[Protective effect of vitamin D in mice with acute liver failure].

Objective: To explore the protective effect of vitamin D in acute liver failure through a mouse model. Methods: Acute liver failure was induced by combining D-galactosamine (D-GalN) lipopolysaccharide (LPS) to observe the effect of long-term vitamin D deficiency on liver injury and inflammatory signals in a mouse model. Acute liver failure was induced by thioacetamide (TAA) to observe the effect of vitamin D deficiency on the survival rate, and further high-dose of vitamin D supplementation protective effect was determined in a mouse model. Liver function was evaluated by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver inflammation by hematoxylin-eosin staining. The expressions of tumor necrosis factor (TNF-α), interleukin (IL) -1ß, NOD-like receptor family, pyrin domain containing 3 (NLRP-3), chemokines (CCL2, CXCL1 and CXCL2), etc. in liver tissues were detected by RT-qPCR. The quantitation of macrophages in liver tissue was detected by immunohistochemistry. The comparison between groups were performed by t-test. The survival curve was analyzed by log-rank (Mantel-Cox) test. Results: Long-term vitamin D deficiency had increased acute liver failure sensitivity in mice, which was manifested by increased blood cell extravasation, massive necrosis of parenchymal cells, up-regulation of TNF-α, IL-1ß, and NLRP-3 mRNA expression (P < 0.05), and increased macrophages quantitation (P < 0.05) in liver tissues. At the same time, vitamin D deficiency had increased the mice mortality rate because of liver injury (P < 0.01). On the contrary, pre-administration of high dose of vitamin D (100 IU/g) had significantly reduced liver injury, inhibited ALT and AST rise (P < 0.01), alleviated liver necrosis, and down-regulated the mRNA expression of inflammatory factors in liver tissues (P < 0.05). Conclusion: Mouse model shows that long-term vitamin D deficiency can aggravate drug-induced acute liver failure and reduce survival rates. Furthermore, high-dose of vitamin D has a certain hepatoprotective effect, which can significantly improve liver necrosis condition and inhibit inflammation. Therefore, adequate vitamin D can retain liver physiological balance to resist liver injury.

Immunorelated gene polymorphisms associated with acute myeloid leukemia.

Although the pathogenesis of acute myeloid leukemia (AML) is still unknown, accumulating evidence has revealed that immune response plays a vital part in the pathogenesis. Here, we investigated the involvement of 21 single nucleotide polymorphisms (SNPs) of immunorelated genes, including cytokines [interleukin (IL)-2, IL-4, IL-9, IL-12A, IL-22, interferon (IFN-α) and transforming growth factor (TGF)-ß1], transcriptional regulatory genes (TBX21, STAT1, STAT3, STAT5B, STAT6, GATA3, FOXP3 and IRF4) and others (IL2RA, IL6R, NFKBIA) in 269 AML in-patients and 200 healthy controls. Furthermore, we analyzed the relationship between the SNPs and clinical characteristics. Immunorelated SNP genotyping was performed on the Sequenom MassARRAY iPLEX platform. All the SNPs in healthy controls were consistent with Hardy-Weinberg equilibrium. All final P-values were adjusted by Bonferroni multiple testing. Our results showed that IL-22 (rs2227491) was significantly associated with the white blood cell (WBC) counts. Signal transducer and activator of transcription 5B (STAT-5B) (rs6503691) showed a close relationship with the recurrent genetic abnormalities in patients with AML. We verified the negatively independent effect of age and risk of cytogenetics on overall survival (OS). More importantly, the GG genotype of IL-12A (rs6887695) showed a negative impact on AML prognosis independently. Furthermore, the relative expression of IL-12 was decreased in GG genotype, no matter under a co-dominant or recessive model. However, no correlation was observed between the SNPs mentioned above and disease susceptibility, risk stratification and survival. Our findings suggest that immunorelated gene polymorphisms are associated with prognosis in AML, which may perform as novel inspection targets for AML patients.

[Proteomics analysis of erythrocyte membrane in rats with high altitude polycythemia before and after intervention with salidroside].

To investigate the effect of salidroside on the proteomics of erythrocyte membrane in high altitude erythrocytosis(HAPC) rats, in order to explore the mechanism of salidroside in improving HAPC based on the proteomics analysis. First, HPAC rat models were established, and 16 rats were randomly divided into HAPC model group and salidroside(100 mg·kg~(-1)) treatment group(8 rats per group). Saline was administered to the HAPC model group, while salidroside treatment group was given 100 mg·kg~(-1) salidroside once a day. After continuous oral administration with salidroside for 40 days(once a day), blood was collected from the femoral artery to obtain total red blood cell membrane proteins. Two-dimensional electrophoresis was used to separate total proteins. The two-dimensional electrophoresis of erythrocyte membrane proteins was analyzed before and after salidroside intervention, and the proteins with significant differences were identified by mass spectrometry. Finally, biological functions were analyzed using bioinformatics. A two-dimensional electrophoresis method was used to establish a protein expression profile with a high resolution and reproducibility of erythrocyte membranes in HAPC rats. Salidroside treatment significantly changed 18 protein spots in the 2-DE map of erythrocyte membranes, of which 13 proteins were up-regulated and 5 proteins were down-regulated. Eight differential proteins were successfully identified by mass spectrometry. Moreover, bioinformatics analysis found that these differential proteins were involved in such biological processes as oxidative stress, redox, and peroxisome pathway, which are mainly associated with peroxisome and MAPK signaling pathways. Therefore, salidroside could significantly change the expressions of erythrocyte membrane proteins in HAPC rats. Eight differential proteins were identified by a proteomic-based approach. The differential proteins were involved in such biological processes as oxidative stress, redox, peroxisome pathway.

[Promoting migration and apoptosis of glioma cells by macrophage migration inhibitory factor].

Objective: To investigate the effect of macrophage migration inhibitory factor (MIF) on the biology of glioma U87MG and U251 cells. Methods: Silencing MIF gene expression in U87MG cells by RNA interference was monitored by Western blot. MIF low expressing U251 cells were treated at different concentrations of recombinant human MIF (rhMIF) and scratching test and flow cytometry were used to detect cell migration and apoptosis. The protein expression of bcl-2, bax, AKT, p-AKT was detected by Western blot. Results: The ability of migration and anti-apoptosis of U87MG cells silenced by siRNA decreased significantly, and the expression levels of p-AKT and anti-apoptotic protein bcl-2 also decreased; in contrast, the expression level of apoptosis protein bax increased. With increase of rhMIF treatment concentration, the expression levels of MIF protein, p-AKT and bcl-2 in U251 cells were gradually enhanced, whereas the level of apoptosis protein bax was inhibited. Conclusion: MIF promotes cell migration and inhibits apoptosis of both U87MG and U251 cells, likely through the regulation of PI3K/AKT signaling pathway.

A composite of exhaled LTB4 , LXA4 , FeNO, and FEV1 as an "asthma classification ratio" characterizes childhood asthma.

BACKGROUND: Aberrant generation of eicosanoids is associated with asthma, but the evidence remains incomplete and its potential utility as biomarkers is unclear. Major eicosanoids in exhaled breath condensates (EBCs) were assessed as candidate markers for childhood asthma. METHODS: Ten exhaled eicosanoid species was evaluated using ELISA in the discovery phase, followed by prediction model-building and validation phases. RESULTS: Exhaled LTB4 , LTE4 , PGE2, and LXA4 showed significant difference between asthmatics (N = 60) and controls (N = 20). For validation, an expanded study population consisting of 626 subjects with asthma and 161 healthy controls was partitioned into a training subset to establish a prediction model and a test sample subset for validation. Receiver operating characteristic (ROC) analyses of the training subset revealed the level of exhaled LTB4 to be the most discriminative among all parameters, including FeNO, and a composite of exhaled LTB4 , LXA4 , together with FeNO and FEV1 , distinguishing asthma with high sensitivity and specificity. Further, the Youden index (J) indicated the cut point value of 0.598 for this composite of markers as having the strongest discriminatory ability (sensitivity = 85.2% and specificity = 83.6%). The predictive algorithm as "asthma classification ratio" was further validated in an independent test sample with sensitivity and specificity being 84.4% and 84.8%, respectively. CONCLUSIONS: In a pediatric study population in Taiwan, the levels of exhaled LTB4 , LTE4 , LXA4, and PGE2 in asthmatic children were significantly different from those of healthy controls, and the combination of exhaled LTB4 and LXA4 , together with FeNO and FEV1 , best characterized childhood asthma.

Tobacco smoke exposure and multiplexed immunoglobulin E sensitization in children: a population-based study.

BACKGROUND: Although there is evidence that exposure to tobacco smoke is harmful to children's respiratory health, the effects of tobacco smoke exposure on the regulation of immunoglobulin E (IgE)-mediated immune responses to specific allergens remain unclear. This study aimed to investigate the relationship between objectively assessed tobacco smoke exposure and specific IgE profiles for a broad spectrum of allergens in a population setting. METHODS: Children aged 5-18 years (N = 1315) were assessed using serum cotinine measurement and microarray-based multiplexed detection of specific IgE against 40 allergens. RESULTS: Serum cotinine levels were positively associated with sensitization to foods (adjusted odds ratio [AOR] = 4.95; 95% CI: 1.59-15.34), cockroaches (AOR = 3.77; 95% CI: 1.49-9.51), and pollen (AOR = 2.84; 95% CI: 1.20-6.73) while the association was borderline significant for animals (AOR = 2.53; 95% CI: 0.92-6.93). No associations were found for sensitization against mites, mold, and latex. When considering the degree of allergic sensitization, serum cotinine levels were positively correlated to the number of sensitization to cockroaches (P = 0.004), pollen (P = 0.006), and foods (P < 0.001), with statistically significant positive dose-response relationships (all P < 0.01). Similar results were observed when summing up specific IgE concentrations for the aforementioned allergen categories. CONCLUSIONS: The association between tobacco smoke exposure and IgE sensitization to environmental allergens varies for different allergens among children. This study demonstrates that elevated serum cotinine levels are significantly associated with IgE sensitization to cockroaches, grass pollen, and certain foods, with potential dose-dependent relationships.

Multiplexed immunoglobulin E sensitization in relation to exhaled nitric oxide in a population sample of children.

This study investigated the relationship between the specific immunoglobulin E (IgE) profile for 40 allergens using a novel microarray technique (BioIC) and fraction of exhaled nitric oxide (FeNO) in a population sample of 1321 children. Significant positive associations were found between FeNO and sensitization to mites (P < 0.001), animals (P = 0.001), cockroaches (P < 0.001), and foods (P = 0.042), and furthermore, between FeNO and the number of sensitizations (all P < 0.05) or the sum of specific IgE (all P ≤ 0.01) against the aforementioned allergen categories. Specifically, sensitization to the following allergens was significantly related to higher FeNO: Dermatophagoides pteronyssinus, Dermatophagoides farina, Blomia tropicalis, cat, German cockroach, Oriental cockroach, codfish, crab, shrimp, and cheese (all P ≤ 0.01). In conclusion, IgE sensitization to mites, pets, cockroaches, seafood, and cheese, respectively, is significantly associated with elevated FeNO levels in a dose-dependent fashion in children. Our results provide new evidence that sensitization to certain food allergens may contribute to prompt inflammation in the airways.

In Vitro Functional Profiling of Fentanyl and Nitazene Analogs at the µ-Opioid Receptor Reveals High Efficacy for Gi Protein Signaling.

Novel synthetic opioids (NSOs), including both fentanyl and non-fentanyl analogs that act as µ-opioid receptor (MOR) agonists, are associated with serious intoxication and fatal overdose. Previous studies proposed that G-protein-biased MOR agonists are safer pain medications, while other evidence indicates that low intrinsic efficacy at MOR better explains the reduced opioid side effects. Here, we characterized the in vitro functional profiles of various NSOs at the MOR using adenylate cyclase inhibition and ß-arrestin2 recruitment assays, in conjunction with the application of the receptor depletion approach. By fitting the concentration-response data to the operational model of agonism, we deduced the intrinsic efficacy and affinity for each opioid in the Gi protein signaling and ß-arrestin2 recruitment pathways. Compared to the reference agonist [d-Ala2,N-MePhe4,Gly-ol5]enkephalin, we found that several fentanyl analogs were more efficacious at inhibiting cAMP production, whereas all fentanyl analogs were less efficacious at recruiting ß-arrestin2. In contrast, the non-fentanyl 2-benzylbenzimidazole (i.e., nitazene) analogs were highly efficacious and potent in both the cAMP and ß-arrestin2 assays. Our findings suggest that the high intrinsic efficacy of the NSOs in Gi protein signaling is a common property that may underlie their high risk of intoxication and overdose, highlighting the limitation of using in vitro functional bias to predict the adverse effects of opioids. In addition, the extremely high potency of many NSOs now infiltrating illicit drug markets further contributes to the danger posed to public health.

Inhibition of p38/Mk2 signaling pathway improves the anti-inflammatory effect of WIN55 on mouse experimental colitis.

P38/Mk2 (mitogen-activated protein kinase (MAPK)-activated protein kinase-2, also known as MAKAP kinase-2) is a member of the mitogen-activated protein kinases (MAPKs) family, and participates in inflammatory responses directly or indirectly. WIN55, 212-2 (WIN55) is a synthetic non-selective agonist of cannabinoid (CB) receptors with remarkable anti-inflammatory properties. This study was to explore the roles of WIN55 and p38/Mk2 signaling pathway in dextran sodium sulfate (DSS)-induced mouse colitis and ascertain their anti-inflammatory mechanisms. Colitis was induced in C57BL Mk2 gene homozygous deletion (Mk2-/-) and wild-type mice by replacing the drinking water with 4% DSS solution for 7 days. DSS-treated mice developed bloody stool, weight loss, and eye-visible multiple bleeding ulcers on colon mucosa. The mRNA expressions levels of TNF-α and IL-6, as well as the protein levels of p38 and its phosphorylated form (p-p38), were upregulated in the colon. The plasma levels of TNF-α, IL-6, cytokine-induced neutrophil chemoattractant-1 (CINC-1), monocyte chemoattractant protein-1 (MCP-1), and lung myeloperoxidase (MPO) activities were raised; however, all these changes were less severe in Mk2-/- mice. After WIN55 intervention, the Mk2-/- mice recovered faster and better from the induced colitis than their wild-type counterparts. The results indicate that the Mk2 homozygous deletion in mice impedes the induction of experimental colitis by DSS, confirming the notion that p38/Mk2 is involved in this inflammatory response. WIN55 protects mice against DSS-induced colitis, in particular when the p38/Mk2 pathway is obstructed, implying that the activation of CB system, together with blocking of p38/Mk2 pathway, serves as a potential drug target for colitis treatment.

Cardioankle vascular index evaluations revealed that cotreatment of ARB Antihypertension medication with traditional Chinese medicine improved arterial functionality.

Qian Yang He Ji (QYHJ) is a traditional Chinese medicine composed of Digitalis purpurea, Uncaria gambir, Fructus tribuli terrestris, and Ligustrum lucidum. Here, we explored whether combining an antihypertensive angiotensin II receptor blocker (ARB) therapy with QYHJ can improve the arterial functionality of hypertensive patients. One hundred and eight hypertensive patients were randomized into 2 groups; 1 group (n = 53) was treated with ARB and the other group (n = 55) was treated with ARB combined with QYHJ. Each of the 2 groups included 3 subgroups (pure hypertension, hypertension with diabetes, and hypertension with coronary heart disease) and was further divided into patients with and without complications. The cardioankle vascular index and intima-media thickness and pulse pressure were the outcome evaluation parameter. Combined QYHJ and ARB treatment reduced the values of cardioankle vascular index, systolic blood pressure, diastolic blood pressure, and pulse pressure to significantly lower levels than ARB treatment alone did in hypertension patients after 6 months of treatment. ARB improves hypertension, but a combined QYHJ treatment can additionally ameliorate the arterial functionality not only in solely hypertensive patients but also in hypertensive patients with diabetes and coronary heart disease complications. QYHJ coapplication might be a choice to further improve the arterial functionality during an ARB hypertension treatment.

Simultaneous detection and degradation patterns of kresoxim-methyl and trifloxystrobin residues in citrus fruits by HPLC combined with QuEChERS.

This study aimed to investigate the residues, kinetics and dissipation patterns of kresoxim-methyl, (E)-methoxyimino[α-(o-tolyloxy)-o-tolyl]acetate, and trifloxystrobin, methyl(E)-methoxyimino-{(E)-α[1-(α,α,α-trifluoro-m-tolyl)ethylideneaminooxy]-o-tolyl}acetate". A simple and sensitive liquid chromatography-ultraviolet detection (LC-UV) method combined with the 'Quick Easy Cheap Effective Rugged and Safe' (QuEChERS) protocol was developed to quantify the levels of kresoxim-methyl and trifloxystrobin residues in citrus. More than 97% of the kresoxim-methyl and trifloxystrobin deposists gradually dissipated from the citrus peels within 15 days. The half-lives of kresoxim-methyl and trifloxystrobin in the peels were in the ranges of 2.63-2.66 d and 3.12-3.15 d, respectively, and the pattern of decline in the peels followed first-order kinetics. The kresoxim-methyl and trifloxystrobin residues in the pulp dissipated below the detectable level of 0.01 mg kg(-1) after 9 days. Kresoxim-methyl and trifloxystrobin were easily decomposed (T1/2 < 30 d), and the observed dissipation patterns could support the application of these two fungicides in the postharvest storage of citrus fruits.

Comparative neuropharmacology of structurally distinct non-fentanyl opioids that are appearing on recreational drug markets worldwide.

BACKGROUND: The emergence of novel synthetic opioids (NSOs) is contributing to the opioid overdose crisis. While fentanyl analogs have historically dominated the NSO market, a shift towards non-fentanyl compounds is now occurring. METHODS: Here, we examined the neuropharmacology of structurally distinct non-fentanyl NSOs, including U-47700, isotonitazene, brorphine, and N-desethyl isotonitazene, as compared to morphine and fentanyl. Compounds were tested in vitro using opioid receptor binding assays in rat brain tissue and by monitoring forskolin-stimulated cAMP accumulation in cells expressing the human mu-opioid receptor (MOR). Compounds were administered subcutaneously to male Sprague-Dawley rats, and hot plate antinociception, catalepsy score, and body temperature changes were measured. RESULTS: Receptor binding results revealed high MOR selectivity for all compounds, with MOR affinities comparable to those of morphine and fentanyl (i.e., nM). All drugs acted as full-efficacy MOR agonists in the cyclic AMP assay, but nitazene analogs had greater functional potencies (i.e., pM) compared to the other drugs (i.e., nM). When administered to rats, all compounds induced opioid-like antinociception, catalepsy, and body temperature changes, but nitazenes were the most potent. Similar to fentanyl, the nitazenes had faster onset and decline of in vivo effects when compared to morphine. In vivo potencies to induce antinociception and catalepsy (i.e., ED50s) correlated with in vitro functional potencies (i.e., EC50s) but not binding affinities (i.e., Kis) at MOR. CONCLUSIONS: Collectively, our findings indicate that non-fentanyl NSOs pose grave danger to those individuals who use opioids. Continued vigilance is needed to identify and characterize synthetic opioids as they emerge in clandestine drug markets.

The in vitro functional profiles of fentanyl and nitazene analogs at the µ-opioid receptor - high efficacy is dangerous regardless of signaling bias.

Novel synthetic opioids (NSOs), including both fentanyl and non-fentanyl analogs that act as the µ-opioid receptor (MOR) agonists, are associated with serious intoxication and fatal overdose. Previous studies proposed that G protein biased MOR agonists are safer pain medications, while other evidence indicates that low intrinsic efficacy at MOR better explains reduced opioid side effects. Here, we characterized the in vitro functional profiles of various NSOs at MOR using adenylate cyclase inhibition and ß-arrestin2 recruitment assays, in conjunction with the application of the receptor depletion approach. By fitting the concentration-response data to the operational model of agonism, we deduced the intrinsic efficacy and affinity for each opioid in the Gi protein signaling and ß-arrestin2 recruitment pathways. Compared to the reference agonist DAMGO, we found that several fentanyl analogs were more efficacious at inhibiting cAMP production, whereas all fentanyl analogs were less efficacious at recruiting ß-arrestin2. In contrast, the non-fentanyl 2-benzylbenzimidazole (i.e., nitazene) analogs were highly efficacious and potent in both the cAMP and ß-arrestin2 assays. Our findings suggest that the high intrinsic efficacy of the NSOs in Gi protein signaling is a common property that may underlie their high risk of intoxication and overdose, highlighting the limitation of using in vitro functional bias to predict the adverse effects of opioids. Instead, our results show that, regardless of bias, opioids with sufficiently high intrinsic efficacy can be lethal, especially given the extremely high potency of many of these compounds that are now pervading the illicit drug market.

Alkoxy chain length governs the potency of 2-benzylbenzimidazole 'nitazene' opioids associated with human overdose.

RATIONALE: Novel synthetic opioids (NSOs) are emerging in recreational drug markets worldwide. In particular, 2-benzylbenzimidazole 'nitazene' compounds are problematic NSOs associated with serious clinical consequences, including fatal respiratory depression. Evidence from in vitro studies shows that alkoxy chain length can influence the potency of nitazenes at the mu-opioid receptor (MOR). However, structure-activity relationships (SARs) of nitazenes for inducing opioid-like effects in animal models are not well understood compared to relevant opioids contributing to the ongoing opioid crisis (e.g., fentanyl). OBJECTIVES: Here, we examined the in vitro and in vivo effects of nitazene analogues with varying alkoxy chain lengths (i.e., metonitazene, etonitazene, isotonitazene, protonitazene, and butonitazene) as compared to reference opioids (i.e., morphine and fentanyl). METHODS AND RESULTS: Nitazene analogues displayed nanomolar affinities for MOR in rat brain membranes and picomolar potencies to activate MOR in transfected cells. All compounds induced opioid-like effects on locomotor activity, hot plate latency, and body temperature in male mice, and alkoxy chain length markedly influenced potency. Etonitazene, with an ethoxy chain, was the most potent analogue in MOR functional assays (EC50 = 30 pM, Emax = 103%) and across all in vivo endpoints (ED50 = 3-12 µg/kg). In vivo SARs revealed that ethoxy, isopropoxy, and propoxy chains engendered higher potencies than fentanyl, whereas methoxy and butoxy analogues were less potent. MOR functional potencies, but not MOR affinities, were positively correlated with in vivo potencies to induce opioid effects. CONCLUSIONS: Overall, our data show that certain nitazene NSOs are more potent than fentanyl as MOR agonists in mice, highlighting concerns regarding the high potential for overdose in humans who are exposed to these compounds.

Binding preference at the µ-opioid receptor underlies distinct pharmacology of cyclopropyl versus valeryl analogs of fentanyl.

Illicitly manufactured fentanyl is driving the current opioid crisis, and various fentanyl analogs are appearing in recreational drug markets worldwide. To assess the potential health risks posed by fentanyl analogs, it is necessary to understand structure-activity relationships for these compounds. Here we compared the pharmacology of two structurally related fentanyl analogs implicated in opioid overdose: cyclopropylfentanyl and valerylfentanyl. Cyclopropylfentanyl has a three-carbon ring attached to the carbonyl group on the fentanyl scaffold, whereas valerylfentanyl has a four-carbon chain at the same position. In vitro assays examining µ-opioid receptor (MOR) coupling to G proteins in CHO cells showed that cyclopropylfentanyl is a full agonist (EC50 = 8.6 nM, %Emax = 113%), with potency and efficacy similar to fentanyl (EC50 = 10.3 nM, %Emax = 113%). By contrast, valerylfentanyl is a partial agonist at MOR (EC50 = 179.8 nM, %Emax = 60%). Similar results were found in assays assessing MOR-mediated ß-arrestin recruitment in HEK cells. In vivo studies in male CD-1 mice demonstrated that both fentanyl analogs induce naloxone-reversible antinociception and respiratory suppression, but cyclopropylfentanyl is 100-times more potent as an antinociceptive agent (ED50 = 0.04 mg/kg, s. c.) than valerylfentanyl (ED50 = 4.0 mg/kg, s. c.). Molecular simulation results revealed that the alkyl chain of valerylfentanyl cannot be well accommodated by the active state of MOR and may transition the receptor toward an inactive state, converting the fentanyl scaffold to a partial agonist. Taken together, our results suggest that cyclopropylfentanyl presents much greater risk of adverse effects when compared to valerylfentanyl. Moreover, the summed findings may provide clues to the design of therapeutic opioids with reduced adverse side effects.

First Report of Leaf Spot Disease Caused by Exserohilum rostratum on Pineapple in Hainan Province, China.

Pineapple (Ananas comosus (L.) Merr.) is an important perennial monocotyledonous plant that serves as an important fruit crop globally and is also produced in the Hainan Province of China where production in 2009 was 296,600 t. In July 2009, atypical symptoms of a leaf spot disease were observed on mature pineapple leaves in Chengmai County; approximately 15% of plants propagated from suckers became symptomatic after 150 to 300 days, eventually causing a 3 to 10% yield loss. In the initial infection stage, grayish white-to-yellowish white spots emerged on the leaf surfaces that ranged from 1.0 to 2.4 × 0.3 to 0.7 cm; black specks were not always present in the spots. Leaf spots also had distinctive light brown-to-reddish brown banding pattern on the edges. Several spots would often merge to form large lesions, 6.5 to 15.4 × 2.5 to 5.6 cm, covering more than 67% of the leaf surface, which can lead to death of the plant. Infected pineapple leaves collected from an orchard of Chengmai County were surface sterilized (75% ethanol for 30 s, 0.1% HgCl2 for 2 min, and rinsed three times in sterile distilled water). Leaf pieces were placed on potato dextrose agar medium and then incubated at 25°C. The emerging fungal colonies were grayish white to brown. Similar strains were obtained from Qionghai City and Wanning City subsequently. Two isolates, ITF0706-1 and ITF0706-2, were used in confirmation of the identity of the pathogen and in pathogenicity tests. Colonies were fast growing (more than 15 mm per day at 25 to 30°C) with dense aerial mycelia. Conidia were fusiform, pyriform to oval or cylindrical, olive brown to dark brown, 3 to 10 septate (typically 5 to 8), 33.2 to 102.5 × 9.0 to 21.3 µm, with a strongly protruding hilum bulged from the basal cell, which were similar to the Type A conidia described by Lin et al. (3). The strains were subjected to PCR amplification of the internal transcribed spacer (ITS)1-5.8S-ITS2 regions with universal primer pair ITS1/ITS4. The ITS sequence comparisons (GenBank Accession Nos. JN711431 and JN711432) shared between 99.60 and 99.83% identity with the isolate CATAS-ER01 (GenBank Accession No. GQ169762). According to morphological and molecular analysis, the two strains were identified as Exserohilum rostratum (Drechs.) Leonard & Suggs. Pathogenicity experiments were conducted five times and carried out by spraying a conidial suspension (105 CFU/ml) on newly matured leaves of healthy pineapple plants; plants sprayed with sterile water served as the negative control. Plants were incubated in the growth chamber at 20 to 25°C. Symptoms of leaf spot developed on test plants 7 days after inoculation while the control plants remained asymptomatic. Koch's postulates were fulfilled with the reisolation of the two fungal strains. Currently, E. rostratum is one of the most common pathogens on Bromeliads in Florida (2) and has been reported on Zea mays (4), Musa paradisiacal (3), and Calathea picturata (1) in China, but to our knowledge, this is the first report of leaf spot disease caused by E. rostratum on pineapple in Hainan Province of P.R. China. References: (1) L. L. Chern et al. Plant Dis. 95:1033, 2011. (2) R. M. Leahy. Plant Pathol. Circ. No. 393. Florida Department of Agriculture and Consumer Services Division of Plant Industry, 1999. (3) S. H. Lin et al. Australas. Plant Pathol. 40:246, 2011. (4) J. N. Tsai et al. Plant Pathol. Bull. 10:181, 2001.

Bronchial asthma and risk of 4 specific cardiovascular diseases and cardiovascular mortality: a meta-analysis of cohort studies.

OBJECTIVE: It has been shown that asthma is significantly associated with the risk of cardiovascular disease (CVD). Under this background, this study aimed to systematically classify and summarize the epidemiological evidence of asthma and the risk of 4 specific cardiovascular diseases (CVDs) and cardiovascular mortality (CVM). MATERIALS AND METHODS: PubMed and Embase databases were searched from inception to December 1st, 2021 in order to identify relevant studies. The random-model was used to assess the pooled results. All pooled results were expressed as risk ratios (RRs) and corresponding 95% confidence intervals (CIs). RESULTS: Finally, a total of 18 studies were included in the present meta-analysis. Compared with non-asthmatic group, patients with asthma had significantly increased risks of subsequent cardiovascular heart disease (CHD, RR 1.33; 1.19-1.50, I2=80.3%; p<0.001), and CVM (RR 1.35; 1.15-1.59, I2=0%; p<0.001). Similarly, the risks of heart failure (HF, RR 2.10; 1.98-2.22, I2=17.4%; p<0.001) and myocardial infraction (MI, RR 1.39; 1.16-1.66, I2=59.3%; p<0.001) were higher in the asthmatic population. However, the higher risk of atrial fibrillation (RR 1.70; 1.45-2.00, I2=0%; p<0.001) was observed only in the active asthmatic population. CONCLUSIONS: In general, asthma is associated with subsequent increased risks of CHD, MI, AF, HF, and CVM. In addition, among patients with asthma, females have a higher risk of CHD than males, while active asthmatic patients have a higher risk of CVM than non-active asthmatic patients.

Active Precipitation of Radiation Belt Electrons Using Rocket Exhaust Driven Amplification (REDA) of Man-Made Whistlers.

Ground-based very low frequency (VLF) transmitters located around the world generate signals that leak through the bottom side of the ionosphere in the form of whistler mode waves. Wave and particle measurements on satellites have observed that these man-made VLF waves can be strong enough to scatter trapped energetic electrons into low pitch angle orbits, causing loss by absorption in the lower atmosphere. This precipitation loss process is greatly enhanced by intentional amplification of the whistler waves using a newly discovered process called rocket exhaust driven amplification (REDA). Satellite measurements of REDA have shown between 30 and 50 dB intensification of VLF waves in space using a 60 s burn of the 150 g/s thruster on the Cygnus satellite that services the International Space Station. This controlled amplification process is adequate to deplete the energetic particle population on the affected field lines in a few minutes rather than the multi-day period it would take naturally. Numerical simulations of the pitch angle diffusion for radiation belt particles use the UCLA quasi-linear Fokker Planck model to assess the impact of REDA on radiation belt remediation of newly injected energetic electrons. The simulated precipitation fluxes of energetic electrons are applied to models of D-region electron density and bremsstrahlung X-rays for predictions of the modified environment that can be observed with satellite and ground-based sensors.

[Clinical case of the month. Sudden orbital cellulitis in the emergency unit]. / Le cas clinique du mois. Exophtalmie aiguë au service des urgences.

We report a case of infectious orbital cellulitis complicating a frontal sinusitis in a seventy-three-year-old patient. The onset of this orbital complication was sudden. A clinical examination and an orbital CT-scan allowed an early diagnosis. Despite an appropriate surgical and medical treatment, the patient retains an altered visual function. We consider the clinical causes and consequences of orbital cellulitis as well as their surgical indications.

FOXN2 suppresses the proliferation and invasion of human hepatocellular carcinoma cells.

OBJECTIVE: The aim of this study was to explore the roles of FOXN2 (Fork head Box N2) in mediating the proliferation and invasion of hepatocellular carcinoma (HCC) cells. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to determine expression of FOXN2 in HCC tissues and cells. Transfection of plasmid containing FOXN2 was used to exogenously overexpress FOXN2 in vitro. Cell Counting Kit-8 (CCK-8) assay and transwell assay were applied to detect the proliferation and invasion of HCC cells, respectively. RESULTS: FOXN2 expression decreased significantly in both HCC tissues and cells (p<0.05). Upregulation of FOXN2 significantly inhibited the proliferation and invasion of HCC cells (p<0.05). CONCLUSIONS: FOXN2 acts as a regulator in the progression of HCC. Our findings suggest that FOXN2 may be a novel therapeutic monitoring and prognosis biomarker in HCC.