Source to risk receptor transport and spatial hotspots of heavy metals pollution in peri-urban agricultural soils of the largest megacity in China.

The traditional concentration-based health risk assessment of heavy metal (HMs) pollution in soil has often overlooked the initial loading and toxicity differences of HMs from various sources. This oversight hinders effective identification of the risky source, complicating precise risk management of soil HMs pollution. This study applied a source-oriented health risk assessment framework that integrates source profiling, exposure risk assessment, and spatial cluster analysis. Taking the Shanghai City, the largest megacity in China as a case, the findings revealed that overall environmental quality of peri-urban agricultural soil in Shanghai remains good, though 3.03 % of Cd concentrations exceeded the national reference standards. Industrial & traffic activities, primarily contributing Hg, Cd, and Pb, accounted for the highest proportion (44.3 %) of total metal concentrations and posed the greatest non-cancer risk (54.6 % for children and 53.1 % for adults). Notably, natural activities, mainly contributing Cr, ranked only third in concentration contribution (26.55 %) but induced the highest cancer risk (58.55 % for children and 57.08 % for adults). These findings suggest that sources with lower concentration contributions may still pose significant health risk. Integrating source apportionment with health risk assessment can more precisely identify the risky source and target areas for mitigating the human health hazards.

Appropriate sulfur fertilization in contaminated soil enhanced the cadmium uptake by hyperaccumulator Sedum alfredii Hance.

The biogeochemical processes of sulfur and heavy metals in the environment are closely related to each other. We investigated the influence of sulfur addition on hyperaccumulator Sedum alfredii Hance growth, cadmium (Cd) accumulation, soil Cd bioavailability, soil bacterial communities and plant transcriptome responses. The results showed that an appropriate rate of sulfur addition (1.0 or 2.5 g/kg) enhanced the growth of Sedum alfredii Hance plants as well as their accumulation of Cd. A high rate of sulfur addition (5.0 or 10.0 g/kg) causes toxicity to Sedum alfredii Hance plants. The application of an appropriate amount of sulfur to the soil increased the abundance of sulfur-oxidizing bacteria such as Sulfuriferula and Thiobacillus; acid-fast bacillus such as Alicyclobacillus; and cadmium-tolerant bacteria such as Bacillus and Rhodanobacter. This led to a decrease in pH and an increase in bioavailable Cd in the soil. RNA sequencing revealed that the addition of sulfur to soils led to the up regulation of most of the differentially expressed genes (DEGs) involved in "photosynthesis" and "photosynthesis, light reaction" in Sedum alfredii Hance leaves. Moreover, the "plant hormone signal transduction" pathway was significantly enriched with sulfur addition. Sulfur assimilation in Sedum alfredii Hance plants may promote photosynthesis and hormone synthesis, leading to Cd tolerance in these plants. Our study revealed that sulfur fertilization enhanced the efficiency of Cd phytoremediation in Sedum alfredii Hance plants.

Long-Term Stable Superlubricity Coatings Enabled by the Interaction between the Polydimethylsiloxane Brush and Silicone Oil.

Recently, materials with superlubricity captured widespread attention on account of their great potential in energy savings and environmental protection. However, certain issues still remain to be solved for the traditional materials, such as the dependence on strict conditions and an unstable superlubricity state. Herein, a long-term stable superlubricity coating was prepared using a low-cost and simple method via an epoxy-based coating with polydimethylsiloxane (PDMS) brushes under silicone oil (SO) lubrication conditions. Compared with the pure epoxy resin matrix, the friction coefficient and wear track width of the superlubricity coating with the optimal amount of 6 wt % PDMS are reduced to 0.006 and 50.9 µm (reduced by 10-fold and 5.6-fold decrease, respectively). In addition, the coating can maintain a stable superlubricity state during a 5 h tribological test. The superlubricity of the coating results from the synergistic lubrication effect of the PDMS brush and SO. First, PDMS brushes with high-stretched conformation due to the swelling effect of the SO can significantly reduce friction. Second, a stable oil film is generated between the contact surfaces, which significantly improves the frictional performance. Moreover, the PDMS incorporated into the coating matrix, along with oil-swelling PDMS brushes on the surface, is highly beneficial for enhancing corrosion resistance of the epoxy resin matrix. Such an epoxy-based coating with long-term stable superlubricity is considered as a potential lubricating and protective surface for tribological components for long-term service.

Hemolymph Node - An Immunomorphlogical Organ: Modeling the Hemolymph Node by Allografting Renal Tissue in the Rat.

There is no authoritative characterization of the attributes of the hemolymph node (HLN) since Gibbes' first description in 1884. Early reports showed that HLN are found near the kidney in human and animals with the feature of numerous erythrocytes in sinuses. Subsequent studies mainly focused on anatomy and histology, such as the source, distribution, and quantity of erythrocytes in sinuses. Recent articles mentioned that the emergence of HLN was related to immunity, but there was no strong evidence to support this hypothesis. Therefore, it is still uncertain whether the HLN is an organ of anatomy, histology, or immunology. It has been found that the development of HLN could be elicited in the parathymic area by stimuli such as Escherichia coli, allogeneic breast cancer cells, and renal tissue that were injected/transplanted into the tail of rats in our pilot studies. In this study, the model of the HLN was established by transferring allogeneic renal tissue in the rat. Intrasinusoidal erythrocytes of the node were the component for producing a red macroscopic appearance, while macrophage-erythrocyte-lymphocyte rosettes were the major immunomorphological changes, reflecting the immune activity against the invasion of the allogeneic tissue within the node. Therefore, the HLN is an immunomorphological organ.

Prognostic analysis of hepatocellular carcinoma with macrovascular invasion after liver resection and a successful case of conversion therapy.

Objective: Macrovascular invasion (MVI) is an important factor leading to poor prognosis in hepatocellular carcinoma (HCC). Liver resection may offer favorable prognosis for selected patients with HCC. This study aimed to analyze the prognostic factors of HCC with MVI after liver resection as well as demonstrate a case of conversion therapy in an HCC patient with portal vein tumor thrombus (PVTT). Methods: A total of 168 HCC patients with MVI who underwent primary liver resection at the Affiliated Hospital of Qingdao University between January 2013 and October 2021 were enrolled in the study. Clinicopathological data were collected retrospectively. Univariate and multivariate regression analyses were used to investigate the risk factors influencing recurrence and overall survival. Additionally, conversion therapy with drug-eluting bead transarterial chemoembolization (D-TACE), and sorafenib plus sintilimab treatment was performed in an HCC patient with PVTT. Results: Among the 168 patients with HCC, 11 were diagnosed with hepatic vein tumor thrombosis, and the rest were diagnosed with PVTT. The 1-year disease-free survival rate was 37.5%, and the 3-year overall survival rate was 52.7%. Univariate and multivariate regression analyses revealed that HBsAg positivity, alpha-fetoprotein (AFP) level ≥400 ng/ml, liver capsule invasion, and tumor number ≥2 were independent prognostic factors for tumor recurrence, whereas HBsAg positivity was an independent risk factor for overall survival. Postoperative prophylactic medication did not significantly prolong the recurrence time. The median survival time (MST) after tumor recurrence was 13.4 months. In the patient treated with conversion therapy, the tumor gradually shrank and was eventually surgically resected. Conclusions: This study identified the independent prognostic and risk factors associated with recurrence and overall survival in HCC patients with MVI. Additionally, we successfully performed conversion therapy in an HCC patient with PVTT. The findings would help identify patients at high risk of recurrence and indicate that combined therapy may prolong the survival of HCC patients with PVTT.

[Adsorption Capacity and Mechanism of Biochar Derived from Typical Agricultural Wastes for Cadmium in Aqueous Solutions].

Twelve biochar types were derived from animal manure (cow manure, chicken manure, and pig manure) and crop straw (wheat straw, rice straw, and corn straw) at different temperatures (300℃/700℃ and 300℃/500℃) for Cd2+ in a solution system in the present study. A scanning electron microscope, Fourier infrared spectrometer, X-ray diffraction, and CHN analyzer were applied to analyze the physical and chemical properties, surface structure, and elemental composition of the biochar. The adsorption capacity and related mechanism of biochar for Cd2+ in an aqueous solution was studied. The results showed that the maximum adsorption capacity of cow manure, chicken manure, and pig manure biochar for Cd2+ increased from 83.40, 19.65, and 96.74 mg·g-1 to 106.54, 268.89, and 164.53 mg·g-1, respectively, with the increase in pyrolysis temperature. With the increase in pyrolysis temperature, the pore structure of biochar became more abundant, oxygen-containing functional groups increased, and the aromatic structure appeared. Quantitative analyses revealed that ion exchange accounted for 12%-52%, chemical precipitation accounted for 27%-79%, complexation accounted for 1%-8%, and cation-π accounted for 1%-28% of the total adsorption capacity of Cd2+. With the increase in pyrolysis temperature, the proportion of cation-π interaction increased from 1%-13% to 8%-30%, but the proportion of chemical precipitation and ion exchange were still very high (70%-93%). Therefore, ion exchange and chemical precipitation could be the main mechanisms of agricultural waste biochar adsorption for Cd2+.

[Berberine hydrochloride attenuates liver injury induced by acute hypoxic exposure by inhibiting TNF-α/caspase-8/caspase-3 signaling pathway].

Objective To investigate the protective effect and mechanism of berberine hydrochloride (BBR) on liver after acute hypoxic exposure. Methods C57BL/6 mice were divided into three groups consisting of normoxic group, hypoxic exposure group, and hypoxic exposure combined with BBR group. On the 7th day of the experiment, mice were sacrificed and liver tissue was collected. The pathological changes of liver tissue were observed by HE staining. The mRNA levels of interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) in liver tissue were detected by real time quantitative PCR. The protein levels of TNF-α, cleaved-caspase-3 (c-caspase-3), and caspase-8 in liver tissue were detected by Western blotting. The apoptosis of mouse liver tissue was detected by TUNEL. Results After 7 days of hypoxic exposure, the body mass and liver mass of mice decreased significantly, and the liver tissue damage was obvious; the mRNA levels of TNF-α and IL-1ß and the protein levels of caspase-8 and c-caspase-3 in liver tissue cells significantly increased, and the apoptosis level of liver tissue cells markedly increased as well. BBR treatment significantly increased the body mass and liver mass of mice exposed to hypoxia for 7 days, decreased the mRNA level of TNF-α and the protein expressions of caspase-8 and c-caspase-3, and reduced the apoptosis of liver tissue cells. Conclusion BBR may attenuate liver injury induced by hypoxic exposure by inhibiting TNF-α/caspase-8/caspase-3 signaling pathway.

Sulfoquinovosyl diacylglycerol synthase 1 impairs glycolipid accumulation and photosynthesis in phosphate-deprived rice.

Phosphate (Pi)-starved crops utilize phospholipids as a source for internal Pi supply by replacing non-phosphorus glycolipids. In rice, sulfoquinovosyl diacylglycerol synthase 1 (OsSQD1) functions as a key enzyme in the first step to catalyze sulfoquinovosyldiacylglycerol (SQDG) formation. Here we study differential expression of OsSQD1 in response to Pi, nitrogen, potassium, and iron-deficiencies in rice. Electrophoretic mobility shift assay suggested that OsSQD1 is regulated by OsPHR2 (Phosphate Starvation Response2), a MYB (v-myb avian myeloblastosis viral oncogene homolog) domain-containing transcription factor. The concentrations of different lipid species in ossqd1 knockout mutant demonstrated that OsSQD1 silencing increased the phospholipid content and altered fatty acid composition under Pi-deficiency. Moreover, OsSQD1 silencing reduces glycolipid accumulation under Pi-deficiency, and triggered the saturation of fatty acids in phospholipids and glycolipids treated with different Pi regimes. Relative amounts of transcripts related to phospholipid degradation and glycolipid synthesis were assessed to explore the mechanism by which OsSQD1 exerts an effect on lipid homeostasis under P-deficiency. Furthermore, OsSQD1 silencing inhibited photosynthesis, especially under Pi-deficient conditions, by down-regulating glycolipids in rice shoots. Taken together, our study reveals that OsSQD1 plays a key role in lipid homeostasis, especially glycolipid accumulation under Pi-deficiency, which results in the inhibition of photosynthesis.

Dietary patterns and sarcopenia in a Chinese population.

BACKGROUND AND OBJECTIVES: Malnutrition is implicated as a key modifiable risk factor for sarcopenia. As such, a dietary pattern analysis, rather than an analysis of single food items or nutrients, may provide insights into the comprehensive contribution of diet and nutrition to the risk of sarcopenia. Accordingly, the aim of this study was to evaluate the relationships between main dietary patterns and sarcopenia. METHODS AND STUDY DESIGN: A total of 591 participants aged over 40 years were included in this cross-sectional study. A validated food-frequency questionnaire was used to assess their dietary intake, and principal component analysis (PCA) was used to identify the main dietary patterns. A multivariate logistic regression model was used to explore the associations between their main dietary patterns and the risk of sarcopenia. RESULTS: This study identified 56 cases of sarcopenia, equating to an overall detection rate of 9.48%. The PCA revealed four major dietary patterns among the participants: "coarse cereals and vegetables"; "beverages and animal organs"; "poultry, fish and shrimp"; and "fruits and pasta". After adjusting for age, sex, physical activity and smoking, individuals with the "coarse cereals and vegetables" dietary pattern had a 63.0% reduction in the risk of sarcopenia. CONCLUSIONS: The "coarse cereals and vegetables" dietary pattern is negatively correlated with sarcopenia, and may reduce the risk of sarcopenia.

Influence of elemental sulfur on cadmium bioavailability, microbial community in paddy soil and Cd accumulation in rice plants.

Cadmium (Cd) is highly toxic to living organisms and the contamination of Cd in paddy soil in China has received much attention. In the present study, by conducting pot experiment, the influence of S fertilizer (S0) on rice growth, iron plaque formation, Cd accumulation in rice plants and bacterial community in rice rhizosphere soil was investigated. The biomass of rice plants was significantly increased by S0 addition (19.5-73.6%). The addition of S0 increased the formation of iron plaque by 24.3-45.8%, meanwhile the amount of Cd sequestered on iron plaque increased. In soil treated with 5 mg/kg Cd, addition of 0.2 g/kg S0 decreased the diffusive gradients in thin films (DGT) extractable Cd by 60.0%. The application of S0 significantly decreased the concentration of Cd in rice grain by 12.1% (0.1 g/kg) and 36.6% (0.2 g/kg) respectively. The addition of S0 significantly increased the ratio of Acidobacteria, Bacteroidetes in rice rhizosphere soil. Meanwhile, the ratio of Planctomycetes and Chloroflexi decreased. The results indicated that promoting Fe- and S-reducing and residue decomposition bacterial in the rhizosphere by S0 may be one biological reason for reducing Cd risk in the soil-rice system.

The ferroxidase LPR5 functions in the maintenance of phosphate homeostasis and is required for normal growth and development of rice.

Members of the Low Phosphate Root (LPR) family have been identified in rice (Oryza sativa) and expression analyses have been conducted. Here, we investigated the functions of one of the five members in rice, LPR5. qRT-PCR and promoter-GUS reporter analyses indicated that under Pi-sufficient conditions OsLPR5 was highly expressed in the roots, and specific expression occurred in the leaf collars and nodes, and its expression was increased under Pi-deficient conditions. In vitro analysis of the purified OsLPR5 protein showed that it exhibited ferroxidase activity. Overexpression of OsLPR5 triggered higher ferroxidase activity, and elevated concentrations of Fe(III) in the xylem sap and of total Fe in the roots and shoots. Transient expression of OsLPR5 in Nicotiana benthamiana provided evidence of its subcellular localization to the cell wall and endoplasmic reticulum. Knockout mutation in OsLPR5 by means of CRISPR-Cas9 resulted in adverse effects on Pi translocation, on the relative expression of Cis-NATOsPHO1;2, and on several morphological traits, including root development and yield potential. Our results indicate that ferroxidase-dependent OsLPR5 has both a broad-spectrum influence on growth and development in rice as well as affecting a subset of physiological and molecular traits that govern Pi homeostasis.

Morpho-physiological and transcriptome analysis provide insights into the effects of zinc application on nitrogen accumulation and metabolism in wheat (Triticum aestivum L.).

Nitrogen (N) is the essential nutrient for wheat growth and development, its accumulation and metabolism controlled by many other elements. Zinc (Zn) is one of the important elements which tends to have effects on plant N homeostasis. Here in our study, 0 µM and 5 µM Zn was applied to the wheat seedlings culturing in 5 mM (+N) and 0.5 mM (-N) N treatments, respectively. The results showed that the shoot and root length growth performance, total N, NO3-, and amino acid concentrations, glutamine synthetase (GS) activity of wheat were facilitated by 5 µM Zn application under + N and -N conditions. Quantitative real-time PCR (qRT-PCR) analysis indicated that several NO3- transporters genes (TaNRT2.1, TaNPF7.1 and TaNPF7.2) and the genes encoding GS (TaGS1 and TaGS2) were induced by 5 µM Zn. In addition, transcriptional changes in wheat shoots and roots with Zn application were tested by RNA-seq techniques. A total of 147/551 induced and 36/2162 reduced differentially expression genes (DEGs) was detected in wheat shoots/roots, respectively. GO and KEGG enrichment analyses showed that 5 µM Zn mainly affected the glutathione (GSH) metabolism, phenylpropanoid biosynthesis and amino acid metabolism, involving in N homeostasis. Furthermore, the relative expression of genes related to phenylalanine, cysteine and methionine metabolism was induced by 5 µM Zn to promote the amino acid accumulation. Overall, these results highlight the facilitating of N accumulation by low level Zn, and provide an insight into the effects of Zn on N metabolism in wheat.

OsPDR2 mediates the regulation on the development response and maintenance of Pi homeostasis in rice.

Inorganic orthophosphate (Pi), a major form of essential macronutrient phosphorus (P), is available in rhizosphere for acquisition and assimilation by plants. However, the limited availability of Pi in soils affects the growth and development of plants. In Arabidopsis thaliana (Arabidopsis), Phosphate Deficiency Response2 (AtPDR2), interacts genetically with Low Phosphate Root1 (AtLPR1) in the endoplasmic reticulum (ER) and plays a key role in the inhibition of primary root growth (PRG) during Pi deficiency. However, the role of OsPDR2, the homolog of AtPDR2, either in roots response to Pi deficiency and/or in growth and development has not been elucidated as yet. Therefore, qRT-PCR was employed to determine the spatiotemporal effects and the availability of Pi on the expression of OsPDR2. OsPDR2 showed variable levels of relative expression pattern in vegetative and/or reproductive tissues analyzed at different stages of growth and development (5-17 weeks). Transient expression analysis revealed its subcellular localization to the ER. Further, the reverse genetics approach was employed for determining the function of OsPDR2 by generating RNAi lines (Ri2, Ri9, and Ri18). The study revealed significant inhibitory effects of RNAi-mediated suppression of OsPDR2 on the development of root, male reproductive traits, and yield. Moreover, 32P isotope labeling and split-root experiments under different Pi regime with RNAi lines revealed the function of OsPDR2 in regulating homeostasis of Pi.

Effect of whole-course nutrition management on patients with esophageal cancer undergoing concurrent chemoradiotherapy: A randomized control trial.

OBJECTIVES: Malnutrition is the most common complication of patients with esophageal cancer and can lead to poor prognosis and death. Good nutritional status has been shown to help improve patient outcomes and reduce complications. In the absence of specific evidence on the effect of nutrition in patients with esophageal cancer, the purpose of this study was to investigate the effect of whole-course nutrition management on the prognosis and complications of chemoradiotherapy in patients with esophageal cancer through a randomized controlled trial. METHODS: A total of 96 patients with esophageal cancer treated with concurrent chemoradiation were randomized to an intervention group (treated with whole-course nutrition management from the Nutrition Support Team) and a control group (treated with the general nutritional method) for approximately 6 wk. Dietary surveys and body measurements were conducted at baseline and every day thereafter. Patient-generated Subjective Global Assessment score, blood index, quality of life, and psychological condition were assessed at baseline and every week before discharge. Complications (e.g., radiation esophagitis, myelosuppression, and skin symptoms), completion rates of therapy, short-term efficacy evaluation, as well as clinical outcomes were measured. RESULTS: A total of 85 patients completed the study (intervention group = 45; control group = 40). There were significant differences in the changes of serum albumin and total protein between the two groups throughout the trial (P < 0.05). Complications (e.g., radioactive esophagitis, skin symptom of complications) and quality of life were statistically different before and after the intervention (P < 0.05). The difference in the change of other indicators was not statistically significant. CONCLUSIONS: Whole-course nutrition management can improve the nutritional status of patients with esophageal cancer treated with concurrent chemoradiotherapy, reduce the severity of radiation esophagitis and radiation skin reactions, improve the quality of life, and relieve depressive symptoms.

Transcriptome analysis of rice (Oryza sativa L.) shoots responsive to cadmium stress.

Cadmium (Cd) is highly toxic to living organisms. This study aimed to elucidate the regulation of gene expression in rice shoots under Cd stress. Rice plants were exposed to 0, 50, 75, 100 µmol/L CdCl2 in hydroponic culture for 7 d. Transcriptional changes in rice shoots were examined by transcriptome sequencing techniques. A total of 2197 DEGs (987 up-regulated and 1210 down-regulated) were detected in rice shoots under the exposure of 75 µmol/L CdCl2. GO and KEGG enrichment analyses showed that genes encoding auxin-responsive protein IAA and peroxidase were up-regulated, while genes encoding proteins involved in signal transduction, including TIFY family, ERF and bZIP were down-regulated. Abundant ROS related terms were also identified and grouped into significantly differentially expressed GO terms, including oxidoreductase activity, catalytic activity, oxidation-reduction process, confirming the enhanced oxidative stress of Cd. Genes encoding photosystem I reaction center subunit and photosynthetic NDH subunit of luminal location were up-regulated in pathway of energy metabolism, suggesting an interference of photosynthesis by Cd stress. Our results improve the understanding of the complex molecular responsive mechanisms of rice shoots under Cd stress.

Rapamycin and fingolimod modulate Treg/Th17 cells in experimental autoimmune encephalomyelitis by regulating the Akt-mTOR and MAPK/ERK pathways.

Rapamycin prevents experimental autoimmune encephalomyelitis (EAE) and activates the MAPK/ERK pathway in EAE. Thus, we hypothesized combining rapamycin and fingolimod treatments would have synergistic effects in EAE. We show that combination therapy ameliorated EAE and regulated spinal cord IL-17 and TGF-ß levels in EAE mice. Combination therapy also modulated IL-17 and TGF-ß concentration, RoRγt and Foxp3 mRNA levels, and Th17 cell and Treg frequencies in the spleen. Moreover, rapamycin decreased ps6k and increased pAkt and pERK, while combination therapy downregulated pAkt, ps6 k and pERK in EAE mice. Our findings provide insight into using this drug combination to treat EAE.

The association between dietary isoflavones intake and gastric cancer risk: a meta-analysis of epidemiological studies.

BACKGROUND: Isoflavones, a class of phytoestrogenic compounds, are abundant in soybeans. A number of epidemiological studies have investigated the association between dietary isoflavones intake and the risk of gastric cancer. However, the results are inconclusive. Therefore, the meta-analysis was conducted to evaluate the effect of dietary isoflavones intake on the risk of gastric cancer. METHODS: Relevant studies from May 1992 to May 2017 were identified through searching PubMed and Web of Science. Additional articles were identified from the reference lists of relevant review articles. Pooled risk ratios (RRs) or odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a fixed-effects model. Funnel plot and Egger's test were used to evaluate publication bias. RESULTS: Seven articles reporting 12 studies were included in the current meta-analysis. We found no significant association between dietary isoflavones intake and gastric cancer risk with the highest versus the lowest categories of dietary isoflavones intake (OR = 0.97, 95% CI = 0.87-1.09, I2 = 27.5%). Subgroup analyses generally yield similar results. CONCLUSIONS: Higher dietary isoflavones intake is not associated with a decline in the risk of gastric cancer.

Fingolimod ameliorates the development of experimental autoimmune encephalomyelitis by inhibiting Akt-mTOR axis in mice.

Fingolimod is a new immunosuppressive agent approved by Food and Drug Administration (FDA) for treating multiple sclerosis (MS). It acts as a functional antagonist to downregulate the S1P1 receptor, which is known to signal through the Akt-mTOR pathway. We investigated the mechanism of fingolimod action in the classical animal model of MS: experimental autoimmune encephalomyelitis (EAE). Fingolimod treatment significantly reduced clinical scores and histopathology in this model, even when treatment was begun after the onset of pathology. The Akt-mTOR signaling pathway was shown to be activated in the EAE model, by measuring the abundance of downstream activation markers, pAkt and ps6k. And this pathway was inhibited when EAE mice were treated with fingolimod. Mice with EAE exhibited an increased frequency of Th1 cells in the spleen, with concomitant increases in the mRNA levels of Tbet and Ifng and increased IFN-γ production by activated splenocytes; the frequency of Treg cells, as well as mRNA levels of Foxp3 and Tgfb, was reduced, as was TGF-ß production by activated splenocytes. After treatment with fingolimod, these parameters were reversed, suggesting that fingolimod treatment inhibits the Akt-mTOR axis in EAE, which affects the differentiation and function of Th1 and Treg cells. These results provide an insight into the mechanism of action of fingolimod treatment and may provide new ideas for treating EAE and MS.

Bufei Jianpi granules improve skeletal muscle and mitochondrial dysfunction in rats with chronic obstructive pulmonary disease.

BACKGROUND: Bufei Jianpi granules has been confirmed effective in improving pulmonary function, alleviating acute exacerbations, improving six-minute walk distance and quality of life, and benefited in 12-month follow-up in chronic obstructive pulmonary disease (COPD) patients with syndrome of lung-spleen qi deficiency. Skeletal muscle dysfunction (SMD), an important extrapulmonary complication, occurs in the very initiation of COPD and is closely related to morbidity and mortality. To evaluate the efficacy of Bufei Jianpi granules on SMD, we observed skeletal muscular function and histomorphology, mitochondrial morphormetry and proteins in COPD rats induced by cigarette-smoke and Klebsiella pneumoniae. METHODS: Seventy-two Sprague-Dawley rats were randomized into Control + Saline, Control + Bufei Jianpi, Control + Aminophylline, COPD + Saline, COPD + Bufei Jianpi and COPD + Aminophylline groups. From week 9 to 20, rats were administrated intragastricly by normal saline, Bufei Jianpi granules and aminophylline, respectively. Muscular tension and fatigue index of intercostal muscle, quadriceps, biceps and soleus were detected by using electrophysiological technology. Pathological and ultrastructural changes and expressions of mitochondrial Bcl-2 nineteen-kilodalton interacting protein 3 (Bnip3) and cytoplasm cytochrome C (Cyto C) in the four skeletal muscles were observed by using optical and electron microscope and western blotting. RESULTS: There was no statistical difference among the control rats treated with saline, Bufei Jianpi granules or aminophylline in above-mentioned parameters. Muscular tension, mitochondria volume density (Vv) and compared membrane surface (δm) of the four muscles were significantly lower in COPD + Saline group compared to Control + Saline group, while fatigue index, mitochondria surface area (δ), Bnip3 and Cyto C were higher (P < 0.05). COPD rats showed more morphological changes in muscle tissues than controls, such as atrophy, degeneration, necrosis and matrix hyperplasia. Utrastructurally, mitochondria populations decreased significantly in the four muscles, and were shrunken and even cavitation changed. The up-mentioned parameters were improved in Bufei Jianpi group (P < 0.05) in the four muscles. CONCLUSIONS: Bufei Jianpi granules can improve skeletal muscle function via improving mitochondria population and function, reducing apoptotic factors such as Bnip3 and Cyto C, and is more effective than aminophylline.