Transcriptional mechanism of differential sugar accumulation in pulp of two contrasting mango (Mangifera indica L.) cultivars.

Temporal transcriptome analysis combined with targeted metabolomics was employed to investigate the mechanisms of high sugar accumulation in fruit pulp of two contrasting mango cultivars. Ten sugar metabolites were identified in mango pulp with the most dominant being d-glucose. Analysis of the gene expression patterns revealed that the high-sugar cultivar prioritized the conversion of sucrose to d-glucose by up-regulating invertases and ß-glucosidases and increased other genes directly contributing to the synthesis of sucrose and d-glucose. In contrast, it repressed the expression of genes converting sucrose, d-glucose and other sugars into intermediates compounds for downstream processes. It also strongly increased the expression of alpha-amylases which may promote high degradation of starch into d-glucose. Besides, ¾ of the sugar transporters was strongly up-regulated, indicative of their preponderant role in sugar accumulation in mango fruit. Overall, this study provides a good insight into the regulation pattern of high sugar accumulation in mango pulp.

Pd-Catalyzed, Highly Selective C(sp²)-Br Bond Coupling Reactions of o-(or m-, or p-) Chloromethyl Bromobenzene with Arylboronic Acids.

Highly selective C(sp²)-C(sp²) cross-coupling of dihalogenated hydrocarbons comprising C(sp²)-Br and C(sp³)-Cl bonds with arylboronic acids is reported. This highly selective coupling reaction of the C(sp²)-Br bond is successfully achieved using Pd(OAc)2 and PCy3·HBF4 as the palladium source and ligand, respectively. A series of chloromethyl-1,1'-biphenyl compounds are obtained in moderate-to-excellent yields. Moreover, this protocol can be extended to the one-pot dual arylation of 1-bromo-4-(chloromethyl)benzene with two arylboronic acids, leading to diverse unsymmetrical 4-benzyl-1,1'-biphenyl derivatives.

Analysis of the Volatile Profile of Core Chinese Mango Germplasm by Headspace Solid-Phase Microextraction Coupled with Gas Chromatography-Mass Spectrometry.

Despite abundant published research on the volatile characterization of mango germplasm, the aroma differentiation of Chinese cultivars remains unclear. Using headspace solid phase microextraction (HS-SPME) coupled with gas chromatography⁻mass spectrometry (GC-MS), the composition and relative content of volatiles in 37 cultivars representing the diversity of Chinese mango germplasm were investigated. Results indicated that there are distinct differences in the components and content of volatile compounds among and within cultivars. In total, 114 volatile compounds, including 23 monoterpenes, 16 sesquiterpenes, 29 non-terpene hydrocarbons, 25 esters, 11 aldehydes, five alcohols and five ketones, were identified. The total volatile content among cultivars ranged from 211 to 26,022 µg/kg fresh weight (FW), with 123-fold variation. Terpene compounds were the basic background volatiles, and 34 cultivars exhibited abundant monoterpenes. On the basis of hierarchical cluster analysis (HCA) and principal component analysis (PCA), terpinolene and α-pinene were important components constituting the aroma of Chinese mango cultivars. Most obviously, a number of mango cultivars with high content of various aroma components were observed, and they can serve as potential germplasms for both breeding and direct use.

The Verticillium-specific protein VdSCP7 localizes to the plant nucleus and modulates immunity to fungal infections.

Fungal pathogens secrete effector proteins to suppress plant basal defense for successful colonization. Resistant plants, however, can recognize effectors by cognate R proteins to induce effector-triggered immunity (ETI). By analyzing secretomes of the vascular fungal pathogen Verticillium dahliae, we identified a novel secreted protein VdSCP7 that targets the plant nucleus. The green fluorescent protein (GFP)-tagged VdSCP7 gene with either a mutated nuclear localization signal motif or with additional nuclear export signal was transiently expressed in Nicotiana benthamiana, and investigated for induction of plant immunity. The role of VdSCP7 in V. dahliae pathogenicity was characterized by gene knockout and complementation, and GFP labeling. Expression of the VdSCP7 gene in N. benthamiana activated both salicylic acid and jasmonate signaling, and altered the plant's susceptibility to the pathogens Botrytis cinerea and Phytophthora capsici. The immune response activated by VdSCP7 was highly dependent on its initial extracellular secretion and subsequent nuclear localization in plants. Knockout of the VdSCP7 gene significantly enhanced V. dahliae aggressiveness on cotton. GFP-labeled VdSCP7 is secreted by V. dahliae and accumulates in the plant nucleus. We conclude that VdSCP7 is a novel effector protein that targets the host nucleus to modulate plant immunity, and suggest that plants can recognize VdSCP7 to activate ETI during fungal infection.

[Recent development of non-steroidal anti-inflammatory drugs on the neuro-inflammation of Alzheimer's disease].

Neuropathological, clinical epidemiology and animal models studies provide clear evidence for the activation of neuroinflammation in Alzheimer's disease (AD), and long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) is linked with reduced risk to develop the disease. But the clinical trials got a negative outcome with traditional NSAIDs treating AD. The therapeutic effects of NSAIDs on Alzheimer's disease are still not clear based on the present research. Profound study for anti-inflammatory mechanisms and standardized clinical trials are needed. As cause and effect relationships between neuroinflammation and AD are being worked out, the challenge is how to realize the effect of traditional NSAIDs on treating AD.

[Diagnostic accuracy of adenosine triphosphate stress echocardiography derived coronary flow reserve for detecting significant coronary stenosis].

OBJECTIVE: To assess the diagnostic accuracy of coronary flow reserve measured by transthoracic Doppler echocardiography (TTDE) associated with adenosine triphosphate (ATP) stress for detecting coronary stenosis in patients with chest pain. METHODS: A total of 125 patients scheduled for elective coronary angiography (CAG) due to chest pain were recruited. ATP stress echocardiography were performed to measure CFR in left anterior descending (LAD) by TTDE with 2 days pre-CAG. Coronary flow reserve (CFR) was calculated as peak diastolic velocity during maximum hyperemia (PDV2) divided by baseline (PDV1). According to the coronary angiography results, all patients were divided into group A (stenosis < 50% in LAD, n = 57), group B (stenosis of 50% - 75% in LAD, n = 20) and group C (stenosis > 75% in LAD, n = 48). Then CFR was compared among three groups. The receiver operating characteristic curve (ROC) was used to assess the value of CFR for detecting LAD stenosis. RESULTS: CFR was significantly different among three groups (group A: 3.02 ± 0.85, group B: 2.49 ± 0.65, group C: 1.82 ± 0.56; all P < 0.01). With ROC analysis, CFR < 2.2 was the best cut-off value for diagnosing significant LAD stenosis (area under curve: 0.86 (95% CI 0.80 to 0.93)), with sensitivity of 81%, specificity of 83% and accuracy of 82%; CFR < 2.2 for diagnosing LAD stenosis > 50% (area under curve: 0.81 (95%CI 0.74 - 0.89, P < 0.01)), with a sensitivity of 59%, a specificity of 82% and an accuracy of 70%. CONCLUSIONS: CFR measured by TTDE associated with ATP stress is a valuable tool for screening significant stenosis in patients with chest pain. Its advantages are non-invasiveness, easy availability, safety and inexpensiveness.

[A clinical analysis of reninoma-induced hypertensive crisis associated with reversible posterior encephalopathy syndrome].

OBJECTIVE: Reninoma is a rare benign tumor of the renal juxtaglomerular cell apparatus that causes hypertension and hypokalemia via hypersecretion of renin, while it is extremely rare that reninoma induced hypertensive crisis with reversible posterior encephalopathy syndrome (RPES). To improve the clinical understanding for this disease, we conducted a case-analysis. METHODS: To analyze the clinical and pathological data of a case of reninoma-induced hypertensive crisis with reversible posterior encephalopathy syndrome, who was admitted to Peking University First Hospital in November, 2007 and follow-up. RESULTS: This was a 16-year old female patient, onset with suddenly spasm with loss of consciousness, while blood pressure stepped up to 210/140 mm Hg (1 mm Hg = 0.133 kPa), and the head magnetic resonance imaging (MRI) revealed "multiple long-T(2) signal", and hypokalemia (2.8 - 3.2 mmol/L), urine protein positive, ultrasound cardiogram revealed left ventricular hypertrophy, laboratory study revealed hyperreninism (38.23 ng·ml(-1)×h(-1), normal range 0.07 - 1.15 ng·ml(-1)×h(-1)) and hyperaldosteronism (660.9 ng/L, normal range 60 - 174 ng/L), abdominal CT-Scan revealed a mass at right kidney, blood pressure achieved safety range and the head MRI was rechecked and revealed "the abnormal long-T(2) signal disappeared". The clinical diagnosis was reninoma induced hypertensive crisis with RPES. The tumor was resected and the pathologic diagnosis was reninoma. The patient remained normotensive in the postoperative period without any medication. CONCLUSIONS: Reninoma represents a rare but surgically curable cause of hypertension, thus the clinical suspicion of it is very important in young patients. If the diagnosis is confirmed, positive treatment must be done immediately to improve the prognosis. The most common cause of RPES is hypertension, and the diagnosis depends on the distinctive head MRI. There is always a good prognosis with the decline of blood pressure rapidly.

Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation.

AIM: To identify the role of metformin in cardiac hypertrophy and investigate the possible mechanism underlying this effect. METHODS: Wild type and AMPKα2 knockout (AMPKα2⁻/⁻) littermates were subjected to left ventricular pressure overload caused by transverse aortic constriction. After administration of metformin (200 mg·kg⁻¹·d⁻¹) for 6 weeks, the degree of cardiac hypertrophy was evaluated using echocardiography and anatomic and histological methods. The antihypertrophic mechanism of metformin was analyzed using Western blotting. RESULTS: Metformin significantly attenuated cardiac hypertrophy induced by pressure overload in wild type mice, but the antihypertrophic actions of metformin were ablated in AMPKα2⁻/⁻ mice. Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in response to pressure overload in wild type mice, but not in AMPKα2⁻/⁻ mice. CONCLUSION: Long-term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation. These findings may provide a potential therapy for patients at risk of developing pathological cardiac hypertrophy.

Effects of non-driving related tasks on readiness to take over control in conditionally automated driving.

OBJECTIVE: At conditionally automated driving, the driver can temporarily engage in non-driving related tasks (NDRTs). However, they must safely take over control when the automated driving system reaches its operation limit. Thus, understanding the effects of the NDRTs on driver take-over performance is essential. The present work investigates the effects of various NDRTs on motor readiness in take-over scenarios during conditionally automated driving. METHODS: Three driving simulator studies were conducted. 48, 49, and 22 participants were recruited in three experiments, respectively. The participants were distracted by different NDRTs (everyday task in Experiment 1, arrow task in Experiment 2, and SuRT in Experiment 3) on a tablet mounted in the vehicle. The everyday task included reading the news and watching a video, and the arrow task included a set of arrow matrices presented to the participants in sequence. The time budgets in Experiment 1 included 3 s, 4 s, and 5 s, and the time budgets in Experiment 2 and 3 included 5 s and 7 s. A take-over request (TOR) warning was issued in the automated driving condition when the participants encountered a broken-down car in front. The participants must regain control of the vehicle with the given time budget. The hands-on time was evaluated, measuring the time from the TOR until the hands touch the steering wheel. RESULTS: The task (arrow task and SuRT), time budget (5 s and 7 s), and gender did not affect the hands-on time. However, the hands-on time for the drivers with the everyday task was significantly shorter than that for the drivers with the arrow task in the 5 s time budget. CONCLUSIONS: In conditionally automated driving, the arrow task and SuRT imposed a similar workload on readiness to take over control. Compared to the everyday task, the engagement in the arrow tasks consumed more workload on readiness to take over control.

Gastrointestinal stromal tumor with multisegmental spinal metastases as first presentation: A case report and review of the literature.

BACKGROUND: Gastrointestinal stromal tumor (GIST) usually originates in the stomach, followed by the small intestine, rectum, and other parts of the gastrointestinal tract. The most common sites of metastasis are the liver and peritoneum, whereas spinal metastases from GIST are extremely rare. CASE SUMMARY: We found a case of GIST with the first presentation of multilevel spinal metastases involving the thoracic and lumbar vertebrae. A 61-year-old Chinese man presented to our clinic because of pain in his lower back and hip for 10 d without cause. Subsequently, computed tomography (CT) and magnetic resonance imaging (MRI) revealed abnormal signals in the vertebral appendages of T12 and L4 accompanied by spinal canal stenosis, which was considered as tumor metastasis. As there were no metastases to vital organs, posterior thoracic and lumbar spinal decompression + adnexal mass resection + pedicle internal fixation was adopted to achieve local cure and prevent nerve compression. The results of histopathological studies were consistent with the metastasis of GIST. No local recurrence or new metastases were found at the 6-mo follow-up at the surgical site. The patient has no neurological symptoms at present. It is worth mentioning that a rectal mass was found and surgically removed 1 mo after the patient was discharged from hospital, and the pathological diagnosis of the mass was GIST. CONCLUSION: By reviewing 26 previously reported cases of spinal metastasis in GIST, it was found that spinal metastasis of GIST has become more common in recent years, so the possibility of early spinal metastasis should be recognized. CT and MRI are of great value in the diagnosis of spinal metastatic tumors, and pathological biopsy is the gold standard for the diagnosis of metastatic tumors. It is safe and feasible to treat isolated spinal metastasis in GIST by excising metastatic masses, decompressing the spinal canal, and stabilizing the spine.

A distinct AMP-activated protein kinase phosphorylation site characterizes cardiac hypertrophy induced by L-thyroxine and angiotensin II.

1. The purpose of the present study was to evaluate differences in the AMP-activated protein kinase (AMPK) phosphorylation sites in cardiac hypertrophy induced by L-thyroxine and angiotensin (Ang) II. 2. Cardiac hypertrophy was induced in wild-type and AMPKalpha2-knockout mice by treatment with 1 mg/kg, i.p., thyroxine or 1.44 mg/kg per day AngII for 14 days. The phenotype of the hypertrophy was evaluated using echocardiographic measurements and histological analyses. The phosphorylation of AMPK at alpha-Ser(485/491) and alpha-Thr(172) was determined by western blot analysis. 3. In wild-type mice, the phosphorylation of AMPKalpha-Ser(485/491) was significantly elevated in the AngII-treated group, but not in the thyroxine-treated group, compared with the vehicle control group. In contrast, the phosphorylation of AMPKalpha-Thr(172) was significantly increased by thyroxine, but not AngII, treatment compared with the vehicle control group. Furthermore, knockout of the AMPKalpha2 subunit abolished phosphorylation at the alpha-Ser(485/491) site and significantly suppressed phosphorylation at the alpha-Thr(172) site, resulting in alleviation of thyroxine- but not AngII-induced hypertrophy. 4. In conclusion, L-thyroxine and AngII induce the phosphorylation of distinct sites of AMPK in cardiac hypertrophy. Phosphorylation of AMPK alpha-Thr(172) may contribute to thyroxine-induced cardiac hypertrophy.

Earlier Nutrient Fortification of Breastmilk Fed LBW Infants Improves Jaundice Related Outcomes.

This study aimed to evaluate jaundice outcomes of low-birthweight premature infants commenced on earlier versus later nutrient supplementation (80 mL/kg/day vs. 160 mL/kg/day; total fluid intake, F80 vs. F160). Demographics, feeding regimens, and clinical outcomes data were collected. Infant and maternal characteristics were similar. Earlier nutrient supplementation was associated with multiple improved jaundice outcomes: total (TSBR), unconjugated and conjugated (CSBR) serum bilirubin values (196 ± 46 vs. 228 ± 52, 184 ± 44 vs. 212 ± 50, 12 ± 4 vs. 16 ± 5, respectively, all p < 0.001); phototherapy (39% vs. 64%, p < 0.0001). % CSBR/TSBR ratio was similar between groups. For those on phototherapy, duration and median irradiance were similar. F80 infants experienced reduced: feeding intolerance (26.0% vs. 45.2%, p = 0.007); length of stay (16.0 ± 0.64 vs. 18.8 ± 0.74 days, p = 0.03), maximum weight loss as % birth weight (5% vs. 6%, p = 0.03); decrease in weight Z-score at 10 days (-0.70 ± 0.03 vs. -0.79 ± 0.03, p = 0.01). F80 infants regained birthweight earlier (10.0 ± 0.3 days vs. 11.5 ± 0.3 days, p < 0.0001) and had no differences in adverse clinical outcomes. We speculate that earlier nutrient supplementation improved jaundice outcomes due to enhanced excretion/elimination of bilirubin.

Association between climatic factors and varicella incidence in Guangzhou, Southern China, 2006-2018.

OBJECTIVE: To analyze the correlation between climatic factors and the incidence of varicella in Guangzhou, and improve the prevention measures about public health. METHODS: Data for daily climatic variables and varicella incidence from 2006 to 2018 in Guangzhou were collected from the Guangzhou Meteorological Bureau and the National Notifiable Disease Report System. Distributed lag nonlinear models were applied to evaluate the association between climatic factors and varicella incidence. RESULTS: The nonlinear effects of meteorological factors were observed. At lag day21，when the mean temperature was 31.8 °C, the relative risk was the highest as 1.11 (95% CI: 1.07-1.16). When the diurnal temperature range was 24.0 °C at lag day 20, the highest RR was 1.11 (95% CI: 1.05-1.17). For rainfall, the highest RR was 1.09 (95% CI: 1.01-1.19) at lag day 21，when the aggregate rainfall was 160 mm. When air pressure was 1028 hPa, the highest RR was 1.08 (95% CI: 1.04-1.13) at lag day 21. When wind speed was 0.7 m/s, the highest RR was 1.07 (95% CI: 1.04-1.11) at lag day 7. When the hours of sunshine were 9.0 h at lag day 21, the RR was highest as 1.04 (95% CI: 1.02-1.05). Aggregate rainfall, air pressure, and sunshine hours were positively correlated with the incidence of varicella, which was inconsistent with the wind velocity. Mean temperature showed a reverse U-shape curve relationship with varicella, while the diurnal temperature range showed a binomial distribution curve. The extreme effect of climatic factors on the varicella cases was statistically significant, apart from the extremely low effect of rainfall. CONCLUSION: Our preliminary results offered fundamental knowledge which might be benefit to give an insight into epidemic trends of varicella and develop an early warning system. We could use our findings about influential factors to strengthen the intervention and prevention of varicella.

Adherence to recommendations at a Canadian tertiary care Family Travel Clinic - A single centre analysis.

BACKGROUND: Infectious and non-infectious risks associated with international travel can be reduced with adherence to pre-travel advice from practitioners trained in travel medicine. METHODS: A prospective cohort study was conducted in a tertiary care children's hospital to assess adherence to malaria chemoprophylaxis, safe water and food consumption, mosquito bite protection, motor vehicle safety and travel vaccines using structured questionnaires. High risk groups assessed included child travelers and those visiting friends and relatives (VFRs). RESULTS: In total, 290 participants (133 children and 157 adults) were enrolled and completed at least one study questionnaire. In general, with the exception of vaccines, adherence to recommendations was sub-optimal. Among children and adults, adherence to malaria prophylaxis recommendations was lower in VFRs than in non-VFRs. The proportion of children VFRs (cVFRs) and adult VFRs (aVFRs) who adhered to the following recommendations were malaria chemoprophylaxis (47%, 33%), safe water (71%, 74%) and food recommendations (18%, 6%), insect bite avoidance (21%, 12%), and motor vehicle safety (13%, 11%) respectively. Adherence to recommended vaccines uptake was greater than 90% in all groups. CONCLUSION: With the exception of vaccine uptake, sub-optimal adherence levels to travel recommendations was identified in all groups, and in particular VFRs, highlighting the need for proactive discussions around barriers to adherence.

Transmission risk of avian influenza virus along poultry supply chains in Guangdong, China.

OBJECTIVES: Avian influenza viruses (AIVs) poise significant risk to human health and the poultry industry. We evaluated the transmission risk along the poultry supply chain. METHODS: During October 2015 and July 2016, four rounds of cross-sectional surveys were performed to characterize AIV spread in farms, transport vehicles, slaughterhouses, wholesale and retail live poultry markets (LPMs). Poultry cloacal and oral swabs, environmental swabs, bioaerosol samples and human sera were collected. Poultry and environmental samples were tested for AIVs by rRT-PCR, further subtyped by next generation sequencing. Previous human H9N2 infections were identified by hemagglutination inhibition and microneutralization tests. Logistic regression was fitted to compare AIV transmission risk in different settings. RESULTS: AIVs was detected in 23.9% (424/1771) of the poultry and environmental samples. AIV detection rates in farms, transport vehicles, wholesale and retail LPMs were 4.5%, 11.1%, 30.3% and 51.2%, respectively. 5.2%, 8.3% and 12.8% of the poultry workers were seropositive in farms, wholesale and retail LPMs, respectively. The regression analysis showed that virus detection and transmission risk to human increased progressively along the poultry supply chain. CONCLUSIONS: Strengthening control measures at every level along the poultry supply chain, using a one health approach, is crucial to control AIV circulation.

Solid fuel use for cooking and its health effects on the elderly in rural China.

Indoor air pollution is mainly caused by solid fuel use for cooking in developing countries. Many previous studies focused on its health risks on the children and in specific local area. This paper investigates household energy usage and transition for cooking in rural China and the health effects on the elderly. A national large-scale dataset CHARLS (China Health and Retirement Longitudinal Study) covering 450 villages and communities is employed. Logit regressions were used to quantitatively estimate the effects, after controlling for some factors such as income, demographic, and geographical variables. The results robustly show that compared to non-solid fuels, solid fuel use significantly increases the possibility of chronic lung diseases (30%), exacerbation of chronic lung diseases (95%), seizure of heart disease (1.80 times), and decreases self-evaluated health status of the elderly (1.38 times). Thus, it is urgent to improve clean energy access for cooking in rural China.

Enriched environment elevates expression of growth associated protein-43 in the substantia nigra of SAMP8 mice.

An enriched environment protects dopaminergic neurons from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury, but the underlying mechanism for this is not clear. Growth associated protein-43 (GAP-43) is closely associated with neurite outgrowth and axon regeneration during neural development. We speculate that an enriched environment can reduce damage to dopaminergic neurons by affecting the expression of GAP-43. This study is designed to test this hypothesis. Three-month-old female senescence-accelerated mouse prone 8 (SAMP8) mice were housed for 3 months in an enriched environment or a standard environment. These mice were then subcutaneously injected in the abdomen with 14 mg/kg MPTP four times at 2-hour intervals. Morris water maze testing demonstrated that learning and memory abilities were better in the enriched environment group than in the standard environment group. Reverse-transcription polymerase chain reaction, immunohistochemistry and western blot assays showed that mRNA and protein levels of GAP-43 in the substantia nigra were higher after MPTP application in the enriched environment group compared with the standard environment group. These findings indicate that an enriched environment can increase GAP-43 expression in SAMP8 mice. The upregulation of GAP-43 may be a mechanism by which an enriched environment protects against MPTP-induced neuronal damage.

Left Atrial Appendage Thrombus Formation in a Patient on Dabigatran Therapy Associated With ABCB1 and CES-1 Genetic Defect.

Dabigatran, directly targeting thrombin, is widely used for the prevention of stroke in nonvalvular atrial fibrillation (NVAF). We reported a rare case of left atrial appendage thrombus formation in a persistent NVAF patient despite the 31 months uninterrupted treatment with dabigatran 110 mg twice daily. The patient is a carrier of ABCB1 variant alleles with 7 heterozygote single nucleotide polymorphisms (SNPs: rs4148738, rs2235046, rs1128503, rs10276036, rs1202169, rs1202168, rs1202167) as well as CES-1 variant alleles with 2 homozygote SNPs (rs2244613 and rs4122238) and 2 heterozygote SNPs (rs8192935 and rs4580160), which may contribute to the changes of dabigatran plasma concentration. In addition, Drug-drug interaction with atorvastatin may also play a role to decrease dabigatran plasma concentration. There are only four such cases till date, of which had thrombus in the left atrium, reported in the literature. We firstly reported the documented case in a Chinese patient carrying multiple alleles of ABCB1 and CES-1, who suffered from thrombus in the left atrial appendage despite long-term anticoagulation with dabigatran. More clinical data are required to elucidate the impact of CES-1 and ABCB1 polymorphism on dabigatran pharmacokinetics, especially for Asian.

Retracted Article: High-throughput metabolomics identifies serum metabolic signatures in acute kidney injury using LC-MS combined with pattern recognition approach.

Metabolomics, as a promising and powerful approach, refers to comprehensive assessment and identification of small molecule endogenous metabolites in a biological system which is capable of further understanding the mechanisms of diseases for early diagnosis, effective treatment and prognosis. Acute kidney injury (AKI) induced by contrast is a serious complication in patients undergoing administration of iodinated contrast media. It is becoming a major health concern in clinic, however, the molecular mechanisms of contrast-induced acute kidney injury (CI-AKI) have not been well characterized. In this study, we used serum metabolomics based on liquid chromatography-mass spectrometry (LC-MS) combined with pattern recognition to explore and characterize potential metabolites and metabolic pathway in an experimental model for CI-AKI. Seventeen differentiating metabolites in the serum were identified involving the pivotal metabolic pathways related to tryptophan metabolism, glycerophospholipid metabolism, steroid hormone biosynthesis, pyrimidine metabolism, sphingolipid metabolism, aminoacyl-tRNA biosynthesis. Our study provides novel insight into pathophysiologic mechanisms of AKI by changing biomarkers and pathways.

Nanomicelle-Assisted Targeted Ocular Delivery with Enhanced Antiinflammatory Efficacy In Vivo.

Ocular inflammations are common diseases that may lead to serious vision-threatening obstacles. Eye drops for antiinflammation therapy need to be administered multiple times daily at a high dosage due to the rapid precorneal removal and low bioavailability of drugs. To overcome these problems, a cRGD-functionalized DSPE-PEG2000 nanomicelle (DSPE-PEG2000-cRGD) encapsulated with flurbiprofen is proposed. The tailored nanomicelles trigger specific binding to integrin receptors on the ocular surface, which leads to rapid and robust mucoadhesion, superior ocular surface retention, and transcorneal penetration behaviors of nanomicelles. Due to the enhanced drug delivery on ocular surface and in aqueous humor, the functionalized nanoformulation significantly improves ocular antiinflammation efficacy at a low dosage by blocking the synthesis of inflammatory mediators and cytokines. The present study demonstrates a promising strategy that uses a functional peptide combined with nanomicelles for targeted delivery to the eye in ophthalmologic applications.