Microbiota derived D-malate inhibits skeletal muscle growth and angiogenesis during aging via acetylation of Cyclin A.

Metabolites derived from the intestinal microbiota play an important role in maintaining skeletal muscle growth, function, and metabolism. Here, we found that D-malate (DMA) is produced by mouse intestinal microorganisms and its levels increase during aging. Moreover, we observed that dietary supplementation of 2% DMA inhibits metabolism in mice, resulting in reduced muscle mass, strength, and the number of blood vessels, as well as the skeletal muscle fiber type I/IIb ratio. In vitro assays demonstrate that DMA decreases the proliferation of vascular endothelial cells and suppresses the formation of blood vessels. In vivo, we further demonstrated that boosting angiogenesis by muscular VEGFB injection rescues the inhibitory effects of D-malate on muscle mass and fiber area. By transcriptomics analysis, we identified that the mechanism underlying the effects of DMA depends on the elevated intracellular acetyl-CoA content and increased Cyclin A acetylation rather than redox balance. This study reveals a novel mechanism by which gut microbes impair muscle angiogenesis and may provide a therapeutic target for skeletal muscle dysfunction in cancer or aging.

Peroxiredoxin 2 regulates DAF-16/FOXO mediated mitochondrial remodelling in response to exercise that is disrupted in ageing.

OBJECTIVES: A decline in mitochondrial function and increased susceptibility to oxidative stress is a hallmark of ageing. Exercise endogenously generates reactive oxygen species (ROS) in skeletal muscle and promotes mitochondrial remodelling resulting in improved mitochondrial function. It is unclear how exercise induced redox signalling results in alterations in mitochondrial dynamics and morphology. METHODS: In this study, a Caenorhabditis elegans model of exercise and ageing was used to determine the mechanistic role of Peroxiredoxin 2 (PRDX-2) in regulating mitochondrial morphology. Mitochondrial morphology was analysed using transgenic reporter strains and transmission electron microscopy, complimented with the analysis of the effects of ageing and exercise on physiological activity. RESULTS: The redox state of PRDX-2 was altered with exercise and ageing, hyperoxidised peroxiredoxins were detected in old worms along with basally elevated intracellular ROS. Exercise generated intracellular ROS and rapid mitochondrial remodelling, which was disrupted with age. The exercise intervention promoted mitochondrial ER contact sites (MERCS) assembly and increased DAF-16/FOXO nuclear localisation. The prdx-2 mutant strain had a disrupted mitochondrial network as evidenced by increased mitochondrial fragmentation. In the prdx-2 mutant strain, exercise did not activate DAF-16/FOXO, mitophagy or increase MERCS assembly. The results demonstrate that exercise generated ROS increased DAF-16/FOXO transcription factor nuclear localisation required for activation of mitochondrial fusion events that were blunted with age. CONCLUSIONS: The data demonstrate the critical role of PRDX-2 in orchestrating mitochondrial remodelling in response to a physiological stress by regulating redox dependent DAF-16/FOXO nuclear localisation.

Radiomics analysis in differentiating osteosarcoma and chondrosarcoma based on T2-weighted imaging and contrast-enhanced T1-weighted imaging.

This study was performed to investigate the diagnostic value of radiomics models constructed by fat suppressed T2-weighted imaging (T2WI-FS) and contrast-enhanced T1-weighted imaging (CET1) based on magnetic resonance imaging (MRI) for differentiation of osteosarcoma (OS) and chondrosarcoma (CS). In this retrospective cohort study, we included all inpatients with pathologically confirmed OS or CS from Second Xiangya Hospital of Central South University (Hunan, China) as of October 2020. Demographic and imaging variables were extracted from electronic medical records and compared between OS and CS group. Totals of 530 radiomics features were extracted from CET1 and T2WI-FS sequences based on MRI. The least absolute shrinkage and selection operator (LASSO) method was used for screening and dimensionality reduction of the radiomics model. Multivariate logistic regression analysis was performed to construct the radiomics model, and receiver operating characteristic curve (ROC) was generated to evaluate the diagnostic accuracy of the radiomics model. The training cohort and validation cohort included 87 and 29 patients, respectively. 8 CET1 features and 15 T2WI-FS features were screened based on the radiomics features. In the training group, the area under the receiver-operator characteristic curve (AUC) value for CET1 and T2WI-FS sequences in the radiomics model was 0.894 (95% CI 0.817-0.970) and 0.970 (95% CI 0.940-0.999), respectively. In the validation group, the AUC value for CET1 and T2WI-FS sequences in the radiomics model was 0.821 (95% CI 0.642-1.000) and 0.899 (95% CI 0.785-1.000), respectively. In this study, we developed a radiomics model based on T2WI-FS and CET1 sequences to differentiate between OS and CS. This model exhibits good performance and can help clinicians make decisions and optimize the use of healthcare resources.

Microbiota-derived 3-phenylpropionic acid promotes myotube hypertrophy by Foxo3/NAD+ signaling pathway.

BACKGROUND: Gut microbiota and their metabolites play a regulatory role in skeletal muscle growth and development, which be known as gut-muscle axis. 3-phenylpropionic acid (3-PPA), a metabolite produced by colonic microorganisms from phenylalanine in the gut, presents in large quantities in the blood circulation. But few study revealed its function in skeletal muscle development. RESULTS: Here, we demonstrated the beneficial effects of 3-PPA on muscle mass increase and myotubes hypertrophy both in vivo and vitro. Further, we discovered the 3-PPA effectively inhibited protein degradation and promoted protein acetylation in C2C12 and chick embryo primary skeletal muscle myotubes. Mechanistically, we supported that 3-PPA reduced NAD+ synthesis and subsequently suppressed tricarboxylic acid cycle and the mRNA expression of SIRT1/3, thus promoting the acetylation of total protein and Foxo3. Moreover, 3-PPA may inhibit Foxo3 activity by directly binding. CONCLUSIONS: This study firstly revealed the effect of 3-PPA on skeletal muscle growth and development, and newly discovered the interaction between 3-PPA and Foxo3/NAD+ which mechanically promote myotubes hypertrophy. These results expand new understanding for the regulation of gut microbiota metabolites on skeletal muscle growth and development.

Rheological and physicochemical properties of heat-induced ovalbumin gels in presence of sodium carboxymethyl cellulose.

In this study, the effect of sodium carboxymethylcellulose (CMC-Na) on the rheological and physicochemical properties of heat-induced ovalbumin (OVA) gels was evaluated. The OVA/CMC-Na composite gels were prepared by heat-induced (85 °C, pH 7.0) a mixture of CMC-Na (0, 0.2, 0.4, 0.8 and 1%) and OVA. The results revealed that the addition of CMC-Na dramatically reduced the springiness and hardness of the composite gels, while slightly enhancing the intermolecular hydrogen bonding interactions, which facilitated the improvement of the softness of the gels. It can be observed by SEM that the added CMC-Na was stacked on the surface of the OVA, resulting in visible "linear bumps". All gel samples exhibited shear-thinning behavior. The apparent viscosity of the composite gels increased with the addition of CMC-Na, and the OVA gel with 1% CMC-Na showed the highest apparent viscosity and the lowest storage modulus (G'). Additionally, low field nuclear magnetic resonance (LF-NMR) measurements indicated that the increasing CMC-Na boosted the water mobility of the composite gel. This study offers a novel approach to the development of ovalbumin-based soft gel foods, especially for certain populations with swallowing difficulties.

Construction of astaxanthin loaded Pickering emulsions gel stabilized by xanthan gum/lysozyme nanoparticles with konjac glucomannan from structure, protection and gastrointestinal digestion perspective.

Pickering emulsion gels have demonstrated their efficacy in delivering bioactive compounds by effectively preventing droplet aggregation, Ostwald maturation, and phase separation through gel network. Astaxanthin (AST) Pickering emulsion gels stabilized by xanthan gum/lysozyme nanoparticles (XG/Ly NPs) and konjac glucomannan (KGM) were studied from rheological tests and textural analysis. The Pickering emulsion gel demonstrated the highest water holding capacity (WHC) at concentration of 2 % XG/Ly NPs, 60 % oil phase fraction, and 0.5 % KGM concentration. The presence of KGM was observed to enhance the plasticity of Pickering emulsion gels, as evidenced by the dense gel network structure formed on the surface of the droplets. Furthermore, the utilization of Pickering emulsion gels containing AST has demonstrated enhanced photostability and a protective effect on AST, as evidenced by antioxidant experiments. Moreover, the incorporation of KGM in Pickering emulsion gels has been found to reduce the release of free fatty acids (FFA) and the bioaccessibility of AST, as indicated in vitro digestion results. Overall, these findings indicate the potential of KGM-based Pickering emulsion gels as effective vehicles for the delivery of hydrophobic bioactive compounds within the food industry.

Single Modified Posterior Approach through the Space of the Proximal Radioulnar Joint for Terrible Triad Injury: A Comparative Study.

OBJECTIVE: In order to reduce surgical scars and the risk of neurovascular injury for the treatment of terrible triad injuries of the elbow (TTI), minimally invasive and better therapeutic effect approaches are being explored to replace the conventional combined lateral and medial approach (CLMA). This study was performed to compare the clinical effect and security of the modified posterior approach (MPA) through the space of the proximal radioulnar joint vs the CLMA for treatment of TTI. METHODS: This study retrospectively analyzed 76 patients treated for TTI from January 2009 to December 2020 (MPA: n = 44; CLMA: n = 32). Treatment involved plate and screw fixation or Steinmann pin fixation for the radial head and ulnar coronoid process fractures. Surgeons only sutured the lateral ligament because the medial collateral ligament was usually integrated in the TTI. The continuous variables were compared by the independent Student t-test and the categorical variables by the χ2 -test or Fisher's exact test. RESULTS: Both groups of patients attained a satisfactory MEPS after the operation. The MEPS (MPA: 96.82 ± 6.04 vs CLMA: 96.56 ± 5.51) was not significantly different between the two groups (p > 0.05). However, the MPA resulted in better elbow flexion and extension (MPA: 123.98 ± 10.09 vs CLMA: 117.66 ± 8.29), better forearm rotation function (MPA: 173.41 ± 6.81 vs CLMA: 120.00 ± 12.18), and less intraoperative hemoglobin (MPA: 9.34 ± 5.64 vs CLMA: 16.5 ± 8.75) and red cell volume loss (MPA: 3.09 ± 2.20 vs CLMA: 6.70 ± 2.97) (All p < 0.05). Although the CLMA had a shorter surgery time (MPA: 171.73 ± 80.68 vs CLMA: 130.16 ± 71.50) (p < 0.05), it had a higher risk of neurologic damage (MPA: 0 vs CLMA: 4) (p < 0.05). Four patients developed forearm or hand numbness after the CLMA, but no patients developed numbness after the MPA. All 76 patients were followed up for 15 months postoperatively. CONCLUSION: The MPA through the space of the proximal radioulnar joint has more prominent advantages than the CLMA for TTI, including single scar, clear exposure, good fixation, lower risk of neurovascular injury, and better elbow joint motion. It is a safe and effective surgical approach that is worthy of clinical promotion.

α-Ketoglutaric acid ameliorates hyperglycemia in diabetes by inhibiting hepatic gluconeogenesis via serpina1e signaling.

Previously, we found that α-ketoglutaric acid (AKG) stimulates muscle hypertrophy and fat loss through 2-oxoglutarate receptor 1 (OXGR1). Here, we demonstrated the beneficial effects of AKG on glucose homeostasis in a diet-induced obesity (DIO) mouse model, which are independent of OXGR1. We also showed that AKG effectively decreased blood glucose and hepatic gluconeogenesis in DIO mice. By using transcriptomic and liver-specific serpina1e deletion mouse model, we further demonstrated that liver serpina1e is required for the inhibitory effects of AKG on hepatic gluconeogenesis. Mechanistically, we supported that extracellular AKG binds with a purinergic receptor, P2RX4, to initiate the solute carrier family 25 member 11 (SLC25A11)-dependent nucleus translocation of intracellular AKG and subsequently induces demethylation of lysine 27 on histone 3 (H3K27) in the seprina1e promoter region to decrease hepatic gluconeogenesis. Collectively, these findings reveal an unexpected mechanism for control of hepatic gluconeogenesis using circulating AKG as a signal molecule.

In situ biodiesel production from fast-growing and high oil content Chlorella pyrenoidosa in rice straw hydrolysate.

Rice straw hydrolysate was used as lignocellulose-based carbon source for Chlorella pyrenoidosa cultivation and the feasibility of in situ biodiesel production was investigated. 13.7 g/L sugar was obtained by enzymatic hydrolyzation of rice straw. Chlorella pyrenoidosa showed a rapid growth in the rice straw hydrolysate medium, the maximum biomass concentration of 2.83 g/L was obtained in only 48 hours. The lipid content of the cells reached as high as 56.3%. In situ transesterification was performed for biodiesel production. The optimized condition was 1 g algal powder, 6 mL n-hexane, and 4 mL methanol with 0.5 M sulfuric acid at the temperature of 90°C in 2-hour reaction time, under which over 99% methyl ester content and about 95% biodiesel yield were obtained. The results suggested that the method has great potential in the production of biofuels with lignocellulose as an alternative carbon source for microalgae cultivation.

Erdheim-Chester disease with asymmetric talus involvement: A case report.

BACKGROUND: Erdheim-Chester disease (ECD) is a rare multi-system or multi-organ histiocytic proliferative disease with diverse clinical manifestations, and the development of the disease is complex, which makes clinical diagnosis and treatment difficult. The characteristic clinical manifestations include multi-organ involvement, especially in the symmetrical diaphysis and metaphysis of the bilateral extremities. ECD with a unilateral talus lesion is extremely rare. Here, we report an unusual case of ECD invading the asymmetric talus and tibia without involving other organs. The patient had good outcome after surgery. CASE SUMMARY: We report a case of a 67-year-old man who was referred to our outpatient department because of left ankle chronic pain for 5 years, which exacerbated after a foot sprain 6 mo previously. We discovered multiple sclerotic lesions of the tibia and talus on his previous X-ray films, which were initially missed in a local hospital. Therefore, enhanced computer computed tomography (CT) and magnetic resonance imaging were performed. These examinations showed multiple lesions in the bone marrow cavity of the left tibia, and cortical sclerosis and osteonecrosis of the left talus. Specimens were collected via bone puncture from the two lesions, and a final diagnosis of ECD was confirmed by pathological and immunohistochemical examinations. In addition, other auxiliary examinations including head CT, pulmonary CT, spinal CT, abdominal CT, cardiac ultrasound and thyroid ultrasound showed no obvious abnormalities. The patient underwent surgery for the tibia lesion scraping and talus lesion scraping combined with cement casting. The patient started on a progressive rehabilitation at 4 wk, and felt no pain after surgery. During a 2-year follow-up period, the patient exercised normally without pain, and there were no signs of recurrence. CONCLUSION: This study shows that surgery treatment may also achieve good results for ECD patients with only bone involvement.

Mitochondria-acting nanomicelles for destruction of cancer cells via excessive mitophagy/autophagy-driven lethal energy depletion and phototherapy.

Mitophagy is a specific self-protective autophagic process that degrades damaged or dysfunctional mitochondria, and is generally considered to reduce the effectiveness of mitochondria-targeted therapies. Here, we report an energy depletion-based anticancer strategy by selectively activating excessive mitophagy in cancer cells. We fabricate a type of mitochondria-targeting nanomicelles via the self-assembly of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and dc-IR825 (a near-infrared cyanine dye and a photothermal agent). The TPGS/dc-IR825 nanomicelles enable mitochondrial damage in cancer cells, which, for self-protection, activate two autophagic pathways, (1) mitophagy and (2) adenosine triphosphate (ATP) shortage-triggered autophagy. However, the excessive mitophagy/autophagy activities far surpass the degradative capacity of autolysosomes, leading to the formation of micrometer-sized vacuoles and degradation blockage. Immunofluorescence staining and Western blot analysis reveal that the nanomicelle-treated cancer cells are under severe ATP shortage, which eventually causes substantial cell death. Moreover, the nanomicelles intravenously injected into tumor-bearing mice show high tumor accumulation, long tumor retention, and inhibit the tumor growth by inducing excessive mitophagy/autophagy and energy depletion in tumor cells. Additional near-infrared laser irradiation treatment further enhances the in vitro and in vivo anticancer efficiencies of the nanomicelles, due to the excellent photothermal and photodynamic effects of dc-IR825. We believe that this work highlights the important role of mitophagy/autophagy in treating cancers.

CO2 biofixation and fatty acid composition of Scenedesmus obliquus and Chlorella pyrenoidosa in response to different CO2 levels.

In this study, Scenedesmus obliquus SJTU-3 and Chlorella pyrenoidosa SJTU-2 were cultivated with 0.03%, 5%, 10%, 20%, 30%, 50% CO(2). The two microalgae could grow at 50% CO(2) (>0.69 g L(-1)) and grew well (>1.22 g L(-1)) under CO(2) concentrations ranging from 5% to 20%. Both of the two examined microalgae showed best growth potential at 10% CO(2). The maximum biomass concentration and CO(2) biofixation rate were 1.84 g L(-1) and 0.288 g L(-1) d(-1) for S. obliquus SJTU-3 and 1.55 g L(-1) and 0.260 g L(-1) d(-1) for C. pyrenoidosa SJTU-2, respectively. The main fatty acid compositions of the two examined microalgae were fatty acids with C(16)-C(18) (>94%) under different CO(2) levels. High CO(2) levels (30-50%) were favorable for the accumulation of total lipids and polyunsaturated fatty acids. The present results suggested that the two microalgae be appropriate for mitigating CO(2) in the flue gases and biodiesel production.