Automated and ultrasensitive point-of-care glycoprotein detection using boronate-affinity enhanced organic electrochemical transistor patch.

Quantifying trace glycoproteins in biofluids requires ultrasensitive components, but feedback is not available in the current portable platforms of point-of-care (POC) diagnosis technologies. A compact and ultrasensitive bioelectrochemical patch was based on boronate-affinity amplified organic electrochemical transistors (BAAOECTs) for POC use was developed to overcome this dilemma. Benefit from the cascading signal enhancement deriving from boronate-affinity targeting multiple regions of glycoprotein and OECTs' inherent signal amplification capability, the BAAOECTs achieved a detection limit of 300 aM within 25 min, displaying about 3 orders of magnitude improvement in sensitivity compared with the commercial electrochemical luminescence (ECL) kit. By using a microfluidic chip, a microcontroller module, and a wireless sensing system, the testing workflows of the above patch was automated, allowing for running the sample-to-answer pipeline even in a resource-limited environment. The reliability of such portable biosensing platform is well recognized in clinical diagnostic applications of heart failure. Overall, the remarkable enhanced sensitivity and automated workflow of BAAOECTs biosensing platform provide a prospective and generalized design policy for expanding the POC diagnosis capabilities of glycoproteins.

Injectable Mesh-Like Conductive Hydrogel Patch for Elimination of Atrial Fibrillation.

Irregular electrical impulses in atrium are the leading cause of atrial fibrillation (AF), resulting in fatal arrhythmia and sudden cardiac death. Traditional medication and physical therapies are widely used, but generally suffer problems in serious physical damage and high surgical risks. Flexible and soft implants have great potential to be a novel approach for heart diseases therapy. A conductive hydrogel-based mesh cardiac patch is developed for application in AF elimination. The designed mesh patch with rhombic-shaped structure exhibits excellent flexibility, surface conformability, and deformation compliance, making it fit well with heart surface and accommodate to the deformation during heart beating. Moreover, the mechanical elastic and shape-memory properties of the mesh patch enable a minimally invasive injection of the patch into living animals. The mesh patch is implanted on the atrium surface for one month, indicating good biocompatibility and stability. Furthermore, the conductive patch can effectively eliminate AF owing to the conductivity and high charge storage capability (CSC) of the hydrogel. The proposed scheme of cardiac bioelectric signal modulation using conductive hydrogel brings new possibility for the treatment of arrhythmia diseases.

Black Phosphorus Flake-Enabled Wireless Neuromodulation for Epilepsy Treatment.

Epilepsy is a prevalent and severe neurological disorder and generally requires prolonged electrode implantation and tether brain stimulation in refractory cases. However, implants may cause potential chronic immune inflammation and permanent tissue damage due to material property mismatches with soft brain tissue. Here, we demonstrated a nanomaterial-enabled near-infrared (NIR) neuromodulation approach to provide nongenetic and nonimplantable therapeutic benefits in epilepsy mouse models. Our study showed that crystal-exfoliated photothermal black phosphorus (BP) flakes could enhance neural activity by altering the membrane capacitive currents in hippocampus neurons through NIR photothermal neuromodulation. Optical stimulation facilitated by BP flakes in hippocampal slices evoked action potentials with a high spatiotemporal resolution. Furthermore, BP flake-enabled NIR neuromodulation of hippocampus neural circuits can suppress epileptic signals in epilepsy model mice with minimal invasiveness and high biocompatibility. Consequently, nanomaterial-enabled NIR neuromodulation may open up opportunities for nonimplantable optical therapy of epilepsy in nontransgenic organisms.

Wearable bioelectronic masks for wireless detection of respiratory infectious diseases by gaseous media.

Respiratory infectious diseases (H1N1, H5N1, COVID-19, etc.) are pandemics that can continually spread in the air through micro-droplets or aerosols. However, the detection of samples in gaseous media is hampered by the requirement for trace amounts and low concentrations. Here, we develop a wearable bioelectronic mask device integrated with ion-gated transistors. Based on the sensitive gating effect of ion gels, our aptamer-functionalized transistors can measure trace-level liquid samples (0.3 µL) and even gaseous media samples at an ultra-low concentration (0.1 fg/mL). The ion-gated transistor with multi-channel analysis can respond to multiple targets simultaneously within as fast as 10 min, especially without sample pretreatment. Integrating a wireless internet of things system enables the wearable mask to achieve real-time and on-site detection of the surrounding air, providing an alert before infection. The wearable bioelectronic masks hold promise to serve as an early warning system to prevent outbreaks of respiratory infectious diseases.

Multi-channel AgNWs-doped interdigitated organic electrochemical transistors enable sputum-based device towards noninvasive and portable diagnosis of lung cancer.

Biochemical monitoring of bodily fluidics such as sweat, urine, and tears have been extensively developed, but reliable biochemical analysis of sputum biospecimens remains limited and challenging due to the low abundance of biomarkers in intrinsically viscous sputum. We reported a portable multi-channel sputum-based interdigitated organic electrochemical transistors (SiOECTs) device for noninvasive sputum diagnosis. We tailored the AgNWs-doped organic electrochemical transistors, integrating with multiplexed aptamer-antigen assays, to realize the signal amplification and simultaneous detection of biomarkers in raw sputum biospecimens from lung cancer patients. Clinical validation studies demonstrated favorable correlation coefficients between the sputum and serum biospecimens. By utilizing our portable multi-channel iOECTs devices, lung cancer patients were differentiated from health control with an optimum area under the curve (AUC) of 0.931, sensitivity of 87.0%, and specificity of 86.5%. Our miniaturized and portable device could even realize the continuous in-home tracking of the biomarkers change for lung cancer patients after radiotherapy/chemotherapy. It is envisaged that the SiOECTs will shed light on noninvasive diagnostics platforms for sputum-related diseases.

High-performance field-effect transistor glucose biosensors based on bimetallic Ni/Cu metal-organic frameworks.

Accurate detection of glucose is essential for the diagnosis of diabetes, wherein effective and sensitive biosensors for glucose detection are needed. Here, we fabricated a glucose sensor based on field-effect transistor (FET) with bimetallic nickel-copper metal-organic frameworks (Ni/Cu-MOFs) as its channel layers which were grown in-situ through a simple one-step hydrothermal method and modified with glucose oxidase (GOD) by using glutaraldehyde (GA) as linkers. Due to the synergistic effect of Ni ions and Cu ions in MOFs, the sensor (GOD-GA-Ni/Cu-MOFs-FET) showed good field effect performance and great responses to glucose through enzymatic reactions. It displayed a piecewise linear relationship in the wide range (1 µM-20 mM), and provided high sensitivity (26.05 µAcm-2mM-1) in the low concentration (1-100 µM) and a low detection limit (0.51 µM). The sensor also had these advantages of high specificity, excellent reproducibility, good short-term stability and fast response time. Especially, it is indicated that the Ni/Cu-MOFs-FETs with high performance have the potential to be available sensors, paving the way for the application of bimetallic MOFs in biosensing.

Anti-Cancer Effects of 3, 3'-Diindolylmethane on Human Hepatocellular Carcinoma Cells Is Enhanced by Calcium Ionophore: The Role of Cytosolic Ca2+ and p38 MAPK.

Purpose: 3,3'-Diindolylmethane (DIM), derived from indole-3-carbinol (I3C) in the Brassica species of cruciferous vegetables, has anticancer effects, but its exact underlying mechanism of action is unknown. We explored the roles of cytosolic free calcium ([Ca2+]i) and p38 MAPK in the anti-cancer effects of DIM in human hepatocellular carcinoma cells. Methods: Cell proliferation was measured with a Cell Counting Kit-8 (CCK-8) and the clonogenic formation assay. Cell apoptosis was examined by flow cytometric analysis and Hoechst dye staining. Cleaved-caspase3, cleaved-PARP, Bax, total, and phosphorylated p38 MAPK were assayed by western blotting. [Ca2+]i was measured with Fluo-3/AM by fluorescence microscopy. A23187, a calcium ionophore, was used to increase [Ca2+]i levels. Results: DIM inhibited cell proliferation in both SMMC-7721 and HepG2 cells in a concentration- and time-dependent manner. DIM also enhanced phosphorylation of p38 MAPK (p-p38), which was attenuated by SB203580. The proliferation inhibition and apoptosis induction by DIM were also blunted. In addition, DIM increased [Ca2+]i in HCC cells, and this effect was inhibited by the calcium chelator, BAPTA-AM, resulting in reduced p-p38 MAPK activation and apoptosis in DIM-treated cells, though the proliferation inhibition by DIM was unchanged. However, the DIM-induced cell proliferation inhibition and apoptosis were significantly enhanced by A23187, a selective calcium ionophore, which was attributed to exaggerated p-p38 MAPK. Conclusions: The calcium ionophore enhanced DIM-induced anti-cancer effects in hepatocellular carcinoma cells, secondary to [Ca2+]i-dependent activation of p38 MAPK. Treatment with a combination of DIM and calcium ionophore may offer a new approach to enhance the chemotherapeutic efficacy in liver cancer.

Field-Effect Transistor Based on an in Situ Grown Metal-Organic Framework Film as a Liquid-Gated Sensing Device.

Ni3(HITP)2, a novel and promising two-dimensional metal-organic framework (MOF) material, has been utilized in the areas of catalysis, sensing, and supercapacitors. It is very suitable for preparing field-effect transistor (FET) devices due to its good conductivity, porous structure, as well as easy film formation. Nevertheless, there is a challenge to transfer membrane materials undamaged to the substrates. Here, we reported a simple approach to fabricate the Ni-MOF-based FET with an in situ grown Ni3(HITP)2 membrane as the channel material of the FET. With this method, we obtained a large-area, dense, and uniform film composed of thin sheets, and the thickness and density of the MOF film were tunable through changing the reaction time. The as-prepared Ni-MOF-FET had a good mobility of 45.4 cm2 V-1 s-1 and on/off current ratio of 2.29 × 103. Moreover, this FET served as a liquid-gated device for the first time with bipolar behavior and good response to the gluconic acid at the range from 10-6 to 10-3 g/mL, verifying the potential of the Ni-MOF-FET as biosensors.

Prognostic value of NM23 in patients with gastric cancer: A systematic review and meta-analysis.

AIM OF STUDY: NM23, as a possible biomarker of prognosis in malignant tumors, has generated remarkable interest in this critical period of the high morbidity and mortality of malignancies. Thus, we launched this meta-analysis to investigate the predictive value of NM23 expression in patients with gastric cancer. MATERIALS AND METHODS: We searched PubMed, Embase, and Web of Science for relevant articles. The pooled odds ratios (ORs) and corresponding 95% confidence interval (CI) were calculated to evaluate the prognostic value of NM23 expression in patients with gastric cancer and the association between NM23 expression and clinicopathological factors. We also performed subgroup analyses to find the source of heterogeneity. RESULTS: Exactly, 2674 patients were pooled from 19 available studies in total. The incorporative OR combined by 11 studies with overall survival (OS) showed no significance (OR = 0.90, 95% CI: 0.51-1.58, P = 0.71). Although we failed to find any significance in N status and tumor node metastasis (TNM) staging (P = 0.23 and P = 0.74, respectively), elevated NM23 expression was related to well tumor differentiation (OR = 0.62, 95% CI: 0.41-0.95, P = 0.03). However, in the subgroup analyses, we could not find any potential source of heterogeneity. CONCLUSION: The results showed that statistically significant association was found between NM23 expression and the tumor differentiation of patients with gastric cancer, but no significance was found in OS, N status, and TNM staging. More and further researches should be conducted to reveal the prognostic value of NM23.

Application of sEST+EPBD in patients with mild or moderate biliary pancreatitis / 中国内镜杂志

Objective To explore the clinical value of sEST+EPBD applied in patients with mild-to-moderate biliary pancreatitis. Methods We selected out 60 cases mild or moderate biliary pancreatitis from January, 2013 to December, 2015, and randomly divided these cases into control group, EST group and sEST + EPBD group. We compared serological indexes, postoperative inflammation index, concurrent operation, hospitalization and follow-up indicators of these three groups. Results The levels of serum amylase, CRP and PCT were no statistical significance in three groups (P > 0.05). Total lengths of hospital stay and recurrence of pancreatitis in EST groups and sEST + EPBD group were significantly shorter than in control group (P < 0.05), and the total cost of hospitalization in sEST + EPBD group was obviously lower than in control group (P < 0.05). The level of postoperative serum amylase in sEST + EPBD group was obviously higher than in EST group, and the total length of hospital stay, cost and operative complications in sEST+EPBD group was significantly lower than that in EST group (P < 0.05); However, within one year, recurrences of pancreatitis and rates of cholecystectomy were no significant differences in these two groups. Conclusion sEST+EPBD is an effective and safe treatment in mild or moderate biliary pancreatitis, and can reduce the length of hospital stay and cost, operative complications, and assist the implementation of interval laparoscopic cholecystectomy.

Modified Sequential Therapy Regimen versus Conventional Triple Therapy for Helicobacter Pylori Eradication in Duodenal Ulcer Patients in China: A Multicenter Clinical Comparative Study.

Objective. Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. To observe the effect of eradicating Helicobacter pylori (H. pylori) and the treatment of duodenal ulcer by 2 kinds of modified sequential therapy through comparing with that of 10-day standard triple therapy. Methods. A total of 210 patients who were confirmed in duodenal ulcer active or heal period by gastroscopy and H. pylori positive confirmed by rapid urease test, serum anti-H. pylori antibody (ELASE), or histological examination enrolled in the study. All the patients were randomly divided into three groups: group A (70 cases) and group B (70 cases) were provided 10-day modified sequential therapy; group C (70 cases) was provided 10-day standard triple therapy. Patients of group A received 20 mg of Esomeprazole, 500 mg of Clarithromycin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group B received 20 mg of Esomeprazole, 1000 mg of Amoxicillin for the first 5 days, followed by 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for the remaining 5 days. Group C received 20 mg of Esomeprazole, 500 mg of Clarithromycin, and 1000 mg of Amoxicillin for standard 10-day therapy. All drugs were given twice daily. H. pylori eradication rate was checked four to eight weeks after taking the medicine by using a (13)C urea breath test. In the first, second, third, seventh, twenty-first, thirty-fifth days respectively, the symptoms of patients such as epigastric gnawing, burning pain, and acidity were evaluated simultaneously. Results. Overall, 210 patients accomplished all therapy schemes, 9 case patients were excluded. The examination result indicated that the H. pylori eradication rate of each group was as follows: group A 92.5% (62/67), group B 86.8% (59/68), and group C 78.8% (52/66). The H. pylori eradication rate of group A was slightly higher than group B (P < 0.05) and both of them were obviously higher than group C (P < 0.05). Modified sequential therapy was significantly more effective in patients with clarithromycin-resistant strains (80%/67% versus 31%; P = 0.02). Symptoms improvement: all the three groups could improve the symptoms such as epigastric gnawing, burning pain, and acidity since the first day. There was no significant difference in total score descending of symptoms between each group (P > 0.05). Conclusions. All the three therapy schemes could alleviate symptoms of duodenal ulcer patients in China efficiently. But as far as eradicating H. pylori is concerned, the modified sequential therapy was better than standard triple therapy, especially the therapy scheme used in group A.

Inhibitory effects of Broccolini leaf flavonoids on human cancer cells.

Broccolini (Brassica oleracea Italica × Alboglabra) is a hybrid between broccoli and Gai Lan, also known as Chinese broccoli and Chinese kale. The aim of this study was to assess the antitumor activity of Broccolini leaf flavonoids (BLF). Cell growth inhibition was evaluated using a standard colorimetric MTT assay, cellular morphology was observed using phase contrast microscopy and flow cytometry was introduced to further investigate cells apoptosis effect. The results showed that BLF possess a dose-dependent antiproliferative effects on four human cancer cell lines (SW480, HepG2, Hela, and A549) and apoptosis induction activity on SW480 cell line. Thus, the hybrid species Broccolini could be considered as a functional vegetable with potential in assisting for the treatment of four human cancers examined here.

Volatile components of ethanolic extract from broccolini leaves.

Broccolini (Brassica oleracea Italica × Alboglabra) is a hybrid of broccoli and kai-lan, Chinese broccoli. To date, no study has been reported on the chemical composition of the volatile fractions of this raw material. In this study, the volatile constituents from the ethanolic extract of broccolini leaves were analysed by gas chromatography-mass spectrometry (GC-MS). Sixteen compounds were identified. The major components include 5-phenyl-undecane (11%), n-hexadecanoic acid (9.34%), octadecanoic acid (6.39%), 1,1,3-trimethyl-3-phenyl-indan (4.0%), 3-(2-phenylethyl)benzonitrile (3.48%) and phytol (3.37%).