Semiarbitrary qPCR for Sensitive Detection of Circulating miRNA via Terminal Deoxynucleotidyl Transferase-Assisted RNA-Primed DNA Polymerization.

Circulating microRNAs (miRNAs) have recently emerged as noninvasive disease biomarkers. Quantitative detection of circulating miRNAs could offer significant information for clinical diagnosis due to its significance in the development of biological processes. In response to the current challenges of circulating miRNA detection, we introduce a sensitive, selective, and versatile circulating miRNA detection strategy using terminal deoxynucleotidyl transferase (TdT)-catalyzed RNA-primed DNA polymerization (TCRDP) coupled with semiarbitrary qPCR (SAPCR). Semiarbitrary qPCR was first developed here to detect long fragment targets with only a short-known sequence or to detect a short fragment target after extension with terminal transferase. Besides, the subsequent results show that TdT has a preference for RNA, particularly for extending RNAs with purine-rich and unstructured ends. Consequently, utilizing this assay, we have successfully applied it to the quantitative analysis of circulating miR-122 in animal models, a sensitive and informative biomarker for drug-induced liver injury, and as low as 200 zmol of the target is detected with desirable specificity and sensitivity, indicating that the TCRDP-SAPCR can offer a promising platform for nucleic acids analysis.

The Change in Fibrinogen is Associated with Outcome in Patients with Acute Ischemic Stroke Treated with Endovascular Thrombectomy.

BACKGROUND: Fibrinogen has been identified as a modulator of the coagulation and inflammatory process. There is uncertainty about the relationship between the dynamic profile of fibrinogen levels and its impact on clinical outcomes in patients with acute ischemic stroke treated with endovascular thrombectomy. METHODS: We consecutively enrolled patients with acute ischemic stroke who underwent endovascular thrombectomy. Fibrinogen was measured on admission and during hospitalization. The change in fibrinogen (Δfibrinogen) was calculated as the highest follow-up fibrinogen minus admission fibrinogen, with a positive Δfibrinogen indicating an increase in fibrinogen level. Functional outcome was assessed by the modified Rankin Scale at 3 months. Poor outcome was defined as modified Rankin Scale > 2. RESULTS: A total of 346 patients were included (mean age 67.4 ± 13.6 years, 52.31% men). The median fibrinogen on admission was 2.77 g/L (interquartile range 2.30-3.39 g/L). The median Δfibrinogen was 1.38 g/L (interquartile range 0.27-2.79 g/L). Hyperfibrinogenemia (> 4.5 g/L) on admission was associated with an increased risk of poor outcome [odds ratio (OR) 5.93, 95% confidence interval (CI) 1.44-24.41, p = 0.014]. There was a possible U-shaped association of Δfibrinogen with outcomes, with an inflection point of - 0.43 g/L (p = 0.04). When Δfibrinogen was < - 0.43 g/L, a higher decrease in fibrinogen (lower Δfibrinogen value) was associated with a higher risk of poor outcome (OR 0.22, 95% CI 0.02-2.48, p = 0.219). When Δfibrinogen was > - 0.43 g/L, the risk of poor outcome increased with increasing fibrinogen (OR 1.27, 95% CI 1.04-1.54, p = 0.016). CONCLUSIONS: In patients with endovascular thrombectomy, hyperfibrinogenemia on admission was associated with poor functional outcomes at 3 months, whereas Δfibrinogen was associated with poor 3-month outcomes in a possible U-shaped manner.

Prevalence and Predictors of Hemorrhagic Foci on Long-term Follow-up MRI of Recent Single Subcortical Infarcts.

Hemorrhagic foci surrounding the lacune in the long-term evolution of recent single subcortical infarcts (RSSIs) remains largely unexplored. We aimed to determine the prevalence, characteristics, and predictors of hemorrhagic foci in patients with RSSI. From a prospective, longitudinal study of RSSIs, we recruited patients who underwent multimodal MRI assessments both at baseline and approximately one year after the stroke onset. Hemorrhagic foci were identified using susceptibility-weighted imaging (SWI). Among 101 patients with RSSI, nearly half (n = 45, 44.6%) had hemorrhagic foci within the index RSSI lesions on follow-up SWI. RSSIs with hemorrhagic foci formation were associated with a longer time to follow-up imaging (median 449 versus 401 days, P = 0.005) and higher likelihood of being located in the anterior circulation compared to those without hemorrhagic foci (88.9% versus 64.3%, P = 0.003). Hemorrhagic foci were also associated with larger lesion size (P < 0.001), a higher proportion of cavitation formation (P = 0.003), higher baseline NIHSS scores (P = 0.004), and poorer functional outcomes (P = 0.001). In the subset of RSSIs in the lenticulostriate artery (LSA) territory, after adjustment for covariates, larger initial lesion volume (OR 1.80, 95% CI 1.13-2.87; P = 0.014) and greater decreases in LSA total length (OR 0.59, 95% CI 0.36-0.96; P = 0.035) were independently associated with hemorrhagic foci formation. The extent of ischemia in the initial infarct is predictive of the presence of hemorrhagic residues. Our findings contribute to the current understanding of the mechanisms underlying the evolution of RSSIs.

Impact Ionization Coefficient Prediction of a Lateral Power Device Using Deep Neural Network.

Nowadays, the impact ionization coefficient in the avalanche breakdown theory is obtained using 1-D PN junctions or SBDs, and is considered to be a constant determined by the material itself only. In this paper, the impact ionization coefficient of silicon in a 2D lateral power device is found to be no longer a constant, but instead a function of the 2D coupling effects. The impact ionization coefficient of silicon that considers the 2D depletion effects in real-world devices is proposed and extracted in this paper. The extracted impact ionization coefficient indicates that the conventional empirical impact ionization in the Fulop equation is not suitable for the analysis of 2D lateral power devices. The veracity of the proposed impact ionization coefficient is validated by the simulations obtained from TCAD tools. Considering the complexity of direct modeling, a new prediction method using deep neural networks is proposed. The prediction method demonstrates 97.67% accuracy for breakdown location prediction and less than 6% average error for the impact ionization coefficient prediction compared with the TCAD simulation.

Experimental Study on the Rupture Behavior of the Liquid Bridge between Three Rigid Spheres.

The powder process is dynamic at the microscale level. Due to the capillary effect, the viscous attraction of the liquid phase between particles alters the strength and stability of wet granular materials. In this paper, experiments on the rupture behavior of the funicular liquid bridge between three rigid spheres have been presented. The results show that the peak force and rupture distance of the funicular liquid bridges are affected by the size and relative position of the spheres, volume and viscosity of the liquid, and separation rate; the coalescence of the liquid bridges causes a decrease in peak force and an increase in rupture distance, and the rupture distance shows a nonmonotonic functional correlation with the separation rate. Finally, an empirical equation of the correlation between the rupture distance and liquid volume is proposed, whose rationality is verified by comparing it with the results of the existing models.

WITHDRAWN: A deep learning framework for diagnosing periprosthetic joint infections using X-ray images: a discovery and validation study.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Self-Assembly of DNA Tiles with G-Quadruplex DNAzyme Catalytic Activity for Sensing Applications.

DNA tiles form through self-assembly of a small number of DNA strands that interact through basic repeated interactions, allowing the growth of nanoscale structures seeded by molecular inputs. If an approach for catalytic signal amplification can be integrated into the resultant nanostructure, then one can anticipate biosensing or diagnostic applications mediated by DNA tile self-assembly. Here, two-dimensional DNA tiles with split quadruplexes were designed as diagnostic tools for nucleic acid sensing without the use of protein enzymes. The presence of a target sequence leads to formation of extended microscale structures with arrayed multiple G-quadruplexes across the tile plane, with catalytic activity coupled to a colorimetric reporter. Such a mechanism has potential for low-cost signal amplification using unmodified DNA without the use of protein enzymes for biosensing.

Association of compromised cerebral perfusion with lenticulostriate artery impairments in the subacute phase of branch atheromatous disease.

Background Purpose: Whether altered cerebral perfusion is associated with the pathogenesis of single subcortical infarctions (SSIs) in the lenticulostriate artery (LSA) territory remains unclear. Objective: We aimed to assess whether cerebral perfusion abnormalities are related to LSA impairments in the subacute phase of SSIs and then to examine their correlations with etiological subtypes of SSIs. Methods: A total of 110 patients with acute SSIs in the LSA territory were prospectively recruited between July 2017 and October 2021, and they underwent magnetic resonance perfusion-weighted imaging (PWI) and whole-brain vessel-wall imaging (VWI) within 7 days of stroke onset. Based on VWI, patients were assigned to one of two SSI subtypes: branch atheromatous disease (BAD, n = 78, 70.9%) or lacunar infarction related to cerebral small vessel disease (CSVD-related LI, n = 32, 29.1%). Perfusion maps and LSA morphology were also quantitatively assessed. Results: Based on PWI, 22 patients (20%) had hypoperfusion and 88 (80%) showed normal perfusion. Compared with normal individuals, patients with hypoperfusion showed shorter average LSA length (23.48 ± 4.81 mm versus 25.47 ± 3.74 mm, p = 0.037). Compared with patients with CSVD-related LI, patients with BAD had significantly lower relative cerebral blood flow [0.95 (IQR 0.81-1.12) versus 1.04 (IQR 0.92-1.22); p = 0.036] and cerebral blood volume [0.95 (IQR 0.84-1.15) versus 1.14 (IQR 0.97-1.27); p = 0.020] after adjusting for hypertension, number of LSA branches, and infarct volume. Conclusion: Compromised cerebral perfusion is associated with impairments in the LSA and with BAD pathogenesis. Perfusion magnetic resonance imaging can provide important insights into acute SSI pathophysiology, and it may be useful for determining the clinical significance of perfusion abnormalities in BAD occurrence.

COVID-19 impact on mental health.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has posed a significant influence on public mental health. Current efforts focus on alleviating the impacts of the disease on public health and the economy, with the psychological effects due to COVID-19 relatively ignored. In this research, we are interested in exploring the quantitative characterization of the pandemic impact on public mental health by studying an online survey dataset of the United States. METHODS: The analyses are conducted based on a large scale of online mental health-related survey study in the United States, conducted over 12 consecutive weeks from April 23, 2020 to July 21, 2020. We are interested in examining the risk factors that have a significant impact on mental health as well as in their estimated effects over time. We employ the multiple imputation by chained equations (MICE) method to deal with missing values and take logistic regression with the least absolute shrinkage and selection operator (Lasso) method to identify risk factors for mental health. RESULTS: Our analysis shows that risk predictors for an individual to experience mental health issues include the pandemic situation of the State where the individual resides, age, gender, race, marital status, health conditions, the number of household members, employment status, the level of confidence of the future food affordability, availability of health insurance, mortgage status, and the information of kids enrolling in school. The effects of most of the predictors seem to change over time though the degree varies for different risk factors. The effects of risk factors, such as States and gender show noticeable change over time, whereas the factor age exhibits seemingly unchanged effects over time. CONCLUSIONS: The analysis results unveil evidence-based findings to identify the groups who are psychologically vulnerable to the COVID-19 pandemic. This study provides helpful evidence for assisting healthcare providers and policymakers to take steps for mitigating the pandemic effects on public mental health, especially in boosting public health care, improving public confidence in future food conditions, and creating more job opportunities. TRIAL REGISTRATION: This article does not report the results of a health care intervention on human participants.

Targeting PSD95/nNOS by ZL006 alleviates social isolation-induced heightened attack behavior in mice.

RATIONALE: Deregulated attack behaviors have devastating social consequences; however, satisfactory clinical management for the behavior is still an unmet need so far. Social isolation (SI) has been common during the COVID-19 pandemic and may have detrimental effects on mental health, including eliciting heightened attack behavior. OBJECTIVES: This study aims to explore whether injection of ZL006 can alleviate SI-induced escalation of attack behavior in mice. METHODS: Pharmacological tools, biochemical methods, and behavioral tests were used to explore the potential therapeutic effects of ZL006 targeting postsynaptic density 95 (PSD95)/neuronal nitric oxide synthase (nNOS) pathway on escalation of attack behavior induced by SI in mice. RESULTS: ZL006 mitigated SI-induced escalated attack behaviors and elevated nitric oxide (NO) level in the cortex of the SI mice. The beneficial effects of ZL006 lasted for at least 72 h after a single injection of ZL006. Potentiation of NO levels by L-arginine blocked the effects of ZL006. Moreover, a sub-effective dose of 7-NI in combination with a sub-effective dose of ZL006 decreased both SI-induced escalated attack behaviors and NO levels in mice subjected to SI. CONCLUSIONS: Our study highlights the importance of the PSD95/nNOS pathway in mediating SI-induced escalation of attack behavior. ZL006 may be a promising therapeutic strategy for treating aggressive behaviors.

Bactericidal efficiency and photochemical mechanisms of micro/nano bubble-enhanced visible light photocatalytic water disinfection.

Microbial contamination of water in the form of highly-resistant bacterial spores can cause a long-term risk of waterborne disease. Advanced photocatalysis has become an effective approach to inactivate bacterial spores due to its potential for efficient solar energy conversion alongside reduced formation of disinfection by-products. However, the overall efficiency of the process still requires significant improvements. Here, we proposed and evaluated a novel visible light photocatalytic water disinfection technology by its close coupling with micro/nano bubbles (MNBs). The inactivation rate constant of Bacillus subtilis spores reached 1.28 h-1, which was 5.6 times higher than that observed for treatment without MNBs. The superior performance for the progressive destruction of spores' cells during the treatment was confirmed by transmission electron microscopy (TEM) and excitation-emission matrix (EEM) spectra determination. Experiments using scavengers of reactive oxygen species (ROSs) revealed that H2O2 and •OH were the primary active species responsible for the inactivation of spores. The effective supply of oxygen from air MNBs helped accelerate the hole oxidation of H2O2 on the photocatalyst (i.e. Ag/TiO2). In addition, the interfacial photoelectric effect from the MNBs was also confirmed to contribute to the spore inactivation. Specifically, MNBs induced strong light scattering, consequently increasing the optical path length in the photocatalysis medium by 54.8% at 700nm and enhancing light adsorption of the photocatalyst. The non-uniformities in dielectricity led to a high-degree of heterogeneity of the electric field, which triggered the formation of a region of enhanced light intensity which ultimately promoted the photocatalytic reaction. Overall, this study provided new insights on the mechanisms of photocatalysis coupled with MNB technology for advanced water treatment.

An integrated approach using ozone nanobubble and cyclodextrin inclusion complexation to enhance the removal of micropollutants.

Ozone (O3) has been widely used for the elimination of recalcitrant micropollutants in aqueous environments, due to its strong oxidation ability. However, the utilization efficiency of O3 is constrained by its low solubility and short half-life during the treatment process. Herein, an integrated approach, using nanobubble technology and micro-environmental chemistry within cyclodextrin inclusion cavities, was studied in order to enhance the reactivity of ozonisation. Compared with traditional macrobubble aeration with O3 in water, nanobubble aeration achieved 1.7 times higher solubility of O3, and increased the mass transfer coefficient 4.7 times. Moreover, the addition of hydroxypropyl-ß-cyclodextrin (HPßCD) further increased the stability of O3 through formation of an inclusion complex in its molecule-specific cavity. At a HPßCD:O3 molar ratio of 10:1, the lifespan of O3 reached 18 times longer than in a HPßCD-free O3 solution. Such approach accelerated the removal efficiency of the model micropollutant, 4-chlorophenol by 6.9 times, compared with conventional macrobubble ozonation. Examination of the HPßCD inclusion complex by UV-visible spectroscopy and Nuclear Magnetic Resonance analyses revealed that both O3 and 4-chlorophenol entered the HPßCD cavity, and Benesi-Hildebrand plots indicated a 1:1 stoichiometry of the host and guest compounds. Additionally, molecular docking simulations were conducted in order to confirm the formation of a ternary complex of HPßCD:4-chlorophenol:O3 and to determine the optimal inclusion mode. With these results, our study highlights the viability of the proposed integrated approach to enhance the ozonation of organic micropollutants.

Numerical study on the adhesion of a circulating tumor cell in a curved microvessel.

The adhesion of a circulating tumor cell (CTC) in a three-dimensional curved microvessel was numerically investigated. Simulations were first performed to characterize the differences in the dynamics and adhesion of a CTC in the straight and curved vessels. After that, a parametric study was performed to investigate the effects of the applied driven force density f (or the flow Reynolds number Re) and the CTC membrane bending modulus Kb on the CTC adhesion. Our simulation results show that the CTC prefers to adhere to the curved vessel as more bonds are formed around the transition region of the curved part due to the increased cell-wall contact by the centrifugal force. The parametric study also indicates that when the flow driven force f (or Re) increases or when the CTC becomes softer (Kb decreases), the bond formation probability increases and the bonds will be formed at more sites of a curved vessel. The increased f (or Re) brings a larger centrifugal force, while the decreased Kb generates more contact areas at the cell-wall interface, both of which are beneficial to the bond formation. In the curved vessel, it is found that the site where bonds are formed the most (hotspot) varies with the applied f and the Kb. For our vessel geometry, when f is small, the hotspot tends to be within the first bend of the vessel, while as f increases or Kb decreases, the hotspot may shift to the second bend of the vessel.

Construction of a Novel Biosensor Based on the Self-assembly of Dual-Enzyme Cascade Amplification-Induced Copper Nanoparticles for Ultrasensitive Detection of MicroRNA153.

MicroRNAs (miRNAs) have received extensive attention because of their potential as biomarkers for cancer diagnosis and monitoring, and their effective detection is very significant. Here, a specific, one-pot, rapid, femtomolar sensitive miRNAs detection biosensor was developed based on the target-triggered three-way junction (3-WJ) and terminal deoxynucleotide transferase (TDT)/Nt.BspQI in combination with activated copper nanoparticles (CuNPs) self-assembly. To this end, a 3-WJ hairpin probe and helper probe were designed to selectively identify the target miRNA, so as to form a stable 3-WJ structure that further triggered the double-enzyme cycling to produce poly T to activate the self-assembly of CuNPs. Based on the simplicity of CuNPs generation, the poly T template fluorescence CuNPs can detect the minimum detection limit of 1 fm within 1.75 h. In addition, the applicability of this method in complex samples was demonstrated by analyzing the whole-blood RNA extraction from Parkinson patients, consisting of the results of commercial miRNA kits. The developed strategy performs powerful implications for miRNA detection, which may be beneficial for the effective diagnostic assays and biological research of Parkinson's disease.

Nonenzyme Cascaded Amplification Biosensor Based on Effective Aggregation Luminescence Caused by Disintegration of Silver Nanoparticles.

Sensitive and portable quantification of biomarkers has particular significance in the monitoring and treatment of clinical diseases. Conventional immunoassays were accustomed to introducing or incorporating enzymes for signal amplification, which commonly suffered from poor stability and inferior tolerance. Herein, we constructed a novel nonenzyme amplification methodology based on fluorogenic Ag+-tetrazolate aggregation coupled with silver corrosion sensitization for biomarker determination. A significant cascade enhancement strategy was achieved by the valid aggregation luminescence caused by the potent disintegration of silver nanoparticles. Furthermore, efficient magnetic separation was also combined and performed for the rapidity and simplicity of operation. As the target, the detection limit of prostate-specific antigen was 15.66 pg/mL in our designed biosensor. Besides, a good linear relationship was obtained. The designed biosensor demonstrated good specificity and was successfully applied to clinical serum sample detection.

Numerical study on the dynamics of primary cilium in pulsatile flows by the immersed boundary-lattice Boltzmann method.

An explicit immersed boundary-lattice Boltzmann method is applied to numerically investigate the dynamics of primary cilium in pulsatile blood flows with two-way fluid-structure interaction considered. To well characterize the effect of cilium basal body on cilium dynamics, the cilium base is modeled as a nonlinear rotational spring attached to the cilium's basal end as proposed by Resnick (Biophys J 109:18-25, 2015. https://doi.org/10.1016/j.bpj.2015.05.031). After several careful validations, the fluid-cilium interaction system is investigated in detail at various pulsatile flow conditions that are characterized by peak Reynolds numbers ([Formula: see text]) and Womersley numbers ([Formula: see text]). The periodic flapping of primary cilium observed in our simulations is very similar to the in vivo ciliary oscillation captured by O'Connor et al. (Cilia 2:8, 2013. https://doi.org/10.1186/2046-2530-2-8). The cilium's dynamics is found to be closely related to the [Formula: see text] and [Formula: see text]. Increase the [Formula: see text] or decrease the [Formula: see text] bring to an increase in the cilium's flapping amplitude, tip angular speed, basal rotation, and maximum tensile stress. It is also demonstrated that by reducing the [Formula: see text] or enhancing the [Formula: see text] to a certain level, one can shift the flapping pattern of cilium from its original two-side one to a one-side one, making the stretch only happen on one particular side. During the flapping process, the location of the maximum tensile stress is not always found at the basal region; instead, it is able to propagate from time to time within a certain distance to the base. Due to the obstruction of the primary cilium, the distribution of wall shear stress no longer remains uniform as in the absence of cilia. It oscillates in space with the minimum magnitude which is always found near where the cilium is located. The presence of cilium also reduces the overall level of wall shear stress, especially at the region near the cilium's anchor point.

Revisiting spin-lattice relaxation time measurements for dilute spins in high-resolution solid-state NMR spectroscopy.

Numerous nuclear magnetic resonance (NMR) measurements of spin-lattice relaxation times (T1S) for dilute spins such as (13)C have led to investigations of the motional dynamics of individual functional groups in solid materials. In this work, we revisit the Solomon equations and analyze how the heteronuclear cross relaxation between the dilute S (e.g. (13)C) and abundant I (e.g. (1)H) spins affects the measured T1S values in solid-state NMR in the absence of (1)H saturation during the recovery time. It is found theoretically that at the beginning of the S spin magnetization recovery, the existence of non-equilibrium I magnetization introduces the heteronuclear cross relaxation effect onto the recovery of the S spin magnetization and confirmed experimentally that such a heteronuclear cross relaxation effect results in the recovery overshoot phenomena for the dilute spins when T1S is on the same order of T1H, leading to inaccurate measurements of the T1S values. Even when T1S is ten times larger than T1H, the heteronuclear cross relaxation effect on the measured T1S values is still noticeable. Furthermore, this cross relaxation effect on recovery trajectory of the S spins can be manipulated and even suppressed by preparing the initial I and S magnetization, so as to obtain the accurate T1S values. A sample of natural abundance l-isoleucine powder has been used to demonstrate the T1S measurements and their corresponding measured T1C values under various experimental conditions.

Controlled synthesis and tunable upconversion luminescence of NaYW2O8:Yb3+/Ho3+ nanocrystals.

Tetragonal phase NaYW2O8:Yb3+/Ho3+ nanocrystals were successfully synthesized using a hydrothermal method with a subsequent calcination treatment. Under 980 nm excitation, the 5S2/5F4 --> 5I8 and 5F5 --> 5I8 emissions were observed. The relative intensity of the 5F5 --> 5I8 to the 5S2/5F4 -->5I8 in the samples increased with increasing the pH values of the resultant solutions. The CIE coordinates of the upconversion luminescence were (0.43, 0.54), (0.41, 0.55), (0.40, 0.56), (0.39, 0.54), (0.37, 0.49), (0.35, 0.44), and (0.33, 0.37) for the samples prepared at pH = 7, 8, 9, 10, 11, 13, and 14, respectively. In addition, the upconversion mechanism was also investigated.

Distributed MLEM: an iterative tomographic image reconstruction algorithm for distributed memory architectures.

The processing speed for positron emission tomography (PET) image reconstruction has been greatly improved in recent years by simply dividing the workload to multiple processors of a graphics processing unit (GPU). However, if this strategy is generalized to a multi-GPU cluster, the processing speed does not improve linearly with the number of GPUs. This is because large data transfer is required between the GPUs after each iteration, effectively reducing the parallelism. This paper proposes a novel approach to reformulate the maximum likelihood expectation maximization (MLEM) algorithm so that it can scale up to many GPU nodes with less frequent inter-node communication. While being mathematically different, the new algorithm maximizes the same convex likelihood function as MLEM, thus converges to the same solution. Experiments on a multi-GPU cluster demonstrate the effectiveness of the proposed approach.