Characterization of newly diagnosed type 1 diabetes in children and adolescents from 2017 to 2022 in China: a single-center analysis.

OBJECTIVE: This study investigated the characteristics of newly diagnosed type 1 diabetes mellitus (T1DM) related to autoimmunity and the frequency of diabetic ketoacidosis (DKA) in children and adolescents from 2017-2022 in China. RESEARCH DESIGN AND METHODS: Single-center regional data from the Department of Pediatric Endocrinology, Tongji Hospital, were used to compare 88 children and adolescents newly diagnosed with T1DM from 2020 to 2022 (i.e. during the COVID-19 pandemic in China) and 76 children and adolescents diagnosed with T1DM from 2017 to 2019. Auto-antibodies, including glutamic acid decarboxylase-65 and insulin auto-antibodies, were detected by enzyme-linked immunoassays. DKA was defined as a pH < 7.3 and/or a bicarbonate level < 15 mmol/L. RESULTS: The median age of the 164 children and adolescents newly diagnosed with T1DM from 2017 to 2022 was 7.0 years (interquartile range [IQR]: 3.8-10.0 years; 51.83% male). The mean annual incidence of T1DM was 2.98 per 1,000,000 child years. The estimated frequency of auto-antibody positivity was 51.22% (n = 84), and there was no difference between the 2020-2022 group and 2017-2019 group (55.68% [n = 49] vs. 46.5% [n = 35]; p = 0.219). The frequency of DKA among the entire cohort was 57.93% (n = 95), and peaked in 2020 at 78.9% (15/19 patients). The frequency of DKA was not significantly higher in the 2020-2022 group compared with the 2017-2019 group (60.23% [n = 53] vs. 55.26% [n = 42]; p = 0.521). We found no significant difference in the frequency of DKA between patients who were negative vs. positive for auto-antibodies in the 2020-2022 group (64.10% [n = 25] vs. 57.14% [n = 28], p > 0.05). The C-peptide level and HbA1c (%) were positively correlated with onset age (R1 = 0.389, p < 0.01; R2 = 0.371, p < 0.01), and the estimated mean C-peptide level was 0.26 ng/ml (IQR: 0.2-0.4 ng/ml) in patients with DKA and 0.370 ng/ml (IQR: 0.2-0.6 ng/ml) in patients without DKA (p = 0.044). CONCLUSIONS: This study showed the annual incidence of T1DM was 2.98 per 1,000,000 child years, gradually increased over the study period, and there was no significant increase in T1DM with auto-antibody positivity in children and adolescents newly diagnosed from 2020-2022 in China compared with the previous 3 years. Furthermore, the frequency of DKA was peaked in 2020, and were not significantly different between patients who were negative vs. positive for auto-antibodies.

Concentrations, influencing factors, risk assessment methods, health hazards and analyses of polycyclic aromatic hydrocarbons in dairies: a review.

The occurrence of polycyclic aromatic hydrocarbons (PAHs) in dairies has been widely reported. Consumers may be overly exposed to PAHs through dairies causing health risks. Hazards can be reduced by controlling influencing factors in the full-chain of dairy production. This review briefly introduces research trends and analytical methods concerning PAHs in dairies. Additionally, this review discusses influencing factors of PAH concentrations in various dairies to avoid PAHs' formation and accumulation during manufacture. Relevant regulations are referred to and the reported risk assessment methods are summarized. Furthermore, indicators of health risks including TEQBaP, the number and the rate of over-standard are calculated based on PAH concentrations. Through analyses, we find PAH and BaP contamination in dairies are complex problems depending on environment, processing and storage. There was a significant correlation between fat contents and PAH concentrations. Results of infant formula in certain research were worrying and those of smoked cheeses are remarkably high indicating the dangerous smoking process. It is significant to monitor PAHs and calculate TEQBaP from meadows to feeders. Moreover, the existing regulations are insufficient and need strengthening. The data and discussions in this review contribute to worldwide Big Data, further scientific investigation and regulations for PAHs in dairies.

Difficult Blood Typing Caused by Rouleaux Agglutination in Patient with Acute Brain Trauma: a Case Report.

BACKGROUND: Rouleaux agglutination is a common cause of difficult blood typing, but it is rarely reported in patients with acute brain trauma. METHODS: This article describes a 69-year-old male with head injury who was admitted to the hospital. Blood typing showed type O, Rh(D) positive, but the Rh(D) control was also positive. After ruling out the possibility of the patient having abnormal autoantibodies, it was suspected that rouleaux agglutination might be the cause. Microscopic examination of the specimen revealed rouleaux agglutination, which was believed to be the cause of the false-positive Rh(D) control result. The patient's red blood cells were treated with physiological saline and retested by microcolumn gel card testing. RESULTS: The retest showed negative Rh(D) control results, indicating normal results. The patient subsequently received normal blood transfusion. CONCLUSIONS: Laboratory personnel should be aware of the possibility of difficult blood typing caused by rouleaux agglutination in various diseases, especially in relatively rare traumatic diseases.

Pneumonia During the COVID-19 Pandemic in Hubei Province, China: a Case Report of Mucormycosis.

BACKGROUND: Mucor infection cannot be ignored in patients with pulmonary shadowing with cavitation. This paper reports a case of mucormycosis during the COVID-19 pandemic in Hubei Province, China. METHODS: An anesthesiology doctor was initially diagnosed as COVID-19 due to changes in lung imaging. After anti-infective, anti-viral, and symptomatic supportive treatment, some of symptoms were relieved. But some symptoms -'chest pain and discomfort', accompanied by chest sulking and short breath after activities, did not ease. At last, Lichtheimia ramose was detected later by metagenomic next generation sequencing (mNGS) in the bronchoalveolar lavage fluid (BALF). RESULTS: After adjusting amphotericin B for anti-infective treatment, the patient's infection lesions were shrunk and the symptoms were significantly relieved. CONCLUSIONS: The diagnosis of invasive fungal infections is very difficult, and mNGS can make an accurate pathogenic diagnosis of invasive fungal diseases for the clinic and provide a basis for clinical treatment.

Oxygenated polycyclic aromatic hydrocarbons in food: toxicity, occurrence and potential sources.

Oxygenated polycyclic aromatic hydrocarbons (OPAHs) are polycyclic aromatic hydrocarbons (PAHs) functionalized with at least one carbonyl group and are generally thought to be more toxic than PAHs. In this review, the physical-chemical properties, toxicity, occurrence, and potential sources of OPAHs in food were comprehensively discussed. The toxicities of 1,2-naphthoquinone, 1,4-naphthoquinone, 6H-benzo[cd]pyren-6-one, benzo[a]anthracene-7,12-quinone and 9,10-phenanthrenequinone were prominent among the OPAHs. Both 1,4-naphthoquinone and 1,2-naphthoquinone exhibited strong genotoxicity, cytotoxicity, and developmental toxicity. 6H-benzo[cd]pyren-6-one and benzo[a]anthracene-7,12-quinone showed high genotoxicity and cardiovascular toxicity. Although 9,10-phenanthrenequinone showed no genotoxicity, it exhibited almost the strongest cytotoxicity. For the majority of foods, the concentrations of OPAHs and PAHs were on the same order of magnitude. OPAHs tend to be positively correlated with the corresponding PAH concentrations in oil and fried food, while for barbequed food and seafood, no obvious correlation was found. In addition, 9-fluorenone, 9,10-anthraquinone, benzanthrone and 1,2-acenaphthenequinone had high abundance in food. Environmental pollution, food composition, storage conditions, heating methods, and other treatments influence the accumulation of OPAHs in food. Furthermore, oxygen and water played an important role in the transformation from PAHs to OPAHs. In short, this review guides the evaluation and further reduction of OPAH-related health risks in food.

A novel KLF11 variant in a family with maturity-onset diabetes of the young.

OBJECTIVE: The Krüppel-like factor 11 (KLF11) gene causes maturity-onset diabetes of the young 7 (MODY7). There are few reports on the clinical and functional characteristics of KLF11 mutations in patients with MODY7, making diagnosis and treatment complicated. RESEARCH DESIGN AND METHODS: We report a novel KLF11 variant associated with MODY7 in a Chinese family. The proband had hyperglycemia at 9 years of age, and his mother had developed diabetes at age 28 years. Both required insulin injections from the initial phase of the disease. They were negative for islet cell autoantibodies and had normal fasting C-peptide levels. We observed changes in the levels of fasting blood glucose, C-peptide, and islet cell autoantibodies in the proband over 4.5 years. RESULTS: Whole-exon sequencing was used to screen the proband and his family members for KLF11 variants. The heterozygous KLF11 variant (c.1045C>T, p. Pro349Ser) was identified in the proband, his mother, his maternal grandmother, and an elderly aunt, although the latter two individuals were unaffected. In silico analyses indicated that this variant involved a change in the amino acid side chain in the transcriptional regulatory domain 3. Luciferase reporter assays revealed that the variant had impaired insulin promoter regulation activity. Moreover, in vitro analyses showed that this variant impaired insulin secretion from pancreatic beta cells. CONCLUSIONS: This study documents a novel heterozygous KLF11 variant (p. Pro349Ser) as a potential monogenic mutation associated with MODY7 in a family. This variant impairs insulin secretion from pancreatic beta cells, possibly by repressing insulin promoter regulation activity.

Decreased circulating levels of free triiodothyronine in Sepsis children and correlation analysis.

BACKGROUND: Intensive physical stress in sepsis can induce the disorder of endocrine function and impact the clinical course and prognosis. Low T3 syndrome has been verified to be the predictive indicator of poor prognosis in several researches. Reports on the influence factors of thyroid hormonal levels in children with severe sepsis are rare. We aim to investigate the thyroid hormonal variations in the course of sepsis and analyze that how to be affected by clinical data and inflammatory biomarkers. METHODS: In the case-control study, 184 children with sepsis and 323 controls were included in Tongji Hospital, Wuhan, China, in 2019. Data on clinical and inflammatory parameters were collected from all participants. Circulating FT3(Free Triiodothyronine) levels were measured by Electrochemiluminescence immunoassay. Finally, we investigated the correlation between FT3 and related variables with linear regression analysis. RESULTS: Serum FT3 was lower in the sepsis group than in control group(2.59 + 1.17 vs 2.83 + 1.01 pg/mL, p < 0.05). Significant moderately negative correlations(|r| > 0.3) of FT3 levels with ferritin, PCT, duration of symptoms, SOFA score, and mortality were revealed. Moreover, we observed that FT3 had the positive correlation with albumin, as well as white blood cell count. CONCLUSIONS: Concentrations of serum FT3 are dramatically declined in sepsis children than in control children. Our results demonstrate that recognizing the potential abnormality of thyroid hormones in sepsis patients and examine timely through abnormal common clinical data and inflammatory biomarkers is a fine option.

Dietary exposure and risk assessment of European Union priority (EU 15+1) polycyclic aromatic hydrocarbons from milks and milk powders in China.

Dairy products, characterized by rich nutrition and unique flavor, occupy an increasing share of the human diet with the development of higher living standards. However, trace hazardous contaminants in dairy products, such as polycyclic aromatic hydrocarbons (PAH), are arousing public concern. In this study, we investigated 82 milks and milk powders from Shanghai markets for the occurrence of 20 PAH, including 16 European Union priority (EU 15+1) PAH and 4 derivatives. Furthermore, we carried out a risk assessment of dietary exposure of PAHs from dairy products based on detection results and data on body weight and dietary intake obtained from questionnaires. Two assessment methods were used in this study: the incremental lifetime cancer risk (ILCR) and margin of exposure (MOE) methods. The ILCR of all age groups was 10-6 to 10-4, indicating a potential but acceptable carcinogenic risk. The MOE of the 4 groups (divided by age and sex) was >104, indicating no significant carcinogenic risk of PAH exposure from dairy products. In both methods, children had the highest risk because of their greater consumption of dairy products, followed by seniors, young adults, and middle-aged adults. Results of this study provide reference data on the exposure level and health risk of PAHs from dairy product intake.

Efficient degradation of organic compounds in landfill leachate via developing bio-electro-Fenton process.

Efficient and harmless disposal of landfill leachate has attracted increasing attention. In this study, the bio-electro-Fenton method was investigated and developed to degrade the organic compounds in landfill leachate by hydroxyl radical oxidation. The optimal operational parameters (i.e., pH and external voltage) of the bio-electro-Fenton system were detected. Under the conditions of pH 2, 0.6 V, the highest total chemical oxygen demand (COD) decrement efficiency was obtained (about 70%), with apparent removal constant at 6 h (kapp-6h) of about 0.12 h-1. Subsequently, to further increase the degradation efficiency, functionalized carbon black and functionalized carbon nanotube (FCNT) were prepared as catalysts for the cathode electrode modification. With 0.4 mg/cm2 FCNT coated on the cathode electrode, 91.3% of the organic compounds were degraded, remaining only 84 mg/L COD (kapp-6h = 0.24 h-1). In all the reactors, the COD was mainly decreased in 0-6 h, contributing to over 68% of the total degradation efficiency. In the bio-electro-Fenton system, the bio-anode electrode could enhance H2O2 production and the conversion between Fe2+ and Fe3+ by strengthening electrons generation and transportation via the oxidation of organics by biofilms (dominant with Geobacter) covered on the carbon brush.

Enhanced degradation of glucocorticoids, a potential COVID-19 remedy, by co-fermentation of waste activated sludge and animal manure: The role of manure type and degradation mechanism.

Waste activated sludge (WAS) and animal manure are two significant reservoirs of glucocorticoids (GCs) in the environment. However, GC degradation during anaerobic digestion (AD) of WAS or animal manure has rarely been investigated. In this study, co-fermentation of WAS and animal manure was conducted to investigate the performance of AD in controlling GC dissemination. Effects of manure type on GC degradation and sludge acidification were investigated. The results showed that co-fermentation of WAS and chicken manure (CM) significantly enhanced the degradation of hydrocortisone (HC) to 99%, betamethasone (BT) to 99%, fluocinolone acetonide (FA) to 98%, and clobetasol propionate (CP) to 82% in 5 days with a mixing ratio of 1:1 (g TS sludge/g dw manure) at 55 °C and initial pH of 7. Simultaneously, sludge reduction was increased by 30% and value-added volatile fatty acid (VFA) production was improved by 40%. Even a high GC content of biomass (3.6 mg/g TS) did not impact both sludge hydrolysis and acidification. The amendment of WAS with CM increased soluble organic carbon, Ca2+, and relative abundance of anaerobes (Eubacterium) associated with organic compound degradation. Furthermore, 44 transformation products of HC, BT, FA, and CP with lower lipophilicity and toxicity were identified, indicating possible degradation pathways including hydroxylation, ketonization, ring cleavage, defluorination, hydrogenation, methylation, and de-esterification. Overall, this study provides a practical way to control GC pollution and simultaneously promote waste reduction and VFA production. Animal manure type as an overlooked factor for influencing co-fermentation performance and pollutant degradation was also highlighted.

Intensifying niacin-based biosynthesis of NAD+ to enhance 3-hydroxypropionic acid production in Klebsiella pneumoniae.

OBJECTIVE: Glycerol-based biosynthesis of 3-hydroxypropionic acid (3-HP) in Klebsiella pneumoniae involves two reactions: glycerol conversion to 3-hydroxypropionaldehyde (3-HPA) by glycerol dehydratase, and 3-HPA conversion to 3-HP by aldehyde dehydrogenase (ALDH). The ALDH catalysis consumes a lot of cofactor nicotinamide adenine dinucleotide (NAD+), which constrains 3-HP production. RESULTS: Here we report that intensifying niacin-based biosynthesis of NAD+ can substantially enhance 3-HP production. We constructed tac promoter-driven NAD+ synthesis pathway in K. pneumoniae. The strain only overexpressing nicotinate phosphoribosyltransferase (PncB) showed 14.24% increase in the production of NAD+ relative to the stain harboring an empty vector. When PncB was coexpressed with PuuC (one of native ALDHs), the recombinant strain exhibited increased ALDH activity but slightly reduced 3-HP production due to plasmid burden. When 30 mg niacin l-1 (a substrate for biosynthesis of NAD+) was added into shake flask, the strain produced 0.55 g 3-HP l-1, which was 2.75 times that of the control. In a 5-L bioreactor, replenishment of niacin led to 36.43% increase of 3-HP production. CONCLUSIONS: These results indicated that intensifying niacin-based biosynthesis of NAD+ boosts 3-HP production.

Optimization of remedial nano-agent and its effect on dominant algal species succession in eutrophic water body.

A new method for algal community restructuring is proposed, where harmful algae growth is inhibited through the addition of remedial nano-agent, while probiotic algae growth is promoted or only affected indistinctively. In this paper, the inhibiting effects of five different nanomaterials on Microcystis aeruginosa (M. aeruginosa) and Cyclotella sp. were studied, and the optimal nanomaterial was served as algae-inhibition ingredient of the remedial agent. The effects of the remedial agent on algal growth and their physiological characteristics were investigated, and the restructuring of algal community in actual water samples was explored. The results indicated that the inhibition ratio of 10 mg/L nm-Cu2O/SiO2 on M. aeruginosa and Cyclotella sp. could reach 293.1% and 82.8% respectively, acting as the best candidate for algae-inhibiting ingredient. After adding the remedial nano-agent made with nm-Cu2O/SiO2, the content of chlorophyll a, protein, and polysaccharides of M. aeruginosa decreased sharply, while the physiological characteristics of Cyclotella sp. were not significantly affected. Besides, the total biomass and proportion of cyanobacteria dropped (P < 0.05), but the Bacillariophyta biomass increased significantly (P < 0.05). The uniformity index, Shannon-Wiener index, and richness index all increased significantly (P < 0.05). Meanwhile, the quality of actual water samples has been improved evidently (P < 0.001). Therefore, the prepared remedial nano-agent in this study can control the harmful algae bloom to a certain extent by restructuring the algal community in eutrophic water bodies.

Potential Link between Equol Pollution and Field-Observed Intersex in Wild So-iuy Mullets (Mugil soiuy).

Gonadal intersex has been observed in wild fishes and is attributed to endocrine-disrupting chemicals but the specific causes remain controversial. Here, a forensic analysis utilizing field and laboratory studies was conducted to explore the causal agent(s). In a 2008-2009 survey of Liaodong Bay, China, 20.7-33.3% incidences of gonadal intersex were observed in male so-iuy mullets (Mugil soiuy), a wild sentinel fish species. Steroidal estrogen (estrone, 17ß-estradiol, estriol, and ethinylestradiol) and phytoestrogen (equol) were detected in seawater where the fishes were collected with median concentrations of 0.42 ng/L (0.02-1.42 ng/L) E2 equivalent (EEQ-E2) and 22.81 ng/L (0.10-155.99 ng/L) equol. A probabilistic model was used to evaluate the ecological risk of these estrogenic chemicals based on their distribution in the field and dose-response relationship from the laboratory surrogate Japanese medaka (Oryzias latipes) fish. The probability of the incidences of gonadal intersex due to equol exposure was estimated to be 13.5 ± 12.1%, which is considerably higher than that for EEQ-E2, (7.2 ± 68.8) × 10-4. The agonistic activity of equol to the estrogen receptor α of so-iuy mullets was 3.5-fold higher than that to the estrogen receptor α of Japanese medaka, indicating that equol shows a stronger potential for inducing intersex in so-iuy mullets than in medaka. These results demonstrate that equol, rather than steroid estrogens, is a more likely causal agent for the field-observed intersex in male wild so-iuy mullets.

The Diagnostic Value of Multi-Index Combined Detection in Patients with COVID-19.

BACKGROUND: To investigate the clinical value of multi-index combined detection in the diagnosis of new coronavirus disease 2019 (COVID-19). METHODS: A total of 63 laboratory confirmed patients treated in our hospital were selected as the COVID-19 group, including 28 severe patients and 35 non-severe patients. Another 50 healthy subjects undergoing physical examination simultaneously were selected as the healthy group. Here we performed a study on the laboratory characteristics and explored their efficacy for diagnosis of the disease. RESULTS: Compared with healthy people, the abnormal indicators of patients with COVID-19 are low levels of lymphocytes (LYM), red blood cells (RBC), hemoglobin (HGB), platelets (PLT), total protein (TP), and albumin (ALB), and high levels of monocytes (MON), aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), and C-reactive protein (CRP). The level of MON and CRP in severe patients were significantly increased compared with non-severe pneumonia patients, and indicators such as LYM and ALB were significantly reduced (p < 0.05). The sensitivity and specificity of the combined detection of LYM, MON, RBC, HGB, PLT, TP, ALB, AST, GGT, and CRP was 97.7% and 91.7%, which was higher than the single item (p < 0.05). The sensitivity and specificity of combined detection of LYM, MON, ALB, and CRP to predict the severity of COVID-19 were 96.4% and 73.0%, which were higher than those of separate detections (p < 0.05). CONCLUSIONS: The index of LYM, MON, RBC, HGB, PLT, TP, ALB, AST, GGT, and CRP can be used for the diagnosis of new COVID-19, and the indicators of LYM, MON, ALB, and CRP may be predictors of severe pneumonia. The combined detection of the laboratory indexes can diagnose COVID-19 and predict the severity more effectively and accurately.

Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance.

BACKGROUND AND AIMS: A novel bioactive peptide, mitochondrial-derived peptide (MOTS-c), has recently attracted attention as a potential prevention or therapeutic option for obesity and type 2 diabetes mellitus (T2DM). MOTS-c profiles have not yet been reported in human obesity and T2DM. We aimed to determine circulating MOTS-c levels in obesity and explore the association between MOTS-c levels and various metabolic parameters. METHODS: In this case-control study, 40 obese children and adolescents (27 males) and 57 controls (40 males) were recruited in the Hubei Province of China in 2017. Circulating MOTS-c levels were measured, clinical data (eg, glucose, insulin, and lipid profile) were recorded, and anthropometric measurements were performed. Finally, we investigated correlations between MOTS-c levels and related variables. RESULTS: MOTS-c levels were significantly decreased in the obese group compared with the control group (472.61 ±22.83 vs 561.64 ±19.19 ng/mL, P <.01). After classification by sex, MOTS-c levels were significantly decreased in obese male children and adolescents compared to their counterparts (465.26 ±24.53 vs 584.07 ±21.18 ng/mL, P <.001), while they were comparable between the obese and healthy female subjects (487.89 ±49.77 vs 508.85 ±38.76 ng/mL, P >.05). Further, MOTS-c levels were negatively correlated with body mass index (BMI), BMI SD score, waist circumference, waist-to-hip ratio, fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR), and glycated hemoglobin (HbA1c) in the male cohort. CONCLUSIONS: Circulating MOTS-c levels were decreased in obese male children and adolescents and correlated with markers of insulin resistance and obesity.

Characterisation of betatrophin concentrations in childhood and adolescent obesity and insulin resistance.

BACKGROUND AND OBJECTIVE: Betatrophin, a novel hormone, is correlated with insulin resistance and promotes pancreatic ß-cell growth in mice. The aim of this study was to determine circulating betatrophin levels in overweight or obese children and adolescents. METHODS: The following pairs of subjects were included: (i) normal-weight healthy (n = 27) and overweight or obese (n = 28); (ii) non-insulin-resistant overweight or obese (n = 25) and insulin-resistant obese (n = 15); (iii) normal-weight males (n = 18) and females (n = 20); (4) 5 to 8 yr olds (n = 20) and 8 to 14 yr olds (n = 18). Circulating betatrophin levels were measured using enzyme-linked immunosorbent assay (ELISA). In addition, clinical data were recorded and anthropometrical measurements were performed. RESULTS: Circulating betatrophin levels were increased significantly in obese children and adolescents with insulin resistance (365.77 ± 30.86 pg/mL) compared with overweight or obese subjects without insulin resistance (274.25 ± 26.52 pg/mL; p < 0.05). However, no differences in betatrophin levels were seen between lean and overweight or obese children (323.18 ± 25.91 vs. 348.27 ± 18.91 pg/mL, respectively; p > 0.05). In the normal-weight cohort, males had higher serum betatrophin level than did females, and subjects <8 yr old had lower serum betatrophin levels compared with those >8 yr. Surprisingly, betatrophin concentrations were correlated negatively with body mass index (BMI), but not with the BMI Z-score, in non-insulin-resistant children and adolescents. CONCLUSIONS: These results demonstrated that circulating betatrophin levels were increased in insulin-resistant obese children or adolescents and might act as a potential biomarker of insulin resistance in these populations. Furthermore, serum betatrophin concentrations might vary during the development of children and adolescents, as well as between genders.

Balancing the Budget: Accounting for Glucocorticoid Bioactivity and Fate during Water Treatment.

Numerous studies have identified the presence and bioactivity of glucocorticoid receptor (GR) active substances in water; however, the identification and activity-balance of GR compounds remained elusive. This study determined the occurrence and attenuation of GR bioactivity and closed the balance by determining those substances responsible. The observed in vitro GR activity ranged from 39 to 155 ng dexamethasone-equivalent/L (ng Dex-EQ/L) in the secondary effluents of four wastewater treatment plants. Monochromatic ultraviolet light of 80 mJ/cm(2) disinfection dose was efficient for GR activity photolysis, whereas chlorination could not appreciably attenuate the observed GR activity. Ozonation was effective only at relatively high dose (ozone/TOC 1:1). Microfiltration membranes were not efficient for GR activity attenuation; however, reverse osmosis removed GR activity to levels below the limits of detection. A high-sensitivity liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was then developed to screen 27 GR agonists. Twelve were identified and quantified in effluents at summed concentrations of 9.6-21.2 ng/L. The summed Dex-EQ of individual compounds based on their measured concentrations was in excellent agreement with the Dex-EQ obtained from bioassay, which demonstrated that the detected glucocorticoids can entirely explain the observed GR bioactivity. Four synthetic glucocorticoids (triamcinolone acetonide, fluocinolone acetonide, clobetasol propionate, and fluticasone propionate) predominantly accounted for GR activity. These data represent the first known publication where a complete activity balance has been determined for GR agonists in an aquatic environment.

Aptamer against mannose-capped lipoarabinomannan inhibits virulent Mycobacterium tuberculosis infection in mice and rhesus monkeys.

The major surface lipoglycan of Mycobacterium tuberculosis (M. tb), mannose-capped lipoarabinomannan (ManLAM), is an immunosuppressive epitope of M. tb. We used systematic evolution of ligands by exponential enrichment (SELEX) to generate an aptamer (ZXL1) that specifically bound to ManLAM from the virulent M. tb strain H37Rv. Aptamer ZXL1 had the highest binding affinity, with an equilibrium dissociation constant (Kd) of 436.3 ± 37.84 nmol/l, and competed with the mannose receptor for binding to ManLAM and M. tb H37Rv. ZXL1 significantly inhibited the ManLAM-induced immunosuppression of CD11c(+) dendritic cells (DCs) and enhanced the M. tb antigen-presenting activity of DCs for naive CD4(+) Th1 cell activation. More importantly, we demonstrated that injection of aptamer ZXL1 significantly reduced the progression of M. tb H37Rv infections and bacterial loads in lungs of mice and rhesus monkeys. These results suggest that the aptamer ZXL1 is a new potential antimycobacterial agent and tuberculosis vaccine immune adjuvant.

MiR-141 targets ZEB2 to suppress HCC progression.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Increasing evidence suggests that microRNAs (miRNAs) are associated with HCC tumorigenesis. The present study was designed to define the role of miR-141 in HCC. The expression of miR-141 was significantly decreased in four HCC cell lines. Overexpression of miR-141 suppressed both the growth and the motility of HCC cells. Furthermore, we identified zinc finger E-box binding homeobox 2 (ZEB2) as a target of miR-141 and miR-141 functioned as a tumor suppressor via ZEB2 targeting in HCC. These data provide a novel potential therapeutic target for HCC treatment.

Advanced glycation end products promote differentiation of CD4(+) T helper cells toward pro-inflammatory response.

This study investigated the effect of advanced glycation end products (AGEs) on differentiation of naïve CD4(+) T cells and the role of the receptor of AGEs (RAGE) and peroxisome proliferator-activated receptors (PPARs) activity in the process in order to gain insight into the mechanism of immunological disorders in diabetes. AGEs were prepared by the reaction of bovine serum albumin (BSA) with glucose. Human naïve CD4(+) T cells, enriched from blood of healthy adult volunteers with negative selection assay, were cultured in vitro and treated with various agents including AGEs, BSA, high glucose, PGJ2 and PD68235 for indicated time. In short hairpin (sh) RNA knock-down experiment, naïve CD4(+) T cells were transduced with media containing shRNA-lentivirus generated from lentiviral packaging cell line, Lent-X(TM) 293 T cells. Surface and intracellular cytokine stainings were used for examination of CD4(+) T cell phenotypes, and real-time PCR and Western blotting for detection of transcription factor mRNA and protein expression, respectively. The suppressive function of regulatory T (Treg) cells was determined by a [(3)H]-thymidine incorporation assay. The results showed that AGEs induced higher pro-inflammatory Th1/Th17 cells differentiated from naïve CD4(+) T cells than the controls, whereas did not affect anti-inflammatory Treg cells. However, AGEs eliminated suppressive function of Treg cells. In addition, AGEs increased RAGE mRNA expression in naïve CD4(+) T cells, and RAGE knock-down by shRNA eliminated the effect of AGEs on the differentiation of CD4(+) T cells and the reduction of suppressive function of Treg cells. Furthermore, AGEs inhibited the mRNA expression of PPARγ, not PPARα PPARγ agonist, PGJ2, inhibited the effect of AGEs on naïve CD4(+) T cell differentiation and reversed the AGE-reduced suppressive function of Treg cells; on the other hand, PPARγ antagonist, PD68235, attenuated the blocking effect of RAGE shRNA on the role of AGEs. It was concluded that AGEs may promote CD4(+) T cells development toward pro-inflammatory state, which is associated with increased RAGE mRNA expression and reduced PPARγ activity.