PPARα/δ dual agonist H11 alleviates diabetic kidney injury by improving the metabolic disorders of tubular epithelial cells.

Diabetic kidney disease (DKD) is responsible for nearly half of all end-stage kidney disease and kidney failure is a major driver of mortality among patients with diabetes. To date, few safe and effective drugs are available to reverse the decline of kidney function. Kidney tubules producing energy by fatty acid metabolism are pivotal in development and deterioration of DKD. Peroxisome proliferator-activated receptors (PPARs), comprising PPARα, PPARδ and PPARγ play a senior role in the pathogenesis of DKD for their functions in glycemic control and lipid metabolism; whereas systemic activation of PPARγ causes serious side-effects in clinical settings. Compound H11 was a potent PPARα and PPARδ (PPARα/δ) dual agonist with potent and well-balanced PPARα/δ agonistic activity and a high selectivity over PPARγ. In this study, the potential therapeutic effects of compound H11 were determined in a db/db mouse model of diabetes. Expressions of PPARα and PPARδ in nuclei of tubules were markedly reduced in diabetes. Transcriptional changes of tubular cells showed that H11 was an effective PPARα/δ dual agonist taking effects both in vivo and in vitro. Systemic administration of H11 showed glucose tolerance and lipid metabolic benefits in db/db mice. Moreover, H11 treatment exerted protective effects on diabetic kidney injury. In addition to fatty acid metabolism, H11 also regulated diabetes-induced metabolic alternations of branch chain amino acid degradation and glycolysis. The present study demonstrated a crucial role of H11 in regulation of energy homeostasis and metabolism in glucose-treated tubular cells. Overall, compound H11 holds therapeutic promise for DKD.

GLP-1 receptor agonist attenuates tubular cell ferroptosis in diabetes via enhancing AMPK-fatty acid metabolism pathway through macropinocytosis.

Kidney tubules are mostly responsible for pathogenesis of diabetic kidney disease. Actively reabsorption of iron, high rate of lipid metabolism and exposure to concentrated redox-active compounds constructed the three main pillars of ferroptosis in tubular cells. However, limited evidence has indicated that ferroptosis is indispensable for diabetic tubular injury. Glucagon-like peptide-1 receptor agonist (GLP-1RA) processed strong benefits on kidney outcomes in people with diabetes. Moreover, GLP-1RA may have additive effects by improving dysmetabolism besides glucose control and weight loss. Therefore, the present study aimed at exploring the benefits of exendin-4, a high affinity GLP-1RA on kidney tubular dysregulation in diabetes and the possible mechanisms involved, with focus on ferroptosis and adenosine 5'-monophosphate-activated protein kinase (AMPK)-mitochondrial lipid metabolism pathway. Our data revealed that exendin-4 treatment markedly improved kidney structure and function by reducing iron overload, oxidative stress, and ACSL4-driven lipid peroxidation taken place in diabetic kidney tubules, along with reduced GPX4 expression and GSH content. AMPK signaling was identified as the downstream target of exendin-4, and enhancement of AMPK triggered the transmit of its downstream signal to activate fatty acid oxidation in mitochondria and suppress lipid synthesis and glycolysis, and ultimately alleviated toxic lipid accumulation and ferroptosis. Further study suggested that exendin-4 was taken up by tubular cells via macropinocytosis. The protective effect of exendin-4 on tubular ferroptosis was abolished by macropinocytosis blockade. Taken together, present work demonstrated the beneficial effects of GLP-1RA treatment on kidney tubular protection in diabetes by suppressing ferroptosis through enhancing AMPK-fatty acid metabolic signaling via macropinocytosis.

Ultrasonic optic nerve sheath diameter can be used as a diagnostic measure after accidental dural puncture during cesarean section: a case report.

BACKGROUND: Parturients are prone to postdural puncture headache (PDPH) after epidural puncture. Cerebral venous sinus thrombosis (CVST) is a fatal complication of PDPH. The main symptom of both is headache, however, the mechanism is not similar. For persistent PDPH, early differential diagnosis from CVST is essential. Optic nerve sheath diameter (ONSD) measurements can be used to identify changes in intracranial pressure as an auxiliary tool to distinguish the cause of headache. CASE PRESENTATION: The dura of a 32-year-old woman undergoing cesarean section was accidentally penetrated while administering epidural anesthesia, and the patient developed PDPH the subsequent day. The patient refused epidural blood patch (EBP) treatment and was discharged after conservative treatment. Fourteen days post-discharge, she was readmitted for a seizure. Magnetic resonance imaging (MRI) and Magnetic resonance angiography (MRA) indicated low cranial pressure syndrome and superior sagittal sinus thrombosis with acute infarction. The next morning, the EBP was performed with 15 ml autologous blood. Subsequently, the headache symptoms decreased during the day and worsened at night. ONSD measurement suggested dilation of the optic nerve sheath, and subsequently, the patient showed intracranial hypertension with papilledema. After dehydration and anticoagulant treatment, the patient's symptoms were relieved and she was discharged from the hospital 49 days later. CONCLUSIONS: Headache is the main symptom of PDPH and cerebral venous thrombosis, which are difficult to distinguish. ONSD measurement may help to estimate the intracranial pressure, and early measurement may be helpful for women with PDPH to avoid serious complications, such as CVST.

Clusters of Body Fat and Nutritional Parameters are Strongly Associated with Diabetic Kidney Disease in Adults with Type 2 Diabetes.

INTRODUCTION: Diabetic kidney disease (DKD) has become the leading cause of chronic kidney disease and end-stage renal failure in most developed and many developing countries. Strategies aimed at identifying potential modifiable risk factors for DKD are urgently needed. Here, we investigated the association between clusters of body fat and nutritional parameters with DKD in adults with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study of 184 participants with T2DM. Biochemical parameters including fasting blood glucose, hemoglobin A1c, hemoglobin, albumin, creatinine, and urinary albumin-to-creatinine ratio (UACR) were measured. The data for percentage of body fat mass (PBF), visceral fat area (VFA), phase angle at 50 kHz (PA50), and body cell mass (BCM) were obtained by bioelectrical impedance analysis (BIA). DKD was diagnosed by UACR and estimated glomerular filtration rate. Factor analysis was used for dimensionality reduction clustering among variables. The association of clusters with the presence of DKD was assessed using binary logistic regression analysis. RESULTS: Factor analysis identified two clusters which were interpreted as a body fat cluster with positive loadings of VFA, body mass index, waist circumstance, and PBF and a nutritional parameters cluster with positive loadings of PA50, hemoglobin, BCM, and albumin. Participants were divided into the four groups based on the sex-specific cutoff value (median) of each cluster score calculated using the cluster weights and the original variable values. Only participants with high body fat and poor nutritional parameters (OR 3.43, 95% CI 1.25-9.42) were associated with increased odds of having DKD. CONCLUSION: Body fat and nutritional parameters were strongly associated with and considerably contributed to the presence of DKD, suggesting that body fat and nutrition might be promising markers representing metabolic state in pathogenesis of DKD and clinical utility of BIA might provide valuable recommendations to patients with T2DM.

Effect of Microwave Treatments Combined with Hot-Air Drying on Phytochemical Profiles and Antioxidant Activities in Lily Bulbs (Lilium lancifolium).

Lily bulbs (Lilium lancifolium Thunb.) are rich in phytochemicals and have many potential biological activities which could be deep-processed for food or medicine purposes. This study investigated the effects of microwaves combined with hot-air drying on phytochemical profiles and antioxidant activities in lily bulbs. The results showed that six characteristic phytochemicals were identified in lily bulbs. They also showed that with an increase in microwave power and treatment time, regaloside A, regaloside B, regaloside E, and chlorogenic acid increased dramatically in lily bulbs. The 900 W (2 min) and the 500 W (5 min) groups could significantly suppress the browning of lily bulbs, with total color difference values of 28.97 ± 4.05 and 28.58 ± 3.31, respectively, and increase the content of detected phytochemicals. The highest oxygen radical absorbance activity was found in the 500 W, 5 min group, a 1.6-fold increase as compared with the control (57.16 ± 1.07 µmol TE/g DW), which was significantly relevant to the group's phytochemical composition. Microwaves enhanced the phytochemicals and antioxidant capacity of lily bulbs, which could be an efficient and environmentally friendly strategy for improving the nutrition quality of lily bulbs during dehydration processing.

Urinary metabolites associate with the presence of diabetic kidney disease in type 2 diabetes and mediate the effect of inflammation on kidney complication.

AIMS: Diabetic kidney disease (DKD) is the one of the leading causes of end-stage kidney disease. Unraveling novel biomarker signatures capable to identify patients with DKD is favorable for tackle the burden. Here, we investigated the possible association between urinary metabolites and the presence of DKD in type 2 diabetes (T2D), and further, whether the associated metabolites improve discrimination of DKD and mediate the effect of inflammation on kidney involvement was evaluated. METHODS: Two independent cohorts comprising 192 individuals (92 DKD) were analyzed. Urinary metabolites were analyzed by targeted metabolome profiling  and inflammatory cytokine IL-18 were measured by ELISA. Differentially expressed metabolites were selected and mediation analysis was carried out. RESULTS: Seven potential metabolite biomarkers (i.e., S-Adenosyl-L-homocysteine, propionic acid, oxoadipic acid, leucine, isovaleric acid, isobutyric acid, and indole-3-carboxylic acid) were identified using the discovery and validation design. In the pooled analysis, propionic acid, oxoadipic acid, leucine, isovaleric acid, isobutyric acid, and indole-3-carboxylic acid were markedly and independently associated with DKD. The composite index of 7 potential metabolite biomarkers (CMI) mediated 32.99% of the significant association between the inflammatory IL-18 and DKD. Adding the metabolite biomarkers improved the discrimination of DKD. CONCLUSIONS: In T2D, several associated urinary metabolites were identified to improve the prediction of DKD. Whether interventions aimed at reducing CMI also reduce the risk of DKD especially in patients with high IL-18 needs further investigations.

Urinary IL-18 is associated with arterial stiffness in patients with type 2 diabetes.

Objective: Diabetic kidney disease (DKD) has been shown to be associated with an excess risk of cardiovascular death. Inflammation has been considered central to type 2 diabetes (T2D) pathophysiology, and inflammation markers have been linked to cardiovascular disease. The serum and urinary IL-18 levels were significantly elevated in patients with T2D; however, whether interleukin 18 (IL-18) are associated with the severity of arterial stiffness remains to be determined. This study examined the relationship of IL-18 levels with pulse wave velocity (PWV) as a reflector for arterial stiffness in patients with T2D. Methods: A total of 180 participants with T2D who had undergone PWV examination were enrolled. Serum and urinary IL-18 levels were measured using sandwich enzyme linked immunosorbent assay (ELISA) kits. Arterial stiffness was determined by carotid-femoral PWV (cf-PWV) and carotid-radial PWV (cr-PWV). Results: The urinary IL-18 levels correlated positively with cf-PWV in patients with T2D with DKD (r = 0.418, p < 0.001); however, we found no significant correlation between urinary IL-18 and cf-PWV in diabetic subjects without DKD. In addition, we found no significant correlation between urinary IL-18 and cr-PWV in participants with T2D with or without DKD. Moreover, the association remained significant when controlling for arterial stiffness risk factors, urinary albumin-to-creatinine ratio and estimated glomerular filtration rate. cf-PWV was greater in the higher group of urinary IL-18 than in the lower group. Nevertheless, we found no significant correlation between serum IL-18 and cf-PWV in participants with T2D. Conclusion: The urinary IL-18 levels appear to be associated with greater cf-PWV, suggesting the link between urinary IL-18 and arterial stiffness in patients with T2D.

In Situ Monitoring of DNA-Hg2+ Binding Reaction within Confined Nanospace of Metamaterial Nanochannel by Plasmon-Enhanced Raman Scattering.

Nanochannel-based plasmon-enhanced Raman scattering (PERS) substrates can simulate biological environments, revealing the recognition and conformation information on biomolecules in confined spaces. In this work, a metamaterial nanochannel-based PERS platform was constructed for highly sensitive analysis of DNA recognition to Hg2+ with the lowest Hg2+ concentration down to 1.0 pM. The established platform enables in situ monitoring of the thermodynamics and kinetics of DNA-Hg2+ recognition reaction in a confined nanospace. The recognition reaction in a nanospace shows good reversibility and specificity, and the isotherm follows well the Freundlich adsorption model. Compared to its folding on a rough Au nanofilm, the folding time of ssDNA-Rox decorated in nanochannels is remarkably increased, and the folding process can be tuned through varying the pore size and ionic strength. The presented PERS platform is promising for studying biomolecule-ion binding events and biomolecule conformation change under nanochannel-confined conditions.

SGLT2 inhibitor counteracts NLRP3 inflammasome via tubular metabolite itaconate in fibrosis kidney.

Large clinical trials and real-world studies have demonstrated that the beneficial effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on renal outcomes regardless of the presence of diabetes. However, the mechanism remains obscure. Here, we analyze the anti-fibrotic and anti-inflammatory effects of dapagliflozin, a SGLT2 inhibitor, on renal alternations using the ischemia/reperfusion-induced fibrosis model. Transcriptome and metabolome analysis showed that the accumulation of tricarboxylic acid (TCA) cycle metabolites and upregulation of inflammation in fibrosis renal cortical tissue were mitigated by dapagliflozin treatment. Moreover, dapagliflozin markedly relieved the activation of mammalian target of rapamycin and hypoxia inducible factor-1α signaling and restored tubular cell-preferred fatty acid oxidation. Notably, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation was strikingly blocked by dapagliflozin. We further demonstrated that the immunomodulatory metabolite itaconate derived from the TCA cycle was significantly boosted as a result of decreased isocitrate dehydrogenase 2 and increased immune-responsive gene 1 and mitochondrial citrate carrier in dapagliflozin-treated mice, which contributed to the inhibitory effect of dapagliflozin on NLRP3 inflammasome activation. Furthermore, administration of cell-permeable itaconate surrogate prevented activation of NLRP3 inflammasome and protected kidney against fibrosis development. Our results identify a novel mechanism coupling metabolism and inflammation for kidney benefits of SGLT2 inhibition in progressive chronic kidney disease.

CPT1α maintains phenotype of tubules via mitochondrial respiration during kidney injury and repair.

Impaired energy metabolism in proximal tubular epithelial cells (PTECs) is strongly associated with various kidney diseases. Here, we characterized proximal tubular phenotype alternations during kidney injury and repair in a mouse model of folic acid nephropathy, in parallel, identified carnitine palmitoyltransferase 1α (CPT1α) as an energy stress response accompanied by renal tubular dedifferentiation. Genetic ablation of Cpt1α aggravated the tubular injury and interstitial fibrosis and hampered kidney repair indicate that CPT1α is vital for the preservation and recovery of tubular phenotype. Our data showed that the lipid accumulation and mitochondrial mass reduction induced by folic acid were persistent and became progressively more severe in PTECs without CPT1α. Interference of CPT1α reduced capacities of mitochondrial respiration and ATP production in PTECs, and further sensitized cells to folic acid-induced phenotypic changes. On the contrary, overexpression of CPT1α protected mitochondrial respiration and prevented against folic acid-induced tubular cell damage. These findings link CPT1α to intrinsic mechanisms regulating the mitochondrial respiration and phenotype of kidney tubules that may contribute to renal pathology during injury and repair.

Cisatracurium inhibits the growth and induces apoptosis of ovarian cancer cells by promoting lincRNA-p21.

As a common muscle relaxant, cisatracurium has shown good antitumor effect on some tumors. Recent studies reported that cisatracurium could inhibit the progression of colon cancer by upregulating tumor suppressor gene p53. However, its role in ovarian cancer and its regulatory effect on p53 and p53 downstream targeting gene long intergenic noncoding RNA p21 (lincRNA-p21) is still unknown. Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) was used to assess the expression of p53, lincRNA-p21 and miR-181b. Cell viability and proliferation were detected by CCK-8 assay and Edu staining, respectively. Wound-healing and Transwell assays were performed to determine the abilities of cell migration and invasion. Apoptosis was evaluated by TUNEL staining. Luciferase reporter assay was conducted to detect the relationship between lincRNA-p21 and miR-181b. As a result, cisatracurium could increase the expressions of p53 and lincRNA-p21 of ovarian cancer cell line (OVCAR-3) in a dose-dependent manner. In addition, cisatracurium significantly inhibited the proliferation, migration and invasion of OVACR-3 cells, and induced apoptosis. However, these above changes in biological function can be attenuated by lincRNA-p21 knockdown. Next, lincRNA-p21 could directly target miR-181b and negatively regulate its expression by luciferase reporter assay. In conclusion, cisatracurium inhibited the progression of OVCAR-3 cells through upregulation of lincRNA-p21 expression activated by p53 inhibiting miR-181b expression. The experimental results provide a new research idea for the application of cisatracurium in ovarian cancer.

Ultrasensitive plasmon enhanced Raman scattering detection of nucleolin using nanochannels of 3D hybrid plasmonic metamaterial.

Detection of cancer biomarker is of great significance in cancer diagnostics. In this work, we propose an ultrasensitive and in situ method for plasmon enhanced Raman scattering (PERS) detection of nucleolin (NCL) using a 3D hybrid plasmonic metamaterial (PM). In this aptasensor, thiolated complementary DNA (cDNA) immobilized on PM can hybridize with Rox-labeled NCL-binding aptamer (AS1411-Rox) to form a rigid double-stranded DNA (dsDNA). When NCL passes through the PM nanochannels under a transmembrane voltage bias, it interacts with AS1411-Rox to form G-quadruplexes (G4-AS1411-Rox), resulting in the release of AS1411-Rox from the nanochannels surface and the decrease in PERS signal of the reporter Rox. This change in PERS signals can be recorded in situ without the interference of external environment. With the help of the enrichment function of nanochannel, the present method is able to achieve fast NCL detection within 10 min with a detection limit as low as 71 pM. Furthermore, our method shows excellent specificity, reversibility, uniformity (relative standard deviation of ~6.86%) and reproducibility (~6.65%), providing a new platform for reliable cancer auxiliary diagnosis and drug screening.

Three-Dimensional Metamaterial for Plasmon-Enhanced Raman Scattering at any Excitation Wavelengths from the Visible to Near-Infrared Range.

Plasmonic materials with highly confined electromagnetic fields at resonance wavelengths have been widely used to enhance Raman scattering signals. To achieve the maximum enhancement, the resonance peaks of the plasmonic materials should overlap with the excitation and emission wavelengths of target molecules, which is difficult for most of the plasmonic materials possessing a few narrow resonance peaks. Here, we report an ultrabroadband plasmonic metamaterial absorber (BPMA) that can absorb 99% of the incident light energy and excite plasmon resonance from the ultraviolet to near-infrared range (250-1900 nm), which allows us to observe efficient plasmon-enhanced Raman scattering (PERS) with any excitation sources. As demonstrated by the investigation on a self-assembled monolayer of the nonresonant molecule 4-mercaptobenzonitrile, the BPMA exhibits high PERS performance with a detection limit of down to 10-12 M under any excitation sources of three different lasers and excellent uniformity (∼5.51%) and reproducibility (∼5.50%), which corroborates the potential for high-throughput production with low cost and at a large scale. This work offers a novel platform for anti-interference PERS analysis in dynamic and complex environments.

pH-Dependent Slipping and Exfoliation of Layered Covalent Organic Framework.

Layered/two-dimensional covalent organic frameworks (2D COF) are crystalline porous materials composed of light elements linked by strong covalent bonds. Interlayer force is one of the main factors directing the formation of a stacked layer structure, which plays a vital role in the stability, crystallinity, and porosity of layered COFs. The as-developed new way to modulate the interlayer force of imine-linked 2D TAPB-PDA-COF (TAPB = 1,3,5-tris(4-aminophenyl)benzene, PDA = terephthaldehyde) by only adjusting the pH of the solution. At alkaline and neutral pH, the pore size of the COF decreases from 34 Šdue to the turbostratic effect. Under highly acidic conditions (pH 1), TAPB-PDA-COF shows a faster and stronger turbostratic effect, thus causing the 2D structure to exfoliate. This yields bulk quantities of an exfoliated few/single-layer 2D COF, which was well dispersed and displayed a clear Tyndall effect (TE). Furthermore, nanopipette-based electrochemical testing also confirms the slipping of layers with increase towards acidic pH. A model of pH-dependent layer slipping of TAPB-PDA-COF was proposed. This controllable pH-dependent change in the layer structure may open a new door for potential applications in controlled gas adsorption/desorption and drug loading/releasing.

UCP2-induced hypoxia promotes lipid accumulation and tubulointerstitial fibrosis during ischemic kidney injury.

Mitochondrial dysfunction leads to loss of renal function and structure; however, the precise mechanisms by which mitochondrial function can regulate renal fibrosis remain unclear. Proximal tubular cells (PTCs) prefer fatty acid oxidation as their energy source and dysregulation of lipid metabolism has been linked to tubulointerstitial fibrosis (TIF). Here, we demonstrated that mitochondrial uncoupling protein 2 (UCP2) regulates TIF through the stimulation of lipid deposition and extracellular matrix (ECM) accumulation. We show that UCP2 expression was increased in human biopsy sample and mouse kidney tissues with TIF. Moreover, UCP2-deficient mice displayed mitigated renal fibrosis in I/R-induced mouse model of TIF. Consistent with these results, UCP2 deficiency displayed reduced lipid deposition and ECM accumulation in vivo and in vitro. In UCP2-deficient PTCs, inhibition of TIF resulted from downregulation of hypoxia-inducible factor-1α (HIF-1α), a key regulator of lipid metabolism and ECM accumulation. Furthermore, we describe a molecular mechanism by which UCP2 regulates HIF-1α stabilization through regulation of mitochondrial respiration and tissue hypoxia during TIF. HIF-1α inhibition by siRNA suppressed lipid and ECM accumulation by restoration of PPARα and CPT1α, as well as suppression of fibronectin and collagen I expression in PTCs. In conclusion, our results suggest that UCP2 regulates TIF by inducing the HIF-1α stabilization pathway in tubular cells. These results identify UCP2 as a potential therapeutic target in treating chronic renal fibrosis.

Graphene Plasmon-Enhanced IR Biosensing for in Situ Detection of Aqueous-Phase Molecules with an Attenuated Total Reflection Mode.

Graphene plasmon has attracted extensive interest due to the unprecedented electromagnetic confinement, long propagation distance, and tunable plasmonic frequency. Successful applications of graphene plasmon as infrared sensors have been recently demonstrated, yet they are mainly focused on solid/solid and solid/gas interfaces analysis. Herein, we, for the first time, propose a graphene plasmon-enhanced infrared sensor based on attenuated total reflection configuration for in situ analysis of aqueous-phase molecules. This IR sensor includes a boron-doped graphene (BG) nanodisk array fabricated on top of a ZnSe prism surface that supports attenuated total reflection surface-enhanced infrared absorption spectroscopy (ATR-SEIRA). Our ATR-SEIRA platform is efficient and straightforward for in situ and label-free monitoring of the interaction of biomolecules without interference from the environments, allowing for the extraction of instant spectroscopic information in a complex biological event. Utilizing the near-field enhancement of graphene plasmon, the binding interaction of L-selectin with its aptamer as a demonstration has been investigated to evaluate the specific protein recognition process. The detection limit of the target protein reaches 0.5 nM. Our work demonstrates that chemical-doped graphene plasmon combined with ATR-SEIRA is a promising signal enhancement platform for in situ aqueous-phase biosensing.

Au/ZnSe-Based Surface Enhanced Infrared Absorption Spectroscopy as a Universal Platform for Bioanalysis.

A versatile and sensitive platform for label-free bioanalysis has been proposed on the basis of attenuated total reflection-surface enhanced infrared absorption spectroscopy (ATR-SEIRAS) using Au/ZnSe as the enhancement substrate that allows a wide spectral range down to 700 cm-1. Au nanoparticles are stably deposited on the surface of a ZnSe prism due to the formation of Au-Se bonds via electroless deposition, and the enhancement factor of the resultant Au/ZnSe substrate is about 2 times larger than that of the commonly used Au/Si substrate. As a demonstration, the Au/ZnSe-based SEIRAS has been applied to obtain abundant structural information in the fingerprint region and quantitative analysis of various biomolecular interactions such as DNA hybridization and immunoreaction without any labeling process.

Anti-photobleaching flower-like microgels as optical nanobiosensors with high selectivity at physiological conditions for continuous glucose monitoring.

Optical glucose detection holds considerable promise for continuous in vivo glucose monitoring with wireless transdermal transmission and long-lasting activity. To construct a new class of optical glucose nanobiosensors with high sensitivity and selectivity at physiological conditions, the first generation of fluorescent poly(amido amine) (G1.0 PAMAM), serving as the optical code, was introduced into glucose-sensitive poly(N-isopropylacrylamide-(2-dimethylamino)ethyl methacrylate-3-acrylamidephenylboronic acid) copolymer microgels via a facile method. The fabricated microgels display the ability of adapting to the surrounding medium of different glucose concentrations over a clinically relevant range (0-20 mM) and convert biochemical signals into optical signals. As nanobiosensors, the G1.0 PAMAM functionalized microgels exhibit high selectivity for glucose over various kinds of potential primary interferents, such as lactate, human serum albumin and metal ions, in the physiologically important glucose concentration range. Compared to traditional fluorescent dyes and quantum dots, which are limited by photobleaching and toxicity, this microgel with remarkable anti-photobleaching property and low toxicity makes it possible to be used for long-term continuous glucose monitoring. Through in vivo investigations, it can be observed that G1.0 PAMAM functionalized microgels can achieve wireless transdermal detection, indicating that the fabricated microgels have potential applications as a new generation of nanobiosensors for the highly sensitive and minimally invasive continuous glucose monitoring.

[Study on skin sensitization as well as liver and kidney impairment in guinea pigs treated with trichloroethylene].

OBJECTIVE: To study skin sensitization as well as liver and kidney impairment in guinea pigs treated with trichloroethylene (TCE). METHODS: Guinea pig maximization test (GPMT) was applied in this study, guinea pigs were divided into 3 groups, namely negative control, positive control and TCE treatment. Animals of 3 groups were administrated with olive oil, 2, 4-dinitrochlorobenzene (DNCB), and TCE, respectively, by intradermal injection. The animal skin was observed and blood was collected after various treatment, the liver function tests were conducted, including detection of activities of ALT, AST, LDH and levels of creatinine, uric acid, and urea with automatic biochemical analyzer. RESULTS: Obvious skin impairment was observed in the groups of positive control and TCE treatment, the skin impairment included erythema and edema, the sensitization rate was 100% in positive control and 83.3% in TCE treatment group. Additionally, the activities of ALT, AST and LDH increased significantly in the groups of positive control and TCE treatment when compared with the negative control. CONCLUSIONS: Trichloroethylene is one of the strong hypersensitizing substances, it could induce skin allergic reaction and liver impairment in guinea pigs.