Lidar AOD inversion and aerosol extinction profile correction method based on GA-BP neural network.

Lidar is an effective remote sensing method to obtain the vertical distribution of aerosols, and how to select the aerosol extinction-backscattering ratio (AE-BR) during the inversion process is a key step to guarantee the accuracy of the lidar inversion of aerosol optical thickness (AOD) and aerosol extinction coefficient profile (AECP). In this paper, an inversion algorithm for AOD and AECP based on a genetic BP (GA-BP) neural network is proposed. Simultaneous measurements are carried out using CE318 sun photometer and lidar, and the mapping relationship between the lidar echo signal and AOD is established based on the genetic BP (GA-BP) neural network method, which achieves the accurate inversion of AOD with an absolute error mean value of 0.0156. Based on the AOD output from the GA-BP neural network, the real-time best AE- BR to improve the inversion accuracy of AECP. Finally, practical tests show that the method achieves accurate inversion of AOD, determines the range of AE-BR from 20-50sr, realizes real-time dynamic correction of AECP, and has strong generalization ability and applicability in practical situations.

Amniotic membrane mesenchymal stromal cell-derived secretome in the treatment of acute ischemic stroke: A case report.

BACKGROUND: Stroke is the second and third leading cause of death and disability, respectively. To date, no definitive treatment can repair lost brain function. Recently, various preclinical studies have been reported on mesenchymal stromal cells (MSCs) and their derivatives and their potential as alternative therapies for stroke. CASE SUMMARY: A 45-year-old female suffered an acute stroke, which led to paralysis in the left upper and lower limbs. The amniotic membrane MSC-derived secretome (MSC-secretome) was intravenously transplanted once a week for 4 wk. MSC-secretome-regulated regulatory T cells were investigated for the beneficial effects. The clinical improvement of this patient was accompanied by an increased frequency of regulatory T cells after transplantation. CONCLUSION: Intravenous administration of MSC-secretome can potentially treat patients who suffer from acute ischemic stroke.

Hypso- or bathochromic phosphorescent mechanochromic mononuclear Cu(I) complexes with a bis(2-diphenylphosphinophenyl)ether auxiliary ligand.

Six phosphorescence-emitting metal-organic mononuclear Cu(I) complexes, namely four quinoline-containing three-coordinate Cu(I) complexes and two N-heterocyclic carbene-containing four-coordinate Cu(I) complexes, have been successfully developed and fully characterized. All these Cu(I) complexes include the same bis(2-diphenylphosphinophenyl)ether bidentate auxiliary ligand. Significantly, four-coordinate Cu(I) complexes 1 and 2 display typical aggregation-induced emission phenomena. Their solid samples of luminogenic complexes 1-6 emit a variety of different phosphorescence. Furthermore, solid-state phosphorescence of these Cu(I) complexes can be effectively manipulated by external mechanical force. Remarkably, luminophores 1, 2 and 5 exhibit blue-shifted mechanoluminochromism responses, while luminophores 3, 4 and 6 present red-shifted mechanoluminochromism characteristics. All of the observed mechano-responsive phosphorescence changes of solids 1-6 are reversible by the method of solvent fuming. Powder X-ray diffraction results confirm that the reversible mechanically induced phosphorescence changes of complexes 1-6 are due to the mutual transformation of ordered crystalline and metastable amorphous states.

Effect of vitamin supplementation on polycystic ovary syndrome and key pathways implicated in its development: A Mendelian randomization study.

BACKGROUND: Many epidemiologic investigations have explored the relationship between viatmins and polycystic ovary syndrome (PCOS). However, the effectiveness of vitamin, vitamin-like nutrient, or mineral supplementation in reducing the risk of PCOS remains a subject of debate. AIM: To investigate the impact of plasma levels of vitamins A, B12, D, E, and K on PCOS and key pathways implicated in its development, namely, insulin resistance, hyperlipidemia, and obesity, through Mendelian randomization (MR) analysis. METHODS: Single nucleotide polymorphisms associated with vitamin levels were selected from genome-wide association studies. The primary analysis was performed using the random-effects inverse-variance-weighted approach. Complementary analyses were conducted using the weighted median, MR-Egger, MR-robust adjusted profile score, and MR-PRESSO approaches. RESULTS: The results provided suggestive evidence of a decreased risk of PCOS with genetically predicted higher levels of vitamin E (odds ratio [OR] = 0.118; 95% confidence interval [CI]: 0.071-0.226; P < 0.001) and vitamin B12 (OR = 0.753, 95%CI: 0.568-0.998, P = 0.048). An association was observed between vitamin E levels and insulin resistance (OR = 0.977, 95%CI: 0.976-0.978, P < 0.001). Additionally, genetically predicted higher concentrations of vitamins E, D, and A were suggested to be associated with a decreased risk of hyperlipidemia. Increased vitamins K and B12 levels were linked to a lower obesity risk (OR = 0.917, 95%CI: 0.848-0.992, P = 0.031). CONCLUSION: The findings of this MR study suggest a causal relationship between increased vitamins A, D, E, K, and B12 levels and a reduced risk of PCOS or primary pathways implicated in its development.

P1 of turnip mosaic virus interacts with NOD19 for vigorous infection.

P1 protein, the most divergent protein of virus members in the genus Potyvirus of the family Potyviridae, is required for robust infection and host adaptation. However, how P1 affects viral proliferation is still largely elusive. In this work, a total number of eight potential P1-interacting Arabidopsis proteins were identified by the yeast-two-hybrid screening using the turnip mosaic virus (TuMV)-encoded P1 protein as the bait. Among which, the stress upregulated NODULIN 19 (NOD19) was selected for further characterization. The bimolecular fluorescent complementation assay confirmed the interaction between TuMV P1 and NOD19. Expression profile, structure, and subcellular localization analyses showed that NOD19 is a membrane-associated protein expressed mainly in plant aerial parts. Viral infectivity assay showed that the infection of turnip mosaic virus and soybean mosaic virus was attenuated in the null mutant of Arabidopsis NOD19 and NOD19-knockdown soybean seedlings, respectively. Together, these data indicate that NOD19 is a P1-interacting host factor required for robust infection.

Banxia Xiexin decoction alleviates AS co-depression disease by regulating the gut microbiome-lipid metabolic axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin decoction (BXD) is a classic Chinese herbal formulation consisting of 7 herbs including Pinelliae Rhizoma, Scutellariae Radix, Zingiberis Rhizoma, Ginseng Radix, Glycyrrhizae Radix, Coptidis Rhizoma, and Jujubae Fructus, which can exert effects on lowering lipids and alleviating depressive mood disorders via affecting gastrointestinal tract. AIM OF THE STUDY: The pathogenesis of atherosclerosis (AS) co-depression disease has not been well studied, and the current clinical treatment strategies are not satisfactory. As a result, it is critical to find novel methods of treatment. Based on the hypothesis that the gut microbiome may promote the development of AS co-depression disease by regulating host lipid metabolism, this study sought to evaluate the effectiveness and action mechanism of BXD in regulation of the gut microbiome via an intervention in AS co-depression mice. MATERIALS AND METHODS: To determine the primary constituents of BXD, UPLC-Q/TOF-MS analysis was carried out. Sixteen C56BL/6 mice were fed normal chow as a control group; 64 ApoE-/- mice were randomized into four groups (model group and three treatment groups) and fed high-fat chow combined with daily bind stimulation for sixteen weeks to develop the AS co-depression mouse model and were administered saline or low, medium or high concentrations of BXD during the experimental modeling period. The antidepressant efficacy of BXD was examined by weighing, a sucrose preference test, an open field test, and a tail suspension experiment. The effectiveness of BXD as an anti-AS treatment was evaluated by means of biochemical indices, the HE staining method, and the Oil red O staining method. The impacts of BXD on the gut microbiome structure and brain (hippocampus and prefrontal cortex tissue) lipids in mice with the AS co-depression model were examined by 16S rDNA sequencing combined with lipidomics analysis. RESULTS: The main components of BXD include baicalin, berberine, ginsenoside Rb1, and 18 other substances. BXD could improve depression-like behavioral characteristics and AS-related indices in AS co-depression mice; BXD could regulate the abundance of some flora (phylum level: reduced abundance of Proteobacteria and Deferribacteres; genus level: reduced abundance of Clostridium_IV, Helicobacter, and Pseudoflavonifractor, Acetatifactor, Oscillibacter, which were significantly different). The lipidomics analysis showed that the differential lipids between the model and gavaged high-dose BXD (BXH) groups were enriched in glycerophospholipid metabolism, and lysophosphatidylcholine (LPC(20:3)(rep)(rep)) in the hippocampus and LPC(20:4)(rep) in the prefrontal cortex both showed downregulation in BXH. The correlation analysis illustrated that the screened differential lipids were mainly linked to Deferribacteres and Actinobacteria. CONCLUSION: BXD may exert an anti-AS co-depression therapeutic effect by modulating the abundance of some flora and thus intervening in peripheral lipid and brain lipid metabolism (via downregulation of LPC levels).

Gut microbiome metabolites as key actors in atherosclerosis co-depression disease.

Cardiovascular diseases, mainly characterized by atherosclerosis (AS), and depression have a high comorbidity rate. However, previous studies have been conducted under a single disease, and there is a lack of studies in comorbid states to explore the commonalities in the pathogenesis of both diseases. Modern high-throughput technologies have made it clear that the gut microbiome can affect the development of the host's own disorders and have shown that their metabolites are crucial to the pathophysiology of AS and depression. The aim of this review is to summarize the current important findings on the role of gut microbiome metabolites such as pathogen-associated molecular patterns, bile acids, tryptophan metabolites, short-chain fatty acids, and trimethylamine N -oxide in depression and AS disease, with the aim of identifying potential biological targets for the early diagnosis and treatment of AS co-depression disorders.

Activating Transcription Factor 3 Based Early Alarm Model of Acute Kidney Injury after Cardiopulmonary Bypass in Adults.

Acute kidney injury (AKI) is a common complication after cardiopulmonary bypass (CPB) for cardiac surgery, and there is no effective treatment. This study was aimed at constructing an early warning model of AKI after CPB in adults and investigating the performance of this model. Patients who underwent CPB in the Department of Cardiac Surgery, Shanghai Tenth People's Hospital, from January 2018 to December 2019 were recruited into the present study. Blood and urine samples were collected preoperatively (0 h) and 2 h, 6 h, 12 h, 24 h, and 48 h after surgery, and the creatinine and activating transcription factor 3 (ATF3) were detected. According to the diagnostic criteria of AKI, patients were divided into the AKI group and the non-AKI group, and the risk factors for AKI after CPB were screened. The receiver operating characteristic (ROC) curve analysis was used to identify the optimal biomarkers for the establishment of early warning model of AKI after CPB. Finally, the performance of this model was further verified. A total of 83 patients were included in this study, 42 of whom developed AKI after surgery. After CPB, the serum and urine levels of creatinine and ATF3 increased to different degrees, and the increase in urine ATF3 was the most obvious in the AKI group. The area under ROC (AUC) of urine ATF3 at 12 h after surgery was 0.691 (95% CI: 0.576-0.807). When ATF3 was higher than 1216 pg/mL, the sensitivity and specificity of ATF3 in the diagnosis of AKI were 0.43 and 0.85, respectively. The height, conjugated bilirubin on the surgery day, urine ATF3 12 h after surgery, and serum creatinine 24 h after surgery were independent risk factors for postoperative AKI. Urine ATF3 and other factors were used to establish AKI warning model after CPB, which showed good fitting and accuracy. In conclusion, ATF3 is an early biomarker of post-CPB AKI. Addition of urine ATF3 to AKI risk factors can improve the accuracy of early AKI prediction.

Illness uncertainty and its associated factors in coronary heart disease patients with heart stent implantation: a cross-sectional study.

BACKGROUND: The purpose of this study was to investigate the illness uncertainty and its influencing factors in patients after heart stent implantation, and to explore the relationship between uncertainty of disease, self-management behavior of coronary heart disease and quality of life after stenting. METHODS: A cross-sectional study of 168 patients with cardiac stent implantation on illness uncertainty in a tertiary hospital in Shanghai. The General Information Questionnaire and the Mishel's Uncertainty in Illness Scale (MUIS) was used to measure the uncertainty of disease in patients after coronary stenting, and the Coronary Self-Management Scale (CSMS) and 36-item Short Form Health Survey Scale (SF-36) were collected, using Pearson's method for correlation analysis. The indicators with significant statistical differences in univariate analysis were included, and the factors affecting patients' perception of disease uncertainty were analyzed by stepwise regression fitting multiple linear regression equations. RESULTS: The study showed that the mean score for disease uncertainty was 79.83±14.05 out of 160 points. By the multiple stepwise linear regression analysis, the results showed that subjective symptom improvement, follow-up with nurses after discharge, care and support from family members after discharge, quality of the quantity of stents, guidance and support from nurses during hospitalization, and educational level had a significant impact on the total uncertainty score, and were the most important factor of patient illness uncertainty. In patients with coronary heart disease, uncertainty was moderately negatively correlated with self-management ability (P<0.05, r=-0.636), and highly negatively correlated with overall quality of life scores (P<0.05, r=-0.857). CONCLUSIONS: Overall, patients with coronary stents had moderate disease uncertainty, suggesting that uncertainty is common among patients after cardiac stenting. In order to improve the uncertainty of disease in patients after with heart stent implantation (especially for patients with a large number of implanted stents), family members should give sufficient care; doctors and nurses should provide patients with adequate health education, assist patients in establishing healthy behaviors, and strengthen its self-management ability, thereby reducing the patient's sense of uncertainty, thereby improving the long-term prognosis and the patient's quality of life.

Effects of the Lipid Metabolites and the Gut Microbiota in ApoE-/- Mice on Atherosclerosis Co-Depression From the Microbiota-Gut-Brain Axis.

Background: The diagnosis, treatment, and prevention of atherosclerosis co-depression are poor, so it is urgent to explore new targets. Based on the "microbiota-gut-brain axis," this study aimed to investigate the changes of lipid metabolites in the prefrontal cortex and hippocampus regions and the characteristics of the gut microbiota in ApoE-/- mice with atherosclerosis co-depression. Methods: ApoE-/- mice (hyperlipid feeding combined with binding, HFB group, n = 14, male) fed a high-fat diet for 16 weeks with binding stimulation were used as an animal model for atherosclerosis co-depression. The depression degree of mice was evaluated by body weight, sucrose preference test, open field test, and tail suspension test. Oil-red O staining, HE staining, and biochemical parameters were used to evaluate the damage degree of atherosclerosis in mice. LC-MS/MS technique for non-targeted lipidomics analysis was used to analyze the differential lipid metabolites in the prefrontal cortex and hippocampus regions of mice. 16S rDNA amplification sequencing was used to screen the differential gut microbial, and association analysis was performed with the differential lipid metabolites. Results: Compared with the normal control group (NC group), the HFB group showed depression-like behaviors and atherosclerosis-related pathological indicators. The differential lipid metabolites in the prefrontal cortex and hippocampus regions were mainly LPC, LPE, LPS, PC, PE, PS, PI, and GD1a, and were mainly enriched in the glycerophospholipid metabolism pathway and the retrograde endocannabinoid signaling pathway. At the same time, there were significant differences in the structure of the gut microbial community between the two groups. The abundance of Deferribacteres and Proteobacteria in the HFB group increased, while the abundance of Verrucomicrobia and Actinobacteria decreased at the phylum level; the abundance of Desulfovibrio, Clostridium_IV, Helicobacter and Pseudoflavonifractor increased, while the abundance of Akkermansia decreased at the genus level. Conclusion: Atherosclerosis co-depression of ApoE-/- mice of the prefrontal cortex and hippocampus lipid metabolism pathways of disorder and the changes of to the gut microbiota, which leads to abnormal white matter and synaptic dysfunction, increased gut inflammation, and decreased gut permeability, leading to the release of inflammatory cytokines, there is a strong correlation between both, it further confirmed the existence of the "microbiota-gut-brain axis."

Effects of dietary tryptophan on muscle growth, protein synthesis and antioxidant capacity in hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂.

The present study evaluated effects of dietary supplementation with tryptophan (Trp) on muscle growth, protein synthesis and antioxidant capacity in hybrid catfish Pelteobagrus vachelli♀ × Leiocassis longirostris♂. Fish were fed six different diets containing 2·6 (control), 3·1, 3·7, 4·2, 4·7 and 5·6 g Trp/kg diet for 56 d, respectively. Results showed that dietary Trp significantly (1) improved muscle protein content, fibre density and frequency of fibre diameter; (2) up-regulated the mRNA levels of PCNA, myf5, MyoD1, MyoG, MRF4, IGF-I, IGF-II, IGF-IR, PIK3Ca, TOR, 4EBP1 and S6K1; (3) increased phosphorylation levels of AKT, TOR and S6K1; (4) decreased contents of MDA and PC, and increased activities of CAT, GST, GR, ASA and AHR; (5) up-regulated mRNA levels of CuZnSOD, CAT, GST, GPx, GCLC and Nrf2, and decreased Keap1 mRNA level; (6) increased nuclear Nrf2 protein level and the intranuclear antioxidant response element-binding ability, and reduced Keap1 protein level. These results indicated that dietary Trp improved muscle growth, protein synthesis as well as antioxidant capacity, which might be partly related to myogenic regulatory factors, IGF/PIK3Ca/AKT/TOR and Keap1/Nrf2 signalling pathways. Finally, based on the quadratic regression analysis of muscle protein and MDA contents, the optimal Trp requirements of hybrid catfish (21·82-39·64 g) were estimated to be 3·94 and 3·93 g Trp/kg diet (9·57 and 9·54 g/kg of dietary protein), respectively.

Characterization of MRF genes and their tissue distributions and analysis of the effects of starvation and refeeding on the expression of these genes in Acipenser dabryanus muscle.

The purpose of the study was to clone the sequences of myogenic regulatory factors in Acipenser dabryanus and explore the changes in their expression during starvation and refeeding in A. dabryanus muscle. One hundred twenty fish (60.532 ± 0.284 g) were randomly assigned to four groups (fasted for 0, 3, 7 or 14 d and then refed for 14 d). Our predictions showed that the coding sequences of myod1, myf5, myog and myf6 in A. dabryanus encoded 275, 248, 248 and 243 amino acids, respectively, and the expression of the four genes was the highest in muscle. During fasting, the expression of myod1 in muscle was significantly decreased in the 14 d group. The expressions of myf5 and myf6 were increased significantly at first and then decreased with prolonged starvation time. The expression of myog in the 14 d group was significantly decreased compared with other groups (P < 0.05). During refeeding, the highest values of myod1 and myf6 expression were found in the 3 d group (P < 0.05).The expressions of myf5 and myog in 0 d and 3 d group were significantly higher than those in 7 d and 14 d group (P < 0.05). These results indicate that myogenic regulatory factors (MRFs) play important roles in muscle growth and development in A. dabryanus. The inhibition of long-term starvation (14 d) on the expression of myogenic regulatory factors is probably one of the reasons why it can not achieve full compensation for growth.

Minor allele of rs55763075 located in MTHFR is associated with the risk of cognitive impairment after anesthesia via modulating miR-34b.

This study aimed to investigate the association between cognitive impairment after general anesthesia and rs55763075 polymorphisms. We enrolled and grouped patients undergoing general anesthesia according to their genotypes of rs55763075 polymorphism. Mini-Mental State Examination (MMSE) scoring was performed to evaluate the cognitive status of patients. Quantitative real-time PCR was carried out to analyze the expression of methylenetetrahydrofolate reductase (MTHFR) mRNA and miR-34b while Western blot was performed to evaluate the expression of MTHFR protein. Furthermore, we studied the effect of rs55763075 polymorphism on the expression of MEHFR via luciferase assay. Accordingly, we found that the MMSE score in GG/GA groups was significantly higher than that in AA group. And a significant reduction of MTHFR mRNA expression was observed in the serum and peripheral blood mononuclear cells (PBMCs) of patients carrying AA genotype compared with the patients carrying GG/GA genotypes. Moreover, the MTHFR expression was much lower in the cultured AA-genotyped cells transfected with miR-34b. Luciferase assay results also showed that miR-34b transfection reduced luciferase activity in the cells carrying A allele but not in cells carrying G allele. In summary, the data of this study showed that minor allele (A) of rs55763075 polymorphisms in the 3'-untranslated region of MTHFR mRNA generated a potential binding site for miR-34b, which led to reduced level of folic acid in the patients carrying the AA genotype. Furthermore, we found that the MMSE score of AA-genotyped patients was lower than that of patients carrying GG/GA genotypes.

Effects of starvation and refeeding on growth performance, appetite, growth hormone-insulin-like growth factor axis levels and digestive function of Acipenser dabryanus.

The aim of this study was to explore the effects and mechanisms of different starvation treatments on the compensatory growth of Acipenser dabryanus. A total of 120 fish (60·532 (sem 0·284) g) were randomly assigned to four groups (fasting 0, 3, 7 or 14 d and then refed for 14 d). During fasting, middle body weight decreased significantly with prolonged starvation. The whole-body and muscle composition, serum biochemical indexes, visceral indexes and digestive enzyme activities had been effected with varying degrees of changes. The growth hormone (GH) level in serum was significantly increased in 14D; however, insulin-like growth factor-1 (IGF-1) showed the opposite trend. The neuropeptide Y (npy) mRNA level in brain was significantly improved in 7D; peptide YY (pyy) mRNA level in intestine was significantly decreased during fasting. After refeeding, the final body weight, percentage weight gain, specific growth rate, feed intake, feed efficiency and protein efficiency ratio showed no difference between 0D and 3D. The changes of whole-body and muscle composition, serum biochemical indexes, visceral indexes and digestive enzyme activities had taken place in varying degrees. GH levels in 3D and 7D were significantly higher than those in the 0D; the IGF-1 content decreased significantly during refeeding. There was no significant difference in npy and pyy mRNA levels. These results indicated that short-term fasting followed by refeeding resulted in full compensation and the physiological and biochemical effects on A. dabryanus were the lowest after 3 d of starvation and 14 d of refeeding. Additionally, compensation in A. dabryanus may be mediated by appetite genes and GH, and the degree of compensation is also affected by the duration of starvation.

Effects of Intensive Fattening With Total Mixed Rations on Carcass Characteristics, Meat Quality, and Meat Chemical Composition of Yak and Mechanism Based on Serum and Transcriptomic Profiles.

The objective of this study was to investigate the effects of intensive fattening with total mixed rations (TMR) on carcass characteristics, meat quality, and chemical composition of the yak meat. Theoretical data has been provided for evaluating the quality of yak meat during natural grazing and short-term fattening. Based on the analysis, we found that in fattening yak, the carcass weight (CWT) was increased by 106.43%, whereas the cooking loss, tenderness, and drop loss were significantly improved due to higher intramuscular fat content and lower moisture (P < 0.05). Protein, fat, calcium, and amino acids were also much higher (P < 0.01) in fattening yak compared with the grazing yak. The levels of albumin (ALB), lactate dehydrogenase (LDH), triglyceride (TRIG), and amylase (AMYL) in serum indicated better nutritional status for fattening yaks. The transcriptomics analysis showed that the high expression of ACSL1 and ACACB genes improved the synthesis and deposition of fat in fattening yak, whereas the regulation of SLC7A8, ATP1A4, ATP1A1, SLC3A2, and CPA3 gene expression weakened the proteolysis. These results indicated that fattening with TMR improves the yield and quality of the yak meat.

[1,2,4]Triazolo[1,5-a]pyrimidine derivative (Mol-5) is a new NS5-RdRp inhibitor of DENV2 proliferation and DENV2-induced inflammation.

Dengue fever is an acute infectious disease caused by dengue virus (DENV) and transmitted by Aedes mosquitoes. There is no effective vaccine or antiviral drug available to date to prevent or treat dengue disease. Recently, RNA-dependent RNA polymerase (RdRp), a class of polymerases involved in the synthesis of complementary RNA strands using single-stranded RNA, has been proposed as a promising drug target. Hence, we screened new molecules against DENV RdRp using our previously constructed virtual screening method. Mol-5, [1,2,4]triazolo[1,5-a]pyrimidine derivative, was screened out from an antiviral compound library (~8000 molecules). Using biophysical methods, we confirmed the direct interactions between mol-5 and purified DENV RdRp protein. In luciferase assay, mol-5 inhibited NS5-RdRp activity with an IC50 value of 1.28 ± 0.2 µM. In the cell-based cytopathic effect (CPE) assay, mol-5 inhibited DENV2 infectivity with an EC50 value of 4.5 ± 0.08 µM. Mol-5 also potently inhibited DENV2 RNA replication as observed in immunofluorescence assay and qRT-PCR. Both the viral structural (E) and non-structural (NS1) proteins of DENV2 were dose-dependently decreased by treatment with mol-5 (2.5-10 µM). Mol-5 treatment suppressed DENV2-induced inflammation in host cells, but had no direct effect on host defense (JAK/STAT-signaling pathway). These results demonstrate that mol-5 could be a novel RdRp inhibitor amenable for further research and development.

A simple method for in vitro preparation of natural killer cells from cord blood.

BACKGROUND: Cord Blood (CB) has been considered a promising source of natural killer (NK) cells for cellular immunotherapy. However, it is difficult to expand the large numbers of highly pure NK cells from CB without cell sorting and feeder cells/multiple cytokines. In this study, we try to develop a simple, safe and economical method for ex vivo expansion and purification of NK cells from CB without cell sorting and feeder cells/multiple cytokines. RESULTS: The large numbers (mean: 1.59 × 1010) of highly pure (≥90%) NK cells from CB could be obtained through interleukin-2, group A streptococcus and zoledronate stimulation of mononuclear cells using the 21-day culture approach. When compared to resting NK cells, expanded NK cells were a higher expression of activating receptors CD16, NKG2D, NKp30, NKp44, NKp46 and activating markers CD62L and CD69, while the inhibitory receptors, CD158a and CD158b remained largely unchanged. In addition, these cells showed a higher concentration of IFN-γ, TNF-α and GM-CSF secretion and cytotoxicity to K562 cells and acute myeloid leukemia targets than resting NK cells. CONCLUSION: We develop a simple, safe and economical method to obtain high yield, purity, and functionality NK cells from CB without cell sorting and feeder cells/multiple cytokines.

Immunosuppressive Effect of Exosomes from Mesenchymal Stromal Cells in Defined Medium on Experimental Colitis.

BACKGROUND AND OBJECTIVES: The exosomes released by mesenchymal stromal cells (MSCs) in classical FBS-containing media have been demonstrated as an alternative, cell-free therapy in various diseases including inflammatory bowel disease (IBD). It has been found that the function of exosomes is affected by culture condition. We previously developed a serum-free, xeno-free and chemically defined medium, and umbilical cord-derived MSCs in this medium retained the immunosuppressive capability. METHODS: In this study, we evaluated the immunosuppressive function of exosomes from MSCs (MSC-Exo) in defined medium and their therapeutic effect on treating colitis. RESULTS AND CONCLUSIONS: In vitro studies indicated that MSC-Exo reduced the concentration of pro-inflammatory cytokines IFN-γ, TNF-α and IL-1ß, and increased the secretion of anti-inflammatory cytokines TGF-ß1 and IL-10, but no significant change of inhibitory effect on peripheral blood mononuclear cells proliferation was shown. In vivo experimental colitis showed that administration of MSC-Exo was able to significantly ameliorate the disease activity index score, weight loss, colon shortening, and the histological colitis score through up-regulation anti-inflammatory responses and down-regulation of inflammatory responses. Moreover, the use of MSC-Exo (200 µg) led to an improved therapeutic efficacy when compared with MSCs at a dose of 1×106 cells. Our findings indicate that the exosomes from MSCs in defined medium possess a certain degree of immunosuppressive effect in vitro and exhibit a therapeutic capability in a mouse model of DSS-induced colitis through suppressing inflammation mechanism.

Dietary tryptophan affects growth performance, digestive and absorptive enzyme activities, intestinal antioxidant capacity, and appetite and GH-IGF axis-related gene expression of hybrid catfish (Pelteobagrus vachelli♀ × Leiocassis longirostris♂).

The 56-day feeding trial was carried out to investigate the effects of dietary tryptophan (Trp) on growth performance, digestive and absorptive enzyme activities, intestinal antioxidant capacity, and appetite and GH-IGF axis-related genes expression of hybrid catfish (Pelteobagrus vachelli♀ × Leiocassis longirostris♂). A total of 864 hybrid catfish (21.82 ± 0.14 g) were fed six different experimental diets containing graded levels of Trp at 2.6, 3.1, 3.7, 4.2, 4.7, and 5.6 g kg-1 diet. The results indicated that dietary Trp increased (P < 0.05) (1) final body weight, percent weight gain, specific growth rate, feed intake, feed efficiency, and protein efficiency ratio; (2) fish body protein, lipid and ash contents, protein, and ash production values; (3) stomach weight, stomach somatic index, liver weight, intestinal weight, length and somatic index, and relative gut length; and (4) activities of pepsin in the stomach; trypsin, chymotrypsin, lipase, and amylase in the pancreas and intestine; and γ-glutamyl transpeptidase, Na+, K+-ATPase, and alkaline phosphatase in the intestine. Dietary Trp decreased malondialdehyde content, increased antioxidant enzyme activities and glutathione content, but downregulated Keap1 mRNA expression, and upregulated the expression of NPY, ghrelin, GH, GHR, IGF1, IGF2, IGF1R, PIK3Ca, AKT1, TOR, 4EBP1, and S6K1 genes. These results indicated that Trp improved hybrid catfish growth performance, digestive and absorptive ability, antioxidant status, and appetite and GH-IGF axis-related gene expression. Based on the quadratic regression analysis of PWG, SGR, and FI, the dietary Trp requirement of hybrid catfish (21.82-39.64 g) was recommended between 3.96 and 4.08 g kg-1 diet (9.4-9.7 g kg-1 of dietary protein).