Deciphering environmental factors influencing phytoplankton community structure in a polluted urban river.

Tuojiang River Basin is a first-class tributary of the upper reaches of the Yangtze River-which is the longest river in China. As phytoplankton are sensitive indicators of trophic changes in water bodies, characterizing phytoplankton communities and their growth influencing factors in polluted urban rivers can provide new ideas for pollution control. Here, we used direct microscopic count and environmental DNA (eDNA) metabarcoding methods to investigate phytoplankton community structure in Tuojiang River Basin (Chengdu, Sichuan Province, China). The association between phytoplankton community structure and water environmental factors was evaluated by Mantel analysis. Additional environmental monitoring data were used to pinpoint major factors that influenced phytoplankton growth based on structural equation modeling. At the phylum level, the dominant phytoplankton taxa identified by the conventional microscopic method mainly belonged to Bacillariophyta, Chlorophyta, and Cyanophyta, in contrast with Chlorophyta, Dinophyceae, and Bacillariophyta identified by eDNA metabarcoding. In α-diversity analysis, eDNA metabarcoding detected greater species diversity and achieved higher precision than the microscopic method. Phytoplankton growth was largely limited by phosphorus based on the nitrogen-to-phosphorus ratios > 16:1 in all water samples. Redundancy analysis and structural equation modeling also confirmed that the nitrogen-to-phosphorus ratio was the principal factor influencing phytoplankton growth. The results could be useful for implementing comprehensive management of the river basin environment. It is recommended to control the discharge of point- and surface-source pollutants and the concentration of dissolved oxygen in areas with excessive nutrients (e.g., Jianyang-Ziyang). Algae monitoring techniques and removal strategies should be improved in 201 Hospital, Hongrihe Bridge and Colmar Town areas.

Declined intrinsic capacity predicts long-term mortality in Chinese older adults: Beijing Longitudinal Study of Aging.

BACKGROUND: Intrinsic capacity reflects an individual's functions and capacities across their lifetime. There are few studies on whether the level of intrinsic capacity can predict long-term mortality in Chinese populations. OBJECTIVE: To explore the effects of intrinsic capacity on long-term outcomes in older Chinese adults. METHODS: Data were obtained from the Beijing Longitudinal Study of Aging. Overall, 1699 community-dwelling adults aged ≥60 years were included and followed up for 8 years. Intrinsic capacity was determined according to the World Health Organization definition. The predictive ability for adverse outcomes was assessed using the age- and sex-adjusted Cox proportional hazards model. RESULTS: A decline in intrinsic capacity domains was observed in 729 (42.9 %) participants. Declines in the mobility, cognition, vitality, sensory and psychology domains were observed in 21.8 %, 15.1 %, 11.4 %, 9.10 %, and 14.2 % of the participants, respectively. Low intrinsic capacity was associated with worse physical performance, frailty, social frailty, chronic diseases, fracture, and falls. A greater decline in intrinsic capacity predicted an elevated 8-year mortality rate (decline in overall intrinsic capacity hazard ratio 2.91, 95 % confidence interval 2.44-3.47, P < 0.001; decline in one domain hazard ratio 2.11, 95 % confidence interval 1.71-2.61, P < 0.001; decline in two domains hazard ratio 3.54, 95 % confidence interval 2.81-4.45, P < 0.001; decline in three or more domains hazard ratio 5.30, 95 % confidence interval 4.09-6.87, P < 0.001); adjusted models did not affect prediction performance. Among the five domains of intrinsic capacity, cognition was the strongest predictor of mortality (hazard ratio 3.17, 95 % confidence interval 2.63-3.81, P < 0.001). CONCLUSIONS: Intrinsic capacity is useful in identifying older adults at higher risk of adverse outcomes, presenting significant implications for healthcare policies in China.

From biological aging to functional decline: Insights into chronic inflammation and intrinsic capacity.

Intrinsic capacity is the sum of an individual's physical and mental capacities, which helps determine functional ability. Intrinsic capacity decline is an important predictor of adverse health outcomes and can identify individuals at higher risk of functional decline. Aging is characterized by a decrease in physiological reserves and functional abilities. Chronic inflammation, a mechanism of aging, is associated with decreased intrinsic capacity, which may mirror the broader relationship between aging and functional ability. Therefore, it is crucial for maintaining functional ability and promoting healthy aging to study the mechanisms of intrinsic capacity decline, identify easily available markers, and make targets for intervention from the perspective of chronic inflammation. We reviewed the current research on chronic inflammation, inflammation-related markers, and intrinsic capacity. To date, there is still no inflammatory markers with high specificity and sensitivity to monitor intrinsic capacity decline. Interleukin-6, C-reactive protein, and tumor necrosis factor-alpha may potentially indicate changes in intrinsic capacity, but their results with intrinsic capacity or each intrinsic capacity domain are inconsistent. Considering the variations in individual responses to changes in inflammatory markers, it may be beneficial to explore the use of multiple analytes instead of relying on a single marker. This approach could be valuable in monitoring the decline of intrinsic capacity in the future.

Exploring the Intricate Nexus of Sarcopenia and Cognitive Impairment.

Sarcopenia, a group of skeletal muscle diseases with high prevalence in older adults, usually manifests as loss of muscle mass and strength, and/or physical performance decline. Cognitive impairment, defined as impaired function in one or more cognitive domains such as memory, language, computation, comprehension, executive, and visuospatial skills, affects the quality of life and social functioning of patients. Both sarcopenia and cognitive impairment are common geriatric syndromes, and the two disorders interact and influence each other. Declining muscle function accelerates cognitive impairment, and cognitive impairment in turn affects muscle strength. Potential common pathological mechanisms between the two include chronic inflammation, mitochondrial dysfunction and oxidative stress, and gut microbiota disorder. Additionally, neuroendocrine connections including testosterone, insulin, and growth factors have important effects on muscle and brain function. Recently, the development of applied metabolomics technologies has shown significant potential in uncovering shared biochemical pathways and exploring potential biomarkers. Exercise, nutritional, and cognitive interventions are significant as nonpharmacologic approaches in the treatment of sarcopenia and cognitive impairment. However, the specific mechanism of interaction between two diseases, biomarkers and effective therapeutic medications still has knowledge gaps that need to be further explored.

Modified Laryngeal Forceps for Arytenoid Cartilage Dislocation Caused by Endotracheal Intubation: A Retrospective Case-Control Pilot Study.

Background: Arytenoid cartilage dislocation is considered as a rare laryngeal injury and closed reduction is commonly used as the first choice for the arytenoid dislocation. However, the tools of closed reduction vary, and there is no dedicated tool for closed reduction, and the treatment outcome varies from person to person. This study compared the treatment outcome of the modified laryngeal forceps and traditional laryngeal forceps. Material and Methods: This study conformed to the strengthening the reporting of observational studies in epidemiology guidelines regarding retrospective studies. From May 2021 to February 2023, the records of 28 patients with arytenoid cartilage dislocation caused by endotracheal intubation were reviewed. They were divided into the traditional group (n = 14) and the modified group (n = 14) by gender. Indirect or direct laryngoscopy, video stroboscopy, high-resolution computed tomography, and cricoarytenoid joint 3-dimensional reconstruction were used to evaluate arytenoid position and motion. Clinical characteristics, voice function, procedural skill, and treatment outcome for each case were recorded. Results: Each patient was diagnosed with arytenoid dislocation caused by endotracheal intubation. There was no significant difference in the treatment outcome between the traditional group and the modified group (P > .05). However, the median time interval between closed reduction and the return of normal voice in the traditional group was 31.08 ± 10.56 days, which was significantly longer than the median time of 17.92 ± 3.83 days in the modified group (P < .05). Conclusion: Closed reduction with the modified laryngeal forceps under local anesthesia is an effective and safe procedure. Compared with traditional laryngeal forceps, the modified laryngeal forceps can shorten the treatment duration.

Spatial variation of dissolved organic matter in the Tuojiang River Basin in Chengdu, China: insights based on EEMs-PARAFAC analysis.

Three-dimensional excitation-emission matrix fluorescence spectroscopy coupled with parallel factor analysis was adopted to investigate the characteristics of dissolved organic matter (DOM) components in water samples collected from the Tuojiang River Basin in Chengdu, including its main stream and tributaries. Four DOM components that matched with three fluorescence peaks were identified in the whole river basin and tributaries; while three components corresponding to four fluorescence peaks were identified in the main stream. In all cases, humic-like components accounted for high proportions of the DOM. Correlation analysis revealed the same sources for four components in the whole river basin and its tributaries, whereas two components had different sources in the main stream. Ultraviolet absorbance parameters (SUVA254, SR) and fluorescence parameters (BIX, HIX, FI, ß:α) indicated the dominant autochthonous sources of DOM in the whole river basin. Higher terrestrial inputs of DOM were observed in the tributaries than in the main stream. In the areas influenced by human activities (6#, 17#, 18#), the sources of DOM showed strong terrestrial characteristics and high degrees of humification and aromatization, as well as serious pollution. The results of this study have potentially far-reaching implications for environmental water management in the area.

SSR markers development and their application in genetic diversity evaluation of garlic (Allium sativum) germplasm.

Garlic (Allium sativum), an asexually propagated vegetable and medicinal crop, has abundant genetic variation. Genetic diversity evaluation based on molecular markers has apparent advantages since their genomic abundance, environment insensitivity, and non-tissue specific features. However, the limited number of available DNA markers, especially SSR markers, are insufficient to conduct related genetic diversity assessment studies in garlic. In this study, 4372 EST-SSR markers were newly developed, and 12 polymorphic markers together with other 17 garlic SSR markers were used to assess the genetic diversity and population structure of 127 garlic accessions. The averaged polymorphism information content (PIC) of these 29 SSR markers was 0.36, ranging from 0.22 to 0.49. Seventy-nine polymorphic loci were detected among these accessions, with an average of 3.48 polymorphic loci per SSR. Both the clustering analyses based on either the genotype data of SSR markers or the phenotypic data of morphological traits obtained genetic distance divided the 127 garlic accessions into three clusters. Moreover, the Mantel test showed that genetic distance had no significant correlations with geographic distance, and weak correlations were found between genetic distance and the phenotypic traits. AMOVA analysis showed that the main genetic variation of this garlic germplasm collection existed in the within-population or cluster. Results of this study will be of great value for the genetic/breeding studies in garlic and enhance the utilization of these garlic germplasms.

The Ottawa Decision-Making Supportive Framework-Based Nursing Care in the Outcome of Patients with Chronic Heart Failure.

Objective: To examine the psychological, compliance, and prognostic impact of care based on the Ottawa Decision Support Framework on patients with chronic heart failure. Methods: The medical profiles of 80 individuals with permanent heart failure from January 2020 to January 2021 were retrospectively analyzed. The care was provided in the framework of Ottawa Decision Support alongside the clinical standard of care. The self-assessment anxiety scale (SAS), Frankel treatment adherence scale, Minnesota quality of life questionnaire for heart failure, self-care competence scale (ESCA), complication rates, and readmission rates were compared prior to and postcare. Results: Following three-month nursing care, the score of the SAS scale was remarkably fewer, and the difference was statistically significant (P < 0.05). Three months of care later, the scores on the Frank Scale were substantially superior to those before care, and the difference was statistically significant (P < 0.05). Aftercare, the Minnesota quality of life questionnaire for heart failure was clearly inferior to precare, and the difference was statistically significant (P < 0.05). The ESCA scale scores were found to be considerably more favorable after three months of care than before care, and the difference was statistically significant (P < 0.05). After nursing care, one arrhythmia (1.25%) and one pulmonary infection (1.25%) were noted, and the difference was statistically significant (P < 0.05). The prevalence of complications was 2.50%, and the difference was statistically significant (P < 0.05). Three cases were readmitted for recurrent chronic heart failure, which was a 2.75% readmission rate. Conclusion: Continuous nursing based on the Ottawa Decision Support Framework has significant application value in an anxiety state, treatment compliance, and prognosis of patients with chronic heart failure, which can more effectively reduce patients' anxiety and the incidence of complications and readmission rate, in the meanwhile, effectively improve treatment compliance, quality of life, self-care ability, and prognosis, which is worthy of clinical application.

Genome-Wide Identification and Characterization of KNOTTED-Like Homeobox (KNOX) Homologs in Garlic (Allium sativum L.) and Their Expression Profilings Responding to Exogenous Cytokinin and Gibberellin.

Garlic (Allium sativum L.) is an important vegetable and is cultivated and consumed worldwide for its economic and medicinal values. Garlic cloves, the major reproductive and edible organs, are derived from the axillary meristems. KNOTTED-like homeobox (KNOX) proteins, such as SHOOT MERISTEM-LESS (STM), play important roles in axillary meristem formation and development. However, the KNOX proteins in garlic are still poorly known. Here, 10 AsKNOX genes, scattered on 5 of the 8 chromosomes, were genome-wide identified and characterized based on the newly released garlic genome. The typical conserved domains of KNOX proteins were owned by all these 10 AsKNOX homologs, which were divided into two Classes (Class I and Class II) based on the phylogenetic analysis. Prediction and verification of the subcellular localizations revealed the diverse subcellular localization of these 10 AsKNOX proteins. Cis-element prediction, tissue expression analysis, and expression profilings in responding to exogenous GA3 and 6-BA showed the potential involvement of AsKNOX genes in the gibberellin and cytokinin signaling pathways. Overall, the results of this work provided a better understanding of AsKNOX genes in garlic and laid an important foundation for their further functional studies.

The integrity and barrier function of porcine vocal fold epithelium: its susceptibility to damage by deoxycholic acid compared with pepsin.

PURPOSE: In this study, we aim to systematically evaluate the damaging role of gastric (pepsin and acid) and duodenal ingredients (bile acids) on vocal fold epithelium in excised porcine larynges. METHODS: Fresh ex vivo porcine larynges were exposed to one of five experimental conditions for 1 h. These conditions will be referred to as alkaline deoxycholic acid, acidic pepsin, acid pH3 only, acid pH5 only, and control, respectively. A Franz diffusing cell was used to evaluate the barrier function of vocal fold epithelium by measuring the permeability to fluorescein isothiocyanate dextran of 4 kDa. Histological changes were observed using transmission electron microscopy. RESULTS: After immersing the fresh porcine larynges in the five solution groups, we found that the vocal fold epithelium in the deoxycholic acid group had more permeability to FD4 than the pepsin group (P < 0.001). Fragmentation and desquamation of dead cell layers were observed in both the pepsin and deoxycholic acid groups, but were more severe in the deoxycholic acid group than the pepsin group. The thickness of the dead epithelial cell layer gradually increased with increasing acid concentration (P < 0.05). Additionally, the thickness of the dead epithelial cell layer in the deoxycholic acid group was significantly higher than that in the pepsin group (P < 0.01). CONCLUSION: Deoxycholic acid in a weakly acidic condition is more likely than pepsin to induce apoptosis in ex vivo porcine vocal fold epithelium, destroy the link proteins between epithelial cells, and affect their integrity and barrier function.

A dual prediction strategy with inverse model for evolutionary dynamic multiobjective optimization.

In practical applications and daily life, dynamic multiobjective optimization problems (DMOPs) are ubiquitous. The purpose of dealing with DMOPs is to track moving Pareto Front (PF) and find a series of Pareto Set (PS) at different times. Prediction-based strategies improve the performance of multiobjective evolutionary algorithms in dynamic environments. However, how to ensure the accuracy of prediction models is always a challenge. In this study, a dual prediction strategy with inverse model (DPIM) is developed, to alleviate the negative impact of inaccurate prediction. When a change is confirmed, DPIM responses to it by predicting the individuals in the objective space. Furthermore, the inverse model is established to connect the decision space with the objective space, which can guide the search for promising decision areas. Specifically, the inverse model is also predicted to minimize the error in the process of mapping the population from the objective space back to the decision space. The effectiveness of the proposed DPIM is proved by comparison with four effective DMOEAs on 14 benchmark problems with various real-word scenarios. The experimental results show that DPIM can obtain high-quality populations with good convergence and distribution in dynamic environments.

Visual detection of tropomyosin, a major shrimp allergenic protein using gold nanoparticles (AuNPs)-assisted colorimetric aptasensor.

A gold nanoparticle-based label-free colorimetric assay was developed to detect the shrimp allergenic protein tropomyosin (TM), an important biomarker responsible for severe clinical reactivity to shellfish. In a gold nanoparticles (AuNPs)-tropomyosin-binding aptamer (TMBA) complex, the aptamer adsorbs onto the surface of AuNPs and dissociates in the presence of TM. In addition, AuNPs tend to aggregate in the presence of ionic salt, revealing a color change (i.e., wine-red to purple/blue) with a shift in the maximum absorption peak from 520 nm. In the presence of specific binding TM, the aptamer folds into a tertiary structure where it more efficiently stabilizes AuNPs toward the salt-induced aggregation with a hypsochromic shift in the absorption spectra compared to the stabilized AuNPs by aptamer alone. Based on the aggregation and sensitive spectral transformation principle, the AuNPs-based colorimetric aptasensor was successfully applied to detect TM with a range of 10-200 nmol/L and a low detection limit of 40 nmol/L in water samples. The reliability, selectivity, and sensitivity of the aptasensor was then tested with food samples spiked with TM. The observed detection limit was as low as 70 nmol/L in shrimp, 90 nmol/L in tofu, and 80 nmol/L in eggs, respectively. We anticipate the proposed AuNPs-based colorimetric aptasensor assay possesses a high potential for the easy and efficient visual colorimetric detection of TM. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-020-00085-5.

Regularity of voice recovery and arytenoid motion after closed reduction in patients with arytenoid dislocation: a self-controlled clinical study.

Background: Closed reduction is an effective treatment for arytenoid dislocation. The treatment is usually given more than once to obtain normal voice. However, when to perform the next closed reduction remains controversial.Objective: This study aimed to observe the regularity of the voice recovery and the arytenoid motion in patients with arytenoid dislocation after closed reduction.Material and methods: Thirty-one patients were recruited from September 2017 to April 2019. Results of their clinical data were reviewed retrospectively.Results: Among the thirty-one patients, their VHI scores, F0, jitter%, shimmer%, glottal-to-noise excitation %(GNE), maximum phonation time (MPT) and GRBAS Scale (G, R, B, A) improved significantly (p < .05), but there was no statistically significant difference for GRBAS Scale (S) (p>.05). The duration between last closed reduction and the restoring normal voice ranged from 1-8 days, with a mean of 4.65 ± 0.57 days, at the same time the glottis was completely closed.Conclusions and significance: Closed reduction for patients with arytenoid dislocation is an effective procedure. A time window between 4.08th and 5.22th day (at a confidence level of 95%) after the last closed reduction was identified to be critical for voice recovery.

Computational Insight into the Mechanism of Ruthenium(II)-Catalyzed α-Alkylation of Arylmethyl Nitriles Using Alcohols.

The ruthenium(II)-catalyzed α-alkylation reaction of arylmethyl nitriles (phenylacetonitrile) using alcohols (ethanol) in toluene has been extensively investigated by means of SMD-M06-2X/6-311G(d,p)-LANL2dz (LAnL2dz for Ru, 6-311G(d,p) for other atoms) calculations. Detailed mechanistic schemes have been proposed and discussed. The catalytically active Ru(II) complex was generated by the base-induced KCl elimination from the catalyst precursor [(PNPPh)RuHCl(CO)]. The overall Ru(II) catalytic cycle consists of three basic processes: (1) ethanol-to-aldehyde transformation catalyzed by the 16-electron unsaturated ruthenium pincer catalyst; (2) a 16-electron unsaturated ruthenium pincer catalyst catalyzed condensation reaction of arylmethyl nitrile with aldehyde, which leads to PhC(CN)=CHCH3; (3) hydrogenation of PhC(CN)=CHCH3, which leads to the formation of the α-alkylated arylmethyl nitrile product (PhCH(CH2CH3)CN). The DFT results revealed that the rate-determining barrier of the overall reaction was 23.9 kcal/mol of the H-transfer step in the third process. The reaction of PhC(CN)=CHCH3 with the dihydride Ru complex, which is generated in the ethanol-to-aldehyde transformation process, is the more preferable hydrogenation mechanism than hydrogenation of vinyl nitrile-Ru complex by H2. Using alcohol as the reactant not only fulfills the requirement of the borrowing-H strategy but also lowers the barriers of the H-migration steps.

One step synthesis of boron-doped carbon nitride derived from 4-pyridylboronic acid as biosensing platforms for assessment of food safety.

The rational design of heteroatom-doped C3N4 offers a great opportunity to optimize C3N4 performance. In this communication, we propose a facile method to fabricate layered-stacked B-doped C3N4 (BCN-800) ultrathin nanosheets via a one-step calcination route. The distinctive layered-stacked structure and the presence of B atoms provide an active attachment point for antibodies and antigens. In addition, the presence of C and N might aid stability and increase conductivity. When used for vomitoxin detection, the BCN-800-based electrochemical biosensor exhibits high sensitivity with a detection limit of 0.32 pg mL-1 and superior selectivity to other interfering agents.

Applications of Metal-Organic-Framework-Derived Carbon Materials.

Carbon materials derived from metal-organic frameworks (MOFs) have attracted much attention in the field of scientific research in recent years because of their advantages of excellent electron conductivity, high porosity, and diverse applications. Tremendous efforts are devoted to improving their chemical and physical properties, including optimizing the morphology and structure of the carbon materials, compositing them with other materials, and so on. Here, many kinds of carbon materials derived from metal-organic frameworks are introduced with a particular focus on their promising applications in batteries (lithium-ion batteries, lithium-sulfur batteries, and sodium-ion batteries), supercapacitors (metal oxide/carbon and metal sulfide/carbon), electrocatalytic reactions (oxygen reduction reaction, oxygen evolution reaction, and hydrogen evolution reaction), water treatment (MOF-derived carbon and other techniques), and other possible fields. To close, some existing problem and corresponding possible solutions are proposed based on academic knowledge from the reported literature, along with a great deal of experimental experience.

Applications of MxSey (M = Fe, Co, Ni) and Their Composites in Electrochemical Energy Storage and Conversion.

Transition-metal selenides (MxSey, M = Fe, Co, Ni) and their composites exhibit good storage capacities for sodium and lithium ions and occupy a unique position in research on sodium-ion and lithium-ion batteries. MxSey and their composites are used as active materials to improve catalytic activity. However, low electrical conductivity, poor cycle stability, and low rate performance severely limit their applications. This review provides a comprehensive introduction to and understanding of the current research progress of MxSey and their composites. Moreover, this review proposes a broader research platform for these materials, including various bioelectrocatalytic performance tests, lithium-sulfur batteries, and fuel cells. The synthesis method and related mechanisms of MxSey and their composites are reviewed, and the effects of material morphologies on their electrochemical performance are discussed. The advantages and disadvantages of MxSey and their composites as well as possible strategies for improving the storage and conversion of electrochemical energy are also summarized.

Electroacupuncture pretreatment induces rapid tolerance to bupivacaine cardiotoxicity in rats.

BACKGROUND: Evidence suggests that electroacupuncture (EA) protects against arrhythmia and myocardial injury induced by myocardial ischaemia-reperfusion. However, to our knowledge, it remains unknown whether EA could alleviate bupivacaine-induced cardiotoxicity. Therefore, we aimed to explore the effect of EA pretreatment on bupivacaine-induced cardiac arrest and outcomes of cardiopulmonary resuscitation (CPR) in rats. METHODS: 24 adult male Sprague-Dawley rats were randomly divided into two groups: EA (n=12), and minimal acupuncture (MA) (n=12). Rats in both groups were needled at bilateral PC6, ST36, and ST40. Needles in the EA group were electrically stimulated for 60 min. ECG and invasive arterial blood pressure measurements were recorded. Two hours after EA or MA, 10 mg/kg bupivacaine was infused intravenously at a rate of 5 mg/kg/min in all rats. Rats suffering cardiac arrest were immediately subjected to CPR. At the end of the experiment, arterial blood samples were taken from surviving rats for blood gas analysis. RESULTS: The time from bupivacaine infusion until 20% prolongation of the QRS and QT interval, and the time to cardiac arrest, were notably increased among the rats pretreated with EA. Moreover, EA pretreatment significantly improved mean arterial pressure and heart rate at all monitored points after bupivacaine infusion. The proportion of animals surviving was higher in the EA group (9/12) than the MA group (3/12) at the end of experiment (p=0.039). CONCLUSIONS: Tolerance to bupivacaine-induced cardiotoxicity appeared to be increased following EA pre-treatment. The mechanism of action underlying the effects of EA on bupivacaine-induced cardiotoxicity requires further investigation.

Improved oral bioavailability of poorly water-soluble glimepiride by utilizing microemulsion technique.

The objective of this work was to prepare an oil/water glimepiride (GM) microemulsion (ME) for oral administration to improve its solubility and enhance its bioavailability. Based on a solubility study, pseudoternary phase diagrams, and Box-Behnken design, the oil/water GMME formulation was optimized and prepared. GMME was characterized by dynamic laser light scattering, zeta potential, transmission electron microscopy, and viscosity. The in vitro drug release, storage stability, pharmacodynamics, and pharmacokinetics of GMME were investigated. The optimized GMME was composed of Capryol 90 (oil), Cremophor RH40 (surfactant), and Transcutol (cosurfactant), and increased GM solubility up to 544.6±4.91 µg/mL. The GMME was spherical in shape. The particle size and its polydispersity index were 38.9±17.46 nm and 0.266±0.057, respectively. Meanwhile, the GMME was physicochemically stable at 4°C for at least 3 months. The short-term efficacy in diabetic mice provided the proof that blood glucose had a consistent and significant reduction at a dose of 375 µg/kg whether via IP injection or IG administration of GMME. Compared with the glimepiride suspensions or glimepiride-meglumine complex solution, the pharmacokinetics of GMME in Wistar rats via IG administration exhibited higher plasma drug concentration, larger area under the curve, and more enhanced oral bioavailability. There was a good correlation of GMME between the in vitro release values and the in vivo oral absorption. ME could be an effective oral drug delivery system to improve bioavailability of GM.

A simple and effective method to improve bioavailability of glimepiride by utilizing hydrotropy technique.

The purpose of this study was to improve the solubility and bioavailability of glimepiride (GLMP) by utilizing hydrotropy technique. Meglumine (MU) as a hydrotrope could form the stable complex with glimepiride. The optimal glimepiride and meglumine (GLMP-MU) complex powder was obtained by using lyophilization. GLMP-MU powder was characterized by Fourier transform infrared spectroscopy (FT IR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). The formation of hydrogen bond between glimepiride and meglumine was confirmed by FT IR. The XRD studies indicated the amorphous state of glimepiride was appeared in the GLMP-MU. The DSC results were further confirmed GLMP-MU complex was prepared successfully. Moreover, the in vitro drug release rate of GLMP-MU powder was dramatically faster than that of glimepiride. Meanwhile, the AUC of GLMP-MU solution at an i.g./or i.v. dose of 5mg/kg in rat was significantly higher than that of the glimepiride suspensions. Together our results showed that hydrotropy technique was a simple and effective method to increase the solubility of glimepiride.