Penetrating the ultra-tough yeast cell wall with finite element analysis model-aided design of microtools.

Microinjecting yeast cells has been challenging for decades with no significant breakthrough due to the ultra-tough cell wall and low stiffness of the traditional injector tip at the micro-scale. Penetrating this protection wall is the key step for artificially bringing foreign substance into the yeast. In this paper, a yeast cell model was built by using finite element analysis (FEA) method to analyze the penetrating process. The key parameters of the yeast cell wall in the model (the Young's modulus, the shear modulus, and the Lame constant) were calibrated according to a general nanoindentation experiment. Then by employing the calibrated model, the injection parameters were optimized to minimize the cell damage (the maximum cell deformation at the critical stress of the cell wall). Key guidelines were suggested for penetrating the cell wall during microinjection.

An electromechanical stimulation regulating model with flexoelectric effect of piezoelectric laminated micro-beam for cell bionic culture.

Cell bionic culture requires the construction of cell growth microenvironments. In this paper, mechanical force and electrical stimulations are applied to the cells cultured on the surface of the piezoelectric laminated micro-beam driven by an excitation voltage. Based on the extended dielectric theory, the electromechanical microenvironment regulating model of the current piezoelectric laminated micro-beam is established. The variational principle is used to obtain the governing equations and boundary conditions. The differential quadrature method and the iterative method are used to solve two boundary value problems for cantilever beams and simply supported beams. In two cases, the mechanical force and electrical stimulations applied to the cells are analyzed in detail and the microscale effect is investigated. This study is meaningful for improving the quality of cell culture and promoting the cross-integration of mechanics and biomedicine.

Gut-on-a-chip for exploring the transport mechanism of Hg(II).

Animal models and static cultures of intestinal epithelial cells are commonly used platforms for exploring mercury ion (Hg(II)) transport. However, they cannot reliably simulate the human intestinal microenvironment and monitor cellular physiology in situ; thus, the mechanism of Hg(II) transport in the human intestine is still unclear. Here, a gut-on-a-chip integrated with transepithelial electrical resistance (TEER) sensors and electrochemical sensors is proposed for dynamically simulating the formation of the physical intestinal barrier and monitoring the transport and absorption of Hg(II) in situ. The cellular microenvironment was recreated by applying fluid shear stress (0.02 dyne/cm2) and cyclic mechanical strain (1%, 0.15 Hz). Hg(II) absorption and physical damage to cells were simultaneously monitored by electrochemical and TEER sensors when intestinal epithelial cells were exposed to different concentrations of Hg(II) mixed in culture medium. Hg(II) absorption increased by 23.59% when tensile strain increased from 1% to 5%, and the corresponding expression of Piezo1 and DMT1 on the cell surface was upregulated.

Microstructural evolution and mechanical properties of TiB2/2195 composites fabricated by ultrasonic-assisted in-situ casting.

The distribution and size of particles in particle-reinforced aluminum matrix composites are crucial to the mechanical properties of the composites. In this paper, 2 wt.% TiB2/2195 composites were prepared by ultrasonic-assisted in-situ casting technology, and the samples' phase composition, microstructure, and mechanical properties were tested. The results showed that: compared with the remelted matrix, the stomatal defects in the composites disappeared, and the grains were refined, but the second phase structure and TiB2 particles agglomerated significantly when no ultrasonic treatment (UT) was applied. The UT made the grains further refined, the area fraction of the coarse second phase network decreased, the concentrations of Ti and Cu elements in the grains increased, and more TiB2 particles entered the grains. At the same time, the formation of TiB2 particles and UT increased the dislocation density in the composites and promoted the precipitation of the T1 phase. With UT for 180 s, the TiB2 particles were evenly distributed, and the size was the smallest. The tensile strength, yield strength, and elongation were increased by 115.4 %, 49.8 %, and 342.9 %, respectively, compared to the remelted matrix, and by 30.9 %, 21.8 %, and 67.2 %, respectively, compared to the composite without UT. The mechanism of the synergistic effect of UT and TiB2 to enhance the mechanical properties of composites was also discussed.

Impact of vanillin on postharvest disease control of apple.

Apple fruits are susceptible to infection by postharvest fungal pathogens, which may cause fruit decay and severe economic losses. This study investigated the antifungal spectrum of vanillin against common decay pathogens of apple and explored the antifungal mechanisms of vanillin in vitro. In vivo experiments were carried out to evaluate the effects of vanillin on apple postharvest disease control and fruit quality. Moreover, the induced resistance mechanism of vanillin on apple fruit was preliminarily explored. The results showed that vanillin has broad-spectrum antifungal effects, especially on Alternaria alternata. Vanillin could significantly inhibit the growth rate, mycelium biomass, and spore germination of pathogenic fungi by increasing the cell membrane permeability and lipid peroxidation. Importantly, vanillin treatment reduced the incidence of apple decay caused by A. alternata and Penicillium expansum, and contributed to improve fruit quality. Further studies indicated that vanillin could induce elevation in the activities of defense-related enzymes in apple fruit, such as phenylalanine ammonia-lyase (PAL), chitinase (CHI) and ß-1,3-glucanase (ß-1,3-GA), and increase total phenols and flavonoids contents. Generally, these results suggest that vanillin may contribute to the induced resistance of apple fruits to pathogenic fungi. To conclude, the results of this research provide theoretical foundations for the application of vanillin in the control of apple postharvest decay caused by fungal pathogens.

QiShenYiQi Pill Ameliorates Cardiac Fibrosis After Pressure Overload-Induced Cardiac Hypertrophy by Regulating FHL2 and the Macrophage RP S19/TGF-ß1 Signaling Pathway.

Purpose: Heart failure (HF) is a leading cause of morbidity and mortality worldwide, and it is characterized by cardiac hypertrophy and fibrosis. However, effective treatments are not available to block cardiac fibrosis after cardiac hypertrophy. The QiShenYiQi pill (QSYQ) is an effective treatment for chronic HF. However, the underlying mechanism remains unclear. Methods: In the present study, a pressure overload-induced cardiac hypertrophy model was established in rats by inducing ascending aortic stenosis for 4 weeks. QSYQ was administered for 6 weeks, and its effects on cardiac fibrosis, myocardial apoptosis, RP S19 release, macrophage polarization, TGF-ß1 production, and TGF-ß1/Smad signaling were analyzed. In vitro studies using H9C2, Raw264.7, and RDF cell models were performed to confirm the in vivo study findings and evaluate the contribution to the observed effects of the main ingredients of QSYQ, namely, astragaloside IV, notoginsenoside R1, 3,4-dihydroxyl-phenyl lactic acid, and Dalbergia odorifera T. C. Chen oil. The role of four-and-a-half LIM domains protein 2 (FHL2) in cardiac fibrosis and QSYQ's effects were assessed by small interfering RNAs (siRNAs). Results: QSYQ ameliorated cardiac fibrosis after pressure overload-induced cardiac hypertrophy and attenuated cardiomyocyte apoptosis, low FHL2 expression, and TGF-ß1 release by the injured myocardium. QSYQ also inhibited the following: release of RP S19 from the injured myocardium, activation of C5a receptors in monocytes, polarization of macrophages, and release of TGF-ß1. Moreover, QSYQ downregulated TGF-ßR-II expression induced by TGF-ß1 in fibroblasts and inhibited Smad protein activation and collagen release and deposition. Conclusion: The results showed that QSYQ inhibited myocardial fibrosis after pressure overload, which was mediated by RP S19-TGF-ß1 signaling and decreased FHL2, thus providing support for QSYQ as a promising therapy for blocking myocardial fibrosis.

Crack Sensing of Cardiomyocyte Contractility with High Sensitivity and Stability.

Measuring myocardial contractility is of great value in exploring cardiac pathogenesis and quantifying drug efficacy. Among the biosensing platforms developed for detecting the weak contractility of a single layer of cardiomyocytes (CMs), thin brittle metal membrane sensors with microcracks are highly sensitive. However, their poor stability limits the application in long-term measurement. Here, we report a high stability crack sensor fabricated by deposition of a 105 nm thick Ag/Cr with microcracks onto a carbon nanotubes-polydimethylsiloxane (CNT-PDMS) layer. This brittle-tough bilayer crack sensor achieved high sensitivity (gauge factor: 108 241.7), a wide working range (0.01-44%), and high stability (stable period >2 000 000 cycles under the strain caused by a monolayer of CMs). During 14-day continuously monitoring CMs culturing and drug treatment testings, the device demonstrated high sensitivity and stability to record the dynamic change caused by contractility of the CMs.

Green Manufacturing of Flexible Sensors with a Giant Gauge Factor: Bridging Effect of CNT and Electric Field Enhancement at the Percolation Threshold.

Toxic organic solvents are commonly used to disperse nanomaterials in the manufacturing of flexible conductive composites (e.g., graphene-PDMS). The dry-blended method avoids toxic organic solvent usage but leads to poor performance. Here, we proposed an innovative manufacturing method by adapting the traditional dry-blended method, including two key steps: minor CNT bridging and high-frequency electric field enhancement at the percolation threshold of graphene-PDMS. Significant improvement was achieved in the electrical conductivity (1528 times), the giant gauge factor (>8767.54), and the piezoresistive strain range (30 times) over the traditional dry-blended method. Further applications in measurements of culturing rat neonatal cardiomyocytes and mouse hearts proved that the proposed method has great potential for the manufacturing of nontoxic flexible sensors.

Electrochemical strategies for the detection of cTnI.

Acute myocardial infarction (AMI) is the main cause of death from cardiovascular diseases. Thus, early diagnosis of AMI is essential for the treatment of irreversible damage from myocardial infarction. Traditional electrocardiograms (ECG) cannot meet the specific detection of AMI. Cardiac troponin I (cTnI) is the main biomarker for the diagnosis of myocardial infarction, and the detection of cTnI content has become particularly important. In this review, we introduced and compared the advantages and disadvantages of various cTnI detection methods. We focused on the analysis and comparison of the main indicators and limitations of various cTnI biosensors, including the detection range, detection limit, specificity, repeatability, and stability. In particular, we pay more attention to the application and development of electrochemical biosensors in the diagnosis of cardiovascular diseases based on different biological components. The application of electrochemical microfluidic chips for cTnI was also briefly introduced in this review. Finally, this review also briefly discusses the unresolved challenges of electrochemical detection and the expectations for improvement in the detection of cTnI biosensing in the future.

Advances in reconstructing intestinal functionalities in vitro: From two/three dimensional-cell culture platforms to human intestine-on-a-chip.

Standard two/three dimensional (2D/3D)-cell culture platforms have facilitated the understanding of the communications between various cell types and their microenvironments. However, they are still limited in recapitulating the complex functionalities in vivo, such as tissue formation, tissue-tissue interface, and mechanical/biochemical microenvironments of tissues and organs. Intestine-on-a-chip platforms offer a new way to mimic intestinal behaviors and functionalities by constructing in vitro intestinal models in microfluidic devices. This review summarizes the advances and limitations of the state-of-the-art 2D/3D-cell culture platforms, animal models, intestine chips, and the combined multi-organ chips related with intestines. Their applications to studying intestinal functions, drug testing, and disease modeling are introduced. Different intestinal cell sources are compared in terms of gene expression abilities and the recapitulated intestinal morphologies. Among these cells, cells isolated form human intestinal tissues and derived from pluripotent stem cells appear to be more suitable for in vitro reconstruction of intestinal organs. Key challenges of current intestine-on-a-chip platforms and future directions are also discussed.

A CNT-PDMS wearable device for simultaneous measurement of wrist pulse pressure and cardiac electrical activity.

Simultaneous measurement of multi-physiological signals can provide effective diagnosis and therapeutic assessment of diseases. This paper reports a carbon nanotube (CNT) - Polydimethylsiloxane (PDMS) - based wearable device with piezo-resistive and voltage-sensing capabilities for simultaneously capturing wrist pulse pressure and cardiac electrical signal. The layout design of sensing elements in the device was guided by analyzing strain distribution and electric field distribution for minimizing the interference between wrist pulse and cardiac electric activity during measurement. Each device was preconditioned under the strain of 20% until the resistance change of the device reached equilibrium. After preconditioning, the relationship between the resistance change and the pressure was calibrated, which determined the device sensitivity to be 0.01 Pa-1 and the linear pressure range of the device to be 0.4 kPa to 14.0 kPa. Mechanisms of CNT-PDMS for sensing strain signal and electrical pulse signal were explored by scanning electron microscopy (SEM) imaging and equivalent circuit modeling. The device was applied to monitor the wrist pulse and ECG signals of volunteers during the recovering process after physical exercises.

Optimized CNT-PDMS Flexible Composite for Attachable Health-Care Device.

The CNT-PDMS composite has been widely adopted in flexible devices due to its high elasticity, piezoresistivity, and biocompatibility. In a wide range of applications, CNT-PDMS composite sensors were used for resistive strain measurement. Accordingly, the percolation threshold 2%~4% of the CNT weight ratio in the CNT-PDMS composite was commonly selected, which is expected to achieve the optimized piezoresistive sensitivity. However, the linear range around the percolation threshold weight ratio (2%~4%) limits its application in a stable output of large strain (>20%). Therefore, comprehensive understanding of the electromechanical, mechanical, and electrical properties for the CNT-PDMS composite with different CNT weight ratios was expected. In this paper, a systematic study was conducted on the piezoresistivity, Young's modulus, conductivity, impedance, and the cross-section morphology of different CNT weight ratios (1 to 10 wt%) of the CNT-PDMS composite material. It was experimentally observed that the piezo-resistive sensitivity of CNT-PDMS negatively correlated with the increase in the CNT weight ratio. However, the electrical conductivity, Young's modulus, tensile strength, and the linear range of piezoresistive response of the CNT-PDMS composite positively correlated with the increase in CNT weight ratio. Furthermore, the mechanism of these phenomena was analyzed through the cross-section morphology of the CNT-PDMS composite material by using SEM imaging. From this analysis, a guideline was proposed for large strain (40%) measurement applications (e.g., motion monitoring of the human body of the finger, arm, foot, etc.), the CNT weight ratio 8 wt% was suggested to achieve the best piezoresistive sensitivity in the linear range.

Evaluation of Helicobacter pylori eradication and drug therapy in patients with functional dyspepsia.

The aim of this study was to assess the effect of Helicobactor pylori (H. pylori) infection and drug therapy on functional dyspepsia (FD) symptoms and gastrointestinal eosinophil count. In this study, 215 continuous FD patients fulfilling Rome III criteria were enrolled. The patients were divided into a H. pylori-positive group and a H. pylori-negative group. The H. pylori-positive group was divided into H. pylori-eradicated and H. pylori-uneradicated groups following H. pylori-eradication treatment, and the H. pylori-negative group was randomly divided into esomeprazole and teprenone treatment groups. The symptom scores of the esomeprazole group were significantly lower compared with those of the teprenone group at week 6 but not at baseline and week 2. Compared with the H. pylori-uneradicated group, eosinophil counts in the antrum and body were significantly reduced in the H. pylori-eradicated group at week 6. The number of gastric eosinophil clusters was significantly higher in the H. pylori-positive group than in the H. pylori-negative group. Eradication was associated with gastric eosinophil counts but did not affect duodenal eosinophil levels. Neither esomeprazole nor teprenone treatments reduced eosinophil levels in the stomach and duodenum of H. pylori-negative patients.