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Existing methods for muscle atrophy evaluation based on muscle size measures from ultrasound images are inadequate in precision. Radiomics has been widely used in various medical studies, but its validity for the evaluation of muscle atrophy has not been fully explored.This study presents a radiomics analysis for muscle atrophy evaluation using ultrasound images. The hindlimb unloading rat model was developed to simulate weightlessness muscle atrophy and ultrasound images of the hind limbs were acquired for both the hindlimb unloaded (HU) and control groups during a 21-day HU period. A total of 368 radiomics features were extracted and the stable and informative features were selected through a two-stage feature selection procedure. The feature change trajectory of the stable features was analyzed using the hierarchical clustering method. Finally, an adaptive longitudinal feature selection and grading network, ALNet, was developed to evaluate muscle atrophy.The clustering trajectories of ultrasound image features showed similar trends to the changes in muscle atrophy at the molecular level. The best grading accuracy achieved by the ALNet was 79.5% for the Soleus (Sol) muscle and 82.6% for the Gastrocnemius (Gas) muscle.The test-retest is essential in performing radiomics analysis on ultrasound images. The longitudinal feature selection is important for muscle atrophy grading. The ultrasound image features of the Gas muscle have better discrimination ability than that of the Sol muscle. This study proves for the first time the capability of ultrasound image features for muscle atrophy evaluation.

Long-term exposure to microgravity leads to muscle atrophy, which is primarily characterized by a loss of muscle mass and strength and reduces one′s functional capability. A weightlessness-induced muscle atrophy model was established using the tail suspension test to evaluate the intervention or therapeutic effect of low-intensity pulsed ultrasound (LIPUS) on muscle atrophy. The rats were divided into five groups at random: the model group (B), the normal control group (NC), the sham-ultrasound control group (SUC), the LIPUS of 50 mW/cm2 radiation group (50 UR), and the LIPUS of 150 mW/cm2 radiation group (150 UR). Body weight, gastrocnemius weight, muscle force, and B-ultrasound images were used to evaluate muscle atrophy status. Results showed that the body weight, gastrocnemius weight, and image entropy of the tail suspension group were significantly lower than those of the control group (p < 0.01), confirming the presence of muscle atrophy. Although the results show that the muscle force and two weights of the rats stimulated by LIPUS are still much smaller than those of the NC group, they are significantly different from those of the pure tail suspension B group (p < 0.01). On day 14, the gastrocnemius forces of the rats exposed to 50 mW/cm2 and 150 mW/cm2 LIPUS were 150% and 165% of those in the B group. The gastrocnemius weights were both 135% of those in the B group. This suggests that ultrasound can, to a certain extent, prevent muscular atrophy.

Skeletal muscle atrophy (SMA) is a dominant symptom induced by estrogen deficiency which can lead to severe health problems of postmenopausal women. Furthermore, estrogen deficiency has severely compromised the maintenance of muscle stem cells as well as impairs self-renewal and differentiation into muscle fibers. Resistance training is commonly considered as a positive and useful intervention in accelerating the rate of muscle growth. As one of the resistance training, whether the weight-bearing exercise can alleviate SMA induced by estrogen deficiency has not been investigated. The rats were divided into 3 groups randomly: sham group, ovariectomized (OVX) group, and weight-bearing exercise (WBE) therapeutic group. The weight that rats were loaded was 35% of their body weight, and the rats were trained by treadmill training (5° slope, 20 m/min, 30 min/day, 6 days/week) for 8 weeks. After training, the quality and strength of skeletal muscle of the WBE rats were improved; meanwhile, the cross-sectional areas of the skeletal muscle were also increased. Moreover, the WBE activated Akt significantly, upregulated the expression of mTOR, and downregulated the expression of MSTN and its receptor ActRIIB and FoxO1, respectively. The SMA phenomena of rats which induced by estrogen deficiency were prevented effectively via WBE, and the MSTN/Akt/mTOR and FoxO1 signaling pathway may be the predominant way in this improvement.

Zearalenone(ZEA) is a kind of mycotoxin widely existing in nature, its toxic effects can lead to the reproductive disorders in humans and animals. The aim of this study was to investigate the mechanism of scutellarin against ovarian granulosa cell(GCs) injury induced by ZEA based on network pharmacology, molecular docking method. The results show that 293 drug targets of scutellarin were found from PhamMapper database, and 583 disease targets were selected from Genecards database. Finally, 57 scutellarin targets were obtained for the repair of GCs injury with gene intersection. The protein-protein interaction(PPI), gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) analysis indicated that MAPK signaling pathway was most likely activated by scutellarin. Scutellarin with JNK or Caspase-3 had minimal and negative free binding energy in molecular docking analysis, indicating that they might be the acting targets of scutellarin. Cell viability was significantly decreased in ZEA treated cells. However, GCs viability, the level of estradiol(E2) and progesterone(P4) were significantly increased with addition of scutellarin to ZEA treated cells. Western blot analysis showed that scutellarin significantly reduced the expression of JNK, c-jun and Cleaved-caspasee-3 in GCs compared with ZEA treatment. In conclusion, scutellarin could alleviate the ovarian GCs injury by down-regulating the expression of JNK, c-jun and Cleaved-caspase-3 through the activation of MAPK/JNK signaling pathway. Our results will provide a theoretical foundation for the treatment of reproductive disorders with scutellarin.

Low-intensity pulsed ultrasound (LIPUS) has been proved to promote the proliferation of myoblast C2C12. However, whether LIPUS can effectively prevent muscle atrophy has not been clarified, and if so, what is the possible mechanism. The aim of this study is to evaluate the effects of LIPUS on muscle atrophy in hindlimb unloading rats, and explore the mechanisms. The rats were randomly divided into four groups: normal control group (NC), hindlimb unloading group (UL), hindlimb unloading plus 30 mW/cm2 LIPUS irradiation group (UL + 30 mW/cm2), hindlimb unloading plus 80 mW/cm2 LIPUS irradiation group (UL + 80 mW/cm2). The tails of rats in hindlimb unloading group were suspended for 28 days. The rats in the LIPUS treated group were simultaneously irradiated with LIPUS on gastrocnemius muscle in both lower legs at the sound intensity of 30 mW/cm2 or 80 mW/cm2 for 20 min/d for 28 days. C2C12 cells were exposed to LIPUS at 30 or 80 mW/cm2 for 5 days. The results showed that LIPUS significantly promoted the proliferation and differentiation of myoblast C2C12, and prevented the decrease of cross-sectional area of muscle fiber and gastrocnemius mass in hindlimb unloading rats. LIPUS also significantly down regulated the expression of MSTN and its receptors ActRIIB, and up-regulated the expression of Akt and mTOR in gastrocnemius muscle of hindlimb unloading rats. In addition, three metabolic pathways (phenylalanine, tyrosine and tryptophan biosynthesis, alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism) were selected as important metabolic pathways for hindlimb unloading effect. However, LIPUS promoted the stability of alanine, aspartate and glutamate metabolism pathway. These results suggest that the key mechanism of LIPUS in preventing muscle atrophy induced by hindlimb unloading may be related to promoting protein synthesis through MSTN/Akt/mTOR signaling pathway and stabilizing alanine, aspartate and glutamate metabolism.

Low-intensity pulsed ultrasound (LIPUS) is effective in promoting bone healing, and a myostatin deficiency also has a positive effect on bone formation. In this study, we evaluated the effects of LIPUS on bone healing in rats in vivo and investigated the mechanisms in vitro, aiming to explore whether LIPUS promotes bone healing through inhibition of the myostatin signaling pathway. Rats with both drill-hole defects and MC3T3-E1 cells were randomly assigned to a LIPUS group and a control group. The LIPUS group received LIPUS treatment (1.5 MHz, 30 mW/cm2) for 20 min/day. After 21 days, the myostatin expression in quadriceps was significantly inhibited in the LIPUS group, and remodeling of the newly formed bone in the drill-hole site was significantly better in the LIPUS group than that in the control group, which was confirmed by micro-CT analysis. After 3 days, LIPUS significantly promoted osteoblast proliferation; inhibited the expression of AcvrIIB (the myostatin receptor), Smad3, p-Smad3, and GSK-3β; and increased Wnt1 and β-catenin expression. Moreover, translocation of β-catenin from the cytolemma to the nucleus was observed in the LIPUS group. However, these effects were blocked by treatment with myostatin recombinant protein. The results indicate that LIPUS may promote bone healing through inhibition of the myostatin signal pathway.

Daya Bay is an ecologically and economically crucial semi-closed bay along the southern coast of China. It is proven to be a stressed ecosystem and therefore obviously vulnerable to further extrinsic disturbance. This study used fish data from bottom-trawl surveys, conducted from 1985 to 2018, to analyze variations in the fish community structure over the past 30 years. The results showed that warm-water fish species were overwhelmingly dominant during all years, suggesting the bay's tropical to subtropical characteristic. By 2015, the number of fish species had decreased by 29.44% of that caught in 1987, moreover, values of the Shannon–Wiener diversity index and the Margalef richness index were lower in 2015 compared to 2004. There were evident shifts in the fish community composition from pelagic to demersal species, as suggested by the dominant species found in springtime, the dominant families, and percentages denoting the numbers of species in the main orders. Average fish body weight in landings declined from 13.4 g to 7.58 g, the body sizes of four typical commercial fish species decreased by varying degrees over the last 30 years. Abundance–biomass comparison curves suggested that the Daya Bay fish community was more stressed in 2015 than in 2004 during all seasons, except winter. In general, the fish community structure in Daya Bay is consequently in an unsteady state. Multiple anthropogenic disturbances, such as fishing (including overfishing and changes in the main fishing gears), the destruction of natural habitats, pollutants, and anthropogenically induced temperature changes, are likely to have caused obvious shifts in the bay's fish community structure. Therefore, we emphasize the need for integrating management of multiple anthropogenic stressors to achieve ecosystem-based management.

The purpose of this study was to investigate whether low-intensity pulsed ultrasound (LIPUS) promotes exercise-induced muscle hypertrophy. Twenty-four adult Sprague-Dawley (SD) rats were randomly assigned to three groups (n = 8 per group): normal control group (NC), treadmill exercise group (TE) and treadmill exercise + LIPUS group (TE + LIPUS). The TE + LIPUS group received a LIPUS treatment (1 MHz, 30 mW/cm2) at the gastrocnemius for 20 min/d after treadmill exercise. The TE group was sham-treated. Eight weeks of treadmill training successfully established the exercise-induced muscle hypertrophy model. Muscle strength, muscle mass and muscle fiber cross-sectional area were significantly increased in the TE + LIPUS group compared with the TE group. Moreover, LIPUS treatment significantly upregulated the expression of Akt, mTOR, p-Akt and p-mTOR and significantly downregulated the expression of MSTN, ActRIIB, FoxO1 and its phosphorylation. The results indicated that LIPUS promotes exercise-induced muscle hypertrophy by facilitating protein synthesis and inhibiting the protein catabolism pathway.

Menopause can lead to osteoporosis, which is characterized by destruction of bone microstructure, poor mechanical properties, and prone to fracture. LIPUS can effectively promote bone formation and fracture healing. MSTN is a transforming growth factor-β family member that acts as a negative regulator of skeletal muscle growth. A MSTN deficiency also has a positive effect on bone formation. However, whether LIPUS could inhibit bone loss and promote healing of bone injury of menopause through the inhibition of the MSTN signaling pathway has not been previously investigated. We herein investigated the effects of LIPUS on bone architecture, mechanical properties, the healing of bone defects, and its potential molecular mechanisms in ovariectomized rats. The rats were randomly divided into three groups: sham ovariectomized group (Sham), ovariectomized model group (OVX), ovariectomized model with LIPUS therapy group (OVX + LIPUS). The OVX + LIPUS rats were treated with LIPUS (1.5 MHz, 30 mW/cm2) on the femur for 20 min/day that lasted for 19 days. LIPUS effectively improved the bone microstructure, increased mechanical properties and promoted the healing of bone defects in ovariectomized rats. Moreover, LIPUS effectively decreased the MSTN content in serum and quadriceps muscle in ovariectomized rats, and inhibited the expression of MSTN downstream signaling molecules and activated the Wnt signaling pathway in the femur. The present study shows that LIPUS improved osteoporosis and promoted bone defect healing in the ovariectomized rats may through the inhibition of the MSTN signal pathway.

Low-intensity pulsed ultrasound (LIPUS) has been used to accelerate bone fracture healing. However, the issue whether LIPUS is effective in preventing osteoporosis has not been clarified, and if so, what possible mechanisms might be responsible. Myostatin (MSTN) is a negative regulator of muscle growth, and its absence will trigger a positive response to bone. In this study, we examined the effects of LIPUS on bone micro-structure, mechanical properties and damage healing of hindlimb-suspended rats, and investigated whether the inhibition of MSTN plays a role in this process. The rats were randomly divided into four groups: Normal control group (NC), Hind limb suspension group (HLS), Hind limb suspension and 80 mW/cm2 LIPUS irradiation group (HLS+ 80 mW/cm2), Hind limb suspension and 30 mW/cm2 LIPUS irradiation group (HLS+ 30 mW/cm2). The HLS+ 80 mW/cm2 rats were treated with LIPUS (1 MHz, 80 mW/cm2) and the HLS+ 30 mW/cm2 rats were treated with LIPUS (1 MHz, 30 mW/cm2) on the femur for 20 min/day for 28 days. MC3T3-E1 cells were respectively cultured with the serum of wild type mouse and MSTN knockout mouse at 1% concentration for 7 days. After 28 days, LIPUS effectively prevented the destruction of bone microstructure and the decline of mechanical properties, and promoted bone defect healing in the tail-suspended rats. In addition, LIPUS effectively reduced the MSTN content in the quadriceps and serum of the tail-suspended rats, inhibited its receptor and downstream signaling molecules and activated the Wnt signaling pathway in femurs. Growth of MC-3T3-E1 cell cultured with the serum of MSTN knockout mice was superior to that with wild mice serum on day 7. These results indicate that MSTN is a key mediator in LIPUS preventing bone loss caused by hindlimb-suspension.

Background Type 1 diabetes mellitus (T1DM) induces serious skeletal muscle atrophy. Low-intensity pulsed ultrasound (LIPUS) is a common treatment for skeletal muscle injury and is effective in accelerating the rate of muscle growth. However, to the best of our knowledge, whether LIPUS can improve skeletal muscle atrophy in type 1 diabetic rats has not been investigated. Methods The rats were randomly divided into four groups: the normal control group (NC); the sham-treated diabetic control group (DC); the diabetic, insulin-treated group (DI) as a positive control; and the diabetic LIPUS therapy group (DL). The DL rats were treated with LIPUS (1 MHz, 30 mW/cm2) on the gastrocnemius for 20 min/day. Results After 6 weeks, the rats in the DC group showed severe muscle atrophy. However, LIPUS significantly improved type 1 diabetes-induced muscle atrophy, as evidenced by significantly enhanced muscle cross-sectional area, muscle mass, and strength. Moreover, compared with the DC group, LIPUS significantly activated Akt and upregulated the expression of mTOR, and LIPUS downregulated the expression of MSTN, its receptor ActRIIB, and FoxO1. Conclusions These results indicate that LIPUS improved muscle atrophy induced by type 1 diabetes, and the MSTN/Akt/mTOR&FoxO1 signaling pathway may play a role in this improvement.

The subventricular zone along the anterior horn (SVZa) of the cerebral lateral ventricle of adult mammals contains multipotent progenitor cells, which supposedly exist in an angiogenic niche. Numerous signals are known to modulate the precursor cell proliferation, migration or differentiation, in rodent models. In contrast, the data on signals regulating the primate SVZa precursors in vivo are scarce. We analyzed the expression at protein level of a panel of angiogenic and/or neurotrophic factors and their receptors in SVZa of adult macaque monkeys, under normal condition or after transient global ischemia which enhances endogenous progenitor cell proliferation. We found that fms-like tyrosine kinase 1 (Flt1), a receptor for vascular endothelial cell growth factor, was expressed by over 30% of the proliferating progenitors, and the number of Flt1-positive precursors was significantly increased by the ischemic insult. Smaller fractions of mitotic progenitors were positive for the neurotrophin receptor tropomyosin-related kinase (Trk) B or the hematopoietic receptor Kit, while immature neurons expressed Flt1 and the neurotrophin receptor TrkA. Further, SVZa astroglia, ependymal cells and blood vessels were positive for distinctive sets of ligands/receptors, which we characterized. The presented data provide a molecular phenotypic analysis of cell types comprising adult monkey SVZa, and suggest that a complex network of angiogenic/neurotrophic signals operating in an autocrine or paracrine manner may regulate SVZa neurogenesis in the adult primate brain.

Molecular signals regulating adult neurogenesis in primates are largely unknown. Here the authors used differential display to analyze gene expression changes that occur in dentate gyrus of adult monkeys after transient global cerebral ischemia. Among 14 genes upregulated, the authors focused on Down syndrome cell adhesion molecule (DSCAM) known to play crucial role during neuronal development, and characterized its expression pattern at the protein level. In contrast with approximately threefold upregulation of Dscam gene on days 5 and 7, immunoblotting and immunofluorescence analyses using specific antibodies showed a gradual decrease of DSCAM after ischemia until day 9 followed by recovery on day 15. In the control, immunofluorescence reactivity of DSCAM was detected in dentate gyrus granule cells and CA4 neurons but decreased after ischemia, being compatible with the immunoblotting data. However, in the subgranular zone, cerebral ischemia led to a marked increase of DSCAM-positive cells on days 9 and 15. DSCAM upregulation was seen in two cell types: one is immature neurons positive for polysialylated neural cell adhesion molecule or βIII-tubulin, while another is astrocytes positive for S100β. Young astrocytes were in intimate contact with newly generated neurons in the subgranular zone. These data suggest implication of DSCAM in the adult neurogenesis of primate hippocampus upregulated after ischemia. © 2006 Wiley-Liss, Inc.