonewtons and correlate them with the formation and subsequent breaking of one or several bonds and assign these bonds. This becomes possible by performing atomic force microcopy (AFM)-based single molecule force spectroscopy of a multifunctional polymer covalently attached to an AFM cantilever tip on a substrate bound polymer layer of the multifunctional polymer. Varying the pH value and the crosslinking state of the polymer layer, we find that bonds of intermediate strength (non-covalent), like coordination bonds, give the highest multivalent bond strength, even outperforming strong (covalent) bonds. At the same time, covalent bonds enhance the polymer layer density, increasing in particular the number of non-covalent bonds. In summary, we can show that the key for the design of stable and durable polymer coatings is to provide a variety of multivalent interactions and to keep the number of non-covalent interactions at a high level.

Preparation of phospholipid-based polycarbonate urethanes for potential applications of blood-contacting implants.

Polyurethanes are widely used in interventional devices due to the excellent physicochemical property. However, non-specific adhesion and severe inflammatory response of ordinary polyurethanes may lead to severe complications of intravenous devices. Herein, a novel phospholipid-based polycarbonate urethanes (PCUs) were developed via two-step solution polymerization by direct synthesis based on functional raw materials. Furthermore, PCUs were coated on biomedical metal sheets to construct biomimetic anti-fouling surface. The results of stress-strain curves exhibited excellent tensile properties of PCUs films. Differential scanning calorimetry results indicated that the microphase separation of such PCUs polymers could be well regulated by adjusting the formulation of chain extender, leading to different biological response. In vitro blood compatibility tests including bovine serum albumin adsorption, fibrinogen adsorption and denaturation, platelet adhesion and whole-blood experiment showed superior performance in inhibition non-specific adhesion of PCUs samples. Endothelial cells and smooth muscle cells culture tests further revealed a good anti-cell adhesion ability. Finally, animal experiments including ex vivo blood circulation and subcutaneous inflammation animal experiments indicated a strong ability in anti-thrombosis and histocompatibility. These results high light the strong anti-adhesion property of phospholipid-based PCUs films, which may be applied to the blood-contacting implants such as intravenous catheter or antithrombotic surface in the future.

Phospholipid-based multifunctional coating via layer-by-layer self-assembly for biomedical applications.

As an important class of biomaterials，bionics inspired materials has been widely used in creating extracorporeal and implantable medical devices. However, specific service environment is often faced with multiple requirements rather than single function. Herein, we designed a phospholipid-based multifunctional coating with phospholipids-based polymers, type I collagen (Col-I) and Arg-Glu-Asp-Val (REDV) peptide, via layer-by-layer assembly. The successful synthesis of the polymers and the coating is proved by a series of characterization methods including Fourier transforming infrared spectra (FTIR), proton nuclear magnetic resonance (1H NMR), ultraviolet-visible spectra (UV) and X-ray photoelectron spectroscopy (XPS), while the assembly process and quality change of the coating were monitored via quartz crystal microbalance (QCM). Besides, hydrophilicity and roughness of this coating was analyzed via water contact angle (WCA) and atomic force microscope (AFM), respectively. Finally, results from platelet adhesion, activation assay, smooth muscle cells (SMCs) and endothelial cells (ECs) cultures indicated that the multifunctional coating could strongly inhibit platelet adhesion and SMCs proliferation, hence provide practical application of the coating with good biocompatibility, especially the anticoagulant property and cell compatibility. It is expected that this coating may be used in blood-contacting fields such as cardiovascular stent or other devices in the future.

Force-Induced Transition of π-π Stacking in a Single Polystyrene Chain.

Although π-π interactions have been studied for several decades, the quantification of the strength of π-π interactions in a macromolecule remains a big challenge. Herein, we utilize single-molecule atomic force microscopy and steered molecular dynamics simulations to study the π-π interactions in polystyrene (PS). It is found that in high vacuum, the single-chain mechanics of PS differs largely from that of polyethylene (PE). Accordingly, the strength of intrachain π-π interactions in PS is estimated to be 0.7 kcal/(mol stack), which is much lower than that in a small-molecule system (benzene dimer, 2-3 kcal/(mol stack)). Further study shows that in high vacuum, there are two types of π-π stacking in the single PS chain, i.e., the every-other-moiety (E) type and the adjacent-moiety (A) type. Upon force stretching, a transition from E-type to A-type π-π stacking can be observed.