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[Display omitted] • The impact of CO adsorption on electric double layer on Cu. • In situ spectroscopic and electrochemical impedance characterizations. • CO adsorption reduces electric double layer capacitance and local cation density. • CO adsorption leads to thicker electric double layer and lower dielectric constant. Understanding the interplay between reactant adsorbate and structure of the electric double layer (EDL) is crucial as it plays a key role in determining the efficiency and kinetics of heterogeneous electrocatalytic reactions. In this context, our study presents a comprehensive experimental analysis of the EDL structure and its interaction with CO adsorption on Cu surfaces. Utilizing in situ surface-enhanced infrared absorption spectroscopy (SEIRAS) and electrochemical impedance characterizations, we investigate the impact of CO adsorption on EDL properties at various CO pressures. Our findings demonstrate a significant decrease in EDL capacitance with increased CO adsorption, linked to reduced cation density, increased EDL thickness, and weakened interfacial electric field strength. Additionally, we observed a considerable decline in the relative dielectric constant of the EDL, which is likely attributable to the influence of adsorbed CO altering the dielectric properties of the medium. These results emphasize the critical role of adsorbate-EDL interactions in electrocatalytic processes, providing new insights into these complex dynamics. [ABSTRACT FROM AUTHOR]

The interest towards application of nanomaterials in field of cancer therapy is that the drawbacks of conventional therapies including chemoresistance, radio-resistance and lack of specific targeting of tumor cells can be solved by nanotechnology. Cyclodextrins (CDs) are amphiphilic cyclic oligosaccharides that can be present in three forms of α-, β- and γ-CDs, and they can be synthesized from natural sources. The application of CDs in cancer shows an increasing trend due to benefits of these nanocomplexes in improving solubility and bioavailability of current bioactives and therapeutics for cancer. CDs are widely utilized in delivery of drugs and genes in cancer therapy, and by targeted delivery of these therapeutics into target site, they improve anti-proliferative and anti-cancer potential. The blood circulation time and tumor site accumulation of therapeutics can be improved using CD-based nanostructures. More importantly, the stimuli-responsive types of CDs including pH-, redox- and light-sensitive types can accelerate release of bioactive compound at tumor site. Interestingly, the CDs are able to mediate photothermal and photodynamic impact in impairing tumorigenesis in cancer, enhancing cell death and improving response to chemotherapy. In improving the targeting ability of CDs, their surface functionalization with ligands has been conducted. Moreover, CDs can be modified with green products such as chitosan and fucoidan, and they can be embedded in green-based nanostructures to suppress tumorigenesis. The internalization of CDs into tumor cells can occur through endocytosis and this can be clethrin-, caveolae- or receptor-mediated endocytosis. Furthermore, CDs are promising candidates in bioimaging, cancer cell and organelle imaging as well as isolating tumor cells. The main benefits of using CDs in cancer therapy including sustained and low release of drugs and genes, targeted delivery, bioresponsive release of cargo, ease of surface functionalization and complexation with other nanostructures. The application of CDs in overcoming drug resistance requires more investigation. [Display omitted] • The cyclodextrins (CDs) are non-viral vectors for targeted delivery. • CDs can internalize into tumor cells through endocytosis. • Bioresponsive kinds of CDs for specific and sustained release of cargo have been designed. • Green modification of CDs can improve potential in cancer suppression. • CDs boost immunotherapy of tumor cells and they can be used for bioimaging. [ABSTRACT FROM AUTHOR]

Gamma irradiation is a non-thermal treatment to effectively eliminate pathogenic microorganisms in citrus production. Here, Cara Cara fruit samples were treated with gamma irradiation (0.3, 0.6, and 0.9 kGy), then their physicochemical quality and antioxidant ability were evaluated for a period of 70 days (d). The irradiated fruit exhibited increases in respiration rate with irradiation dose in the storage period of 0–56 d. During early shelf life (0–42 d), the decay rate of irradiated fruit (0–22%) was higher than that of the control (0–6%) in a dose-dependent manner; while in later shelf life, 0.3 and 0.6 kGy irradiation resulted in lower decay rates. The irradiation showed no significant effect on titratable acidity and total organic acids during storage. Irradiation at 0.6 kGy reduced free sugar content and TSS value, while increased the total phenolic content, DPPH and ABTS values of the fruit at most sampling time points. Considering the reduction of decay rate, respiratory intensity, and weight loss of the fruit under 0.6 kGy irradiation during 56–70 d of storage, 0.6 kGy may be an appropriate radiation dose to maintain the shelf-life quality of Cara Cara fruit, particularly for prolonged postharvest storage. • The effect of gamma irradiation on Cara Cara fruit were evaluated for their prolonged storage. • Lower irradiation dose decreased the decay rate of Cara Cara fruit in the late storage period. • 0.9 kGy resulted in higher respiration, greater weight loss and lower ascorbic acid content. • 0.6 kGy is appropriate irradiation dose particularly for prolonged postharvest storage. [ABSTRACT FROM AUTHOR]

Prolactin (PRL) and growth hormone (GH) play important roles in regulating salt and water balance through osmoregulatory organs in vertebrates. The aim of this study was to investigate the dynamic changes of GH/PRL hormone gene expressions in the pituitary gland and their receptors in gill and kidney, as well as the plasma osmolality when the olive flounder fish Paralichthys olivaceus were acclimated in freshwater (FW) conditions. After transfer from seawater (SW) to freshwater (FW), the osmolality of FW-adaption fish reached the lowest level at 1d which rose slightly afterwards. However, the hormone gene expression of PRL increased from 2d, reaching its peak at 5d, and then decreased at 14d. At this time, the value was still significantly higher than the control, showing a similar trend to the plasma hormone PRL. In contrast, the pituitary mRNA level of GH significantly decreased at 1d and then returned to normal levels. The mRNA levels of PRL receptor (PRLR) in both gill and kidney displayed a similar trend to the pituitary PRL. We also observed the synchronous expression trend of the renal PRLR with pituitary PRL (5d) and the asynchronous expression peaks between branchial (8d) and renal PRLR (5d). Significant responses of GH and its receptor (GHR) in both gill and kidney during the FW-acclimation were not observed. Nevertheless, the gene expression of GH receptor variant (GHR-V) in both gill and kidney declined at 2d, indicating unknown osmoregulatory functions of GHR-V. Collectively, our results provided more insights of the PRL, GH and their corresponding receptors in modulating osmoregulatory responses, representing an important aspect of FW–acclimation in flounder fish. [ABSTRACT FROM AUTHOR]

Extensive global glacial retreats are threatening cryosphere ecosystem functioning and the associated biota in glacier-fed water systems. Understanding multi-group biodiversity distributions and compositional variation across diverse but hydrologically linked habitats under varying glacial influences will help explain the mechanisms underlying glacial community organization and ecosystem processes. However, such data are generally lacking due to the difficulty of obtaining biodiversity information across wide taxonomic ranges. Here, we used a multi-marker environmental DNA metabarcoding approach to simultaneously investigate the spatial patterns of community compositions and assembly mechanisms of four taxonomic groups (cyanobacteria, diatoms, invertebrates, and vertebrates) along the flowpaths of a tributary of Lake Nam Co on the Tibetan Plateau—from its glacier headwaters, through its downstream river and wetlands, to its estuary. We detected 869 operational taxonomic units: 119 cyanobacterial, 395 diatom, 269 invertebrate, and 86 vertebrate. Taxonomic richnesses consistently increased from upstream to downstream, and although all groups showed community similarity distance decay patterns, the trend for vertebrates was the weakest. Cyanobacteria, diatom, and invertebrate community compositions were significantly correlated with several environmental factors, while the vertebrate community was only correlated with waterway width. Variation partitioning analysis indicated that varying extents of environmental conditions and spatial factors affected community organizations for different groups. Furthermore, stochastic processes contributed prominently to the microorganisms' community assembly (Sloan's neutral model R 2 = 0.77 for cyanobacteria and 0.73 for diatoms) but were less important for macroorganisms (R 2 = 0.21 for invertebrates and 0.15 for vertebrates). That trend was further substantiated by modified stochasticity ratio analyses. This study provides the first holistic picture of the diverse biotic communities residing in a series of hydrologically connected glacier-influenced habitats. Our results both uncovered the distinct mechanisms that underlie the metacommunity organizations of different glacial organisms and helped comprehensively predict the ecological impacts of the world's melting glaciers. [Display omitted] • Environmental DNA captured diverse biota along a glacial pathway. • Different organism groups showed variable biodiversity distribution patterns. • Smaller organisms' communities were more correlated with environmental factors. • Stochastic and deterministic processes differentially impacted community assembly. • Multi-group biomonitoring can comprehensively assess ecosystem responses. [ABSTRACT FROM AUTHOR]

The poor dewaterability of fermented sludge is an important factor limiting the development of anaerobic fermentation applications. Herein we reported an efficient strategy, i.e., using acidic regulation to stimulate the release of indigenous enzymes, to enhance the hydrolysis and dewatering of fermented sludge. The results showed that after acidic regulation at pH 4.0 for 1 day, the activity of protease and α-glucosidase were improved by 131.4% and 146.0%, while the capillary suction time and specific resistance to filtration were decreased by 93.8% and 69.5%, respectively. Mechanism study revealed that the method firstly destroyed the slime and bound EPS and cells of fermented sludge, causing the release of indigenous enzymes (i.e., protease and α-glucosidase) contained in. Then, the released enzymes directly accelerated the hydrolysis and acidification of fragmentized extracellular polymeric substances, thereby benefited the release of bound water in sludge particles. Finally, such acidic condition decreased the electrostatic repulsive interactions between destroyed sludge particles, further improving their flocculation. The findings not only deepen the understanding of indigenous enzymes contained in fermented sludge affecting sludge dewatering, but also might guide engineers to develop promising strategies to facilitate fermented sludge dewatering and fermentation liquid recovery in the future. [Display omitted] • Acidic treatment (AT) improved dewaterability of anaerobically fermented sludge. • The minimal capillary suction time was obtained after AT at pH 4.0 for 1 day. • AT destroyed sludge cells and facilitated the release of hydrolytic enzymes. • Acid-driven indigenous enzymatic hydrolysis was major contributor to dewatering. • AT reduced the electrostatic repulsive interactions between sludge particles. [ABSTRACT FROM AUTHOR]

Understanding the intestinal bacteria in ruminants and their population kinetics is essential for their ecological function, as well as their interaction with the host. In this in vitro study, we aimed to determine whether gut region and fiber structure can influence bacterial diversity and functional bacterial population, together with the kinetics of functional bacterial species in the cecal inocula using PCR-DGGE and qPCR. A split plot design was conducted with gut regions (jejunum, ileum, cecum and colon) as main plot, and substrates (neutral detergent fiber (NDF) and cellulose (CEL)) as subplot. Incubation time and gut region affected dominant bacterial diversity. The numbers of total bacteria, cellulolytic bacteria, genus Prevotella and amylolytic bacteria in the hindgut inocula were greater (P < 0.05) than those in the small intestinal inocula. Fiber structure did not significantly influence the dominant bacterial diversity and the numbers of most examined functional bacterial species. The greatest increase rate of cellulolytic bacteria occurred earlier than amylolytic bacteria except for R. albus incubated with NDF. Changes in cellulolytic bacterial populations were not coordinative with alteration of fiber disappearance as well as CMCase and xylanase activities. All these suggest that the hindgut contents have greater potential to digest fiber than small intestinal contents, and cellulolytic bacteria are of significant value at the initial stage of fiber digestion among the fiber digestive microbes in the intestine. [ABSTRACT FROM AUTHOR]

• We propose a network that performs volumetric segmentation of white matter tracts. • The tract correlation is exploited with label embedding in the network design. • Our method was validated on public and private datasets under various settings. • The segmentation quality is improved compared with competing methods. • The improvement is more prominent for challenging tracts in challenging scenarios. [Display omitted] Convolutional neural networks have achieved state-of-the-art performance for white matter (WM) tract segmentation based on diffusion magnetic resonance imaging (dMRI). However, the segmentation can still be difficult for challenging WM tracts with thin bodies or complicated shapes; the segmentation is even more problematic in challenging scenarios with reduced data quality or domain shift between training and test data, which can be easily encountered in clinical settings. In this work, we seek to improve the segmentation of WM tracts, especially for challenging WM tracts in challenging scenarios. In particular, our method is based on volumetric WM tract segmentation, where voxels are directly labeled without performing tractography. To improve the segmentation, we exploit the characteristics of WM tracts that different tracts can cross or overlap and revise the network design accordingly. Specifically, because multiple tracts can co-exist in a voxel, we hypothesize that the different tract labels can be correlated. The tract labels at a single voxel are concatenated as a label vector, the length of which is the number of tract labels. Due to the tract correlation, this label vector can be projected into a lower-dimensional space—referred to as the embedded space—for each voxel, which allows the segmentation network to solve a simpler problem. By predicting the coordinate in the embedded space for the tracts at each voxel and subsequently mapping the coordinate to the label vector with a reconstruction module, the segmentation result can be achieved. To facilitate the learning of the embedded space, an auxiliary label reconstruction loss is integrated with the segmentation accuracy loss during network training, and network training and inference are end-to-end. Our method was validated on two dMRI datasets under various settings. The results show that the proposed method improves the accuracy of WM tract segmentation, and the improvement is more prominent for challenging tracts in challenging scenarios. [ABSTRACT FROM AUTHOR]

Pummelo (Citrus grandis Osbeck.) is a major commercial fruit in the world. In this study, samples of three popular varieties, namely "Huangjin", "Sanhong" and "Dongshizao", were collected from three commercial orchards located in China. A total of 153 metabolites in the pulp were annotated and analyzed using UPLC-QTRAP-MS/MS and GC-MS, and PCA of these metabolites could clearly distinguish the three varieties. The pulp of "Dongshizao" had the most enjoyable taste, and that of "Huangjin" had the strongest aroma. The most important aroma compounds were hexanal, β-myrcene and trans-2-decene. Amino acids were positively correlated with 18 volatile substances, and also affected the tastes of sweetness, sourness and bitterness. Unsaturated fatty acids accounted for 70% of total fatty acids. The types of sugars and organic acids were similar among different varieties, but differences in the contents of individual substances and sugar/acid ratio contributed to different tastes. • Metabolites and aromatic compounds in "Dongshizao" pummelo pulp were first identified. • Quality-related metabolites in "Huangjin" and "Sanhong" pummelo were described. • Differences in taste and aroma among main commercial pummelo varieties were explained. • The work helps to understand the formation of pummelo flavors and breed new varieties. [ABSTRACT FROM AUTHOR]

To investigate the effect of A- and B-type granules of wheat starch on noodle quality, the fractionation and reconstitution method was used to prepare noodles with five different ratios of A-to B-granules (100A-0B, 75A-25B, 50A-50B, 25A-75B, 0A-100B). The pasting and swelling properties of reconstituted flours and the microstructure of noodles observed under a confocal laser scanning microscope (CLSM) indicated that there were at least two aspects were responsible for the changes in noodle quality. First, the water distribution, texture and cooking quality of noodles were influenced by the different physicochemical properties of A- and B-granules; and second, the gluten structure in noodles was altered by the granule size distribution, which further led to a difference in noodle quality. In general, with increasing number of B-granules, the A 22 (the proportion of less immobilized water) of raw noodles and the hardness, resilience and chewiness of cooked noodles increased first and then decreased, while the cooking loss, water absorption and protein loss showed the reverse trend. Raw noodle samples containing 50A-50B had the minimum T 22 (less immobilized water) but the maximum A 22 and, when cooked, had the greatest hardness, chewiness and resilience and the least cooking loss (6.6%) and water absorption (166.1%). These results have important implications for illustrating the mechanism by which A- and B-granules affect noodle quality and guide efforts to improve noodle quality and wheat breeding. Image 100333 • The physicochemical properties and size distribution of A- and B-granules were responsible for noodle quality. • Granule size affected noodle quality by altering gluten structure. • Cooked noodles with equal amounts of A- and B-granules had the highest texture parameters and the lowest cooking loss. • Adjusting the proportion of A- and B-granules of starch was an effective way to improve noodle quality. [ABSTRACT FROM AUTHOR]

[Display omitted] • Electrochemical splitting of CH 4 produces H 2 and allows adjustable carbon quality. • Hydrogen production is physically separated from carbon deposition in melts. • Electrode and kinetics can regulate the composition and structure of carbon products. • The C-Ni-50 mA exhibits CNT structure and good adsorption properties. • The C-Ag-50 mA exhibits open hollow carbon structure and good capacitive properties. Catalytic decomposition of methane offers a viable solution for producing pure hydrogen and nanocarbon without emitting carbon dioxide. However, conventional thermal catalytic processes and catalysts have limitations in terms of poor carbon quality and catalyst deactivation due to carbon deposition. The newly developed electrochemical splitting of methane (ESM) in molten salt has emerged as a promising alternative that allows for the separate production of hydrogen at the anode and carbon deposition at the cathode. In this study, hydrogen produced via ESM while generating nanocarbon with diverse structures through manipulations of the cathode material and kinetics. Carbon nanotubes grown on Ni cathode, possessing high specific surface area and abundant functional groups, displayed excellent adsorptive capacity for dye adsorption. The open hollow nanocarbon grown on the Ag cathode displayed good capacitance performance. ESM technology has immense potential to enhance the utilization value of carbon by-products and the commercial production of green hydrogen. [ABSTRACT FROM AUTHOR]

Chinese mitten crab (Eriocheir sinensis) is one of the most popular aquatic foods in China and Southeast Asian countries. However, the available forms of this commodity such as live individuals and processed products do not fulfil consumer demand because their shelf life is short or do not retain their shape. Here, biochemical and sensory qualities of E. sinensis during storage at −20, −30, and −40 °C for 12 weeks were investigated. Sensitive indices and a shelf-life prediction model were established to demonstrate the feasibility of commercial frozen E. sinensis. Storage at −40 °C reduced the movement of water, oxidation of proteins and lipids, and formation of thiobarbituric acid reactive substances (TBARS) in the edible tissues of E. sinensis. The eating safety of frozen E. sinensis was evaluated using indices such as histamine and total volatile base-nitrogen (TVB-N) content and total viable count (TVC) over 12 weeks. The safety indices and sensory evaluation predicted that the product shelf lives were 56, 59, and 78 d at −20, −30, and −40 °C, respectively. A shelf-life prediction model based on TVB-N content was developed by combining kinetic and Arrhenius equations and confirmed that frozen E. sinensis is feasible and has potential commercial value. • E. sinensis eating safety assessed by histamine & TVB-N content & TVC over 12 wks. • TVB-N is a sensitive indicator to determine the quality of frozen E. sinensis. • Sensory shelf life economically predicted combination kinetic & Arrhenius models. • Frozen E. sinensis shelf life was 56, 59, & 78 d at −20, −30, & −40 °C, respectively. • Frozen E. sinensis has potential commercial value. [ABSTRACT FROM AUTHOR]

The composition, physicochemical and functional properties of dietary fiber (DF) from different tissue parts of Citrus grandis Shatianyu, including seed, pulp, septum, albedo and flavedo, were explored. The total DF (TDF) contents of Shatianyu tissue parts were 13.0–58.5 g/100 g DW with the ratio of insoluble DF (IDF)/soluble DF (SDF) of 2.46–7.22. Septum and albedo showed higher TDF contents than other tissue parts. Shatianyu tissue parts DF were mainly composed of arabinose, galacturonic and galactose, of which the total mol% ranged from 59.4 to 84.7% in IDF and 80.5–94.4% in SDF, respectively. The molecular weight of Shatianyu SDF ranged from 55.3 to 285 kDa. Generally, septum and albedo DF showed higher water swelling, water retention, oil adsorption capacity, together with glucose adsorption capacity than other tissue parts DF, also than DF from byproducts of many commonly consumed fruits. Therefore, Shatianyu, especially its albedo and septum, is good source of DF for nutraceutical applications. • Albedo and septum of Shatianyu showed higher DF contents than other tissue parts. • Shatianyu IDF and SDF were mainly composed of arabinose, galacturonic and galactose. • Albedo and septum SDF showed higher molecular weight than other tissue parts SDF. • Albedo and septum DF showed better physicochemical and functional properties. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • The divergence times based on two evolutionary models are in glaciation periods. • In glaciation periods, the avian populations were isolated by alpine barriers. • Demographic history shows the species experienced bottleneck in glaciation periods. • Glaciation-based isolation contributed to speciation in Palearctic alpine region. Abstract Organisms are unevenly distributed on earth and the evolutionary drivers of that have puzzled ecologists and evolutionary biologists for over a century. Even though many studies have focused on the mechanisms of unevenly distributed fauna and flora, there remains much to learn about the evolutionary drivers behind biodiversity hotspots. In the Tibetan Plateau and Hengduan Mountains, a biodiversity hotspot in the Palearctic realm, alpine uplift cannot be the driver for recent speciation (

The profiles and bioactivity of flavonoids in the different tissue parts of Shatianyu (Citrus grandis L. Osbeck), including flavedo, albedo, septum, pulp and seed, were investigated in the present study. Fourteen flavonoids were identified by UHPLC-ESI-MS/MS using a multiple reaction monitoring (MRM) mode. Melitidin, naringin and bergamjuicin were the main flavonoids in flavedo, albedo, septum and pulp, while naringin, melitidin and neoeriocitrin were the major flavonoids in seed. In addition, cigranoside C, D, E, F, bergamjuicin and neoeriocitrin, which were isolated from Shatianyu pulp with new structure in our previous study, were detected in all tissue parts and took up 8.9%–37.2% of the total contents of detected flavonoids. Besides strong antioxidant activity, the flavedo and seed of Shatianyu showed potent pancreatic lipase inhibitory activity with IC 50 value of 3.9 and 23.1 μg GAE/mL, respectively. Thus, Shatianyu is natural source of flavonoids and possesses potential for application in anti-obesity nutraceutical food. • Fourteen flavonoid compounds were detected in C. grandis Shatianyu tissue parts. • Shatianyu tissue parts showed obviously different flavonoid profiles. • Shatianyu tissue parts exhibited strong antioxidant activity. • The flavedo and seed of Shatianyu are good inhibitors of pancreatic lipase. [ABSTRACT FROM AUTHOR]

Plant cytochrome P450s (CYPs) are well known as the largest family of enzymes that contribute to both primary metabolism and the chemical diversity of plant secondary metabolites. It is important to elucidate the in vivo role of CYPs in secondary metabolism, in order to apply them in the production of valuable metabolites in medicinal plants via metabolic engineering. CYP76AH1 has been suggested to catalyze the conversion of the carbon skeleton miltiradiene into the intermediate ferruginol, which is involved in the biosynthesis of tanshinones, the chief bioactive ingredients of Salvia miltiorrhiza . However, its role in planta remains to be elucidated. In this work, we constructed a CYP76AH1 RNAi system for hairy roots. Metabolic analysis of RNAi-AH1 hairy root lines showed a significantly increased accumulation of miltiradiene compared to the control lines. At the same time, the concentration of ferruginol decreased revealing the in vivo catalytic activity of CYP76AH1. The content of tanshinones decreased significantly after silencing of CYP76AH1 , which verified its key role in the biosynthesis of tanshinones, and indicated that it could be used as a target for metabolic engineering. [ABSTRACT FROM AUTHOR]

Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter. A cell line derived from human embryonic kidney (HEK) 293H cells was used to produce rFVIIIFc. Validation studies evaluated identity, purity, activity, and safety. Process-related impurity clearance and viral clearance spiking studies demonstrate robust and reproducible removal of impurities and viruses, with total viral clearance >8–15 log 10 for four model viruses (xenotropic murine leukemia virus, mice minute virus, reovirus type 3, and suid herpes virus 1). Terminal galactose-α-1,3-galactose and N-glycolylneuraminic acid, two non-human glycans, were undetectable in rFVIIIFc. Biochemical and in vitro biological analyses confirmed the purity, activity, and consistency of rFVIIIFc. In conclusion, this manufacturing process produces a highly pure product free of viruses, impurities, and non-human glycan structures, with scale capabilities to ensure a consistent and adequate supply of rFVIIIFc. [ABSTRACT FROM AUTHOR]

Highlights: [•] Orchidinae is divided into distinct subclades. [•] Habenaria is subdivided into two distantly related groups. [•] We proposed to establish a new genus to accommodate Ponerorchis chrysea. [•] Tsaiorchis and Sirindhornia are distinctive genera. [Copyright &y& Elsevier]

Myocardial ischemia/reperfusion (I/R) injury is closely related to cardiomyocyte apoptosis. Stimulating β2 adrenergic receptor (β2AR) can effectively combat cardiomyocyte apoptosis. Previous studies demonstrate that the gut microbial metabolite phenylacetylglycine (PAGly) can stimulate β2AR. However, the effect of PAGly on myocardial I/R injury remains unknown. Methods : The hypoxia/reoxygenation (H/R) model was established using the neonatal mouse cardiomyocytes (NMCMs). Different doses of PAGly were used to treat NMCMs, and apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) staining. Additionally, the level of cyclic adenosine monophosphate (cAMP) was examined by using a cAMP detection kit. Mouse model of myocardial I/R injury was established in C57BL/6 mice, and different doses of phenylacetic acid were administrated intraperitoneally. Apoptosis of myocardial cells was detected by TUNEL and α-actin staining. The area at risk and the infarct areas were identified by 2,3,5-triphenyltetrazolium chloride (TTC) and Evans blue staining. Western blotting was used to measure the protein expression levels of phosphorylated phosphatidylinositol 3-kinase (p-PI3K), total Akt (t-Akt), phosphorylated Akt (p-AKT), Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), cleaved caspase-3. Results: PAGly significantly suppressed H/R injury-induced apoptosis in NMCMs and inhibited apoptosis in myocardial I/R injured mice in vivo. We verified that PAGly activated the anti-apoptotic Gαi/PI3K/AKT signaling cascade in NMCMs via stimulating β2AR signaling. Continuous administration of PAGly at an appropriate dose could inhibit apoptosis and reduce the infarct size resulting from I/R injury in mice. However, high-dose PAGly treatment was associated with a higher mortality rate. Moreover, we demonstrated that Aspirin reduced the infarct size and the high mortality caused by high doses of PAGly in I/R injured mice. Conclusions: These findings suggest that treatment with the gut microbial metabolite PAGly could suppress cardiomyocyte apoptosis caused by myocardial I/R injury and reduce the infarct size, which provides a novel therapeutic strategy for patients with myocardial infarction. [ABSTRACT FROM AUTHOR]

After spinal cord injury (SCI), the inhibitory molecules derived from scars at the lesion sites and the limited regenerative capacity of neuronal axons pose difficulties for the recovery after SCI. Remodeling of cytoskeleton structures including microtubule assembly and tubulin post-translational modification are widely accepted to play a crucial role in initiation of growth cone and regrowth of injured axon. Although increasing studies have focused on the association between tubulin acetylation and autophagy due to the role of tubulin acetylation in organelles and substances transport, there are no studies exploring the effect of tubulin acetylation on autophagy after spinal cord injury (SCI). Here, we found that histone deacetylase 6 (HDAC6) was significantly up-regulated after SCI, while inhibition of HDAC6 by Tubastatin A induced functional recovery after SCI. In view of enzyme-dependent and -independent mechanisms of HDAC6 to adjust diverse cellular processes, such as autophagy, the ubiquitin proteasome system and post-translational modification of tubulin, we mainly focused on the significance of HDAC6 in axonal regeneration and autophagy after SCI. Western blotting, Co-immunoprecipitation and immunofluorescence staining were conducted to showed that Tubastatin A treatment in nocodazole-treated cells and mice suffering from SCI prompted acetylation and stabilization of microtubules and thus restored transport function, which may contribute to restored autophagic flux and increased axonal length. Whereas inhibition of degradation of autolysosomes by bafilomycin A1 (Baf-A1) reversed functional recovery caused by Tubastatin A, revealing the association between tubulin acetylation and autophagy, which supports HDAC6 inhibition as a potential target for SCI treatment. Unlabelled Image • HDAC6 can affect microtubule system function by deacetylating tubulin. • Decreased acetylation level of α-Tubulin induces axonal transport dysfunction. • Inhibition of HDAC6 by Tubastatin A restores autophagic flux after SCI. • Inhibition of HDAC6 by Tubastatin A promotes functional recovery after SCI. [ABSTRACT FROM AUTHOR]