pH-Triggered Release of Hydrophobic Molecules from Self-Assembling Hybrid Nanoscaffolds

Self-assembling peptide based hydrogels have a wide range of applications in the field of tissue repair and tissue regeneration. Because of its physicochemical properties, (RADA)₄ has been studied as a potential platform for 3D cell culture, drug delivery, and tissue engineering. Despite some small molecule and protein release studies with this system, there is a lack of work investigating the controlled release of hydrophobic compounds (i.e., anti-inflammatory, anticancer, antibacterial drugs, etc.) that are important for many clinical therapies. Attempts to incorporate hydrophobic compounds into self-assembling matrices usually inhibited nanofiber formation, rather resulting in a peptide–drug complex or microcrystal formation. Herein, a self-assembling chitosan/carboxymethyl-β-cyclodextrin nanoparticle system was used to load dexamethasone, which formed within a self-assembling (RADA)₄ nanoscaffold matrix. Nanoparticles dispersed within the matrix were stabilized by the nanofibers within. The in vitro release of dexamethasone from the hybrid system was observed to be pH sensitive. At pH 7, release was observed for more than 8 days, with three distinct kinetic domains in the first 6 days. Data suggest that the deprotonation of chitosan at a solution pH > 6.8 leads to nanoparticle dissociation and ultimately the release of dexamethasone from the hybrid system. This system has the potential to form a multifunctional scaffold that can self-assemble with the ability to control the release of hydrophobic drugs for a wide variety of applications

Characterizing the input and output relationship of IBRP assay using Arl1/GRIP interaction.

<p>(a) Quantification of the input of GST-GRIP used in this study by Coomassie staining. GST-GRIP bead slurry in preparation a, b and c was semi-quantified as 3, 6 and 9 µg/µl, respectively. BSA, bovine serum albumin. (b-d) The assay was conducted using a combination of various inputs of GST-GRIP (bait) and Arl1-GFP (prey). The number of beads quantified (n) for each data point is in between 95 and 141. The same set of data are plotted in three different formats to illustrate the input and output relationship. (b) The linear relationship between the output signal (relative intensity per bead) and the input of Arl1-GFP (relative intensity of the cell lysate). R indicates the R-square values for linear fitting. Error bars represent standard deviations. (c) The linear relationship between the output signal (relative intensity per bead) and the input of GST-GRIP (µg/µl). (d) The relative IBRP affinity, input of Arl1-GFP and input of GST-GRIP are plotted in a 3D graph. The mean±standard deviation of the relative IBRP affinity is 90±10 (n = 12).</p

Low-Dose Trypsin Accelerates Wound Healing <i>via</i> Protease-Activated Receptor 2

The management of wounds remains a significant healthcare challenge, highlighting the need for effective wound healing strategies. To address this, it is crucial to explore the molecular mechanisms underlying tissue repair as well as explore potential therapeutic approaches. Trypsin, as a serine protease, has been clinically utilized for wound healing for decades; however, it still lacks systemic investigation on its role and related mechanism. This study aimed to investigate the effects of low-dose trypsin on wound healing both in vitro and in vivo. While trypsin is an endogenous stimulus for protease-activated receptor 2 (PAR2), we discovered that both low-dose trypsin and synthesized PAR2 agonists significantly enhanced the migration, adhesion, and proliferation of fibroblasts and macrophages, similar to the natural repair mechanism mediated by mast cell tryptase. Moreover, such cell functions induced by trypsin were largely inhibited by PAR2 blockade, indicating the participation of trypsin via PAR2 activation. Additionally, low-dose trypsin notably expedited healing and regeneration while enhancing collagen deposition in skin wounds in vivo. Importantly, upon stimulation of trypsin or PAR2 agonists, there were significant upregulations of genes including claudin-7 (Cldn7), occludin (Ocln), and interleukin-17A (IL-17A) associated with proliferation and migration, extracellular matrix (ECM), tight junction, and focal adhesion, which contributed to wound healing. In summary, our study suggested that a low-dose trypsin could be a promising strategy for wound healing, and its function was highly dependent on PAR2 activation

DataSheet1_Environmental regulations, GHRM and green innovation of manufacturing enterprises: evidence from China.docx

The contradiction between the economy and the environment is becoming more and more prominent. Green innovation is significant for Chinese manufacturing enterprises considering environmental and economic performance. Based on motivation theory and motivation crowding theory, this study aims to explore the impact of environmental regulations on green innovation of Chinese manufacturing enterprises and the mediating role of green human resource management between environmental regulations and green innovation of enterprises. Using structural equation modeling and SPSS macro, the results of the empirical analysis of 127 manufacturing enterprises in Guangdong Province, China, show that command-controlled regulation, market-incentivized regulation, and voluntary regulation positively impact enterprises’ green innovation, and green human resource management positively affects enterprises’ green innovation. Green human resource management only mediates the relationship between voluntary environmental regulation and green innovation. The study systematically reveals the driving mechanism of green innovation in Chinese manufacturing enterprises and enriches the relevant research on green innovation in manufacturing enterprises.</p

Studying the interaction between furin cytosolic domain and clathrin adaptor proteins AP1 and 2 using IBRP assay.

<p>The bead immobilized GST-furin (2 µg/µl) or GST (3 µg/µl, as a negative control) were served as baits to pull down cell lysate containing σ2-GFP, σ1-GFP and GFP (as a negative control). The relative IBRP affinities were calculated and plotted. GST-furin, but not GST, selectively binds σ2-GFP and σ1-GFP. Error bars represent standard deviations. n indicates the number of beads quantified. p indicates the p value of selected pair calculated by t-test.</p

Studying the interaction of Arl1/GRIP by using GST-GRIP as bait and Arl1-GFP as prey in IBRP assay.

<p>(a) GST-GRIP or Y2177A mutant was immobilized onto beads at 16 µg/µl. The beads were incubated with the cell lysate containing Arl1-GFP (in the presence of 100 µM GMPPNP or GDP) or GFP (as a negative control) and imaged under phase contrast (left column) or fluorescence (right column) setting. In the right column, the fluorescence images were linearly scaled for a fair visual comparison of intensity. Scale bar, 100 µm. (b) Relative IBRP affinity of each interaction. Error bars represent standard deviations. n indicates the number of beads quantified. p indicates the p value of selected pair calculated by t-test.</p

Studying the interaction of Arl1/GRIP by using GST-Arl1 as bait and GFP-GRIP as prey in IBRP assay.

<p>GST-Arl1 immobilized on beads (13 µg/µl) was loaded with either GMPPNP or GDP. The beads were incubated with cell lysate containing the following GFP-prey: GFP-GRIP, GFP-GRIP Y2177A or GFP (as a negative control). Relative IBRP affinities were culaculated and plotted. Error bars represent standard deviations. n indicates the number of beads quantified. p indicates the p value of selected pair calculated by t-test.</p

Generating masks for IBRP assay.

<p>(a) A method to mask individual beads using ImageJ. The masks are shown as magenta circles labeled with numbers. (b) The resulted masks are overlaid onto fluorescence and phase contrast images of the same beads. The masks are found to match the physical contour of the corresponding beads.</p

Acceptorless Dehydrogenative Coupling of <i>o</i>‑Aminobenzamides with the Activation of Methanol as a C1 Source for the Construction of Quinazolinones

A strategy for the synthesis of quinazolinones via acceptorless coupling of <i>o</i>-aminobenzamides with methanol has been accomplished in the presence of the metal–ligand bifunctional catalyst [Cp*Ir­(2,2′-bpyO)­(H₂O)]. Notably, this research exhibited the potential of transition-metal-catalyzed activation of methanol as a C1 source for the construction of heterocycles

Descriptive summary.

In a dynamic and competitive business environment, managerial ability emerges as a pivotal strategic factor for capitalizing on new opportunities within the technological revolution and digital transformation of enterprises. Based on data from Chinese A-share listed firms spanning from 2009 to 2019, this study integrates insights from the upper echelons theory and the behavioral theory of the firm to investigate the moderating roles of historical aspiration shortfalls and industrial competitiveness on the relationship between managerial ability and enterprise digital transformation from internal and external pressure perspectives. Our findings indicate a positive impact of managerial ability on digital transformation. The relationship between managerial ability and digital transformation is reinforced by historical aspiration shortfalls; nevertheless, industrial competitiveness has attenuated the aforementioned relationship. This study contributes to a better understanding of the strategic implications of managerial ability within the context of organizational innovation strategies. It offers valuable insights into the decision-making processes of firms as they navigate the challenges of digital transformation within an ever-evolving business environment.</div