Low-intensity focused ultrasound combined with microbubbles for non-invasive downregulation of rabbit carotid body activity in the treatment of hypertension.

Targeting the carotid body (CB) is a new approach in treating hypertension. This study investigates the efficacy and safety of ultrasound combined with microbubbles in targeting CB to treat hypertension. Twenty-seven hypertensive rabbits were randomly assigned to three groups: microbubbles only (sham group, n = 11), ultrasound plus microbubbles (LIFU group, n = 11), and bilateral carotid sinus nerve denervation (CSND group, n = 5). Four weeks post-intervention, blood pressure, hypoxic ventilatory response (HVR), blood pressure variability (BPV), heart rate variability (HRV), biochemical indicators, neurohormones, and histopathology were assessed in all groups. The results indicated significant reductions in systolic and diastolic blood pressure in the LIFU and CSND groups post-intervention, along with decreases in BPV, HRV, and catecholamines. HVR results showed a 35.10% reduction in CB activity in the LIFU group compared to the sham group, which was significantly lower than the reduction in the CSND group compared to the sham group (73.85%). Histopathology and transmission electron microscopy confirmed CB damage and cell apoptosis, with immunofluorescence showing a reduction in type I and II cells. In conclusion, LIFU combined with microbubbles can reduce blood pressure by lowering CB and sympathetic nerve activity.

Astragaloside IV protects brain cells from ischemia-reperfusion injury by inhibiting ryanodine receptor expression and reducing the expression of P-Src and P-GRK2.

Astragaloside IV, a prime active component of Astragalus membranaceus, has potential as a neuroprotectant. We aimed to identify the active ingredients in A. membranaceus and assess if Astragaloside IV can improve cerebral ischemia-reperfusion injury (CIRI) cell apoptosis by reducing P-Src and P-GRK2 via ryanodine receptor (RyR) expression inhibition. We used bioinformatics analysis to examine the effects of A. membranaceus on ischemic stroke. We studied brain samples from middle cerebral artery occlusion (MCAO) mice treated with normal saline, Astragaloside IV, and sham mice for pathology and Western blot tests. We also tested PC12 cells in vitro with or without Astragaloside IV or GSK180736A using Western blotting and fluorescence assays. Our bioinformatics analysis suggested a possible association between A. membranaceus, calcium ion pathways, and apoptosis pathways. Western blot data indicated Astragaloside IV significantly decreased RyR, p-Src, and downstream phosphorylated GRK2, PLC, CaMKII, and IP3R levels in MCAO mice brains. Astragaloside IV also considerably inhibited pro-apoptotic and oxidative stress-associated proteins' expression while boosting anti-apoptotic protein expression. The results suggest Astragaloside IV can inhibit RyR expression, subsequently reducing brain cell apoptosis.

Green one-step synthesis of N-doped carbon quantum dots for fluorescent detection of lemon yellow in soft drinks.

A new fluorescent sensor for the determination of lemon yellow was developed based on nitrogen-doped carbon quantum dots (N-CQDs), which were prepared via a hydrothermal method with dried pomelo peel and L-tyrosine. The N-CQDs exhibited the blue fluorescence with a quantum yield of 28 %. The sensing principle of N-CQDs was quenched by lemon yellow via static quenching. The potential interfering substances showed no influence on the detection of lemon yellow. The limit of detection was 0.023 mg/L and lower than that of national standard. Furthermore, the synthesized N-CQDs have been successfully applied to the measurement of lemon yellow in real samples. Hence, the N-CQDs would be a promising sensor in food analysis.

A simple and sensitive electrochemical biosensor for circulating tumor cell determination based on dual-toehold accelerated catalytic hairpin assembly.

Tumor cells in blood circulation (CTCs) are vital biomarkers for noninvasive cancer diagnosis. We developed a simple and sensitive electrochemical biosensor based on dual-toehold accelerated catalytic hairpin assembly (DCHA) to distinguish CTCs from blood cells. In the presence of CTCs, the aptamer probe initiates the DCHA process, which produces amplified electrochemical signals. Compared with conventional catalytic hairpin assembly (CHA), the proposed DCHA showed high sensitivity, which led to a broader working range of 10-1000 cells mL-1 with a limit of detection of 4 cells mL-1. Furthermore, our method exhibited an excellent capability of distinguishing malignant breast cancers from healthy people, with a sensitivity of 97.4%. In summary, we have established an enzyme-free, easy-to-operate, and nondisruptive method for detecting circulating tumor cells in blood circulation based on the DCHA strategy. Its versatility and simplicity will make it more widely used in clinical diagnosis and biomedical research.

Ultrasound-assisted extraction of tamarind xyloglucan: an effective approach to reduce the viscosity and improve the α-amylase inhibition of xyloglucan.

BACKGROUND: Water extraction (WE) is the classical extraction method for tamarind xyloglucan (XyG), but its low yield, high viscosity and poor dispersion in aqueous solution are not conducive to the industrial applications. To promote the industrial application of tamarind XyG, an ultrasonic-assisted extraction (UAE) method for extracting low-viscosity XyG from tamarind kernel powder was proposed. RESULTS: The yield of UAE-XyG was higher (502.33 ± 0.036 g kg-1 ) than that of WE-XyG (163.43 ± 0.085 g kg-1 ). UAE reduced the molecular weight, monosaccharide content and apparent viscosity of XyG. The hypoglycemic experiment in vitro showed that UAE-XyG had a stronger inhibitory effect on α-amylase activity than WE-XyG, but its glucose dialysis retardation index was lower. CONCLUSION: In sum, UAE is a type of extraction method that could effectively improve the yield of XyG and reduce its viscosity to expand its application without reducing its physiological activity. UAE exhibits an excellent potential in the extraction of XyG. © 2022 Society of Chemical Industry.

Point-of-Care Urinalysis with One Drop of Sample Using an Aggregation-Induced Emission Luminogen under the Coffee-Ring Effect.

Development of a practical point-of-care test for urinalysis is crucial for early diagnosis and treatment of chronic kidney disease (CKD). However, the classical gold standard detection method depends on sophisticated instruments and complicated procedures, impeding them from being utilized in resource-limited settings and daily screening. Herein, we report a rapid point-of-care device for the simultaneous quantification of microalbuminuria and leukocyte using one drop of urine. A luminogen (TTVP) with an aggregation-induced emission property can selectively activate its near-infrared fluorescence in the presence of albumin and leukocyte via hydrophobic or electrostatic interactions. The fluorescence signals from urine albumin and leukocyte could be well-separated combined with the coffee-ring effect. Using a smartphone-based detection device, simultaneous quantification of urine albumin and leukocyte was successfully achieved, which only took 20 min and required one drop of urine. The performance of this system is also verified with 120 clinical samples, which might serve as a simple, low-cost, and rapid tool for CKD screening and disease monitoring at the point of care.

Human-Machine Interaction Methods for Minimally Invasive Surgical Robotic Arms.

Minimally invasive surgery has a smaller incision area than traditional open surgery, which can greatly reduce damage to the human body and improve the utilization of medical devices. However, minimally invasive surgery also has disadvantages such as limited flexibility and operational characteristics. The interactive minimally invasive surgical robot system not only improves the stability, safety, and accuracy of minimally invasive surgery but also introduces force feedback in controlling the surgical robot, which is a new development direction in the field of minimally invasive surgery. This paper reviews the development status of interactive minimally invasive surgical robotic systems and key technologies to achieve human-robot interaction and finally provides an outlook and summary of its development. Fuzzy theory and reinforcement learning are introduced into the parameter adjustment process of the variable guide control model, and a human-robot interaction method for minimally invasive surgical robot posture adjustment is proposed.

Iron(0) tricarbonyl η4-1-azadiene complexes and their catalytic performance in the hydroboration of ketones, aldehydes and aldimines via a non-iron hydride pathway.

Six iron(0) tricarbonyl complexes (1a-f) with a η4-1-azadiene moiety were prepared and their performance in the hydroboration of unsaturated organic compounds was investigated. All the complexes exhibit catalytic activity towards hydroboration of ketones, aldehydes and aldimines with pinacolborane (HBpin) as a hydride source to lead to secondary alcohols, primary alcohols, and secondary amines, respectively, after hydrolysis of the hydroboration products. Of the iron(0) tricarbonyl complexes, complex 1e is the most robust one and was employed throughout the catalytic investigation. Its preference towards the three types of substrates is as follows: aldimines > aldehydes ≫ ketones. In total, 24 substrates were examined for the catalytic hydroboration reactivity and generally, isolation yields ranging from 40% to 95% were achieved. Mechanistic investigation suggests that the catalytic hydroboration of the substrates proceeds via intramolecular hydride transfer without going through an Fe-H intermediate. As indicated by 1H NMR spectroscopic monitoring, the substrates and the borane agent bind to the iron centre and the imine N atom, respectively, which facilitates the hydride transfer by activating the B-H bond and polarizing the double bond of the substrates.

Revealing the Intrinsic Nature of the Synergistic Effect Caused by the Formation of Heterojunctions in Cu-Cu2O/rGO-NH2 Nanomaterials in the Catalysis of Selective Aerobic Oxidation of Benzyl Alcohol.

Ternary nanomaterials Cu-Cu2O/rGO-NH2 (rGO = reduced graphene oxide) exhibited a synergistic effect in the quantitative catalysis of selective aerobic oxidation of benzyl alcohol. The synergistic effect is attributed to the heterojunctions among the three components and in intrinsic nature, the formation of the heterojunctions lowered the conduction band (CB) energy level and raised the valence band (VB) energy level of the main catalyst Cu2O, which eases electron transfer from the catalyst to O2 in its activation and from the substrate to the catalyst in the oxidation, respectively.

Isolation of circulating fetal trophoblasts by a four-stage inertial microfluidic device for single-cell analysis and noninvasive prenatal testing.

Noninvasive detection of circulating fetal cells carrying the entire fetal genome is a promising way for prenatal testing of genetic diseases. However, ideal approaches for efficient separation of these valuable cells are not available. Here, a novel inertial microfluidic chip (CelutriateChip 1) is developed for ultra-fast, label-free enrichment of circulating trophoblasts (CTBs) from the whole blood samples of pregnant women. The unique structural design of the four-stage curved channel in CelutriateChip 1 enables CTBs with larger size to be efficiently separated from the blood samples under the effect of inertial and Dean drag forces. The transition of the target cells among the stages enables CelutriateChip 1 to achieve one or two orders of magnitude higher throughput compared to single channel inertial microfluidic chips. After optimization of conditions, CTBs can be recovered from 2 mL of whole blood within 5 min with an average recovery efficiency ranging from 52.3% to 65.8% and high white blood cell depletion (99.95%). CTBs collected from the chip can be isolated at the single-cell level and used for downstream immunofluorescence staining and genetic genotyping. Clinical tests are performed on 30 pregnant women and the results demonstrate that CTBs are obtainable in 86.67% of pregnancy cases. A single-base variant in the HBB gene can be accurately detected by sequencing of rare CTBs. This simple, antibody-free and low-cost approach holds promise for obtaining rare CTBs for prenatal detection of various genetic diseases.

Coherently enhanced third-harmonic generation in cascaded microfibers.

A scheme using cascaded silica microfibers is proposed for efficient third-harmonic (TH) generation. By tuning the phase difference via input pump power, the TH from the microfibers could overlap coherently, yielding great output enhancement. Conversion efficiency ∼20% is demonstrated analytically and numerically. Moreover, as the TH output features are dominated by behavior analogous to optical interference, the influence of random diameter deviation of each microfiber is reduced, and the conversion process could be well controlled.

A fluorescent immunosensor for determination and imaging of circulating tumor cells based on a bifunctional DNA nanomachine.

A fluorescent platform was developed for the determination and visualization of circulating tumor cells by a toehold-mediated bifunctional DNA nanomachine. In the presence of target tumor cells, the DNA nanomachine was activated. Multiple DNA products were formed, including dendritic DNA products and double-strand DNA products. Dendritic DNA products bound to their target cells for the visualization, while double-strand DNA products were released for the determination of tumor cells. At fluorescence excitation and emission wavelengths of 530 and 550 nm, this method could detect as low as 43 cells/mL (S/N = 3) with a linear range of 100 to 10,000 cells/mL. In clinical hydrothorax samples, this platform exhibited high reliability with a recovery of 93 to 116%. At the fluorescence excitation and emission wavelengths of 490 and 515 nm, the specificity and biocompatibility of this method were further verified by tumor cells imaging. Furthermore, the robustness of the toehold-mediated bifunctional DNA nanomachine was demonstrated by the specific gene mutation detection in single-cell analysis. Graphical abstract Schematic illustration of the fluorescent immunosensor for determination and imaging of circulating tumor cells. The method is based on aptamer-based recognition and toehold-mediated bifunctional DNA nanomachine.

Nondestructive Identification of Rare Trophoblastic Cells by Endoplasmic Reticulum Staining for Noninvasive Prenatal Testing of Monogenic Diseases.

Noninvasive prenatal detection of monogenic diseases based on cell-free DNA is hampered by challenges in obtaining a sufficient fraction and adequate quality of fetal DNA. Analyzing rare trophoblastic cells from Papanicolaou smears carrying the entire fetal genome provides an alternative method for noninvasive detection of monogenic diseases. However, intracellular labeling for identification of target cells can affect the quality of DNA in varying degrees. Here, a new approach is developed for nondestructive identification of rare fetal cells from abundant maternal cells based on endoplasmic reticulum staining and linear discriminant analysis (ER-LDA). Compared with traditional methods, ER-LDA has little effect on cell quality, allowing trophoblastic cells to be analyzed on the single-cell level. Using ER-LDA, high-purity of trophoblastic cells can be identified and isolated at single cell resolution from 60 pregnancies between 4 and 38 weeks of gestation. Pathogenic variants, including -SEA/ deletion mutation and point mutations, in 11 fetuses at risk for α- or ß-thalassemia can be accurately detected by this test. The detection platform can also be extended to analyze the mutational profiles of other monogenic diseases. This simple, low-cost, and noninvasive test can provide valuable fetal cells for fetal genotyping and holds promise for prenatal detection of monogenic diseases.

A novel nest hybridization chain reaction based electrochemical assay for sensitive detection of circulating tumor DNA.

As an ideal biomarker candidate, circulating tumor DNA (ctDNA) plays a vital role in noninvasive diagnosis of cancer. However, most traditional approaches for quantifying ctDNA are cumbersome and expensive. In the present work, a novel electrochemical biosensor based on nest hybridization chain reaction was proposed for the sensitive and specific detection of PIK3CA E545K ctDNA with a simple process. The nest hybridization chain reaction was initiated by the hybridization of two dumbbell-shaped DNA units which were assembled by two classes of well-designed DNA probes respectively, leading to the formation of a complex DNA structure. In the presence of target ctDNA, the amplified hybridization chain reaction products were captured by target ctDNA, resulting in a significant increase of electrochemical signal. Under the optimal conditions, the developed biosensor exhibited good analytical performance for the detection of target ctDNA with the linear range from 5 pM to 0.5 nM and the detection limit of 3 pM. Furthermore, this assay was successfully applied to the detection of ctDNA in spiked-in samples, pleural effusion and serum samples of malignant tumor patients. This simple and cost-effective sensing system holds great potentials for ctDNA detection and cancer diagnosis.

Thoracic vertebra fixation with a novel screw-plate system based on computed tomography imaging and finite element method.

BACKGROUND AND OBJECTIVE: The traditional pedicle screw-rod internal fixation system has been widely used for thoracic diseases in clinical practice, but its high profile increases the damage to soft tissue, leading to long-term intractable back stiffness. The purpose of this study is to compare biomechanical advantages between the new spine pedicle screw-plate internal fixation system and traditional pedicle screw-rod internal fixation system using finite element analysis. METHODS: Based on computed tomography (CT), four three-dimensional finite element models of T7-T9 were constructed. The downward concentrated force of 150 N and the moment of 5 Nm was applied to the models to simulate six physiological activities, including flexion, extension, left and right lateral bending, left and right axial torsion. The maximum displacement, range of motion (ROM) and maximum stress of the two models in six physiological activities, was measured to evaluate the biomechanical advantages of the novel pedicle screw-plate internal fixation system. RESULTS: The novel pedicle screw-plate internal fixation system has a lower profile than the traditional pedicle screw-rod internal fixation system. With regards to the stability, the maximum displacement of the models of two internal fixation systems decreased by 56.2%-91.4% under the six motion status when comparing with the unstable model. Meanwhile, the ROM remained unchanged between the two models of internal fixation systems besides the left lateral bending. However, there is no significant difference in the ROM between the models of the two internal fixation systems in left lateral bending motion (P = 0.203). In terms of the strength, the maximum stress in the model with the new pedicle screw-plate internal fixation system was higher than that of model with the traditional pedicle screw-rod internal fixation system in every motion status but left and right lateral bending motion. CONCLUSIONS: The novel pedicle screw-plate internal fixation system has lower profile in orthopedics and higher strength, However, it has no disadvantage when comparing with the traditional pedicle screw-rod internal fixation system in terms of the stability. In summary, we suggest that the novel spine pedicle screw-plate system can be used as a new internal fixation and provide better comfort for patients.

Enhanced UV third-harmonic generation in microfibers by controlling nonlinear phase modulations.

The influence of nonlinear phase modulations on third-harmonic (TH) conversion in silica microfibers is experimentally demonstrated. By utilizing such influence, enhanced narrow-bandwidth ultraviolet TH is generated at a high signal-to-noise ratio (33 dB) and an average power of several hundred nanowatts. Detailed trends of TH power against input pump power were characterized with peak pump power up to 2.5 kW, and the results agree with predicted features, confirming that harmonic output could be optimized with adaptive control of the phase mismatch.

Pathogenic Effects and Potential Regulatory Mechanisms of Tea Polyphenols on Obesity.

Overweight and obesity are major threats to human health. Tea polyphenols exert multiple beneficial effects on human health and may play a positive regulatory role in fat assumption. However, how tea polyphenols contribute to the regulation of fat metabolism remains unclear to date. Small RNA expression profile can be regulated by tea polyphenols in adipocytes. Therefore, tea polyphenols may regulate fat metabolism by controlling small RNA-associated biological processes. In this study, we developed a systematic research platform based on mouse models and performed small RNA sequencing to identify the specific role of small RNAs in the regulatory effect of tea polyphenols on fat metabolism. We compared the expression levels of different small RNA subtypes, including piRNAs and miRNAs, and identified a group of differentially expressed small RNAs in the experimental and control groups. Most of these small RNAs participate in lipid metabolism, suggesting that small RNAs play a significant role in tea polyphenol-associated obesity and related pathogenesis. Furthermore, gene ontology and KEGG pathway enrichment indicated that small RNAs influence the regulatory effects of tea polyphenols on obesity, revealing the potential pathogenic mechanisms for such nutritional disease.

Optimized microfiber-based third-harmonic generation with adaptive control of phase mismatch.

An effective approach is presented to improve intermodal third-harmonic generation in microfibers. It is demonstrated that structure-independent incident pump power could be utilized, via its effect on nonlinear phase modulations, to compensate for the phase mismatch caused by diameter deviation. The output harmonic of a fabricated microfiber can be optimized adaptively; thus, efficient third-harmonic generation with efficiency reaching several percent could realistically be achieved.

The G2 phase arrest induced by sterigmatocystin is dependent on hMLH1- ERK/p38-p53 pathway in human esophageal epithelium cells in vitro.

Sterigmatocystin (ST), being a precursor of aflatoxin, is categorized as Group 2B carcinogen. Our previous studies found that both mismatch repair (MMR) pathways and p53 signaling pathway were involved in ST-induced G2 cell cycle arrest in human esophageal squamous epithelial cell line, HET-1A, in vitro. Studies showed that ERK, JNK and p38 signaling pathways played important roles in cell cycle arrest induced by several other carcinogens. However, the role of MAPK pathway and the links between the MMR and p53 signaling pathways in ST induced G2 phase arrest is still not clarified. In the present study, we first explored the role of MAPK pathway upon ST induced G2 arrest, and found that ST up-regulated the expression of G2/M regulatory factors through MAPK signaling pathway (both ERK and p38, but not JNK pathway). The inhibition of ERK and p38 significantly inhibited p53 activation by ST. Blockage of MMR pathway by silencing hMLH1 expression inhibited ERK, p38 and p53 activation and then attenuated G2 arrest by ST. Thus, in conclusion, the current study demonstrated that in response to ST induced DNA damage, hMLH1 was first activated, then triggered ERK, p38 and p53 activation and finally resulted in G2 arrest in HET-1A cells.

Self-learning kinetic Monte Carlo simulations of diffusion in ferromagnetic α-Fe-Si alloys.

Diffusion of Si atom and vacancy in the A2-phase of α-Fe-Si alloys in the ferromagnetic state, with and without magnetic order and in various temperature ranges, are studied using AKSOME, an on-lattice self-learning KMC code. Diffusion of the Si atom and the vacancy are studied in the dilute limit and up to 12 at.% Si, respectively, in the temperature range 350-700 K. Local Si neighborhood dependent activation energies for vacancy hops were calculated on-the-fly using a broken-bond model based on pairwise interaction. The migration barrier and prefactor for the Si diffusion in the dilute limit were obtained and found to agree with published data within the limits of uncertainty. Simulations results show that the prefactor and the migration barrier for the Si diffusion are approximately an order of magnitude higher, and a tenth of an electron-volt higher, respectively, in the magnetic disordered state than in the fully ordered state. However, the net result is that magnetic disorder does not have a significant effect on Si diffusivity within the range of parameters studied in this work. Nevertheless, with increasing temperature, the magnetic disorder increases and its effect on the Si diffusivity also increases. In the case of vacancy diffusion, with increasing Si concentration, its diffusion prefactor decreases while the migration barrier more or less remained constant and the effect of magnetic disorder increases with Si concentration. Important vacancy-Si/Fe atom exchange processes and their activation barriers were identified, and the effect of energetics on ordered phase formation in Fe-Si alloys are discussed.