A treadmill exercise reactivates the signaling of the mammalian target of rapamycin (mTor) in the skeletal muscles of starved mice.

It has been well established that a starvation-induced decrease in insulin/IGF-I and serum amino acids effectively suppresses the mammalian target of rapamycin (mTor) signaling to induce autophagy, which is a major degradative cellular pathway in skeletal muscles. In this study, we investigated the systematic effects of exercise on the mTor signaling of skeletal muscles. Wild type C57BL/6J mice were starved for 24h under synchronous autophagy induction conditions. Under these conditions, endogenous LC3-II increased, while both S6-kinse and S6 ribosomal protein were dephosphorylated in the skeletal muscles, which indicated mTor inactivation. Using GFP-LC3 transgenic mice, it was also confirmed that fluorescent GFP-LC3 dots in the skeletal muscles increased, including soleus, plantaris, and gastrocnemius, which clearly showed autophagosomal induction. These starved mice were then subjected to a single bout of running on a treadmill (12m/min, 2h, with a lean of 10 degrees). Surprisingly, biochemical analyses revealed that the exercise elicited a decrease in the LC3-II/LC3-I ratio as well as an inversion from the dephosphorylated state to the rephosphorylated state of S6-kinase and ribosomal S6 in these skeletal muscles. Consistently, the GFP-LC3 dots of the skeletal muscles were diminished immediately after the exercise. These results indicated that exercise suppressed starvation-induced autophagy through a reactivation of mTor signaling in the skeletal muscles of these starved mice.

[Different proportion of potassium chloride and potassium sulphate application on cultivation of Panax notoginseng].

In order to make sure whether Panax notoginseng is sensitive to chloridion and guide fertilization in planting of P. notoginseng, the effects of the different proportion of potassium chloride (KCl) and potassium sulfate (K2SO4) on the yield, quality of P. notoginseng were studied. The results showed that K fertilizer significantly improved the growth of P. notoginseng and increased the biomass per plant or per pot and the content of N, P, K and the content of saponin. In cases of conditions such as potassium, and the effects of K2SO4 on increasing the petiole length, leaf size, rhizome length, root length, and content and accumulation of Ginsenoside Rg1 were better than those of KCl. While compared with K2SO4, KCl was more conducive to augmenting height, root width, the biomass of shoot, rhizome, root and the content of Ginsenoside Rb1 and Rd. There was not remarkable difference in agronomic characters, biomass and the content of N, P, K among KCl, K2SO4 and the combination of KCl and K2SO4. However, the content of saponin of the treatment with combination of KCl and K2SO4 was significant higher than that of single KCl or K2SO4 treatments. K fertilizer significantly increased yield and the content of saponins. And P. notoginseng was not sensitive to chloridion. KCl increased the yield and the content of saponins of P. notoginseng as well as K2SO4, and the combination treatment was superior to single treatment. It is recommended that the KCl should be adopted in production, to reduce the cost of potash fertilizer.

[Comparison of agronomic traits of Panax notoginseng between traditional cultivated fields and new cultivated fields].

OBJECTIVE: In order to provide scientific basis for introduction breeding and production regionalization of Panax notoginseng, the environment of producing area, agronomic traits and medicinal material output were investigated. METHOD: Using field survey sampling at harvest time, agronomic traits indicators of leaf segment, stem segment and roots segment etc. of commodity P. notoginseng, longitude and latitude, elevation, soil type, landform of producing area were measured and observed. RESULT: The P. notogiseng cultivation was expanding from traditional area like Wenshang to new areas as Honghe, Kunming, Qujing at large scale. Comparing with traditional cultivated fields, the elevation of new fields, which are red soil of moderate or low mountain slopes and gentle hills between 1 800-2 130 m, increases markedly. The agronomic traits of new cultivated fields such as plant height, stem diameter, the ground and underground biomass were better than those of traditional cultivated fields in varying degree. Furthermore, the root weight, taproot weight, taproot length and other agronomic index augmented more than 20%. Comparison among different cultivated fields showed P. notoginseng of Honghe Shiping Niujie, Kunming Shilin Guishan, Honghe Jiangshui Guanting etc. had better agronomic traits, the plant were thick and tall, the taproot and the top of reed were large, the number of root was more. Inversely, P. notoginseng of Kunming Guandu Xiaoshao, Guangxi Jingxi Lutong, Wenshang Yanshan Jiangna were thin and small. Cluster analysis showed that cultivated fields of P. notoginseng which was across clustered by traditional and new cultivated fields can be divided into three groups, including a high-yielding region insist of three new cultivated fields Honghe Shiping Niujie, Kunming Shilin Guishan, Honghe Jiangshui Guanting and one traditional cultivated field Wenshan Yanshan Jiangna. Correlation analysis indicated that the size and weight of taproot and top of reed were significantly positive correlated with plant height, stem diameter, leaf size, leaf weight and stem weight. Regression analysis pointed out that stem diameter, leaf width, leaf length/width, leaf weight were the main factors affecting the dry weight of taproot, and the main factors influencing the dry weight of top of reed were plant height, petiole, leaf length, leaf width and other agronomic traits. CONCLUSION: From agronomic traits, P. notoginseng in new cultivated fields were more robust than that in traditional fields, but besides the length of taproot, the difference of rest agronomic traits didn't reach the significant level. It is suggested that, in the west and the north of traditional area, the red soil land of moderate or low mountain slopes and gentle hills where the elevation is between 1 800-2 130 m is suitable for cultivating P. notoginseng. Honghe Shiping Niujie, Honghe Jianshui Guanting, Kuming Shilin Gongshan can be used as vital development area for commodity P. notoginseng.

Ferulic acid induces mammalian target of rapamycin inactivation in cultured mammalian cells.

Ferulic acid (FA), a naturally occurring polyphenol abundant in vegetables and rice bran, is known to possess a potent antioxidant activity, thereby protecting cells from oxidative stress. In the present study, we show that in addition to its known anti-oxidant activity, ferulic acid exerts substantial inhibitory activity on cellular mammalian target of rapamycin (mTor)-signaling pathways. In HeLa cells and mouse primary hepatocytes cultured with conventional nutrient-rich media, ferulic acid (1 mM) elicited dephosphorylation of S6 kinase and its substrate ribosomal S6. The dephosphorylating activity of ferulic acid was almost comparable to that of rapamycin, an established mTor inhibitor (TORC1). We next investigated the effect of ferulic acid on autophagy, a major cellular degradative process, which significantly contributes to the maintenance of cell homeostasis. Using a conventional green fluorescent protein-microtubule-associated protein IA/IB light chain 3 (GFP-LC3) dot assay to evaluate autophagy flux, we showed that ferulic acid caused a significant increase in GFP-LC3 dots under serum-rich conditions in HeLa cells. The enhancement of autophagic flux by ferulic acid was almost equivalent to that of rapamycin. Furthermore, ferulic acid significantly enhanced autophagic degradation of (14)C-leucine-labeled long-lived proteins of cultured mouse hepatocytes under nutrient-rich conditions, but not nutrient-deprived conditions. These results indicate that ferulic acid is almost the equivalent of rapamycin in the ability to inhibit mTor (TORC1), which makes it a potent activator of basal autophagy.

Effects of phosphorus application on yield, quality and phosphorus use efficiency of edible sweetpotato: A case study of Xushu 32.

To explore the appropriate amount of phosphorus (P) fertilizer and improve economic yield and P use efficiency of edible sweetpotato, we took Xushu 32 as an example and compared the effects of different P application rates on yield, quality, P accumulation and P use efficiency of edible sweetpotato based on a two-year field experiment (soil available P content was 31.70 mg·kg-1) from 2018 to 2019. There were five P application levels (P2O5), including 0 (P0), 25 (P25), 50 (P50), 75 (P75) and 100 kg·hm-2(P100). The results showed that, 1) compared with P0, P application significantly increased the yield of fresh sweetpotao and commodity potato, with the effects being the stongest under P75 treatment, followed by P50 treatment. However, there was no significant difference between the two treatments. 2) P application significantly increased the contents of starch and reducing sugar in storage root. The contents of soluble sugar and protein increased significantly under P50 treatment. 3) Du-ring the growth period of 90 to 120 d, P fertilizer supply significantly increased P accumulation and dry matter accumulation of sweetpotato. 4) The apparent P use efficiency (APUE) decreased with increasing P application rates, while P agronomic efficiency (PAE) increased first and then decreased with the increases of P application rates, which was significantly higher under P50 than other treatments. Taking into account the yield, quality, economic yield and P utilization rate of edible sweetpotato, the optimal dosage of P2O5 is 50 kg·hm-2 under the experimental conditions.

Efficacy and safety of pulsatile gonadotropin-releasing hormone therapy in patients with congenital hypogonadotropic hypogonadism: a multicentre clinical study.

BACKGROUND: Pulsatile gonadotropin-releasing hormone (GnRH) therapy may restore function of the hypothalamus-pituitary-gonad axis and induce spermatogenesis in male patients with congenital hypogonadotropic hypogonadism (CHH). The study sought to test the reliability of a newly developed Innopump® hormone pump, and to confirm the efficacy and safety of pulsatile GnRH therapy (by Innopump® hormone pump) in CHH patients. METHODS: From November 2017 to November 2018, 28 male patients with CHH were treated with pulsatile GnRH at Peking Union Medical College Hospital, Beijing Chaoyang Hospital, and Shandong Provincial Hospital. A prospective, self-controlled, 7-day clinical trial was conducted. The primary outcome measures were the efficacy and safety of pulsatile GnRH therapy (which was administered via the Innopump® hormone pump). The secondary outcome measures included total serum testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels. RESULTS: All of the patients participated the clinical study. For 7 days, a dosage prescribed by doctors was accurately administered by the Innopump® hormone pump, and recorded by the pump. During the treatment, LH and FSH levels gradually increased to 2.66±1.74 and 5.05±3.03 IU/L, respectively. Upper respiratory tract infection in 1 patient and slight nausea in another patient were reported, which were confirmed to be unrelated to the pulsatile GnRH therapy. CONCLUSIONS: The Innopump® hormone pump was found to be reliable in drug administration, and to have an accurate alarming system. It effectively and safely treated patients with CHH. Pulsatile GnRH therapy may produce a physiological pattern of GnRH secretion, and re-establish pituitary-gonad axis function by increasing gonadotropin levels.

Mercury, cadmium and lead biogeochemistry in the soil-plant-insect system in Huludao City.

Mercury, cadmium, and lead concentrations of ashed plants and insects samples were investigated and compared with those of soil to reveal their biogeochemical processes along food chains in Huludao City, Liaoning Province, China. Concentration factors of each fragments of the soil-plant-the herbivorous insect-the carnivorous insect food chain were 0.18, 6.57, and 7.88 for mercury; 6.82, 2.01, and 0.48 for cadmium; 1.47, 2.24, and 0.57 for lead, respectively. On the whole, mercury was the most largely biomagnified, but cadmium and lead were not greatly accumulated in the carnivorous insects as expected when the food chain extended to the secondary consumers. Results indicated that concentration factors depended on metals and insects species of food chains.

Bioaccumulation of total and methyl mercury in three earthworm species (Drawida sp., Allolobophora sp., and Limnodrilus sp.).

We determined total and methyl mercury contents in soil, three earthworm species and their vomitus to study the species-specific differences of mercury bioconcentration in Huludao City, a heavily polluted region by chlor-alkali and nonferrous metal smelting industry in Liaoning Province, northeast China. Total and methyl mercury contents were 7.20 mg/kg and 6.94 ng/g in soil, 1.43 mg/kg and 43.03 ng/g in Drawida sp., 2.80 mg/kg and 336.52 ng/g in Alolobophora sp., respectively. Total mercury contents were 0.966 mg/kg in Drawida sp. vomitus and 4.979 mg/kg in Alolobophora sp. vomitus, respectively. Total mercury contents in earthworms and their vomitus were significantly species-specific different and were both in decreasing with earthworms body lengths, which might due to the growth dilution. Among the soil, earthworms and their vomitus, total mercury contents were in the order of soil > earthworms > earthworm vomitus. Methyl mercury was about 3.01% of total mercury in Drawida sp., 12.02% of total mercury in Alolobophora sp., respectively. It suggested that mercury was mostly in inorganic forms in earthworms. Bioaccumulation factors of methyl mercury from soil to earthworms were much higher than those of total mercury, which suggested that methyl mercury might be more easily absorbed by and accumulated in earthworms because of its lipid solubility.

Objectifying research on special region corresponding to five internal organs in colour inspections of Chinese medicine.

OBJECTIVE: To study the differences in a special region (SR) corresponding to five internal organs between the young and the elderly and to verify the effectiveness of a developed system for objectifying research in colour inspections of Chinese medicine (CICM). METHODS: An image acquisition device imitating daylight to meet the requirement of CICM was designed. Image processing software based on CICM theory was developed. A total of 83 normal people were sampled and assigned to two groups. The first group (Group I) included 30 people with an average age of 24±2, and the second group (Group II) included 53 people with an average age of 74±4. After image processing, the chromaticity of 10 SRs corresponding to five internal organs was calculated. R, G, and B represent the chromaticity of color red, green, and blue, L indicates color brightness, whereas a and b denote red and yellow respectively. The difference between the young and the elderly was analyzed. RESULTS: (1) The chromaticity of each SR corresponding to five organs was obtained. The average R, G, B, L, a, and b of the sample were 194.4, 147.6, 119.3, 65.2, 15.5, and 22.3, respectively. (2) The R, G, B, and L of the young were greater than those of the elderly, but the a and b of the young were less than those of the elderly. (3) A statistically significant difference in each SR was found between the young and the elderly (P <0.05). The total differences for the Lung (Fei), Heart (Xin), Liver (Gan), Spleen (Pi), and Kidney (Shen) were 50% (3/6), 66.7% (4/6), 66.7% (4/6), 83.3% (5/6), and 91.7% (33/36), respectively. However, the Kidney SR had the greatest statistical discrepancy. CONCLUSION: The old Chinese saying that human Kidney deficiency worsens with age was verified by the results. The objectifying system used to examine CICM was effective. Thus, this system may be used as a basis for further research.

[Mercury pollution in cricket in different biotopes suffering from pollution by zinc smelting].

Total mercury contents in cricket bodies were studied in different biotopes in the surrounding of Huludao Zinc Plant to discuss the mercury distribution characteristics in cricket and to reveal the effects of environmental mercury accumulation in the short life-cycle insects through comparing cricket with other insect species. The average mercury content in cricket was 0.081 mg x kg(-1) and much higher than those in the control sites (0.012 mg x kg(-1) in average) in different biotopes. Mercury contents were found in the order of cricket head > wing > thorax approximately abdomen > leg. Mercury contents in cricket bodies varied greatly with sample sites. Significant correlation was found between the mercury contents in cricket and the distance from the pollution source as well as the mercury contents in plant stems. No significant correlation was found between the mercury contents in soil and in cricket bodies. Mercury contents in cricket were lower than those in cicadae, similar to those in other insects with shorter life-cycle periods.

Interleukin-11 links oxidative stress and compensatory proliferation.

Apoptotic cells can stimulate the compensatory proliferation of surrounding cells to maintain tissue homeostasis. Although oxidative stress is associated with apoptosis and necrosis, whether it contributes to compensatory proliferation is unknown. Here, we showed that interleukin-11 (IL-11), a member of the IL-6 family of proinflammatory cytokines, was produced by cells in an oxidative stress-dependent manner. IL-11 production depended on the activation in dying cells of extracellular signal-regulated kinase 2, which in turn caused the phosphorylation and accumulation of the transcription factor Fra-1 by preventing its proteasome-dependent degradation. Fra-1 was subsequently recruited to the Il11 promoter and activated gene transcription. Upon acute liver injury in mice, IL-11 was mainly produced by hepatocytes in response to reactive oxygen species that were presumably released from dying hepatocytes. IL-11 that was secreted by the dying cells then induced the phosphorylation of the transcription factor STAT3 in adjacent healthy hepatocytes, which resulted in their compensatory proliferation. Furthermore, an IL-11 receptor (IL-11R) agonist enhanced the proliferation of hepatocytes and ameliorated oxidative stress upon acetaminophen-induced liver injury. Conversely, the effects of acetaminophen were exacerbated in mice deficient in the IL-11R α subunit. Together, these results suggest that IL-11 provides a functional link between oxidative stress and compensatory proliferation.

Liver autophagy contributes to the maintenance of blood glucose and amino acid levels.

Both anabolism and catabolism of the amino acids released by starvation-induced autophagy are essential for cell survival, but their actual metabolic contributions in adult animals are poorly understood. Herein, we report that, in mice, liver autophagy makes a significant contribution to the maintenance of blood glucose by converting amino acids to glucose via gluconeogenesis. Under a synchronous fasting-initiation regimen, autophagy was induced concomitantly with a fall in plasma insulin in the presence of stable glucagon levels, resulting in a robust amino acid release. In liver-specific autophagy (Atg7)-deficient mice, no amino acid release occurred and blood glucose levels continued to decrease in contrast to those of wild-type mice. Administration of serine (30 mg/animal) exerted a comparable effect, raising the blood glucose levels in both control wild-type and mutant mice under starvation. Thus, the absence of the amino acids that were released by autophagic proteolysis is a major reason for a decrease in blood glucose. Autophagic amino acid release in control wild-type livers was significantly suppressed by the prior administration of glucose, which elicited a prompt increase in plasma insulin levels. This indicates that insulin plays a dominant role over glucagon in controlling liver autophagy. These results are the first to show that liver-specific autophagy plays a role in blood glucose regulation.

[Mercury contents and distribution characteristics in cicadae].

Total mercury contents of cicadae bodies, wings and exuviaes were studied in Huludao City to discuss mercury distribution characteristics in cicadae and to reveal the environmental mercury accumulation effects in the long life-cycle insects through comparing cicadae with other insect species. The average mercury contents of cicadae bodies were 2. 64 mg x kg(-1) and much higher than those in the contrast sites (1.00 mg x kg(-1) on average) in Huludao City. Mercury contents were found in the order of cicadae bodies > wings (0.98 mg x kg(-1) on average) > exuviaes (0.50 mg x kg(-1) on average). Sex differences of mercury contents and body weights of cicadae were significantly great. The females had larger body weights (1.11 g on average) and lower mercury contents (1.34 mg x kg(-1) on average) than the males (body weight: 0.54 g on average; mercury contents: 3.38 mg x kg(-1) on average), respectively. Mercury contents of cicada's bodies varied greatly with sample sites, mercury contents of wings changed little. No significant correlation was found between mercury contents of soil and cicadae bodies. Mercury contents of cicadae were lower than those of dragonflies, higher than those of other insects with shorter life-cycle periods and it reflected the accumulation effects of environmental mercury in the long life-cycle insects such as cicadae.

[Heavy metal contents in insects collected from the Huludao City suffering pollution by zinc smelting and cholor-alkai production].

14 insect species, which were classified to three groups: the herbivorous, the polyphagous and the carnivorous, and earthworms were collected from the grasslands in Huludao City, Liaoning Province, China. Mercury, cadmium and lead contents in biota were determined to discuss the heavy metal pollution in organisms. Mercury, cadmium and lead contents were 0.168, 9.19 and 12.58 mg x kg(-1) in the herbivorous insects, respectively; 0.375, 24.43 and 17.71 mg x kg(-1) in the polyphagous insects, respectively; 0.928, 29.78 and 18.39 mg x kg(-1) in the carnivorous insects, respectively. It showed that heavy metal pollution in biota in Huludao City was heavy. Bioaccumulation abilities to heavy metals significantly differed with insect species. Snails and dragonflies could accumulate more mercury than the other insects and spiders could accumulate the most cadmium and lead in all insect species. These three metals investigated in insects were all sorted as the herbivorous < the polyphagous < the carnivorous. Cadmium and lead contents between the polyphagous and the carnivorous varied slightly. Correlation analysis showed that cadmium and lead contents were significantly related, but mercury and cadmium or mercury and lead were not. It indicated that cadmium and lead in insects were from the same pollution sources while mercury was more complex.

[Transfer characteristics of mercury, lead, cadmium, zinc and cuprum from soil to vegetable around zinc smelting plant].

The transfer characteristics of Hg, Pb, Cd, Zn and Cu from soil to vegetables near zinc smelting plant in Huludao City, China were investigated, and the sources of heavy metals in the soil and vegetable were also analyzed. The results indicate that the Hg, Pb, Cd, Zn and Cu contents of vegetables are 0.013, 5.476, 2.852, 41.16 and 1.515 mg/kg (fresh weight), respectively, and the environment around Huludao Zinc Plant are contaminated seriously. The transfer factors (TF) of heavy metals decrease in the order of Cd > Zn > Cu > Pb > Hg. The transfer factors of heavy metals from soil to leaves are higher than from soil to other tissues. The heavy metals in soil derive from atmosphere, and the parts of Pb in the leaves of vegetable derive from atmosphere. Uptake of gaseous mercury is the predominant pathway by which mercury accumulates in the vegetable.

[Total and methyl mercury contents in arthropods].

We researched mercury contents in plants and arthropods collected from the river banks in mercury polluted areas. The results show that total mercury (T-Hg) and methyl mercury (Me-Hg) in Locusta migratoria manilensis and Acrida chinensis are 0.032 - 0.402 mg x kg(-1), 0.023 - 0.362 mg x kg(-1) and 0.003 - 0.031 mg x kg(-1), 0.004 - 0.015 mg x kg(-1) while the proportion of Me-Hg to T-Hg are 3.5% - 49.7% and 2.0% - 44.4%. T-Hg in arthropods is higher than that a magnitude in non-polluted areas. As primary consumers, mercury contents in Locusta migratoria manilensis and Acrida chinensis are lower than plants they eat. That is not consistent with the non-polluted areas. Paratenodera sinensis is the second consumer and there is an obvious mercury accumulation in it. For Locusta migratoria manilensis, T-Hg decreased with the body length while for Acrida chinensis that increased following a decreasing. But Me-Hg in both increased with body length. Mercury contents in tissues of arthropods are significantly different. The order is abdomen > thorax > head. Mercury and methyl mercury contents in arthropods would lead wild birds, fowls and amphibians in the ecologic risk condition.

Sphingosine 1-phosphate protects rat liver sinusoidal endothelial cells from ethanol-induced apoptosis: Role of intracellular calcium and nitric oxide.

In alcoholic liver disease, ethanol-induced damage to sinusoidal endothelial cells (SECs) appears to be important in the progression of liver damage. However, little is known about the mechanisms responsible for protection of SECs against ethanol-induced injury. To elucidate the role of sphingosine 1-phosphate (S1P), which is stored in platelets and may be released from them on their activation, we investigated the effect of S1P on rat liver SECs in primary culture. Pretreatment of cells with 1 mumol/L S1P attenuated ethanol-induced apoptosis. Electron microscopy confirmed this protective effect of S1P on damaged SECs in liver tissues after perfusion of ethanol. In the absence of ethanol, S1P increased DNA synthesis as determined via incorporation of bromodeoxyuridine. S1P also ameliorated the decreased DNA synthesis of cells induced by ethanol. Addition of S1P to cells induced an increase in intracellular calcium concentrations and NO production in cells. Western blotting revealed that S1P significantly induced the activation of endothelial NO synthase (eNOS), but not Akt, and that S1P-induced activation of eNOS was blocked by trifluoperazine, a calmodulin inhibitor. Furthermore, N(G)-nitro-L-arginine methyl ester, a NO synthase inhibitor, cancelled the effect of S1P on DNA synthesis, apoptosis, and NO production in vitro as well as the protective effect of S1P on cell damage in situ. In conclusion, the biological effect of S1P is at least partially mediated by Ca(2+)-sensitive eNOS activation and subsequent NO formation; extracellular S1P could contribute to sinusoidal protection and remodeling in alcoholic liver injury.