Inhibition of SENP2-mediated Akt deSUMOylation promotes cardiac regeneration via activating Akt pathway.

Post-translational modification (PTM) by small ubiquitin-like modifier (SUMO) is a key regulator of cell proliferation and can be readily reversed by a family of SUMO-specific proteases (SENPs), making SUMOylation an ideal regulatory mechanism for developing novel therapeutic strategies for promoting a cardiac regenerative response. However, the role of SUMOylation in cardiac regeneration remains unknown. In the present study, we assessed whether targeting protein kinase B (Akt) SUMOylation can promote cardiac regeneration. Quantitative PCR and Western blotting results showed that small ubiquitin-like modifier-specific protease 2 (SENP2) is up-regulated during postnatal heart development. SENP2 deficiency promoted P7 and adult cardiomyocyte (CM) dedifferentiation and proliferation both in vitro and in vivo. Mice with SENP2 deficiency exhibited improved cardiac function after MI due to CM proliferation and angiogenesis. Mechanistically, the loss of SENP2 up-regulated Akt SUMOylation levels and increased Akt kinase activity, leading to a decrease in GSK3ß levels and subsequently promoting CM proliferation and angiogenesis. In summary, inhibition of SENP2-mediated Akt deSUMOylation promotes CM differentiation and proliferation by activating the Akt pathway. Our results provide new insights into the role of SUMOylation in cardiac regeneration.

A Piezoelectric Wave-Energy Converter Equipped with a Geared-Linkage-Based Frequency Up-Conversion Mechanism.

In this paper, a piezoelectric wave-energy converter (PWEC), consisting of a buoy, a frequency up-conversion mechanism, and a piezoelectric power-generator component, is developed. The frequency up-conversion mechanism consists of a gear train and geared-linkage mechanism, which converted lower frequencies of wave motion into higher frequencies of mechanical motion. The slider had a six-period displacement compared to the wave motion and was used to excite the piezoelectric power-generation component. Therefore, the operating frequency of the piezoelectric power-generation component was six times the frequency of the wave motion. The developed, flexible piezoelectric composite films of the generator component were used to generate electrical voltage. The piezoelectric film was composed of a copper/nickel foil as the substrate, lead-zirconium-titanium (PZT) material as the piezoelectric layer, and silver material as an upper-electrode layer. The sol-gel process was used to fabricate the PZT layer. The developed PWEC was tested in the wave flume at the Tainan Hydraulics Laboratory, Taiwan (THL). The maximum height and the minimum period were set to 100 mm and 1 s, respectively. The maximum voltage of the measured value was 2.8 V. The root-mean-square (RMS) voltage was 824 mV, which was measured through connection to an external 495 kΩ resistive load. The average electric power was 1.37 µW.

Optimized Synthesis and Antioxidant Activity of Anthocyanins Delphinidin-3-O-glucoside and Petunidin-3-O-glucoside.

The chemical synthesis of anthocyanins, especially delphinidin-3-O-glucoside and petunidin-3-O-glucoside, is preferable due to the challenges associated with their extraction and purification. However, the reported methods for the synthesis are scarce and intricate. Our research focused on exploring a one-step ester-to-ketone process and optimizing the ring formation reaction, simplifying and improving the overall synthesis strategy. Through these attempts, we were able to achieve higher production yields of delphinidin-3-O-glucoside and petunidin-3-O-glucoside. According to the results of DPPH, ABTS, and FRAP, the antioxidant activity of anthocyanins was increased with the number of B ring hydroxyl substituent. Additionally, both delphinidin-3-O-glucoside and petunidin-3-O-glucoside exhibited no cytotoxicity effects, highlighting their potential for safe application in various fields.

Lactobacillus fermentation accelerated biotransformation of cranberry anthocyanins towards phenol-pyranoanthocyanins and their stability and antioxidant property.

Phenol-pyranoanthocyanins, a structurally modified type of anthocyanin, has higher stability than anthocyanins. However, their conversion occurs slowly. Therefore, it is crucial to improve the conversion efficiency and production of pyranoanthocyanins. In this study, cranberry anthocyanin (CRAN) was fermented using two Lactobacillus strains along with caffeic acid to form cranberry-derived pyranoanthocyanins (PY-CRAN). PY-CRAN was characterized and identified. The physicochemical properties, antioxidant activity, and tyrosinase inhibitory capacity of PY-CRAN were assessed. The results showed that phenol-pyranoanthocyanins can be rapidly produced through fermentative transformation using Lactiplantibacillus plantarum and Lacticaseibacillus paracasei. Lacticaseibacillus paracasei exhibits a higher propensity for producing phenol-pyranoanthocyanins. PY-CRAN exhibits high stability under light and various pH conditions. Moreover, they possess excellent antioxidant properties and the ability to inhibit tyrosinase. These results suggest that fermentative biotransformation conducted by Lactobacillus is an ideal method for producing cranberry pyranoanthocyanins. The resulting anthocyanins have potential as antioxidant and whitening agents, making them promising bioactive ingredients.

Anthocyanins degradation mediated by ß-glycosidase contributes to the color loss during alcoholic fermentation in a structure-dependent manner.

Anthocyanins deteriorate during fermentation to varying degrees depending on the structure of the anthocyanin, thus affecting the sensory quality of the wine, and the degradation of anthocyanins is closely associated with the ß-glycosidase. In this study, the alcoholic fermentation systems containing cyanidin-3-O-glucoside (C3G), peonidin-3-O-glucoside (Pn3G), delphinidin-3-O-glucoside (D3G), petunidin-3-O-glucoside (Pt3G), and malvidin-3-O-glucoside (M3G) incubated for eight days. Our results indicated that the color of the systems containing different anthocyanins saw significant and dissimilar changes during fermentation, in relation to anthocyanin degradation. The five anthocyanins showed varying degradation degrees, which are relevant to theß-glycosidase produced by yeast. Enzyme kinetics and molecular docking analysis showed the affinity between anthocyanins and ß-glucosidase: C3G < M3G < Pn3G < Pt3G < D3G. This study demonstrated that ß-glycosidase had distinct effects on anthocyanins with diverse structures, resulting in different color changes in fermentation systems. It provided a potential strategy for sensory quality improvement during the fermentation of fruit wines rich in anthocyanins.

Selective Iodination Enables Anthocyanin Synthesis to Be More General.

The current synthesis routes of anthocyanins are relatively complicated, which significantly hinders their development. We optimized the method by introducing a selective iodination reaction and also established a general scheme for preparing anthocyanin diglycosides. This method allows anthocyanin synthesis to require fewer steps and costs. Based on this, we prepared four common anthocyanins and two anthocyanin diglucosides and measured their antioxidant and anti-insulin resistance activities.

LDHA-mediated metabolic reprogramming promoted cardiomyocyte proliferation by alleviating ROS and inducing M2 macrophage polarization.

AIMS: Metabolic switching during heart development contributes to postnatal cardiomyocyte (CM) cell cycle exit and loss of regenerative capacity in the mammalian heart. Metabolic control has potential for developing effective CM proliferation strategies. We sought to determine whether lactate dehydrogenase A (LDHA) regulated CM proliferation by inducing metabolic reprogramming. METHODS AND RESULTS: LDHA expression was high in P1 hearts and significantly decreased during postnatal heart development. CM-specific LDHA knockout mice were generated using CRISPR/Cas9 technology. CM-specific LDHA knockout inhibited CM proliferation, leading to worse cardiac function and a lower survival rate in the neonatal apical resection model. In contrast, CM-specific overexpression of LDHA promoted CM proliferation and cardiac repair post-MI. The α-MHC-H2B-mCh/CAG-eGFP-anillin system was used to confirm the proliferative effect triggered by LDHA on P7 CMs and adult hearts. Metabolomics, proteomics and Co-IP experiments indicated that LDHA-mediated succinyl coenzyme A reduction inhibited succinylation-dependent ubiquitination of thioredoxin reductase 1 (Txnrd1), which alleviated ROS and thereby promoted CM proliferation. In addition, flow cytometry and western blotting showed that LDHA-driven lactate production created a beneficial cardiac regenerative microenvironment by inducing M2 macrophage polarization. CONCLUSIONS: LDHA-mediated metabolic reprogramming promoted CM proliferation by alleviating ROS and inducing M2 macrophage polarization, indicating that LDHA might be an effective target for promoting cardiac repair post-MI.