Study on the Flow Field Distribution in Microfluidic Cells for Surface Plasmon Resonance Array Detection.

This research is dedicated to optimizing the design of microfluidic cells to minimize mass transfer effects and ensure a uniform flow field distribution, which is essential for accurate SPR array detection. Employing finite element simulations, this study methodically explored the internal flow dynamics within various microfluidic cell designs to assess the impact of different contact angles on flow uniformity. The cells, constructed from Polydimethylsiloxane (PDMS), were subjected to micro-particle image velocimetry to measure flow velocities in targeted sections. The results demonstrate that a contact angle of 135° achieves the most uniform flow distribution, significantly enhancing the capability for high-throughput array detection. While the experimental results generally corroborated the simulations, minor deviations were observed, likely due to fabrication inaccuracies. The microfluidic cells, evaluated using a custom-built SPR system, showed consistent repeatability.

Experimental Study on SPR Array Sensing Chip Integrated with Microvalves.

This paper discusses a microfluidic system designed for surface plasmon resonance (SPR) sensing, incorporating integrated microvalves. This system is built from a layered structure of polydimethylsiloxane (PDMS) and polymethylmethacrylate (PMMA). The functionality of the microvalves is verified through a conductance method involving electrodes positioned at the microfluidic channels' inlets and outlets. These microvalves can fully close at a control pressure of 0.3 MPa, with their operation depending on the duration of the applied pressure. The study further explores the coordinated operation of multiple microvalves to regulate the sequential flow of samples and reagents in the system. In SPR detection experiments, the microfluidic system is integrated with an SPR array sensing system to control the injection of NaCl solutions via the microvalves, and the observation of phase change curves in different chip regions are observed. The findings validate the microvalves' dependability and suitability for use in SPR array sensing.

Discussions on Some Key Issues of Two-Dimensional Rotational Ultrasonic Combined Electro-Machining of Composite Materials.

In order to improve the surface forming quality and machining efficiency of composite materials and reduce tool wear, a two-dimensional rotary ultrasonic combined electro-machining (2DRUEM) technology with low electrical conductivity and low current density was proposed in this study. Additionally, a gap detection unit of the machining system was designed with the integration of grinding force and gap current, and the average errors and maximum errors of the model were 5.61% and 12.08%, respectively, which were better than single detection. Furthermore, the machining parameters were optimally selected via NSGA-II, and the maximum machining surface roughness error was 5.9%, the maximum material removal rate error was 5.5%, and the maximum edge accuracy error was 8.9%, as established through experiments.

Effect of Vibration Direction on Two-Dimensional Ultrasonic Assisted Grinding-Electrolysis-Discharge Generating Machining Mechanism of SiCp/Al.

This study proposes the mechanism of two-dimensional ultrasonic assisted grinding- electrolysis-discharge generating machining (2UG-E-DM). It analyzed the influence of vibration directions on grinding characteristics and surface morphology through the motion simulation of an abrasive. Comparative experiments with different vibration directions verified the effect of ultrasonic assistance on the weakening of the grinding force, the widening of the surface pits, and the leveling of the surface morphology of SiCp/Al composites. Simulation analysis of a single abrasive particle verified the test results. The results of machining tests at different amplitudes showed that as the workpiece and tool amplitude increased, the grinding force of the normal force decreased faster than that of the tangential force. The effect of surface electrolysis discharge machining was significant, and the number of exposed particles increased, but the residual height of the surface and the surface roughness were reduced by vibration grinding. When the two-dimensional amplitude was increased to 5 µm, the axial and tangential vibrations increased the grinding domain, and the dragging and rolling of the reinforced particles significantly reduced the surface roughness, which obtained good surface quality.

Experimental Study on Two-Dimensional Rotatory Ultrasonic Combined Electrochemical Generating Machining of Ceramic-Reinforced Metal Matrix Materials.

According to the machining characteristics of ceramic-particle-reinforced metal matrix composites, an experimental study on difficult-to-machine materials was carried out by two-dimensional (2D) rotatory ultrasonic combined electrolytic generating machining (RUCEGM), which organically combined an ultrasonic effect with a high-speed rotating tool electrode and electrolysis. After building the one-dimensional (1D) and 2D-RUCEGM systems, the factors influencing the combined machining process were analyzed and the experiments on RUCEGM were conducted to explore the feasibility and advantages of 2D-RUCEGM. The experimental results showed that, compared with 1D-RUCEGM, 2D-RUCEGM had higher accuracy, which increased about 21% and also reduced the machining time. Under certain conditions, the efficiency of 2D-RUCEGM was proportional to the voltage, and the machining efficiency could be enhanced by increasing the feed rate. The inter-electrode voltage detection module used in the experiment could improve the machining stability of the system.

Study on Generating Machining Performance of Two-Dimensional Ultrasonic Vibration-Composited Electrolysis/Electro-Discharge Technology for MMCs.

Ultrasonic vibration-composited electrolysis/electro-discharge machining technology (UE/DM) is effective for machining particulate-reinforced metal matrix composites (MMCs). However, the vibration of the tool or workpiece suitable for holes limits the application of UE/DM. To improve the generating machining efficiency and quality of flat and curved surfaces, in this study, we implemented two-dimensional ultrasonic vibration into UE/DM and constructed a novel method named two-dimensional ultrasonic vibration-composited electrolysis/electro-discharge machining (2UE/DM). The influence of vibration on the performance of 2UE/DM compared to other process technologies was studied, and an orthogonal experiment was designed to optimize the parameters. The results indicated that the materiel remove rate (MRR) mainly increased via voltage and tool vibration. The change current was responsible for the MRR in the process. Spindle speed and workpiece vibration were not dominant factors affecting the MRR; the spindle speed and tool and workpiece vibration, which reduced the height difference between a ridge and crater caused by abrasive grinding, were responsible for surface roughness (Ra) and form precision (δ). Additionally, the optimized parameters of 1000 rpm, 3 V, and 5 um were conducted on MMCs of 40 SiCp/Al and achieved the maximum MRR and minimum Ra and δ of 0.76 mm3/min, 3.35 um, and 5.84%, respectively. This study's findings provide valuable process parameters for improving machining efficiency and quality for MMCs of 2UE/DM.

Cardiac-specific deletion of FDPS induces cardiac remodeling and dysfunction by enhancing the activity of small GTP-binding proteins.

The mevalonate pathway is essential for cholesterol biosynthesis. Previous studies have suggested that the key enzyme in this pathway, farnesyl diphosphate synthase (FDPS), regulates the cardiovascular system. We used human samples and mice that were deficient in cardiac FDPS (c-Fdps-/- mice) to investigate the role of FDPS in cardiac homeostasis. Cardiac function was assessed using echocardiography. Left ventricles were examined and tested for histological and molecular markers of cardiac remodeling. Our results showed that FDPS levels were downregulated in samples from patients with cardiomyopathy. Furthermore, c-Fdps-/- mice exhibited cardiac remodeling and dysfunction. This dysfunction was associated with abnormal activation of Ras and Rheb, which may be due to the accumulation of geranyl pyrophosphate. Activation of Ras and Rheb stimulated downstream mTOR and ERK pathways. Moreover, administration of farnesyltransferase inhibitors attenuated cardiac remodeling and dysfunction in c-Fdps-/- mice. These results indicate that FDPS plays an important role in cardiac homeostasis. Deletion of FDPS stimulates the downstream mTOR and ERK signaling pathways, resulting in cardiac remodeling and dysfunction. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Shp2 regulates PM2.5-induced airway epithelial barrier dysfunction by modulating ERK1/2 signaling pathway.

The impact of fine particulate matter (PM2.5) on public health has received increasing attention. Through various biochemical mechanisms, PM2.5 alters the normal structure and function of the airway epithelium, causing epithelial barrier dysfunction. Src homology domain 2-containing protein tyrosine phosphatase 2 (Shp2) has been implicated in various respiratory diseases; however, its role in PM2.5-induced epithelial barrier dysfunction remains unclear. Herein, we assessed the regulatory effects of Shp2 on PM2.5-mediated epithelial barrier function and tight junction (TJ) protein expression in both mice and human pulmonary epithelial (16HBE) cells. We observed that Shp2 levels were upregulated and claudin-4 levels were downregulated after PM2.5 stimulation in vivo and in vitro. Mice were exposed to PM2.5 to induce acute lung injury, and disrupted epithelial barrier function, with decreased transepithelial electrical resistance (TER) and increased paracellular flux that was observed in 16HBE cells. In contrast, the selective inhibition or knockdown of Shp2 retained airway epithelial barrier function and reversed claudin-4 downregulation that triggered by PM2.5, and these effects may occur through the ERK1/2 MAPK signaling pathway. These data highlight an important role of Shp2 in PM2.5-induced airway epithelial barrier dysfunction and suggest a possible new course of therapy for PM2.5-induced respiratory diseases.

Correlation between single nucleotide polymorphisms in the 3 primer untranslated region of PTX3 and the risk of essential hypertension: A case-control study.

ABSTRACT: The aim of this study was to investigate the correlation between single-nucleotide polymorphisms (SNPs) in the 3 primer of untranslated region (3'UTR) of the Pentraxin 3 (PTX3) gene and the risk of essential hypertension (EHT).PTX3 genotypes, rs2614, rs111451363, and rs73158510 locus, were found in 260 patients with EHT and 260 healthy controls. Quantitative real-time polymerase chain reaction was used to detect plasma hsa-miR-4766-5p levels. Enzyme-linked immunosorbent assay was used to detect plasma PTX3 levels. The dual-luciferase reporter assay was used to identify the binding site of hsa-miR-4766-5p to the PTX3.PTX3 rs2614 locus T allele was a high risk factor for EHT (odds ratio [OR] = 2.76, 95% confidence interval [CI]: 1.86-4.09, P < .01). Sex and diabetes history affected the correlation between PTX3 gene rs2614 locus SNP and EHT risk. The CCG haplotype was a protective factor for EHT (OR = 0.40, 95% CI: 0.28-0.57, P < .01), whereas the TCG haplotype was a risk factor for EHT (OR = 2.35, 95% CI: 1.51-3.66, P < .01). The plasma PTX3 level of patients with EHT was significantly higher than that of the control group, and the difference was statistically significant (P < .01). The area under the curve for EHT diagnosis in plasma PTX3 levels was 0.62 (95% CI: 0.57-0.66, P < .01). The plasma hsa-miR-4766-5p level in patients with EHT was significantly lower than that in the control group (P < .01). The area under the curve for the diagnosis of EHT according to the plasma hsa-miR-4766-5p level was 0.88 (95% CI: 0.85-0.91, P < .01). Plasma PTX3 levels were significantly negatively correlated with hsa-miR-4766-5p levels in patients with EHT and the control group (r = -0.87, -0.85, P < .01, P < .01). The PTX3 gene rs2614 locus C allele was the target gene of hsa-miR-4766-5p.The PTX3 rs2614 locus SNP is significantly associated with EHT risk.

New perspective on the risk markers for left atrial thrombosis in patients with atrial fibrillation.

BACKGROUND: Anticoagulant therapy is one of the important aspects of atrial fibrillation (AF) management, which can effectively reduce the formation of left atrial thrombosis (LAT) and the occurrence of embolic events. The CHA2DS2-VASc score is a commonly used risk assessment tool for embolic events, and it has guiding significance for anticoagulant therapy. However, a large number of recent studies have clearly shown that some of the markers that are not included in the score affect the formation of LAT. OBJECTIVE: This single-center study probed for risk markers for LAT by analyzing the clinical features of patients who experienced AF. METHODS: We reviewed patients with AF who had undergone a transesophageal echocardiography exam over the past 6 years and used binary logistic regression analysis to identify risk markers other than CHA2DS2-VASc score. For the risk markers found, the propensity score matching (PSM) was used to further evaluate whether it was an independent risk marker for LAT. The newly discovered markers were added to the score, and receiver operating characteristic analysis was used to evaluate whether the ability of the model to predict LAT was improved. RESULTS: A total of 2246 patients were included in the study. In total, 838 of them were anticoagulated (314 with rivaroxaban, 57 with dabigatran, and 467 with warfarin) and 30 patients (1.33%) had LAT. Regression analysis revealed abnormal uric acid metabolism (abUA) and obesity were risk markers for LAT. Further PSM analysis found that abUA was an independent risk marker for LAT. After including abUA, the CHA2DS2-VASc score was more accurate for LAT prediction (area under the curve difference is 0.0651, 95% confidence interval: 0.0247, 0.1050, Z = 3.158, P = 0.0016). CONCLUSIONS: AbUA is an independent risk marker for LAT. After considering abUA, the CHA2DS2-VASc score for LAT is more accurate.

Central nervous system neuroepithelial tumors with MN1-alteration: an individual patient data meta-analysis of 73 cases.

MN1 alteration characterizes a recently described group of neuroepithelial tumors with varied morphological features. In cIMPACT-NOW update 6, only those with astroblastoma morphology has been accepted as a newly recognized tumor type, whereas the rest of morphological variants are considered lesions sub-judice. We perform an individual patient data meta-analysis of MN1-altered neuroepithelial tumors comprising a total of 73 cases, in order to study the survival data and predictive markers for better diagnosis and management of this rare molecular entity. The 5- and 10-year progression-free survival are 38% and 0%, whereas the 5- and 10-year overall survival are 89% and 55%, respectively. Among all the morphological variants of MN1-altered tumor, astroblastoma morphology is significantly associated with an improved overall survival, emphasizing the importance of providing an integrated histologic and molecular diagnosis. Histological grading within the molecularly-defined MN1-altered astroblastoma remains controversial. In tumors with astroblastoma morphology, the odds of MN1-altered status among patients less than 15-year-old is 10.5 times that of those 15-year-old and older, and female of 9.4 times that of the male gender. Gross tumor resection appears as main treatment modality for better disease control based on observational data.

A Gene Cluster for the Biosynthesis of Dibenzodioxocinons in the Endophyte Pestalotiopsis microspora, a Taxol Producer.

The fungal products dibenzodioxocinones promise a novel class of inhibitors against cholesterol ester transfer protein (CEPT). Knowledge as to their biosynthesis is scarce. In this report, we characterized four more dibenzodioxocinones, which along with a previously described member pestalotiollide B, delimit the dominant spectrum of secondary metabolites in P. microspora. Through mRNA-seq profiling in gα1Δ, a process that halts the production of the dibenzodioxocinones, a gene cluster harboring 21 genes including a polyketide synthase, designated as pks8, was defined. Disruption of genes in the cluster led to loss of the compounds, concluding the anticipated role in the biosynthesis of the chemicals. The biosynthetic route to dibenzodioxocinones was temporarily speculated. This study reveals the genetic basis underlying the biosynthesis of dibenzodioxocinone in fungi, and may facilitate the practice for yield improvement in the drug development arena.

Impact of LDB3 gene polymorphisms on clinical presentation and implantable cardioverter defibrillator (ICD) implantation in Chinese patients with idiopathic dilated cardiomyopathy.

OBJECTIVE: Mutations in LIM domain binding 3 (LDB3) gene cause idiopathic dilated cardiomyopathy (IDCM), a structural heart disease with a complicated genetic background. However, the association of polymorphisms in the LDB3 gene with susceptibility to IDCM in Chinese populations remains unexplored as dose the impact on clinical presentation. METHODS: We sequenced all exons and the adjacent part of introns of the LDB3 gene in 159 Chinese Han IDCM patients and 247 healthy controls. Then we detected the distribution of polymorphisms in the LDB3 gene in all participants and assessed their associations with risk of IDCM. Additionally, we conducted a stratified genotype-phenotype correlation analysis. RESULTS: The A allele of rs4468255 was significantly associated with IDCM (P<0.01). The rs4468255, rs11812601, rs56165849, and rs3740346 were also associated with diastolic blood pressure (DBP) and left ventricular ejection fraction (LVEF) (P<0.05). Notably, a higher frequency of rs4468255 polymorphism was observed in implantable cardioverter defibrillator (ICD) recipients under a recessive model (P<0.01), whereas the significant association disappeared after adjusting for potential confounders. However, in the dominant model, notable correlations could only be observed after adjusting for multi parameters. CONCLUSIONS: The rs4468255 was significantly correlated with IDCM of Chinese Han population. A allele of rs4468255 is higher in IDCM patients with ICD implantation, suggesting the influence of genetic background in the generation of this response. In addition, rs11812601, rs56165849, and rs3740346 in LDB3 show association with brain natriuretic peptide, DBP, and LVEF levels in patients with IDCM but did not show any association with IDCM susceptibility.

Endoscopic ultrasound-guided fine-needle aspiration biopsy of gastric schwannoma: Cytomorphologic features and diagnostic pitfalls.

Schwannoma rarely occurs in the stomach. We present a case of gastric schwannoma, which was initially evaluated by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsy and confirmed by surgical resection. The patient was a 57-years-old woman with history of dyspepsia, who was found to have a large submucosal mass in the stomach. EUS-FNA showed scant spindle cells with abundant lymphocytes. The spindle cells were immunoreactive with S100, while negative for CD117, desmin, and CD34. The lymphocytes were mixed B-cells and T-cells. Immunostaining, flow cytometry, and molecular testing showed no evidence of B-cell lymphoma. The diagnosis of gastric schwannoma was confirmed by histopathological evaluation of the resected tumor. Gastric schwannoma has unique features of mixed spindle cells and lymphocytes. The tumor should be differentiated from other gastric mesenchymal tumors, and lymphoproliferative disorder is a pitfall.

In utero exposure to triphenyltin disrupts rat fetal testis development.

Triphenyltin is an organotin that is widely used as an anti-fouling agent and may have endocrine-disrupting effects. The objective of the current study was to investigate effects of triphenyltin on the development of rat fetal testis. Female pregnant Sprague Dawley dams were gavaged daily with triphenyltin (0, 0.5, 1, and 2 mg/kg body weight/day) from gestational day 12 to day 21. Triphenyltin dose-dependently decreased serum testosterone levels (0.971 ±â€¯0.072 and 0.972 ±â€¯0.231 ng/ml at 1 and 2 mg/kg, respectively) from control level (2.099 ±â€¯0.351 ng/ml). Triphenyltin at 1 and 2 mg/kg doses also induced fetal Leydig cell aggregation, decreased fetal Leydig cell size and cytoplasmic size. Triphenyltin decreased the expression levels of Lhcgr, Scarb1, Star, Cyp11a1, Cyp17a1, Insl3, Fshr, Pdgfa, and Sox9 by 0.5 mg/kg dose and above. However, triphenyltin did not affect Leydig and Sertoli cell numbers. In conclusion, the current study indicated that in utero exposure of triphenyltin disrupted fetal Leydig and Sertoli cell development.

A calcium-dependent protein kinase, ZmCPK32, specifically expressed in maize pollen to regulate pollen tube growth.

Calcium-dependent protein kinases (CPKs) play an essential role in the regulation of pollen tube growth. Although CPK genes have been identified in maize, and some have been functionally characterized, the molecular function of ZmCPKs associated with pollen tube development remains less well studied. Here, we report that a pollen-specific CPK, ZmCPK32, is involved in the regulation of pollen germination and tube extension. ZmCPK32 exhibited CPK activity and was localized on the plasma membrane and punctate internal membrane compartments via N-terminal acylation. In situ hybridization and real-time PCR revealed that ZmCPK32 transcripts accumulated in pollen and expression was dramatically upregulated during shedding. To elucidate the function of this gene, we transiently expressed a ZmCPK32-GFP fusion protein in tobacco pollen using microparticle bombardment. ZmCPK32 accumulation inhibited pollen germination and reduced pollen tube growth, but this effect was abolished when the kinase-inactive variant was expressed, indicating that kinase activity is critical for its regulatory function. In addition, the plasma membrane localization of ZmCPK32 is essential for regulating polar growth, as pollen expressing the cytosol-localized kinase displayed reduced tube length but germinated well. Moreover, the constitutively active form of ZmCPK32 enhanced the reduction in the germination rate, indicating that the specific activation of ZmCPK32 via calcium ions at the cortical growth point is essential for regulating appropriate germination. The results suggest that ZmCPK32 is functionally associated with pollen tube growth, and could represent a potential target for breeding male-sterile maize.

Fast field calibration of MIMU based on the Powell algorithm.

The calibration of micro inertial measurement units is important in ensuring the precision of navigation systems, which are equipped with microelectromechanical system sensors that suffer from various errors. However, traditional calibration methods cannot meet the demand for fast field calibration. This paper presents a fast field calibration method based on the Powell algorithm. As the key points of this calibration, the norm of the accelerometer measurement vector is equal to the gravity magnitude, and the norm of the gyro measurement vector is equal to the rotational velocity inputs. To resolve the error parameters by judging the convergence of the nonlinear equations, the Powell algorithm is applied by establishing a mathematical error model of the novel calibration. All parameters can then be obtained in this manner. A comparison of the proposed method with the traditional calibration method through navigation tests shows the classic performance of the proposed calibration method. The proposed calibration method also saves more time compared with the traditional calibration method.