Microfluidic Electrochemical Integrated Sensor for Efficient and Sensitive Detection of Candida albicans.

Traditional methods for the detection of pathogenic bacteria are time-consuming, less efficient, and sensitive, which affects infection control and bungles illness. Therefore, developing a method to remedy these problems is very important in the clinic to diagnose the pathogenic diseases and guide the rational use of antibiotics. Here, microfluidic electrochemical integrated sensor (MEIS) has been investigated, functionally for rapid, efficient separation and sensitive detection of pathogenic bacteria. Three-dimensional macroporous PDMS and Au nanotube-based electrode are successfully assembled into the modeling microchip, playing the functions of "3D chaotic flow separator" and "electrochemical detector," respectively. The 3D chaotic flow separator enhances the turbulence of the fluid, achieving an excellent bacteria capture efficiency. Meanwhile, the electrochemical detector provides a quantitative signal through enzyme-linked immunoelectrochemistry with improved sensitivity. The microfluidic electrochemical integrated sensor could successfully isolate Candida albicans (C. albicans) in the range of 30-3,000,000 CFU in the saliva matrix with over 95% capture efficiency and sensitively detect C. albicans in 1 h in oral saliva samples. The integrated device demonstrates great potential in the diagnosis of oral candidiasis and is also applicable in the detection of other pathogenic bacteria.

Mechanical Strain Induces and Increases Vesicular Release Monitored by Microfabricated Stretchable Electrodes.

Exocytosis involving the fusion of intracellular vesicles with cell membrane, is thought to be modulated by the mechanical cues in the microenvironment. Single-cell electrochemistry can offer unique information about the quantification and kinetics of exocytotic events; however, the effects of mechanical force on vesicular release have been poorly explored. Herein, we developed a stretchable microelectrode with excellent electrochemical stability under mechanical deformation by microfabrication of functionalized poly(3,4-ethylenedioxythiophene) conductive ink, which achieved real-time quantitation of strain-induced vesicular exocytosis from a single cell for the first time. We found that mechanical strain could cause calcium influx via the activation of Piezo1 channels in chromaffin cell, initiating the vesicular exocytosis process. Interestingly, mechanical strain increases the amount of catecholamines released by accelerating the opening and prolonging the closing of fusion pore during exocytosis. This work is expected to provide revealing insights into the regulatory effects of mechanical stimuli on vesicular exocytosis.

Rapid Identification of Constituents in Cephalanthus tetrandrus (Roxb.) Ridsd. et Badh. F. Using UHPLC-Q-Exactive Orbitrap Mass Spectrometry.

Cephalanthus tetrandrus (Roxb.) Ridsd. et Badh. F. (CT) belongs to the Rubiaceae family. Its dried leaves are widely used in traditional Chinese medicine to treat enteritis, dysentery, toothache, furuncles, swelling, traumatic injury, fracture, bleeding, and scalding. In order to further clarify the unknown chemical composition of CT, a rapid strategy based on UHPLC-Q-exactive orbitrap was established for this analysis using a Thermo Scientific Hypersil GOLDTM aQ (100 mm × 2.1 mm, 1.9 µm) chromatographic column. The mobile phase was 0.1% formic acid water-acetonitrile, with a flow rate of 0.3 mL/min and injection volume of 2 µL; for mass spectrometry, an ESI ion source in positive and negative ion monitoring modes was adopted. A total of 135 chemicals comprising 67 chlorogenic acid derivatives, 48 flavonoids, and 20 anthocyanin derivatives were identified by comparing the mass spectrum information with standard substances, public databases, and the literature, which were all discovered for the first time in this plant. This result broadly expands the chemical composition of CT, which will contribute to understanding of its effectiveness and enable quality control.

(-)-Epigallocatechin gallate as an inhibitor of hemoglobin-catalyzed lipid oxidation: molecular mechanism of action and nutritional application.

Hemoglobin (Hb) is effective inducer for lipid oxidation and protein-polyphenol interaction is a well-known phenomenon. The effects of the interaction of (-)-epigallocatechin gallate (EGCG) with Hb on lipid oxidation were rarely elucidated. The detailed interaction between bovine Hb and EGCG was systematically explored by experimental and theoretical approaches, to illustrate the molecular mechanisms by which EGCG influenced the redox states and stability of Hb. EGCG would bind to the central pocket of protein with one binding site to form Hb-EGCG complex. The binding constant for Hb-EGCG complex was 0.34 × 104 M-1 at 277 K, and thermodynamic parameters (ΔH > 0, ΔS > 0 and ΔG < 0) revealed the participation of hydrophobic forces in the binding process. The binding of EGCG would increase the compactness of protein molecule and diminish the crevice near the heme cavity, which was responsible for the reduction of met-Hb to oxy-Hb and inhibition of hemin release from met-Hb. Moreover, EGCG efficiently suppressed Hb-caused lipid oxidation in liposomes and cod muscles, which was possibly attributed to the reduction to oxy-Hb state and declined hemin dissociation from met-Hb. Altogether, our results provide significant insights into the binding of EGCG to redox-active Hb, which represents a novel mechanism for the anti-oxidant capacity of EGCG in human health and is favorable to the applications of natural EGCG in the good quality of Hb-containing products.

Curbing Exosome Communications via Introducing Artificial Membrane Receptors for Metastatic Pancreatic Cancer Therapy.

Tumor-derived exosomes (TDEs) carry various biomolecular cargos and play crucial roles in metastasis. TDEs migrate to distal organs for intercellular communication and induce the formation of pre-metastatic niches (PMNs) to support tumor implantation and proliferation. Precise interference in the bioprocess of TDEs is expected to be efficacious for suppressing tumor metastasis. However, targeting both TDEs and the primary tumor is challenging. Here, based on metabolic glycoengineering and bio-orthogonal click chemistry, a two-step delivery strategy is designed to overcome this. During the first step, the tetraacetylated N-azidoacetyl-d-mannosamine-loaded nanoparticle responds to the metabolic activity of tumor cells in the primary tumor, tagging both tumor cells and TDEs with azide groups; dibenzyl-cyclootyne-modified nanoparticles then can, as the second step, specifically react with tumor cells and TDEs through a bio-orthogonal click reaction. This strategy not only inhibits tumor growth in pancreatic cancer models but also curbs the communicative role of TDEs in inducing liver PMNs and metastasis by tracking and downregulating the exosomal macrophage migration inhibitory factor.

Sequential thermal ablation in combination with sclerotherapy using lauromacrogol as a successful translative therapy for an unresectable huge biliary cystadenocarcinoma: The first experience assisted by contrast-enhanced ultrasound.

Biliary cystadenocarcinoma (BCAC) is an extremely rare intrahepatic cystic tumor. Patients usually present with nonspecific symptoms such as abdominal pain, abdominal distention, and abdominal mass. This tumor occurs most commonly in the left hemiliver and is thought to mainly develop from a benign biliary cystadenoma (BCA). At present, the disease is mainly diagnosed by ultrasound, CT, MR, and other imaging methods, and the main treatment is radical surgical resection. We reported a 75-year-old female with an unresectable huge BCAC (i.e., 161×145×122 mm in three orthogonal directions) and poor general condition (40 in Karnofsky Performance Status, KPS) who received sequential thermal ablation (i.e., cryoablation and microwave ablation) in combination with sclerotherapy using lauromacrogol. The diagnosis of intrahepatic BCAC was confirmed pathologically. Preablation grayscale US showed the BCAC with a clear boundary, regular shape, and cystic-solid mixed echogenicity, which appeared as a huge multilocular cystic lesions with thick internal sepatations. Preablation contrast-enhanced ultrasound (CEUS) showed honeycomb-like hyper-enhancement of the thick internal sepatations and cystic wall in the arterial and portal phase, and sustained enhancement of the thick internal sepatations and cystic wall in the late phase. 6-month postablation CEUS showed non-enhancement in most parts of the lesion in the arterial phase and 6-month postablation MRI showed the volume reduction ratio (VRR) was about 70%. The abdominal pain and abdominal distension were relieved remarkably, and her quality of life was greatly improved (70 in KPS). In conclusion, sequential thermal ablation in combination with sclerotherapy provides a successful translative therapy for this unresectable huge BCAC with a poor general condition, which makes subsequent curative surgery or ablation possible.

The Prevalence of Erosive Tooth Wear and Related Risk Factors in 6- to 12-Year-Old Students.

PURPOSE: To evaluate the epidemiological characteristics of erosive tooth wear in primary school students aged 6-12 in Jinzhou, including: prevalence, severity, extent, intraoral distribution and associated risk factors. MATERIALS AND METHODS: The data collection consists of two parts: the first part is the clinical examination of the participants. All erupted teeth were clinically assessed by three calibrated examiners, and classified according to the basic erosive wear examination (BEWE); The second part is a questionnaire about demographic information, parafunctional movement and lifestyle, completed by the parents or their guardians. RESULTS: A total of 1,469 children were included in this experiment; erosive tooth wear (ETW) prevalence (BEWE ≥ 1) was 54.9%. According to cumulative BEWE index, the proportion of different ETW severity (high, medium, low, none) was 6.8%, 16.3%, 27.0% and 49.9%, respectively. In an analysis of risk factors, family factor, age, gender, extracurricular study time, oral hygiene habit, bruxism, unilateral mastication and acid diet was associated with the prevalence of ETW. CONCLUSIONS: This study shows that ETW has a high prevalence in students aged 6-12, and more common in deciduous molars and deciduous canine. Abrasion, attrition and erosion play an important role in ETW.

Contrast-enhanced ultrasound evaluation of a refractory ovarian endometrial cyst and ultrasound-guided aspiration sclerotherapy using urokinase and lauromacrogol.

Endometriosis is one of the most common diseases that happen in reproductive women. The main symptoms include ovarian endometrial cyst, pelvic pain, and so on. We report a case of a 23-year-old woman with a refractory long-course ovarian endometrial cyst (OEC). The patient was previously identified to have a hypoechoic mass sized 9.7 cm in diameter on ultrasound (US) in the right ovary and was tentatively diagnosed as OEC in another tertiary hospital, who was then subjected to US-guided cyst sclerotherapy while the procedure was failed since only a very small amount of viscous and sticky fluid can be aspirated. The patient was then referred to our hospital for further treatment. Pretreat contrast-enhanced ultrasound (CEUS) showed non-enhancement of the mass with a thin cyst wall and a cyst-in-cyst pattern was observed. The possibility of ovarian malignancy was ruled out and the initial diagnosis of OEC was confirmed. The patient was then subjected to US-guided cyst sclerotherapy with lauromacrogol. The interventional procedure was eventful that no fluid was aspirated as what happened in the previous hospital. Thus urokinase was used to dissolve the old, viscious and sticky blood and finally, all the fluid was aspirated. The total consumption of urokinase was 60,000 U. Then lauromacrogol as a sclerosant was injected into the cyst cavity and the cyst wall was flushed repeatedly with lauromacrogol until the aspirated fluid became light red. Finally, 20 mL lauromacrogol was reserved in the cyst and the interventional procedure cost 2 hours. The post-procedure course was uneventful without any discomfort, and the volume reduction rate of the cyst was 54%at 3-month follow-up. The visual analogue scale for the pain decreased from 4 before treatment to 1 after treatment, indicating a successful and effective outcome for the refractory long-course OEC.