Chemotaxonomic Variation in Volatile Component Contents in Ancient Platycladus orientalis Leaves with Different Tree Ages in Huangdi Mausoleum.

To gain insight into the differences in the composition and volatile components content in ancient Platycladus orientalis leaves with different tree ages in Huangdi Mausoleum, the volatile components were identified by headspace solid-phase microextraction combined with gas chromatography-mass spectrometry (HS-SPME-GC-MS) method. The volatile components were statistically analyzed by orthogonal partial least squares discriminant analysis and hierarchical cluster analysis, and the characteristic volatile components were screened. The results exhibited that a total of 72 volatile components were isolated and identified in 19 ancient Platycladus orientalis leaves with different tree ages, and 14 common volatile components were screened. Among them, the contents of α-pinene (6.40-16.76%), sabinene (1.11-7.29%), 3-carene (1.14-15.12%), terpinolene (2.17-4.95%), caryophyllene (8.04-13.53%), α-caryophyllene (7.34-14.41%), germacrene D (5.27-12.13%), (+)-Cedrol (2.34-11.30%) and α-terpinyl acetate (1.29-25.68%) were relatively higher (>1%), accounting for 83.40-87.61% of the total volatile components. Nineteen ancient Platycladus orientalis trees were clustered into three groups through the HCA method based on the 14 common volatile components content. Combined with the results of OPLS-DA analysis, (+)-cedrol, germacrene D, α-caryophyllene, α-terpinyl acetate, caryophyllene, ß-myrcene, ß-elemene and epiglobulol were the differential volatile components to distinguish ancient Platycladus orientalis with different tree ages. The results revealed that the composition of the volatile components in ancient Platycladus orientalis leaves with different tree ages was different, showing different aroma characteristics, which provided a theoretical reference for the differential development and application of volatile components in ancient Platycladus orientalis leaves.

Risk of anxiety and depression in patients with uveitis: a Meta-analysis.

AIM: To quantitatively evaluate the risk of anxiety and depression in patients with uveitis via performing a Meta-analysis. METHODS: Three electronic database (PubMed, Embase, and Cochrane Library databases) were searched for studies recording data about uveitis and anxiety as well as depression simultaneously up to January 2021. The incidence rate and standard mean difference (SMD) with a 95% confidence interval (95%CI) were calculated to analyse the association using random-effects models based on heterogeneity tests. RESULTS: In total, 12 observational studies containing 874 patients with uveitis were included. The results showed that there was a significant association between uveitis and anxiety (SMD=0.97, 95%CI: 0.39 to 1.54, P=0.0009) and depression (SMD=0.79, 95%CI: 0.51 to 1.07, P<0.00001). The overall morbidities of anxiety and depression in patients with uveitis were 39% and 17%, respectively. With subgroup analysis, the heterogeneity actually came from different kinds of uveitis. Specifically, the incidence rates of both anxiety and depression were relatively low in patients with anterior uveitis (33% and 15%), moderate in patients with infectious uveitis (46% and 22%), and high in patients with unspecified uveitis (59% and 35%). CONCLUSION: It is preliminarily indicated that patients with uveitis may have a high risk of anxiety and depression. Ophthalmologists and psychologists should pay more attention to the psychological state when dealing with patients with uveitis. Further high-quality studies with detailed direct data are needed to draw more precise conclusions.

Chemotaxonomic Identification of Key Taste and Nutritional Components in 'Shushanggan Apricot' Fruits by Widely Targeted Metabolomics.

The chemotypic and the content variation in taste substances and nutrients in 'Shushanggan apricot' fruits were detected by UPLC-MS/MS. A total of 592 compounds were identified, of which sucrose contributed mainly to the sweet taste and malic acid and citric acid were important organic acids affecting sweet-sour taste. γ-linolenic acid, α-linolenic acid and linoleic acid were the dominant free fatty acids, and neochlorogenic acid and chlorogenic acid were the predominant phenolic acids. Fruit taste was positively correlated with sucrose and negatively correlated with malic acid and citric acid. The differential metabolites were significantly enriched in the biosynthesis of amino acids and 2-oxocarboxylic acid metabolism pathways, regulating the sugar and organic acid biosynthesis. Taste and nutrient differences could be revealed by variations in composition and abundance of carbohydrates, organic acids and amino acids. The purpose of this study was to provide a comprehensive chemical characterization of taste and nutrient compounds in 'Shushanggan apricot' fruits.

Restoration of appearance for women after aesthetic eyelash transplantation using a novel eyelash resection technique.

BACKGROUND: Hair transplantation based on the follicular unit extraction provides a new opportunity to improve the appearance of patients with congenital sparse eyelashes. However, disparity between transplanted grafts and original eyelashes and the physiological characteristics of upper eyelid skin cause difficulties with this technique and result in low satisfaction. Removal of unsatisfactory eyelashes is indispensable for restoration of appearance and a second transplantation. Unfortunately, existing methods for hair removal have variable success rates, and hairs frequently regrow. OBJECTIVE: This article introduces an effective method to remove unsatisfactory eyelashes in patients with congenital sparse eyelashes who have undergone eyelash transplantation. METHODS: We used a new technique, which involves resection of eyelashes with a composite strip, to remove unsatisfactory eyelashes in patients who underwent eyelash transplantation. The demographic and clinical characteristics of patients were recorded. Outcomes evaluated included patient satisfaction, hair regrowth, and long-term complications. RESULTS: From 2017 to 2021, 10 patients (20 sides) underwent eyelash removal. All patients were highly satisfied with the outcomes. Unsatisfactory eyelashes were thoroughly removed, and none regrew during 1 year of follow-up. No complications were observed. CONCLUSION: Strip composite eyelash excision is a safe and effective method for patients who have undergone unsatisfactory eyelash transplantation.

Rapid bilateral visual loss as the initial clinical manifestation in idiopathic hypertrophic cranial pachymeningitis.

A 59-year-old patient presented with 4-day acute painless bilateral visual loss, MRI results showed dura enhancement of the frontal, anterior cranial fossa. The patient was considered to have idiopathic hypertrophic cranial pachymeningitis based on laboratory tests and MRI data. After treatment with hormones, the visual acuity obviously improved.

Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites.

Cinnamomum balansae Lecomte (Lauraceae), an economically important forest tree, is distributed in the tropical forests of central and northern Vietnam, which has been threatened in recent decades due to the destruction of its habitat and over-exploitation. The genetic diversity and population structure of the species have not been fully evaluated. We used a set of 15 microsatellites to analyze 161 adult trees from 9 different populations, representing the geographical distribution of C. balansae. Ninety-two different alleles were identified. Here our results showed a low genetic diversity level with an average H o = 0.246 and H e = 0.262, and a high level of genetic differentiation (F ST = 0.601). The bottleneck tests indicated evidence of a reduction in the population size of the two populations (TC and CP). Additionally, all three clustering methods (Bayesian analysis, principal coordinate analysis, and Neighbor-joining tree) were identified in the two genetic groups. The Mantel test showed a significant positive correlation between genetic distance and geographic distance (R 2 = 0.7331). This study will provide a platform for the conservation of C. balansae both in ex-situ and in-situ plans.

Diabetic Ketoacidosis With Acute Pancreatitis in Patients With Type 2 Diabetes in the Emergency Department: A Retrospective Study.

Objective: This study aims to explore the incidence and clinical features of acute pancreatitis (AP) in patients with type 2 diabetes diabetic ketoacidosis (DKA) in the emergency department and discuss the predictive value of some pathological indicators for AP in DKA. Methods: Inpatient medical data of DKA patients hospitalized to our hospital's emergency department between January 2017 and January 2021 were evaluated retrospectively. These DKA patients were split into two groups based on whether they had AP or not. We examined the two groups' epidemiologic features, baseline laboratory results, and clinical outcomes. The Bedside Index for Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation II (APACHE II), and Logistic Organ Failure System (LODS) scores were computed and compared across groups. Results: The prevalence of AP in DKA patients was 15.53%. The difference in Abdominal pain between the two groups of patients was statistically significant (p < 0.001), and there was no statistical difference in age, gender, and BMI. The DKA and AP group LOS (P < 0.001), ICU admission rate (P = 0.046), anion gap (P < 0.001), red blood cell (P = 0.002), hemoglobin (P < 0.001), hematocrit (P = 0.002), serum triglyceride (P < 0.001), serum cholesterol (P < 0.001), serum amylase (P = 0.004), random glucose (P = 0.028), plasma fibrinogen (P < 0.001), glycosylated hemoglobin [HbA1c (%); P = 0.008] higher than the DKA group, pH (P < 0.001), carbon dioxide combining power (CO2CP; P < 0.001), ionized calcium (Ca2+; P = 0.022), ionized sodium (Na+; P = 0.001), and correction Na (P = 0.034) lower than the DKA group. Multivariate analysis showed that low pH (P < 0.05), hypertriglyceridemia (P = 0.001), and hypercholesterolemia (P = 0.01) were risk factors for DKA combined with AP. ROC curve analysis showed that the three cut-off value: serum triglycerides of 10.52 mmol/L, serum cholesterol of 9.03 mmol/L, and pH of 7.214. Serum triglyceride has the largest area under the curve (0.93). Under this cut-off value, the sensitivity (80%) and specificity of serum triglyceride, the degree (93.7%) is the highest, while the positive predictive value (62.0%) and negative predictive value (94.7%) of serum cholesterol are the highest. Conclusions: A severe episode of DKA with significant acidosis and hyperlipidemia is more likely to be linked with AP. The frequently used critical illness score is ineffective in determining the severity of the condition. When the serum triglyceride cut-off value is 10.52mmol/L, it has a higher predicted value for AP in DKA.

Belimumab for Immune-Mediated Necrotizing Myopathy Associated With Anti-SRP Antibodies: A Case Report and Retrospective Review of Patients Treated With Anti-B-Cell Therapy in a Single Center and Literature.

Background: Immune-mediated necrotizing myopathy (IMNM) is characterized by markedly elevated creatinine kinase and histologically scattered necrotic muscle fibers and generally associated with autoantibodies against signal recognition particle (SRP) or 3-hydroxy-3-methylglutaryl-coA-reductase (HMGCR). Poor clinical response to conventional therapies and relapses commonly occur in severe cases. Anti-B-cell therapies have been used in refractory/relapsing cases. Methods: The characteristics of a patient with IMNM associated with anti-SRP antibodies including physical examination, laboratory tests, and disease activity assessment were evaluated. Conventional therapy, belimumab treatment schedule, and follow-up data were recorded. Medical records of IMNM patients treated in our department from September 2014 to June 2021 were reviewed to evaluate the efficacy and safety of anti-B-cell therapy for anti-SRP IMNM. A literature review of patients with anti-SRP IMNM treated with anti-B-cell therapies was performed. Results: We describe a case of a 47-year-old woman with IMNM associated with anti-SRP antibodies who relapsed twice after conventional therapy but showed good response and tolerance to belimumab at 28 weeks follow-up. In this review, three patients from our department were treated with rituximab. Two of the three patients rapidly improved after treatment. Twenty patients and five retrospective studies were included in the literature review. All patients were administered rituximab as an anti-B-cell drug. Conclusion: Despite a lack of rigorous clinical trials, considerable experience demonstrated that anti-B-cell therapy might be effective for patients with IMNM associated with anti-SRP antibodies. Belimumab in association with steroids might be an encouraging option for refractory/relapsing cases.

Analysis of Prognostic Risk Factors of Bloodstream Infections in Beijing Communities: A Retrospective Study from 2015 to 2019.

OBJECTIVE: This study intends to investigate the prognostic risk factors of bloodstream infection in Beijing. METHODS: This study is a clinical retrospective study. Four hundred forty-six patients with community-onset bloodstream infections (COBSI), admitted to the emergency department and inpatient department of Beijing Jishuitan Hospital from January 1, 2015, to December 31, 2019, were selected as the main research objects. According to whether the patient survives for 100 days or not, 363 cases were in the survival group, and 83 cases were in the death group. By analyzing the clinical data of the two groups of patients, the epidemiology, clinical characteristics, bacterial resistance, and risk factors affecting the prognosis of the patients were analyzed. RESULTS: A total of 446 pathogenic bacteria were isolated in this study, including 324 Gram-negative (G-) bacteria (72.6%), 121 Gram-positive (G+) bacteria (27.1%). The results of the study showed that there were significant differences in MDR, initial antibiotic use, solid tumor, CKD, septic shock, acute liver injury, AKI, central venous catheter, urinary catheter, blood replacement therapy, invasive operation, and use of three or more antibiotics between the two groups (p<0.05). The multiple logistic regression analysis showed that solid tumors (OR=3.339, 95% CI: (1.441, 7.734), p=0.005), combined septic shock (OR=20.729, 95% CI: (10.235, 41.982), p<0.001), indwelling catheters (OR=3.556, 95% CI: (1.538, 8.222), p=0.003) and continuous venovenous hemofiltration (CVVH, OR=19.548, 95% CI: (8.724, 35.641), p=0.003) are independent risk factors affecting the prognosis of COBSI patients. Appropriate initial antibiotic therapy is a protective factor affecting the prognosis of COBSI patients. CONCLUSION: Solid tumors, combined septic shock, indwelling catheters, CVVH are independent risk factors affecting the prognosis of COBSI patients.

A Rapid and Highly Sensitive Chemiluminescent Method to Quantify HPV16E7 Antibody Based on Immunomagnetic Separation Methods.

BACKGROUND: In order to detect anti-HPV16E7 antibody in serum, a highly sensitive and rapid detection method based on chemiluminescence immunoassay and immunomagnetic separation was introduced. The technique that was developed is a novel, sensitive chemiluminescence (CL) immunoassay for HPV16E7 antibody detection. METHODS: Balb/C mice were immunized with HPV16E7 fusion protein to prepare monoclonal antibody against HPV16E7. The biotinylated antigen was prepared as immunomagnetic beads and its stability was tested (IMBs). The protocol used horseradish peroxidase (HRP) labeled HPV16E7 antigen and immunomagnetic beads (IMBs). The antibody induced the formation of IMBs-mAbs HPV16E7-HRP labeled antibody structures. IMBs were applied to capture CEA and immobilize CEA through the external magnetic field. Oxidized luminescence substrate can be catalyzed by HRP on antibody surface to generate optical signals which were detected by luminometer. RESULTS: HPV16E7 monoclonal antibody was prepared and validated. The HPV16E7 antigen can efficiently bind to the bead with a conjugation rate of 72%. The biological activity of IMBs did not decrease significantly when stored in the dark at 4℃ for 2 months. The sensitivity and stability of this proposed method were excellent and showed a good linear relationship (Y = 1.3203 X + 0.7, R2 = 0.9952). CONCLUSIONS: This proposed technique showed excellent performance in quantitative measurement of HPV6E7 and was expected to be used in clinical detection.

Long-term outcomes of Roux-en-Y gastric bypass versus medical therapy for patients with type 2 diabetes: a meta-analysis of randomized controlled trials.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) has been widely used for type 2 diabetes (T2D) patients with overweight or obesity. However, the long-term outcomes of RYGB versus medical therapy have not been well compared. OBJECTIVES: To evaluate the long-term outcomes of RYGB versus medical therapy for patients with T2D. SETTING: University-affiliated hospital, China. METHODS: Four electronic databases-PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov-were searched for articles published through February 2021. Eligible studies were randomized controlled trials. RESULTS: Of 7 randomized controlled trials (15 articles), 477 patients were included: 239 were randomly divided into RYGB groups and 238 to medical therapy groups. Statistically higher rates of T2D remission were observed in RYGB groups at 1 year (relative risk [RR], 18.01; 95% confidence interval [CI], 4.53- 71.70; P < .0001), 3 years (RR, 29.58; 95% CI, 5.92-147.82; P < .0001), and 5 years (RR, 16.92; 95% CI, 4.15-69.00; P < .0001). Meanwhile, statistically higher rates of achieving the American Diabetes Association's (ADA's) treatment goal were observed in RYGB groups at 1 year (RR, 3.99; 95% CI, 1.01-15.82; P = .05), 2 years (RR, 2.98; 95% CI, 1.62- 5.48; P = .0004), 3 years (RR, 3.16; 95% CI, 1.33-7.49; P = .009), and 5 years (RR, 6.18; 95% CI, 1.69-22.68; P = .006). CONCLUSION: This meta-analysis indicated that RYGB led to higher rates of T2D remission than medical therapy at 1, 3, and 5 years, as well as higher rates of achieving ADA's composite goal at 1, 2, 3, and 5 years.

Accumulation Pattern of Amygdalin and Prunasin and Its Correlation with Fruit and Kernel Agronomic Characteristics during Apricot (Prunus armeniaca L.) Kernel Development.

To reveal the accumulation pattern of cyanogenic glycosides (amygdalin and prunasin) in bitter apricot kernels to further understand the metabolic mechanisms underlying differential accumulation during kernel development and ripening and explore the association between cyanogenic glycoside accumulation and the physical, chemical and biochemical indexes of fruits and kernels during fruit and kernel development, dynamic changes in physical characteristics (weight, moisture content, linear dimensions, derived parameters) and chemical and biochemical parameters (oil, amygdalin and prunasin contents, ß-glucosidase activity) of fruits and kernels from ten apricot (Prunus armeniaca L.) cultivars were systematically studied at 10 day intervals, from 20 days after flowering (DAF) until maturity. High variability in most of physical, chemical and biochemical parameters was found among the evaluated apricot cultivars and at different ripening stages. Kernel oil accumulation showed similar sigmoid patterns. Amygdalin and prunasin levels were undetectable in the sweet kernel cultivars throughout kernel development. During the early stages of apricot fruit development (before 50 DAF), the prunasin level in bitter kernels first increased, then decreased markedly; while the amygdalin level was present in quite small amounts and significantly lower than the prunasin level. From 50 to 70 DAF, prunasin further declined to zero; while amygdalin increased linearly and was significantly higher than the prunasin level, then decreased or increased slowly until full maturity. The cyanogenic glycoside accumulation pattern indicated a shift from a prunasin-dominated to an amygdalin-dominated state during bitter apricot kernel development and ripening. ß-glucosidase catabolic enzyme activity was high during kernel development and ripening in all tested apricot cultivars, indicating that ß-glucosidase was not important for amygdalin accumulation. Correlation analysis showed a positive correlation of kernel amygdalin content with fruit dimension parameters, kernel oil content and ß-glucosidase activity, but no or a weak positive correlation with kernel dimension parameters. Principal component analysis (PCA) showed that the variance accumulation contribution rate of the first three principal components totaled 84.56%, and not only revealed differences in amygdalin and prunasin contents and ß-glucosidase activity among cultivars, but also distinguished different developmental stages. The results can help us understand the metabolic mechanisms underlying differential cyanogenic glycoside accumulation in apricot kernels and provide a useful reference for breeding high- or low-amygdalin-content apricot cultivars and the agronomic management, intensive processing and exploitation of bitter apricot kernels.

Accurate Identification of Human Phosphorylated Proteins by Ensembling Supervised Kernel Self-organizing Maps.

Protein phosphorylation is a vital physiological process, which plays a critical role in controlling survival differentiation, cell growth, metabolism and apoptosis. The accurate identification of whether a protein will be phosphorylated solely from protein sequence is especially useful for both basic research and drug development. In this study, a new predictor specifically designed for the prediction of human phosphorylated proteins is proposed. The proposed method first train two supervised kernel self-organizing maps (SKSOMs): one is trained with feature from protein physiochemical composition view, while the other is trained with feature from protein evolutionary information view. Then, the two trained SKSOMs are ensembled to perform the final prediction. Rigorous computational experiments show that the proposed method achieves 78.75 % and 0.561 on ACC and MCC, which are 6.96 % and 12.5 % higher than that of the state-of-the-art predictor. Overall, the study demonstrated a new sensitive avenue to identify human phosphorylated proteins and could be readily extended to recognize phosphorylated proteins for other species.

Nitrate Reductase-Mediated Nitric Oxide Regulates the Leaf Shape in Arabidopsis by Mediating the Homeostasis of Reactive Oxygen Species.

As a gaseous biological signaling molecule, nitric oxide (NO) regulates many physiological processes in plants. Over the last decades, this low molecular weight compound has been identified as a key signaling molecule to regulate plant stress responses, and also plays an important role in plant development. However, elucidation of the molecular mechanisms for NO in leaf development has so far been limited due to a lack of mutant resources. Here, we employed the NO-deficient mutant nia1nia2 to examine the role of NO in leaf development. We have found that nia1nia2 mutant plants displayed very different leaf phenotypes as compared to wild type Col-0. Further studies have shown that reactive oxygen species (ROS) levels are higher in nia1nia2 mutant plants. Interestingly, ROS-related enzymes ascorbate peroxidase (APX), catalases (CAT), and peroxidases (POD) have shown decreases in their activities. Our transcriptome data have revealed that the ROS synthesis gene RBOHD was enhanced in nia1nia2 mutants and the photosynthesis-related pathway was impaired, which suggests that NO is required for chloroplast development and leaf development. Together, these results imply that NO plays a significant role in plant leaf development by regulating ROS homeostasis.

Leaf anatomy and ultrastructure in senescing ancient tree, Platycladus orientalis L. (Cupressaceae).

Platycladus orientalis L. (Cupressaceae) has a lifespan of thousands of years. Ancient trees have very high scientific, economic and cultural values. The senescence of ancient trees is a new research area but is poorly understood. Leaves are the primary and the most sensitive organ of a tree. To understand leaf structural response to tree senescence in ancient trees, experiments investigating the morphology, anatomy and ultrastructure were conducted with one-year leaves of ancient P. orientalis (ancient tree >2,000 years) at three different tree senescent levels (healthy, sub-healthy and senescent) at the world's largest planted pure forest in the Mausoleum of Yellow Emperor, Shaanxi Province, China. Observations showed that leaf structure significantly changed with the senescence of trees. The chloroplast, mitochondria, vacuole and cell wall of mesophyll cells were the most significant markers of cellular ultrastructure during tree senescence. Leaf ultrastructure clearly reflected the senescence degree of ancient trees, confirming the visual evaluation from above-ground parts of trees. Understanding the relationships between leaf structure and tree senescence can support decision makers in planning the protection of ancient trees more promptly and effectively by adopting the timely rejuvenation techniques before the whole tree irreversibly recesses.

Successful closure of ileostomy in a patient with intestinal Behçet's disease after therapy with adalimumab: A case report.

RATIONALE: Behçet's disease (BD) is a chronic immune-mediated inflammatory disorder involving multiple organ systems. In BD, intestinal ulcers can present as a refractory lesion capable of perforation, which makes the choice of treatment difficult. PATIENT CONCERNS: A 34-year-old male who was diagnosed with intestinal BD and suffered with an ileocecal perforation. He underwent surgery for an ileostomy and was given corticosteroids as treatment. However, the ulcerative lesion remained resistant to the therapy that was provided which delayed the closure operation. DIAGNOSIS: Intestinal BD with severe post-operative complication. INTERVENTIONS: A course of adalimumab (ADa) therapy was started. Subsequently surgery was performed. And ADa and thalidomide were used as a maintenance therapy. OUTCOMES: In this case, a course of ADa therapy was given which healed the intestinal ulcers and allowed us to successfully perform the closure operation. LESSONS: This case indicates that ADa may be an effective treatment option in future cases, minimizing complications and allowing the closure operation to be performed successfully.

Farrerol attenuates MPP+ -induced inflammatory response by TLR4 signaling in a microglia cell line.

Farrerol was found to possess neuroprotective effect; however, the mechanism remains unknown. The aim of the present study was to explore the effect of farrerol on MPP+ -induced inflammation in mouse microglial BV-2 cells and to elaborate the underlying mechanism. MTT assay was performed to measure the cell viability. The pro-inflammatory mediators and cytokines including interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α); inducible nitric oxide synthase; and cyclooxygenase 2 were measured. The expression of p-p65, p-IκBα, toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 were analyzed by western blot. We found that farrerol treatment improved cell viability in MPP+ -induced BV-2 cells. MPP+ -induced upregulation of IL-6, IL-1ß, and TNF-α was inhibited by farrerol treatment. Farrerol treatment also attenuated MPP+ -induced expression of inducible nitric oxide synthase and cyclooxygenase 2 as well as the activation of NF-κB in BV-2 cells. MPP+ -induced TLR4 signaling was markedly diminished by farrerol treatment. Knockdown of TLR4 attenuated MPP+ -induced inflammatory response in BV-2 cells. In conclusion, farrerol treatment attenuated MPP+ -induced inflammatory response by inhibiting the TLR4 signaling pathway in BV-2 cells. The results indicated that farrerol could be used as a therapeutic agent for preventing or alleviating the neuroinflammation-related diseases, such as Parkinson's disease.

Farrerol attenuates ß-amyloid-induced oxidative stress and inflammation through Nrf2/Keap1 pathway in a microglia cell line.

Farrerol, an important bioactive constituent of rhododendron, exhibits broad activities such as anti-oxidative and anti-inflammatory effects. Recent studies showed that farrerol possesses neuroprotective activity, however, the mechanism has not been reported. The aim of the present study was to investigate the protective effect of farrerol on ß-amyloid (Aß)-induced mouse microglial BV-2 cells and the underlying mechanism. BV-2 cells were pretreated with farrerol for 1 h and then subjected to Aß. MTT assay was performed to measure the mitochondrial metabolic activity in BV-2 cells. The production of reactive oxygen species (ROS) and malondialdehyde (MDA) and superoxide dismutase (SOD) activity were detected to reflect oxidative stress status. The secretion and mRNA levels of interleukin (IL)-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) were measured by ELISA and qRT-PCR. The expressions of NF-E2-related factor (Nrf2), heme oxygenase-1 (HO-1), NAD (P) H: quinone oxidoreductase 1 (NQO1), and Kelch-like ECH-associated protein 1 (Keap1) were measured by western blot. Our results showed that farrerol improved mitochondrial metabolic activity in Aß-induced BV-2 cells. Aß induced the production of ROS and MDA, and inhibited the SOD activity and the expression of SOD1 and SOD2 mRNA, while the effects were attenuated by farrerol. Farrerol also inhibited the induction effect of Aß on IL-6, IL-1ß, and TNF-α. In addition, farrerol enhanced the activation of Nrf2/Keap1 pathway in Aß-induced BV-2 cells. Knockdown of Nrf2 by small interfere RNA (siRNA) targeting Nrf2 (si-Nrf2) abolished the protective effect of farrerol on Aß-induced BV-2 cells. In conclusion, farrerol attenuated Aß-induced oxidative stress and inflammation in BV-2 cells through enhancing the activation of Nrf2/Keap1 pathway. The findings indicated that farrerol could be considered as a therapeutic approach for the treatment of Alzheimer's disease (AD).

Transcriptional responses and mechanisms of copper nanoparticle toxicology on zebrafish embryos.

Copper nanoparticles (CuNPs) are used widely due to their attractive antimicrobial properties. However, their biosafety and kinetics on vertebrate embryogenesis are still limited. In this study, CuNPs were revealed to induce eye hypoplasia and almost no digestive gut in zebrafish embryos in a dose-dependent manner. Then, transcriptional responses of zebrafish embryos to CuNPs were investigated, and it was revealed that the genes related to wound healing and stimulus responses were up-regulated, but the genes associated with phototransduction and metabolisms were down-regulated. Differentially expressed genes (DEGs) in CuNPs-exposed and Cu2+-exposed embryos were compared further. Increased VEGF signaling and expression of fli1 were observed in CuNPs rather than Cu2+ treated embryos, but increased reactive oxygen species (ROS) and the resulting enhanced hemoglobin were observed in both CuNPs and Cu2+ treated embryos. This study for the first time revealed that CuNPs and Cu2+ both down-regulated the genes related to phototransduction and metabolisms, but up-regulated the genes associated with hemoglobin. Additionally, compared with Cu2+, CuNPs might be more effective in elevating blood vessels in embryos. Our results suggest that the biological effects of CuNPs are organogenesis-specific during fish embryogenesis, and both particles and ions might mediate their biological effects on embryogenesis.

[Comorbidity of Autoimmune Diseases: a Field that Needs Multidisciplinary Attention].

Comorbidity of autoimmune diseases is a very important issue but easily ignored in the clinical practice. The treatment of comorbidity of autoimmune diseases needs cooperation of multiple disciplines,which is totally different from traditional clinical disciplines division and treatment mode. Based on the clinical features of the disease,we will comprehensively look through genetic,environmental,and immune factors involving in molecular and immunological compatibility pathogenesis,and also generalize common pathological features,such as immune complex deposition and accumulation of lymphocytes. We will also investigate the association and differences between the diseases with comorbidity,and explore the outcome and prognosis of comorbidity of autoimmune diseases. With clarify of the concept of autoimmune comorbidities,we hope bring more and more attention on this aspect,so as to improve the diagnosis,treatments as well as the prognosis of these diseases.