Effects of sintering additives and sintering methods on the mechanical, antimicrobial and optical properties of Si3N4 bioceramics.

Si3N4 bioceramics were fabricated using GPS and SPS method with MgO-RE2O3 (RE = La, Nd, Gd, Ho and Lu) sintering additives. The effect of sintering methods and sintering additives on the grain growth, mechanical, antimicrobial properties and color of Si3N4 bioceramics were studied. Samples sintered with GPS are composed of ß-Si3N4 and samples sintered with SPS are composed of α-Si3N4 and ß-Si3N4. The growth of ß-Si3N4 grains in samples sintered with GPS are more adequate. Samples sintered with GPS exhibit a S. aureus inactivation rate up to 98% and a bright color appearance with a hardness of about 13 GPa and a fracture toughness up to 7.5 MPa m1/2, suitable for dental implants. And samples sintered with SPS exhibit a hardness of about 17 GPa and a fracture toughness about 6 MPa m1/2.

Regular exercise attenuates alcoholic myopathy in zebrafish by modulating mitochondrial homeostasis.

Alcoholic myopathy is caused by chronic consumption of alcohol (ethanol) and is characterized by weakness and atrophy of skeletal muscle. Regular exercise is one of the important ways to prevent or alleviate skeletal muscle myopathy. However, the beneficial effects and the exact mechanisms underlying regular exercise on alcohol myopathy remain unclear. In this study, a model of alcoholic myopathy was established using zebrafish soaked in 0.5% ethanol. Additionally, these zebrafish were intervened to swim for 8 weeks at an exercise intensity of 30% of the absolute critical swimming speed (Ucrit), aiming to explore the beneficial effects and underlying mechanisms of regular exercise on alcoholic myopathy. This study found that regular exercise inhibited protein degradation, improved locomotion ability, and increased muscle fiber cross-sectional area (CSA) in ethanol-treated zebrafish. In addition, regular exercise increases the functional activity of mitochondrial respiratory chain (MRC) complexes and upregulates the expression levels of MRC complexes. Regular exercise can also improve oxidative stress and mitochondrial dynamics in zebrafish skeletal muscle induced by ethanol. Additionally, regular exercise can activate mitochondrial biogenesis and inhibit mitochondrial unfolded protein response (UPRmt). Together, our results suggest regular exercise is an effective intervention strategy to improve mitochondrial homeostasis to attenuate alcoholic myopathy.

Aerobic exercise enhances mitochondrial homeostasis to counteract D-galactose-induced sarcopenia in zebrafish.

Sarcopenia is a common skeletal muscle degenerative disease characterized by decreased skeletal muscle mass and mitochondrial dysfunction that involves microRNAs (miR) as regulatory factors in various pathways. Exercise reduces age-related oxidative damage and chronic inflammation and increases autophagy, among others. Moreover, whether aerobic exercise can regulate mitochondrial homeostasis by modulating the miR-128/insulin-like growth factor-1 (IGF-1) signaling pathway and can improve sarcopenia requires further investigation. Interestingly, zebrafish have been used as a model for aging research for over a decade due to their many outstanding advantages. Therefore, we established a model of zebrafish sarcopenia using d-galactose immersion and observed substantial changes, including reduced skeletal muscle cross-sectional area, increased tissue fibrosis, decreased motility, increased skeletal muscle reactive oxygen species, and notable alterations in mitochondrial morphology and function. We found that miR-128 expression was considerably upregulated, where as Igf1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were significantly downregulated; moreover, mitochondrial homeostasis was reduced. Four weeks of aerobic exercise delayed sarcopenia progression and prevented the disruption of mitochondrial function and homeostasis. The genes related to atrophy and miR-128 were downregulated, Igf1 expression was considerably upregulated, and the phosphorylation levels of Pi3k, Akt, and Foxo3a were upregulated. Furthermore, mitochondrial respiration and homeostasis were enhanced. In conclusion, aerobic exercise improved skeletal muscle quality and function via the miR-128/IGF-1 signaling pathway, consequently ameliorating mitochondrial homeostasis in aging skeletal muscle.

Exercise intervention improves mitochondrial quality in non-alcoholic fatty liver disease zebrafish.

Introduction: Recent reports indicate that mitochondrial quality decreases during non-alcoholic fatty liver disease (NAFLD) progression, and targeting the mitochondria may be a possible treatment for NAFLD. Exercise can effectively slow NAFLD progression or treat NAFLD. However, the effect of exercise on mitochondrial quality in NAFLD has not yet been established. Methods: In the present study, we fed zebrafish a high-fat diet to model NAFLD, and subjected the zebrafish to swimming exercise. Results: After 12 weeks, swimming exercise significantly reduced high-fat diet-induced liver injury, and reduced inflammation and fibrosis markers. Swimming exercise improved mitochondrial morphology and dynamics, inducing upregulation of optic atrophy 1(OPA1), dynamin related protein 1 (DRP1), and mitofusin 2 (MFN2) protein expression. Swimming exercise also activated mitochondrial biogenesis via the sirtuin 1 (SIRT1)/ AMP-activated protein kinase (AMPK)/ PPARgamma coactivator 1 alpha (PGC1α) pathway, and improved the mRNA expression of genes related to mitochondrial fatty acid oxidation and oxidative phosphorylation. Furthermore, we find that mitophagy was suppressed in NAFLD zebrafish liver with the decreased numbers of mitophagosomes, the inhibition of PTEN-induced kinase 1 (PINK1) - parkin RBR E3 ubiquitin protein ligase (PARKIN) pathway and upregulation of sequestosome 1 (P62) expression. Notably, swimming exercise partially recovered number of mitophagosomes, which was associated with upregulated PARKIN expression and decreased p62 expression. Discussion: These results demonstrate that swimming exercise could alleviate the effects of NAFLD on the mitochondria, suggesting that exercise may be beneficial for treating NAFLD.

Mn4+-Activated Double-Perovskite-Type Sr2LuNbO6 Multifunctional Phosphor for Optical Probing and Lighting.

Multifunctional phosphors have significant application and scientific value and are becoming a research hotspot in the field of luminescent materials. Herein, we report Mn4+-activated double-perovskite-type Sr2LuNbO6 multifunctional phosphors with excellent comprehensive properties in the fields of optical temperature/pressure sensing and w-LED lighting. The crystalline structure, elemental composition, optimal doping concentration, crystal-field strength, and optical bandgap of the phosphors are investigated in detail, and the mechanisms of concentration and thermal quenching are discussed. From the optimal Sr2LuNb0.998O6:0.2%Mn4+ phosphor, a LED lamp for indoor warm-white lighting is successfully fabricated. Further, the thermometric properties of the phosphors are explored for applications as FIR- and lifetime-based thermometers, showing a maximum relative sensitivity of 1.55% K-1 at 519 K. Upon pressure loading, a significant red-shift of the peak centroid is observed, and the pressure sensitivity is determined to be 0.82 nm/GPa. These results suggest that the Mn4+-activated Sr2LuNbO6 multifunctional phosphors have great potential to be utilized in the fields of optical thermometry, manometry, and lighting.

Exercise intervention mitigates zebrafish age-related sarcopenia via alleviating mitochondrial dysfunction.

Sarcopenia is a common disorder that leads to a progressive decrease in skeletal muscle function in elderly people. Exercise effectively prevents or delays the onset and progression of sarcopenia. However, the molecular mechanisms underlying how exercise intervention improves skeletal muscle atrophy remain unclear. In this study, we found that 21-month-old zebrafish had a decreased swimming ability, reduced muscle fibre cross-sectional area, unbalanced protein synthesis, and degradation, increased oxidative stress, and mitochondrial dysfunction, which suggests zebrafish are a valuable model for sarcopenia. Eight weeks of exercise intervention attenuated these pathological changes in sarcopenia zebrafish. Moreover, the effects of exercise on mitochondrial dysfunction were associated with the activation of the AMPK/SIRT1/PGC-1α axis and 15-PGDH downregulation. Our results reveal potential therapeutic targets and indicators to treat age-related sarcopenia using exercise intervention.

Plastic deformation in silicon nitride ceramics via bond switching at coherent interfaces.

Covalently bonded ceramics exhibit preeminent properties-including hardness, strength, chemical inertness, and resistance against heat and corrosion-yet their wider application is challenging because of their room-temperature brittleness. In contrast to the atoms in metals that can slide along slip planes to accommodate strains, the atoms in covalently bonded ceramics require bond breaking because of the strong and directional characteristics of covalent bonds. This eventually leads to catastrophic failure on loading. We present an approach for designing deformable covalently bonded silicon nitride (Si3N4) ceramics that feature a dual-phase structure with coherent interfaces. Successive bond switching is realized at the coherent interfaces, which facilitates a stress-induced phase transformation and, eventually, generates plastic deformability.

Alcohol Induces Zebrafish Skeletal Muscle Atrophy through HMGB1/TLR4/NF-κB Signaling.

Excessive alcohol consumption can cause alcoholic myopathy, but the molecular mechanism is still unclear. In this study, zebrafish were exposed to 0.5% alcohol for eight weeks to investigate the effect of alcohol on skeletal muscle and its molecular mechanism. The results showed that the body length, body weight, cross-sectional area of the skeletal muscle fibers, Ucrit, and MO2max of the zebrafish were significantly decreased after alcohol exposure. The expression of markers of skeletal muscle atrophy and autophagy was increased, and the expression of P62 was significantly reduced. The content of ROS, the mRNA expression of sod1 and sod2, and the protein expression of Nox2 were significantly increased. In addition, we found that the inflammatory factors Il1ß and Tnfα were significantly enriched in skeletal muscle, and the expression of the HMGB1/TLR4/NF-κB signaling axis was also significantly increased. In summary, in this study, we established a zebrafish model of alcohol-induced skeletal muscle atrophy and further elucidated its pathogenesis.

A High-Fat Diet Induces Muscle Mitochondrial Dysfunction and Impairs Swimming Capacity in Zebrafish: A New Model of Sarcopenic Obesity.

Obesity is a highly prevalent disease that can induce metabolic syndrome and is associated with a greater risk of muscular atrophy. Mitochondria play central roles in regulating the physiological metabolism of skeletal muscle; however, whether a decreased mitochondrial function is associated with impaired muscle function is unclear. In this study, we evaluated the effects of a high-fat diet on muscle mitochondrial function in a zebrafish model of sarcopenic obesity (SOB). In SOB zebrafish, a significant decrease in exercise capacity and skeletal muscle fiber cross-sectional area was detected, accompanied by high expression of the atrophy-related markers Atrogin-1 and muscle RING-finger protein-1. Zebrafish with SOB exhibited inhibition of mitochondrial biogenesis and fatty acid oxidation as well as disruption of mitochondrial fusion and fission in atrophic muscle. Thus, our findings showed that muscle atrophy was associated with SOB-induced mitochondrial dysfunction. Overall, these results showed that the SOB zebrafish model established in this study may provide new insights into the development of therapeutic strategies to manage mitochondria-related muscular atrophy.

Cardioprotective responses to aerobic exercise-induced physiological hypertrophy in zebrafish heart.

Herein, we aimed to establish an aerobic exercise-induced physiological myocardial hypertrophy zebrafish (Danio rerio) model and to explore the underlying molecular mechanism. After 4 weeks of aerobic exercise, the AMR and Ucrit of the zebrafish increased and the hearts were enlarged, with thickened myocardium, an increased number of myofilament attachment points in the Z-line, and increased compaction of mitochondrial cristae. We also found that the mTOR signaling pathway, angiogenesis, mitochondrial fusion, and fission event, and mitochondrial autophagy were associated with the adaptive changes in the heart during training. In addition, the increased mRNA expression of genes related to fatty acid oxidation and antioxidation suggested that the switch of energy metabolism and the maintenance of mitochondrial homeostasis induced cardiac physiological changes. Therefore, the zebrafish heart physiological hypertrophy model constructed in this study can be helpful in investigating the cardioprotective mechanisms in response to aerobic exercise.

Recent advances in studies of 15-PGDH as a key enzyme for the degradation of prostaglandins.

15-hydroxyprostaglandin dehydrogenase (15-PGDH; encoded by HPGD) is ubiquitously expressed in mammalian tissues and catalyzes the degradation of prostaglandins (PGs; mainly PGE2, PGD2, and PGF2α) in a process mediated by solute carrier organic anion transport protein family member 2A1 (SLCO2A1; also known as PGT, OATP2A1, PHOAR2, or SLC21A2). As a key enzyme, 15-PGDH catalyzes the rapid oxidation of 15-hydroxy-PGs into 15-keto-PGs with lower biological activity. Increasing evidence suggests that 15-PGDH plays a key role in many physiological and pathological processes in mammals and is considered a potential pharmacological target for preventing organ damage, promoting bone marrow graft recovery, and enhancing tissue regeneration. Additionally, results of whole-exome analyses suggest that recessive inheritance of an HPGD mutation is associated with idiopathic hypertrophic osteoarthropathy. Interestingly, as a tumor suppressor, 15-PGDH inhibits proliferation and induces the differentiation of cancer cells (including those associated with colorectal, lung, and breast cancers). Furthermore, a recent study identified 15-PGDH as a marker of aging tissue and a potential novel therapeutic target for resisting the complex pathology of aging-associated diseases. Here, we review and summarise recent information on the molecular functions of 15-PGDH and discuss its pathophysiological implications.

Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling.

Non-alcoholic fatty liver disease (NAFLD) is a common disease that causes serious liver damage. Exercise is recognized as a non-pharmacological tool to improve the pathology of NAFLD. However, the antioxidative effects and mechanisms by which exercise ameliorates NAFLD remain unclear. The present study conducted exercise training on zebrafish during a 12-week high-fat feeding period to study the antioxidant effect of exercise on the liver. We found that swimming exercise decreased lipid accumulation and improved pathological changes in the liver of high-fat diet-fed zebrafish. Moreover, swimming alleviated NOX4-derived reactive oxygen species (ROS) overproduction and reduced methanedicarboxylic aldehyde (MDA) levels. We also examined the anti-apoptotic effects of swimming and found that it increased the expression of antiapoptotic factor bcl2 and decreased the expression of genes associated with apoptosis (caspase3, bax). Mechanistically, swimming intervention activated SIRT1/AMPK signaling-mediated lipid metabolism and inflammation as well as enhanced AKT and NRF2 activation and upregulated downstream antioxidant genes. In summary, exercise attenuates pathological changes in the liver induced by high-fat diets. The underlying mechanisms might be related to NRF2 and mediated by SIRT1/AMPK signaling.

Identification of Potentially Related Genes and Mechanisms Involved in Skeletal Muscle Atrophy Induced by Excessive Exercise in Zebrafish.

Long-term imbalance between fatigue and recovery may eventually lead to muscle weakness or even atrophy. We previously reported that excessive exercise induces pathological cardiac hypertrophy. However, the effect of excessive exercise on the skeletal muscles remains unclear. In the present study, we successfully established an excessive-exercise-induced skeletal muscle atrophy zebrafish model, with decreased muscle fiber size, critical swimming speed, and maximal oxygen consumption. High-throughput RNA-seq analysis identified differentially expressed genes in the model system compared with control zebrafish. Gene ontology and KEGG enrichment analysis revealed that the upregulated genes were enriched in autophagy, homeostasis, circadian rhythm, response to oxidative stress, apoptosis, the p53 signaling pathway, and the FoxO signaling pathway. Protein-protein interaction network analysis identified several hub genes, including keap1b, per3, ulk1b, socs2, esrp1, bcl2l1, hsp70, igf2r, mdm2, rab18a, col1a1a, fn1a, ppih, tpx2, uba5, nhlrc2, mcm4, tac1, b3gat3, and ddost, that correlate with the pathogenesis of skeletal muscle atrophy induced by excessive exercise. The underlying regulatory pathways and muscle-pressure-response-related genes identified in the present study will provide valuable insights for prescribing safe and accurate exercise programs for athletes and the supervision and clinical treatment of muscle atrophy induced by excessive exercise.

Identification of Potentially Relevant Genes for Excessive Exercise-Induced Pathological Cardiac Hypertrophy in Zebrafish.

Exercise-induced cardiac remodeling has aroused public concern for some time, as sudden cardiac death is known to occur in athletes; however, little is known about the underlying mechanism of exercise-induced cardiac injury. In the present study, we established an excessive exercise-induced pathologic cardiac hypertrophy model in zebrafish with increased myocardial fibrosis, myofibril disassembly, mitochondrial degradation, upregulated expression of the pathological hypertrophy marker genes in the heart, contractile impairment, and cardiopulmonary function impairment. High-throughput RNA-seq analysis revealed that the differentially expressed genes were enriched in the regulation of autophagy, protein folding, and degradation, myofibril development, angiogenesis, metabolic reprogramming, and insulin and FoxO signaling pathways. FOXO proteins may be the core mediator of the regulatory network needed to promote the pathological response. Further, PPI network analysis showed that pik3c3, gapdh, fbox32, fzr1, ubox5, lmo7a, kctd7, fbxo9, lonrf1l, fbxl4, nhpb2l1b, nhp2, fbl, hsp90aa1.1, snrpd3l, dhx15, mrto4, ruvbl1, hspa8b, and faub are the hub genes that correlate with the pathogenesis of pathological cardiac hypertrophy. The underlying regulatory pathways and cardiac pressure-responsive molecules identified in the present study will provide valuable insights for the supervision and clinical treatment of pathological cardiac hypertrophy induced by excessive exercise.

New lignan from the rattan stems of Schisandra chinensis.

A new lignan named schilignan F (1), together with twelve known ones (2-13), were isolated from the rattan stems of Schisandra chinensis. Their chemical structures were elucidated by spectroscopic methods including one and two-dimensional NMR spectra referring to the literatures as well as high-resolution mass spectrometric analysis. All compounds were evaluated for their cytotoxicities against human Hela cancer cell lines in vitro. The results showed that compounds 2, 6 and 8 exhibited weak cytotoxic activity with IC50 values of 30.6, 86.3 and 41.0 µM, and cisplatin showed cytotoxic activity with IC50 value of 27.3 µM.