Functional Components from the Liquid Fermentation of Edible and Medicinal Fungi and Their Food Applications in China.

Functional raw materials rich in various effective nutrients and active ingredients that are of stable quality can be obtained from the liquid fermentation of edible and medicinal fungi. In this review, we systematically summarize the main findings of this comparative study that compared the components and efficacy of liquid fermented products from edible and medicinal fungi with those from cultivated fruiting bodies. Additionally, we present the methods used in the study to obtain and analyze the liquid fermented products. The application of these liquid fermented products in the food industry is also discussed. With the potential breakthrough of liquid fermentation technology and the continued development of these products, our findings can serve as a reference for further utilization of liquid fermented products derived from edible and medicinal fungi. Further exploration of liquid fermentation technology is necessary to optimize the production of functional components from edible and medicinal fungi, and to enhance their bioactivity and safety. Investigation of the potential synergistic effects of combining liquid fermented products with other food ingredients is also necessary to enhance their nutritional values and health benefits.

The key technologies of Ganoderma lucidum liquid spawn preparation and scale expansion.

Ganoderma lucidum possesses a variety of valuable pharmacological activities, and it has long been used to prevent and treat various human diseases. Up to now, far too little attention has been paid to the liquid spawn of G. lucidum, and the development of the G. lucidum industry is constrained by them. This work aimed to study the key technologies and scale-up preparation of G. lucidum liquid spawn, to achieve large-scale preparation of liquid spawn and solve the problem of unstable quality of G. lucidum. The plate culture, primary shake flask culture, shake flask preparation, and fermentor preparation of G. lucidum liquid spawn were explored in the process of liquid fermentation. The results showed that plate broth volume significantly affected mycelial growth rate. Biomass in the primary shake flask culture is significantly influenced by the picking position of plate mycelium. An artificial neural network coupled with a genetic algorithm was used for carbon and nitrogen sources concentration optimization to increase biomass and substrate utilization. The optimized parameter combination is as follows: glucose, 14.5 g L-1; yeast extract powder, 8.5 g L-1. Under this condition, the biomass (9.82 g L-1) and biomass on reducing sugar (0.79 g g-1) increased by 18.03% and 27.41% compared to the control, respectively. The metabolic activity of liquid spawn prepared by different fermentation scales was diverse, and the liquid spawn prepared by the fermentor has better activity. Conceivably, the liquid spawn process can more conducive be applied to large-scale industrial production.

Coevolutionary insights between promoters and transcription factors in the plant and animal kingdoms.

The divergence and continuous evolution of plants and animals contribute to ecological diversity. Promoters and transcription factors (TFs) are key determinants of gene regulation and transcription throughout life. However, the evolutionary trajectories and relationships of promoters and TFs are still poorly understood. Here, we conducted extensive analysis of large-scale multi-omics sequences in 420 animal species and 223 plant species spanning nearly a billion years of evolutionary history. Results showed that promoter GC-content and TF isoelectric points, as features/signatures that accompany long biological evolution, exhibited increasing growth in animal cells but a decreasing trend in plant cells. Furthermore, the evolutionary trajectories of promoter and TF signatures in the animal kingdom provided further evidence that Mammalia as well as Aves evolved directly from the ancestor Reptilia. The strong correlation between promoter and TF signatures indicates that promoters and TFs formed antagonistic coevolution in the animal kingdom, but mutualistic coevolution in the plant kingdom. The distinct coevolutionary patterns potentially drive the plant-animal divergence，divergent evolution and ecological diversity.

Effects of Oleic Acid Addition Methods on the Metabolic Flux Distribution of Ganoderic Acids R, S and T's Biosynthesis.

The effects of oleic acid addition methods on the metabolic flux distribution of ganoderic acids R, S and T's biosynthesis from Ganoderma lucidum were investigated. The results showed that adding filter-sterilized oleic acid in the process of submerged fermentation and static culture is of benefit to the synthesis of ganoderic acids R, S and T. The metabolic fluxes were increased by 97.48%, 78.42% and 43.39%, respectively. The content of ganoderic acids R, S and T were 3.11 times, 5.19 times and 1.44 times higher, respectively, than they were in the control group, which was without additional oleic acid. Ganoderic acids R, S and T's synthesis pathways (GAP), tricarboxylic acid cycles (TCA), pentose phosphate pathways (PP) and glycolysis pathways (EMP) were all enhanced in the process. Therefore, additional oleic acid can strengthen the overall metabolic flux distribution of G. lucidum in a submerged fermentation-static culture and it can reduce the accumulation of the by-product mycosterol. This study has laid an important foundation for improving the production of triterpenes in the submerged fermentation of G. lucidum.

Changes of structures and biosynthesis/hydrolysis-associated genes expression of glucans at different Volvariella volvacea maturity stages.

In the present study, effects of maturity stage on structural characteristics and biosynthesis/hydrolysis-associated genes expression of glucans from Volvariella volvacea fruit body were well investigated. Elongation and pileus expansion stages decreased total soluble carbohydrate and protein contents to 17.09 mg/g and 8.33 mg/g, and significantly accumulated the total amino acids contents to 32.37 mg/g. Yields of crude polysaccharides significantly increased to 8.12% at egg stage and decreased to 3.72% at pileus expansion stage. Purified VVP I-a and VVP I-b were proved to be α-glucans. The maturity process affected the monosaccharide compositions, decreased the molecular weights of VVP I-a and VVP I-b with decreased transcription levels of glucan biosynthesis-associated enzyme genes vvugp and vvgls and increased glucan hydrolysis-associated glucanase gene vvexg2 expression with no significant effects on backbone structures including glycosidic linkages and configurations. The findings would benefit for understanding change patterns of V. volvacea glucan structures and their biosynthesis/hydrolysis-associated genes expression at maturity stages.

Ganoderic acid T improves the radiosensitivity of HeLa cells via converting apoptosis to necroptosis.

The use of natural substances derived from traditional Chinese medicine and natural plants as safe radiosensitizing adjuvants is a new trend for cancer radiotherapy. Ganoderma lucidum has been used as a traditional Chinese medicine with a history of more than 2000 years. Ganoderic acid T (GAT) is a typical triterpene of G. lucidum, which has strong cytotoxicity to cancer cells, but whether it has radiation sensitization effect has not been explored. In this work, we treated the HeLa cells with different concentrations of GAT before exposure to gamma-ray radiation and investigated its influence on the radiosensitivity. The cell viability, apoptosis rate, necoptosis rate, intracellular ATP level, cell cycle, the amount of H2AX and 53BP1, reactive oxygen species, and mitochondrial membrane potential were examined. Apoptotic, necroptotic, and autophagic biomarker proteins, including caspase 8, cytochrome c, caspase 3, RIPK, MLKL, P62, and LC3, were analyzed. As a result, we confirmed that with treatment of GAT, the gamma-ray radiation induced both apoptosis and necroptosis in HeLa cells, and with increase of GAT, the percentage ratio of necroptosis was increased. The involved pathways and mechanisms were also explored and discussed.

Effects of enzymatic reaction on the generation of key aroma volatiles in shiitake mushroom at different cultivation substrates.

Aroma is an important factor affecting mushroom character and quality. According to the different reaction pathway, the key aroma metabolites (sulfur and eight-carbon volatiles) formation can be classified into enzymatic reactions and nonenzymatic reactions. Aroma volatiles are generated from precursors via the biocatalytic activities of various synthases during the growth stages of shiitake mushrooms. Understanding the specific relationships between the key aroma metabolites and their synthases is key to improving shiitake mushroom quality. At the same time, to reduce forest logging and burning of agricultural by-products in farmland, agricultural by-products have been applied to shiitake mushroom cultivation. Nevertheless, how to further improve the production of aroma volatiles in mushroom cultivated with agricultural waste is still a challenge. In order to understand the biosynthesis of volatiles via enzymatic reactions and screen the agricultural by-products that can improve the production of aroma volatiles in mushroom cultivation, the mechanism of producing aroma volatiles needs to be further elucidated. In this study, the activities and gene expression levels of the key synthases involved in volatile metabolism, the contents of key aroma volatiles, and the correlations between related synthetase, volatiles, and cultivation substrate (CS) were investigated. Network models for visualizing the links between synthetase, volatiles, and CSs were built through partial least squares (PLS) regression analysis. The correlation coefficients among three related synthetase and enzymatic gene expression were high, and the combined effects of multiple synthetase promoted the production of volatiles. PLS analysis showed that the corncob and corn meal were more related to the production of volatiles and synthetase gene expression, and they can be added to the CSs as flavor promoting substances. The enrichment of key aroma volatiles in shiitake mushroom cultivated by the gradient of 20% corn meal combination CS was noticeable.

Screening candidate genes related to volatile synthesis in shiitake mushrooms and construction of regulatory networks to effectively improve mushroom aroma.

BACKGROUND: Metabolite formation is a physiological stress response during the growth and development of shiitake mushrooms (Lentinula edodes). The characteristic flavor metabolites are important quality components in shiitake mushrooms. To investigate the formation mechanisms of characteristic flavor metabolites, transcriptome analyses were performed on shiitake mushrooms harvested at different growth stages. RESULTS: In total, 30 genes related to the synthesis of characteristic volatiles of mushrooms were identified via screening. Through KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis of the selected genes and correlation analyses of gene expressions, the main volatile synthesis pathways were determined as histidine metabolism, glutathione metabolism and biosynthesis of unsaturated fatty acids. Gene cluster and correlation analyses were performed to clarify the combined effects of different genes in the enzymatic reactions. Further, a correlation network of candidate genes was built based on the gene expression levels. CONCLUSION: The activities of flavor synthases and the content of characteristic flavor metabolites were analyzed; the enzyme activity changes and metabolic product distribution sites were clarified. A synthesis and regulation network was constructed for the candidate genes and characteristic volatiles, and information was obtained for 16 hub genes. Moreover, it was essential to identify and characterize the key genes and synthases involved in the synthesis of the characteristic volatiles of mushrooms. This information provides us with a better understanding of the biosynthesis and regulation of the volatiles, which will lay the foundation for improving the quality of shiitake mushrooms. © 2021 Society of Chemical Industry.

Mucinous cystic neoplasm of the liver: A case report.

BACKGROUND: Mucinous cystic neoplasm of the liver (MCN-L) is a cyst-forming epithelial neoplasm. The most distinguishing feature is the ovarian-type subepithelial stroma on pathological examination. CASE SUMMARY: An abdominal ultrasound incidentally revealed a liver tumor in a 32-year-old woman. Physical and laboratory examination results did not reveal any abnormalities. Enhanced abdominal computed tomography (CT) revealed a cystic space measuring 7.2 cm × 5.4 cm in the liver. Subsequent CT showed an increase in tumor size. Thus, we performed surgical resection of the tumor and gallbladder. Postoperative histopathological examination confirmed the diagnosis of MCN-L. At the 6-mo of follow-up, no recurrence was observed on ultrasound or CT. CONCLUSION: Since preoperative diagnosis of MCN-L is difficult, active surgery is recommended and helpful for the diagnosis and treatment of MCN-L.

Increased Inhibition Effect of Antrodin C from the Stout Camphor Medicinal Mushroom, Taiwanofungus camphoratus (Agaricomycetes), on A549 through Crosstalk between Apoptosis and Autophagy.

Antrodin C was obtained from Taiwanofungus camphoratus mycelia. The inhibition effect of antrodin C on A549 lung adenocarcinoma cells was evaluated by plate clone formation, wound healing, cell cycle, activated caspase-3, Bax, P53, Bcl-2, and RAPR activities as well as reactive oxygen species release. Plate clone formation assay revealed that antrodin C could significantly inhibit the viability of A549 cells in vitro. Wound healing assay revealed that cell migration was inhibited by exposure to antrodin C at concentrations of 50 and 80 µg/mL. Flow cytometry revealed that antrodin C increased the percentages of cells in the G0/G1 phase at concentrations of 50 and 80 µg/mL and the apoptosis was related to upregulation of caspase-3, Bax, P53 expression, downregulation of Bcl-2, RAPR expression, and the release of reactive oxygen species in the A549 cells. CQ or RAPA could significantly promote or inhibit the inhibition effect on A549 proliferation induced by antrodin C, which suggests that the autophagy played a cytoprotective role on inhibition proliferation of A549 induced by antrodin C. These results indicated that the combination of pro-apoptosis agents and anti-autophagy agents may be a useful strategy in enhancing the anticancer efficacy in non-small cell lung cancer.

Optimization of Ganoderma lucidum Polysaccharides Fermentation Process for Large-Scale Production.

The objective of this study was to increase the intracellular polysaccharide yield of Ganoderma lucidum. The accordingly optimized fermentation medium by central composite design method contains glucose 40 g L-1, yeast powder 12 g L-1, potassium dihydrogen phosphate 3 g L-1, initial pH 5.5, and inoculum size 10 mL 100 mL-1. Under this condition, the predicted value of intracellular polysaccharide yield was 2.03 g L-1. Shake flask experiments confirmed that the average intracellular polysaccharide yield was 1.98 g L-1 similar to the predicted value. The yields of intracellular polysaccharides in the 5-L and 50-L fermentors were 2.59 g L-1 and 2.65 g L-1, respectively. The molecular weight distribution of intracellular and extracellular polysaccharides obtained was determined by HPSEC-MALLS-RI. The results showed that the weight-average molecular weight of component 1 in the intracellular crude polysaccharide was 4.695 × 106 Da and the mass fraction was 58%. The weight-average molecular weight of component 2 in the extracellular polysaccharide was 5.554 × 104 Da. The mass fraction was 94.9%. The liquid submerged fermentation process of G. lucidum mycelium obtained from this study has effectively increased the yield of intracellular polysaccharides. Its intracellular and extracellular polysaccharides have good immunological activity. Conceivably, the optimized process can be applied for the large-scale production.

Chemical Compounds and Antioxidant Activity of Volatile Oil from the White Jelly Mushroom, Tremella fuciformis (Tremellomycetes).

To fully analyze the composition of volatile oil extracted from Tremella fuciformis, hydrodistillation (HD) and solid phase microextraction (SPME) were adopted simultaneously. In both cases, the analysis was carried out using gas chromatography-mass spectrometry and the antioxidant activity of the volatile oil was determined by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method with rutin as a positive control. Nineteen components in HD and 68 components in SPME were identified, respectively. Moreover, the oil obtained from T. fuciformis by HD indicated that aromatic compounds were a major class (93.5%), followed by the terpenes (5.7%), alkanes (0.4%), and alcohols (0.3%). Among them, butylated hydroxytoluene was the highest concentration (92.5%) of the compounds. The compounds detected by SPME were different from those of HD, and the substances with the largest content were esters (57.7%), followed by alcohols (19.0%), acids (7.0%), and aldehydes (6.3%). Only three of the same substances were detected in both of them, namely borneol, (-)-α-terpineol, and acetic acid. In the DPPH assays, strong antioxidant activity (IC50 = 0.176 mg/mL) was evident in volatile oil from T. fuciformis. Antioxidant activity was positively correlated with the concentration of volatile oil.

Dissolution of Bioactive Components from Dried Fruiting Bodies of the Culinary-Medicinal Shiitake Mushroom, Lentinus edodes (Agaricomycetes), during Cleaning, Soaking, and Cooking.

Lentinus edodes fruiting bodies are rich in active substances such as polysaccharides and eritadenine. Patients with gout, however, should avoid or severely limit their intake of foods containing large amounts of purine. In this study we quantitatively analyzed the polysaccharide and purine compounds dissolved from L. edodes fruiting bodies during cleaning, soaking, and cooking. Eritadenine, adenosine, guanosine, guanosine monophosphate, adenosine monophosphate, xanthine, and adenine dissolved from L. edodes fruiting bodies during cleaning with tap water; their dissolution rates ranged between 3.77% and 24.30%. Dissolution rates of polysaccharide and purine compounds in L. edodes fruiting bodies increased linearly with increases in the duration of soaking and cooking, and adding acetic acid or NaHCO3 in the soaking or cooking solutions significantly either inhibited or promoted their dissolution rates. On the basis of these experimental results, we offer science-based suggestions for reasonable treatment of L. edodes fruiting bodies before eating for both patients with gout and healthy people.

Effect of Culture Time on the Bioactive Components in the Fruit Bodies of Caterpillar Mushroom, Cordyceps militaris CM-H0810 (Ascomycetes).

Cordyceps militaris are widely cultivated in China for an important raw material for health foods. CM-H0810 is a C. militaris strain used in the production of C. militaris in Shanghai, the surrounding areas of Shanghai, and Guangdong province in China. We evaluated the effect of culture time on the bioactive components in the fruit bodies of C. militaris CM-H0810 to provide scientific references for production of C. militaris fruit bodies with good quality. The results showed that the polysaccharide contents increased gradually during 35-45 d, but it declined with the prolongation of culture time. The highest polysaccharide content was 3.46% at 45 d. With the prolongation of culture time the cordycepin content gradually increased; the highest cordycepin content was 3.57 µg/mg at 60 d, which increased 321% compared to that at 35 d. Contrary to cordycepin, the adenosine content declined gradually, with the highest content of 1.86 µg/mg at 35 d and the lowest content of 1.48 µg/mg at 60 d. Our study indicates that it is necessary to select suitable harvest times in view of different compounds that are desirable to obtain in high quantities.

Employment of ARTP to Generate Phellinus baumii (Agaricomycetes) Strain with High Flavonoids Production and Validation by Liquid Fermentation.

To obtain Phellinus baumii strain with high flavonoids yield, ARTP was employed to generate mutants of a Ph. baumii strain, which were screened for higher flavonoids content. After five rounds of screening, four mutants were identified to produce more flavonoids than the wild type strain under optimal conditions, of which A67 was the mutant with the highest flavonoids productive capacity. When cultured in shake flasks, the maximum intracellular total flavonoids production of A67 reached 0.56 g/L, 86.67% higher than the total flavonoids in CK. Antagonistic testing, RAPD, and HPLC analysis suggested that ARTP caused changes of the genetic material and metabolites in Ph. baumii. In addition, the superiority of A67 to CK was proved by liquid fermentation using unstructured kinetic models, which was performed in a 50-L fermentor. The maximum intracellular total flavonoids production and dry mycelium weight of A67 reached 0.64 g/L and 15.24 g/L, which was an increase of 88.24% and 18.23% compared with CK, respectively. This work could provide an efficient and practical strategy to obtain high flavonoids production strains and the superiority of A67 could also provide a reference to further increase flavonoids production of Ph. baumii in large-scale production mode by submerged fermentation process.

Triterpenes and Soluble Polysaccharide Changes in Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), During Fruiting Growth.

We analyzed the changes in triterpenes and soluble polysaccharides in Ganoderma lucidum strain G0119 during 4 growth phases in 3 regions of the fruiting bodies using reversed-phase high-performance liquid chromatography, and we also analyzed the soluble polysaccharides using high-performance size-exclusion chroma-tography-multiple-angle laser-light scattering refractive index analysis. The strong polar triterpenes decreased while weak polar triterpenes increased during the growth cycle of G. lucidum. The highest contents of ganoderic acid B, ganoderic acid A, and ganoderenic acid B were detected in the stipe during phase II, and ganoderic acid S, ganoderic acid T, and ganoderiol B peaked in the base during phase IV. The total content of soluble polysaccharides in samples decreased after the primordium developed into a fruiting body. Two high-molecular-weight fractions were detected in the soluble polysaccharide samples: α-l,4-glucan and ß-l,3-glucan, respectively. They were primarily distributed in the pileus during phase II, and both decreased after this phase. These results led us to select a more suitable growth phase and region for harvesting to obtain extracts with higher contents of triterpenes and soluble polysaccharides.

Kinetic models for the effect of temperature on flavonoid production in liquid submerged fermentation by Phellinus baumii.

Kinetic models and temperature control strategy were established to reflect the effect of temperature (22 °C-30 °C) on flavonoid production of Phellinus baumii (P. baumii) in 6-L fermentor. A modified Logistic equation, Hinshelwood model, and Luedeking Piret equation were used to describe mycelial growth and product formation. The influence of temperature on the estimated kinetic parameters was further studied by regression analysis. Based on kinetic parameters analysis, the new temperature control strategy was proposed. Briefly, at 0-43 H, decreasing temperature (30 °C-28 °C) can shorten the lag phase of mycelial growth, and at 43-90 H, fermentation temperature was reduced gradually from 28 °C to 24 °C to keep high flavonoid productivity. At the fermentation anaphase (90-161 H), temperature was controlled at 24 °C to relieve inhibition of flavonoid and maintain constant production capacity of flavonoid. As a result, the maximum flavonoid yield was reached 4.21 mg/100 mg cell dry weight by temperature control strategy, which was 70.45% higher than that at a constant temperature of 26 °C. Additionally, the establishment of kinetic models based on fermentation temperature, which presented here may provide a scientific basis for further large scales flavonoid production of P. baumii in submerged fermentation.

Structural elucidation of a polysaccharide from Flammulina velutipes and its immunomodulation activities on mouse B lymphocytes.

A novel polysaccharide FVPB2 was purified from fruiting bodies of Flammulina velutipes. Its structure was elucidated by monosaccharide composition and methylation analyses, UV-Visible and FTIR spectroscopy as well as NMR. FVPB2 was a homogeneous heteropolysaccharide (molecular weight ~ 1.50 × 104 Da) containing D-galactose, D-mannose, L-fucose, and D-glucose at molar ratio of 1.9:1.2:1:2.5. In vitro immunomodulatory studies showed FVPB2 induced proliferation of mouse spleen lymphocytes in a dose-dependent manner. The levels of IgM and IgG, secreted by B cells, increased after FVPB2 treatment. So FVPB2 has potential to be a new important immunomodulatory nutraceutical.

Structural Characteristics of the Novel Polysaccharide FVPA1 from Winter Culinary-Medicinal Mushroom, Flammulina velutipes (Agaricomycetes), Capable of Enhancing Natural Killer Cell Activity against K562 Tumor Cells.

FVPA1, a novel polysaccharide, has been isolated from fruiting bodies of the culinary-medicinal mushroom Flammulina velutipes, a historically popular, widely cultivated and consumed functional food with an attractive taste, beneficial nutraceutical properties such as antitumor and immunomodulatory effects, and a number of essential biological activities. The average molecular weight was estimated to be ~1.8 × 104 Da based on high-performance size exclusion chromatography. Sugar analyses, methylation analyses, and 1H, 13C, and 2-dimensional nuclear magnetic resonance spectroscopy revealed the following structure of the repeating units of the FVPA1 polysaccharide Identification of this structure would conceivably lead to better understanding of the nutraceutical functions of this very important edible fungus. Bioactivity tests in vitro indicated that FVPA1 could significantly enhance natural killer cell activity against K562 tumor cells.

MicroRNA-214 Affects Fibroblast Differentiation of Adipose-Derived Mesenchymal Stem Cells by Targeting Mitofusin-2 during Pelvic Floor Dysfunction in SD Rats with Birth Trauma.

BACKGROUND/AIMS: This study investigated whether microRNA-214 (miR-214) targets mitofusin-2 (Mfn2) in the process of fibroblast differentiation of adipose-derived mesenchymal stem cells (ADMSCs) during pelvic floor dysfunction (PFD) in Sprague Dawley (SD) rats with birth trauma. METHODS: The ADMSCs were isolated from 4-6 week male SD rats (n = 20) and were cultured and divided into the blank, miR-214 mimic negative control (NC), miR-214 mimic, miR-214 inhibitor NC, miR-214 inhibitor, empty vector, Mfn2 over-expression and miR-214 + Mfn2 over-expression groups. Fibroblast differentiation of ADMSCs was measured with immunocytochemistry and immunofluorescence methods. The expression of miR-214 and the mRNA and protein expression of Mfn2, FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ and Runx2 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, respectively. A dual-luciferase reporter assay was performed to confirm whether Mfn2 was the target gene of miR-214. RESULTS: During ADMSC differentiation into fibroblasts, miR-214 expression was up-regulated, but the expression of Mfn2 was down-regulated. Fibroblast differentiation of ADMSCs was promoted in the miR-214 mimic group but was inhibited in the miR-214 inhibitor and Mfn2 over-expression groups. The expression of Mfn2 was decreased, but the expression of FSP1, Collagen I, Collagen III, Elastin, LOX, Fibulin-5, PPAR-γ or Runx2 was increased in the miR-214 mimic group; the miR-214 inhibitor group and Mfn2 over-expression group exhibited the opposite results. Mfn2 was the target gene of miR-214. CONCLUSIONS: The study provided strong evidence that miR-214 could promote fibroblast differentiation of ADMSCs by down-regulating Mfn2 to improve PFD in SD rats with birth trauma.