Numerical investigation of field-effect control on hybrid electrokinetics for continuous and position-tunable nanoparticle concentration in microfluidics.

We introduce herein an effective way for continuous delivery and position-switchable trapping of nanoparticles via field-effect control on hybrid electrokinetics (HEK). Flow field-effect transistor exploiting HEK delicately combines horizontal linear electroosmosis and transversal nonlinear electroosmosis of a shiftable flow stagnation line (FSL) on gate terminals under DC-biased AC forcing. The microfluidic nanoparticle concentrator proposed herein makes use of a simple device geometry, in which an individual or a series of planar metal strips serving as gate electrode (GE) are subjected to a hybrid gate voltage signal and arranged in parallel between a pair of 3D driving electrodes. On the application of a DC-biased AC electric field across channel length direction, all the GE are electrochemically polarized, and the action of imposed hybrid electric field on the multiple-frequency bipolar counterions within the composite-induced double layer generates two counter-rotating induced-charge electroosmotic (ICEO) micro-vortices on top of each GE. Symmetry breaking in ICEO flow profile occurs once the gate voltage deviates from natural floating potential of corresponding GE. The gate voltage offset not only results in an additional pump motion of working fluid for enhanced electroosmotic transport but also directly changes the location of FSL where nanoparticles are preferentially collected by field-effect HEK. Our results of field-effect control on HEK are supposed to guide an elaborate design of flexible electrokinetic frameworks embedding coplanar metal strips for a high degree of freedom analyte manipulation in modern micro-total-analytical systems.

Model Checking Fuzzy Computation Tree Logic Based on Fuzzy Decision Processes with Cost.

In order to solve the problems in fuzzy computation tree logic model checking with cost operator, we propose a fuzzy decision process computation tree logic model checking method with cost. Firstly, we introduce a fuzzy decision process model with cost, which can not only describe the uncertain choice and transition possibility of systems, but also quantitatively describe the cost of the systems. Secondly, under the model of the fuzzy decision process with cost, we give the syntax and semantics of the fuzzy computation tree logic with cost operators. Thirdly, we study the problem of computation tree logic model checking for fuzzy decision process with cost, and give its matrix calculation method and algorithm. We use the example of medical expert systems to illustrate the method and model checking algorithm.

Quantum Simulation of Resonant Transitions for Solving the Eigenproblem of an Effective Water Hamiltonian.

It is difficult to calculate the energy levels and eigenstates of a large physical system on a classical computer because of the exponentially growing size of the Hilbert space. In this work, we experimentally demonstrate a quantum algorithm which could solve this problem via simulated resonant transitions. Using a four-qubit quantum simulator in which two qubits are used as ancillas for control and measurement, we obtain the energy spectrum of a 2-qubit low-energy effective Hamiltonian of the water molecule. The simulated transitions allow the state of the quantum simulator to transform and access large regions of the Hilbert space, including states that have no overlap with the initial state. Furthermore, we make use of this algorithm to efficiently prepare specific eigenstates on the simulator according to the measured eigenenergies.

Effect of platelet-rich plasma on peri-implant trabecular bone volume and architecture: A preclinical micro-CT study in beagle dogs.

OBJECTIVES: To evaluate the peri-implant trabecular bone volume and architecture changes with 6-month follow-up after local application of platelet-rich plasma (PRP) and platelet-poor plasma (PPP) using high-resolution micro-CT. MATERIAL AND METHODS: Seventy-two dental implants were placed into healed mandibular sites of 9 beagle dogs. Implants were randomly divided into 4 groups following a split-mouth design: control I; control II; PPP; and PRP. Primary and secondary stabilities were assessed using resonance frequency analyses. At 1, 3, and 6 months after implant loading, trabecular structural parameters were evaluated at 0.5, 1, and 1.5 mm away from implants using micro-CT (voxel = 20 µm). RESULTS: Primary and secondary stabilities were equivalent in all conditions. PPP and PRP groups showed higher bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) but lower trabecular separation (Tb.Sp) and total porosity percentage (Po (tot)) at all 3 time points. A significant decrease in BV/TV and Tb.Th was found for the control groups after 3 months of healing, while this was not observed in both the PPP and PRP groups. However, no distinct difference was found between the PRP and PPP groups over time. Moreover, as the investigated distance from the implant surface increased, BV/TV and Po (tot) within the same group and time point stayed the same, yet Tb.Th and Tb.Sp continued to increase. CONCLUSIONS: Platelet-rich plasma and PPP with conventional implant placement lead to similar primary and secondary implant stability, but improved peri-implant bone volume and structural integration. The present research does not seem to suggest a different bone remodeling pattern when using PRP or PPP.

Experimental Adiabatic Quantum Factorization under Ambient Conditions Based on a Solid-State Single Spin System.

The adiabatic quantum computation is a universal and robust method of quantum computing. In this architecture, the problem can be solved by adiabatically evolving the quantum processor from the ground state of a simple initial Hamiltonian to that of a final one, which encodes the solution of the problem. Adiabatic quantum computation has been proved to be a compatible candidate for scalable quantum computation. In this Letter, we report on the experimental realization of an adiabatic quantum algorithm on a single solid spin system under ambient conditions. All elements of adiabatic quantum computation, including initial state preparation, adiabatic evolution (simulated by optimal control), and final state read-out, are realized experimentally. As an example, we found the ground state of the problem Hamiltonian S_{z}I_{z} on our adiabatic quantum processor, which can be mapped to the factorization of 35 into its prime factors 5 and 7.

Direct Measurement of Topological Numbers with Spins in Diamond.

Topological numbers can characterize the transition between different topological phases, which are not described by Landau's paradigm of symmetry breaking. Since the discovery of the quantum Hall effect, more topological phases have been theoretically predicted and experimentally verified. However, it is still an experimental challenge to directly measure the topological numbers of various predicted topological phases. In this Letter, we demonstrate quantum simulation of topological phase transition of a quantum wire (QW), by precisely modulating the Hamiltonian of a single nitrogen-vacancy (NV) center in diamond. Deploying a quantum algorithm of finding eigenvalues, we reliably extract both the dispersion relations and topological numbers. This method can be further generalized to simulate more complicated topological systems.

Experimental Test of Heisenberg's Measurement Uncertainty Relation Based on Statistical Distances.

Incompatible observables can be approximated by compatible observables in joint measurement or measured sequentially, with constrained accuracy as implied by Heisenberg's original formulation of the uncertainty principle. Recently, Busch, Lahti, and Werner proposed inaccuracy trade-off relations based on statistical distances between probability distributions of measurement outcomes [P. Busch et al., Phys. Rev. Lett. 111, 160405 (2013); P. Busch et al., Phys. Rev. A 89, 012129 (2014)]. Here we reformulate their theoretical framework, derive an improved relation for qubit measurement, and perform an experimental test on a spin system. The relation reveals that the worst-case inaccuracy is tightly bounded from below by the incompatibility of target observables, and is verified by the experiment employing joint measurement in which two compatible observables designed to approximate two incompatible observables on one qubit are measured simultaneously.

Blood lipid levels, statin therapy and the risk of intracerebral hemorrhage.

Dyslipidemia has been proven to play an important role in the occurrence and development of the ischemic stroke and lipid-lowering therapy could significantly decrease the risk of the ischemic stroke. However, the association between lipid levels, lipid-lowering therapy and the risk of intracerebral hemorrhage (ICH) is not clear. Studies have shown that low serum levels of total cholesterol might be associated with increasing risk of ICH, whereas the SPARCL study, a large prospective, randomized, placebo-controlled trial, demonstrated an increased risk of hemorrhagic stroke during high-dose statin therapy among the patients with previous stroke. The relationship between lipid-lowering therapy and ICH has become a hot topic in the recent years. We searched PubMed for articles published in English to review the existing evidence on the association of lipid levels, statin therapy and risk of ICH as well as the underlying mechanisms in order to provide practical recommendations for clinical decision-making and a foundation for further researches.

Experimental realization of a quantum support vector machine.

The fundamental principle of artificial intelligence is the ability of machines to learn from previous experience and do future work accordingly. In the age of big data, classical learning machines often require huge computational resources in many practical cases. Quantum machine learning algorithms, on the other hand, could be exponentially faster than their classical counterparts by utilizing quantum parallelism. Here, we demonstrate a quantum machine learning algorithm to implement handwriting recognition on a four-qubit NMR test bench. The quantum machine learns standard character fonts and then recognizes handwritten characters from a set with two candidates. Because of the wide spread importance of artificial intelligence and its tremendous consumption of computational resources, quantum speedup would be extremely attractive against the challenges of big data.

Experimental realization of a compressed quantum simulation of a 32-spin Ising chain.

Certain n-qubit quantum systems can be faithfully simulated by quantum circuits with only O(log(n)) qubits [B. Kraus, Phys. Rev. Lett. 107, 250503 (2011)]. Here we report an experimental realization of this compressed quantum simulation on a one-dimensional Ising chain. By utilizing an nuclear magnetic resonance quantum simulator with only five qubits, the property of ground-state magnetization of an open-boundary 32-spin Ising model is experimentally simulated, prefacing the expected quantum phase transition in the thermodynamic limit. This experimental protocol can be straightforwardly extended to systems with hundreds of spins by compressing them into up to merely 10-qubit systems. Our experiment paves the way for exploring physical phenomena in large-scale quantum systems with quantum simulators under current technology.

Advances in self-assembled nanotechnology in tumor therapy.

The emergence of nanotechnology has opened up a new way for tumor therapy. Among them, self-assembled nanotechnology has received extensive attention in medicine due to its simple preparation process, high drug-loading capacity, low toxicity, and low cost. This review mainly summarizes the preparation methods of self-assembled nano-delivery systems, as well as the self-assembled mechanism of carrier-free nanomedicine, polymer-carried nanomedicine, polypeptide, and metal drugs, and their applications in tumor therapy. In addition, we discuss the advantages and disadvantages, future challenges, and opportunities of these self-assembled nanomedicines, which provide important references for the development and application of self-assembled nanotechnology in the field of medical therapy.

14-3-3 binding motif phosphorylation disrupts Hdac4-organized condensates to stimulate cardiac reprogramming.

Cell fate conversion is associated with extensive post-translational modifications (PTMs) and architectural changes of sub-organelles, yet how these events are interconnected remains unknown. We report here the identification of a phosphorylation code in 14-3-3 binding motifs (PC14-3-3) that greatly stimulates induced cardiomyocyte (iCM) formation from fibroblasts. PC14-3-3 is identified in pivotal functional proteins for iCM reprogramming, including transcription factors and chromatin modifiers. Akt1 kinase and protein phosphatase 2A are the key writer and key eraser of the PC14-3-3 code, respectively. PC14-3-3 activation induces iCM formation with the presence of only Tbx5. In contrast, PC14-3-3 inhibition by mutagenesis or inhibitor-mediated code removal abolishes reprogramming. We discover that key PC14-3-3-embedded factors, such as histone deacetylase 4 (Hdac4), Mef2c, and Foxo1, form Hdac4-organized inhibitory nuclear condensates. PC14-3-3 activation disrupts Hdac4 condensates to promote cardiac gene expression. Our study suggests that sub-organelle dynamics regulated by a PTM code could be a general mechanism for stimulating cell reprogramming.

CD163 protein inhibits lipopolysaccharide-induced macrophage transformation from M2 to M1 involved in disruption of the TWEAK-Fn14 interaction.

Macrophages play a crucial role in regulating inflammation and innate immune responses, and their polarization into distinct phenotypes, such as M1 and M2, is involved in various diseases. However, the specific role of CD163, a scavenger receptor expressed by macrophages, in the transformation of M2 to M1 macrophages remains unclear. Here, dexamethasone-induced M2 macrophages were treated with lipopolysaccharide (LPS) to induce the transformation of M2 to M1 macrophages. We found that treatment with lipopolysaccharide (LPS) induced the transformation of M2-like macrophages to an M1-like phenotype, as evidenced by increased mRNA levels of Il1b and Tnf, decreased mRNA levels of Cd206 and Il10, and increased TNF-α secretion. Knockdown of CD163 enhanced the phenotypic features of M1 macrophages, while treatment with recombinant CD163 protein (rmCD163) inhibited the LPS-induced M2-to-M1 transformation. Furthermore, LPS stimulation resulted in the activation of P38, ERK, JNK, and NF-κB P65 signaling pathways, and this activation was increased after CD163 knockdown and suppressed after rmCD163 treatment during macrophage transformation. Additionally, we observed that LPS treatment reduced the expression of CD163 in dexamethasone-induced M2 macrophages, leading to a decrease in the CD163-TWEAK complex and an increase in the interaction between TWEAK and Fn14. Overall, our findings suggest that rmCD163 can inhibit the LPS-induced transformation of M2 macrophages to M1 by disrupting the TWEAK-Fn14 interaction and modulating the MAPK-NF-κB pathway.

A ubiquitination-mediated degradation system to target 14-3-3-binding phosphoproteins.

The phosphorylation of 14-3-3 binding motif is involved in many cellular processes. A strategy that enables targeted degradation of 14-3-3-binding phosphoproteins (14-3-3-BPPs) for studying their functions is highly desirable for basic research. Here, we report a phosphorylation-induced, ubiquitin-proteasome-system-mediated targeted protein degradation (TPD) strategy that allows specific degradation of 14-3-3-BPPs. Specifically, by ligating a modified von Hippel-Lindau E3-ligase with an engineered 14-3-3 bait, we generated a protein chimera referred to as Targeted Degradation of 14-3-3-binding PhosphoProtein (TDPP). TDPP can serve as a universal degrader for 14-3-3-BPPs based on the specific recognition of the phosphorylation in 14-3-3 binding motifs. TDPP shows high efficiency and specificity to a difopein-EGFP reporter, general and specific 14-3-3-BPPs. TDPP can also be applied for the validation of 14-3-3-BPPs. These results strongly support TDPP as a powerful tool for 14-3-3 related research.

Acute myocardial infarction after inactivated COVID-19 vaccination: a case report and literature review.

A number of vaccines have been developed and deployed globally to restrain the spreading of the coronavirus disease 2019 (COVID-19). The adverse effect following vaccination is an important consideration. Acute myocardial infarction (AMI) is a kind of rare adverse event after COVID-19 vaccination. Herein, we present a case of an 83-year-old male who suffered cold sweat ten minutes after the first inactivated COVID-19 vaccination and AMI one day later. The emergency coronary angiography showed coronary thrombosis and underlying stenosis in his coronary artery. Type II Kounis syndrome might be a potential mechanism, which is manifested as coronary thrombosis secondary to allergic reactions in patients with underlying asymptomatic coronary heart disease. We also summarize the reported AMI cases post COVID-19 vaccination, as well as overview and discuss the proposed mechanisms of AMI after COVID-19 vaccination, thus providing insights for clinicians to be aware of the possibility of AMI following COVID-19 vaccination and potential underlying mechanisms.

14-3-3 binding motif phosphorylation disrupts Hdac4 organized condensates to stimulate cardiac reprogramming.

Cell fate conversion is associated with extensive epigenetic and post translational modifications (PTMs) and architectural changes of sub-organelles and organelles, yet how these events are interconnected remains unknown. We report here the identification of a phosphorylation code in 14-3-3 binding motifs (PC14-3-3) that greatly stimulates induced cardiomyocyte (iCM) formation from fibroblasts. PC14-3-3 was identified in pivotal functional proteins for iCM reprogramming, including transcription factors and epigenetic factors. Akt1 kinase and PP2A phosphatase were a key writer and eraser of the PC14-3-3 code, respectively. PC14-3-3 activation induces iCM formation with the presence of only Tbx5. In contrast, PC14-3-3 inhibition by mutagenesis or inhibitor-mediated code removal abolished reprogramming. We discovered that key PC14-3-3 embedded factors, such as Hdac4, Mef2c, Nrip1, and Foxo1, formed Hdac4 organized inhibitory nuclear condensates. Notably, PC14-3-3 activation disrupted Hdac4 condensates to promote cardiac gene expression. Our study suggests that sub-organelle dynamics regulated by a post-translational modification code could be a general mechanism for stimulating cell reprogramming and organ regeneration. Highlights: A PC14-3-3 (phosphorylation code in 14-3-3 binding motifs) is identified in pivotal functional proteins, such as HDAC4 and Mef2c, that stimulates iCM formation.Akt1 kinase and PP2A phosphatase are a key writer and a key eraser of the PC14-3-3 code, respectively, and PC14-3-3 code activation can replace Mef2c and Gata4 in cardiac reprogramming.PC14-3-3 activation disrupts Hdac4 organized condensates which results in releasing multiple 14-3-3 motif embedded proteins from the condensates to stimulate cardiac reprogramming.Sub-organelle dynamics and function regulated by a post-translational modification code could be a general mechanism in stimulating cell reprogramming and organ regeneration.

Quantum chemistry simulation on quantum computers: theories and experiments.

It has been claimed that quantum computers can mimic quantum systems efficiently in the polynomial scale. Traditionally, those simulations are carried out numerically on classical computers, which are inevitably confronted with the exponential growth of required resources, with the increasing size of quantum systems. Quantum computers avoid this problem, and thus provide a possible solution for large quantum systems. In this paper, we first discuss the ideas of quantum simulation, the background of quantum simulators, their categories, and the development in both theories and experiments. We then present a brief introduction to quantum chemistry evaluated via classical computers followed by typical procedures of quantum simulation towards quantum chemistry. Reviewed are not only theoretical proposals but also proof-of-principle experimental implementations, via a small quantum computer, which include the evaluation of the static molecular eigenenergy and the simulation of chemical reaction dynamics. Although the experimental development is still behind the theory, we give prospects and suggestions for future experiments. We anticipate that in the near future quantum simulation will become a powerful tool for quantum chemistry over classical computations.

In vitro Assessment of Cardiac Reprogramming by Measuring Cardiac Specific Calcium Flux with a GCaMP3 Reporter.

Cardiac reprogramming has become a potentially promising therapy to repair a damaged heart. By introducing multiple transcription factors, including Mef2c, Gata4, Tbx5 (MGT), fibroblasts can be reprogrammed into induced cardiomyocytes (iCMs). These iCMs, when generated in situ in an infarcted heart, integrate electrically and mechanically with the surrounding myocardium, leading to a reduction in scar size and an improvement in heart function. Because of the relatively low reprogramming efficiency, purity, and quality of the iCMs, characterization of iCMs remains a challenge. The currently used methods in this field, including flow cytometry, immunocytochemistry, and qPCR, mainly focus on cardiac-specific gene and protein expression but not on the functional maturation of iCMs. Triggered by action potentials, the opening of voltage-gated calcium channels in cardiomyocytes leads to a rapid influx of calcium into the cell. Therefore, quantifying the rate of calcium influx is a promising method to evaluate cardiomyocyte function. Here, the protocol introduces a method to evaluate iCM function by calcium (Ca2+) flux. An αMHC-Cre/Rosa26A-Flox-Stop-Flox-GCaMP3 mouse strain was established by crossing Tg(Myh6-cre)1Jmk/J (referred to as Myh6-Cre below) with Gt(ROSA)26Sortm38(CAG-GCaMP3)Hze/J (referred to as Rosa26A-Flox-Stop-Flox-GCaMP3 below) mice. Neonatal cardiac fibroblasts (NCFs) from P0-P2 neonatal mice were isolated and cultured in vitro, and a polycistronic construction of MGT was introduced to NCFs, which led to their reprogramming to iCMs. Because only successfully reprogrammed iCMs will express GCaMP3 reporter, the functional maturation of iCMs can be visually assessed by Ca2+ flux with fluorescence microscopy. Compared with un-reprogrammed NCFs, NCF-iCMs showed significant calcium transient flux and spontaneous contraction, similar to CMs. This protocol describes in detail the mouse strain establishment, isolation and selection of neonatal mice hearts, NCF isolation, production of retrovirus for cardiac reprogramming, iCM induction, the evaluation of iCM Ca2+ flux using our reporter line, and related statistical analysis and data presentation. It is expected that the methods described here will provide a valuable platform to assess the functional maturation of iCMs for cardiac reprogramming studies.

WDR73 Depletion Destabilizes PIP4K2C Activity and Impairs Focal Adhesion Formation in Galloway-Mowat Syndrome.

(1) Background: Galloway-Mowat syndrome (GAMOS) is a rare genetic disease, classically characterized by a combination of various neurological symptoms and nephrotic syndrome. WDR73 is the pathogenic gene responsible for GAMOS1. However, the pathological and molecular mechanisms of GAMOS1, especially nephrotic syndrome caused by WDR73 deficiency, remain unknown. (2) Methods and Results: In this study, we first observed remarkable cellular morphological changes including impaired cell adhesion, decreased pseudopodia, and G2/M phase arrest in WDR73 knockout (KO) HEK 293 cells. The differentially expressed genes in WDR73 KO cells were enriched in the focal adhesion (FA) pathway. Additionally, PIP4K2C, a phospholipid kinase also involved in the FA pathway, was subsequently validated to interact with WDR73 via protein microarray and GST pulldown. WDR73 regulates PIP4K2C protein stability through the autophagy-lysosomal pathway. The stability of PIP4K2C was significantly disrupted by WDR73 KO, leading to a remarkable reduction in PIP2 and thus weakening the FA formation. In addition, we found that podocyte-specific conditional knockout (Wdr73 CKO) mice showed high levels of albuminuria and podocyte foot process injury in the ADR-induced model. FA formation was impaired in primary podocytes derived from Wdr73 CKO mice. (3) Conclusions: Since FA has been well known for its critical roles in maintaining podocyte structures and function, our study indicated that nephrotic syndrome in GAMOS1 is associated with disruption of FA caused by WDR73 deficiency.

Association Between Serum Uric Acid Levels and Traditional Cardiovascular Risk Factors in Xiamen Residents of China: A Real-World Study.

Background: Serum uric acid (SUA) levels was associated with cardiovascular diseases and cardiovascular events. However, the relationship between SUA levels and traditional cardiovascular risk factors has not been well-established among Xiamen residents. Our study aimed to estimate the relationship between SUA levels and cardiovascular risk factors among Xiamen residents using real-world data. Methods: Participants were enrolled from eight community health service centers in Xiamen, China. Participants were divided into four groups according to quartiles of the SUA levels. The history of diseases, the use of medications and the levels of laboratory parameters were collected. The China-PAR equation was used to evaluate the 10-year atherosclerotic cardiovascular disease (ASCVD) risk. Results: A total of 1,322 participants were enrolled. About 568 (43.0%) were men and 754 (57.0%) were women. The prevalences of hypertension, elderly, current smokers, and obesity were higher in the quartile 4 (Q4) group than the quartile 1 (Q1) group (all p < 0.001). Multivariable logistic regression analysis showed the OR for hypertension was 2.671 (95% CI 1.777-4.015, p < 0.001) in the Q4 group compared with that in the Q1 group. Further logistic regression showed the OR for hypertension was 3.254 (95% CI 1.756-6.031, p < 0.001) in men and 2.314 (95% CI 1.354-3.955, p = 0.002) in women in the Q4 group compared with that in the Q1 group, respectively. In addition, the percentage of participants with low 10-year ASCVD risk calculated by China-PAR was higher in the Q1 group than that in the Q4 group (55.86 vs. 31.82%, p < 0.001). The percentage of participants with high 10-year ASCVD risk was lower in the Q1 group compared with the Q4 group (15.32 vs. 25.45%, p < 0.001). Multiple linear logistic regression showed the 10-year China-PAR ASCVD risk scores was positively correlated with SUA after adjusting for various factors (ß = 0.135, p = 0.001). Conclusion: Serum uric acid was associated with several cardiovascular risk factors in Xiamen residents. The percentage of high 10-year ASDVD risk was higher in participants with hyperuricemia. Participants with hyperuricemia may experience cardiovascular benefit from uric acid-lowering therapy.