Skin characterization of diabetes mellitus revealed by polarization-sensitive optical coherence tomography imaging.

Significance: Diabetes can lead to the glycation of proteins and dysfunction of skin collagen. Skin lesions are a prevalent clinical symptom of diabetes mellitus (DM). Early diagnosis and assessing the efficacy of treatment for DM are crucial for patient health management. However, performing a non-invasive skin assessment in the early stages of DM is challenging. Aim: By using the polarization-sensitive optical coherent tomography (PS-OCT) imaging technique, it is possible to noninvasively assess the skin changes caused by diabetes. Approach: The PS-OCT was used to monitor the polarization characteristics of mouse skin at different stages of diabetes. Results: Based on a multi-layered adhesive tape model, we found that the polarization characteristics (retardation, optic axis, and polarization uniformity) were sensitive to the microstructure changes in the samples. Through this method, we observed significant changes in the polarization states of the skin as diabetes progressed. This was in line with the detected microstructure changes in skin collagen fibers using scanning electron microscopy. Conclusions: This study presents a highly useful approach for non-invasive skin assessment of diabetes.

Preparation of electrochemical horseradish peroxidase biosensor with black phosphorene-zinc oxide nanocomposite and their applications.

In this work, a novel and sensitive electrochemical biosensor was constructed based on a black phosphorene (BP) and nanosized zinc oxide (ZnO@BP) nanocomposite as a modifier, which was used for the immobilization of horseradish peroxidase (HRP) on a carbon ionic liquid electrode (CILE). The ZnO@BP nanocomposite was synthesized by a simple in situ hydrothermal method with stripped black phosphorus nanoplates and ZnO. The ZnO@BP and HRP-modified electrode was developed by a casting method. ZnO@BP with highly conductivity, large surface area and good biocompatibility could maintain the bioactivity of HRP and accelerate the electron transfer rate. Cyclic voltammetry was used to study the direct electrochemistry of HRP on the Nafion/HRP/ZnO@BP/CILE with the appearance of a pair of distinct redox peaks. The constructed electrochemical HRP biosensor exhibited excellent electrocatalytic effects on the reduction of trichloroacetic acid and sodium nitrite. Real samples were detected with satisfactory results, which demonstrated the potential applications of this electrochemical HRP biosensor.

Electrochemical Biosensor Based on Horseradish Peroxidase and Black Phosphorene Quantum Dot Modified Electrode.

Black phosphorene quantum dots (BPQDs) were prepared by ultrasonic-assisted liquid-phase exfoliation and centrifugation with morphologies proved by TEM results. Furthermore, an electrochemical enzyme sensor was prepared by co-modification of BPQDs with horseradish peroxidase (HRP) on the surface of a carbon ionic liquid electrode (CILE) for the first time. The direct electrochemical behavior of HRP was studied with a pair of well-shaped voltammetric peaks that appeared, indicating that the existence of BPQDs was beneficial to accelerate the electron transfer rate between HRP and the electrode surface. This was due to the excellent properties of BPQDs, such as small particle size, high interfacial reaction activity, fast conductivity, and good biocompatibility. The presence of BPQDs on the electrode surface provided a fast channel for direct electron transfer of HRP. Therefore, the constructed electrochemical HRP biosensor was firstly used to investigate the electrocatalytic behavior of trichloroacetic acid (TCA) and potassium bromate (KBrO3), and the wide linear detection ranges of TCA and KBrO3 were 4.0-600.0 mmol/L and 2.0-57.0 mmol/L, respectively. The modified electrode was applied to the actual samples detection with satisfactory results.

Paravertebral Block Under Direct Vision Versus Local Anesthetic Infiltration for Pediatric Thoracoscopic Surgery.

Background: For children with congenital lung malformations (CLMs), there is insufficient evidence of the efficacy of direct visual paravertebral block (PVB). We aimed to evaluate its effectiveness and safety by comparing it with local anesthetic infiltration (LAI). Materials and Methods: This was a nonrandomized control study of CLMs in children younger than 3 years of age who underwent thoracoscopic surgery in our hospital from January to December 2020. The children were divided into group A (PVB analgesia group) and group B (LAI group). The primary outcome was the incidence of rebound pain within 72 hours. Secondary outcomes included the Face, Legs, Activity, Crying, Consolability (FLACC) pain scores at 0, 6, 12, 24, 36, 48, and 72 hours, side effects, adverse events, the number of rebound pains, and the postoperative family observation scores. Results: The incidence of rebound pain was 10% in group A and 60.5% in group B within 72 hours (P < .001). The PVB was associated with decreased FLACC pain scores at 12, 24, 36, 48, and 72 hours, family observation scores, and the number of rebound pains (P < .001, P = .01, P = .028, P = .005, P = .006, P = .026, and P < .001, respectively). Group B was also associated with a higher rate of side effects and adverse events. There was no difference in the length of hospital stay. Conclusion: The PVB under direct vision analgesia technique is effective and safe for postoperative pain control in pediatric patients with CLMs. It may be an attractive alternative to LAI for pediatric thoracoscopic surgical procedures.

An optical clearing imaging window: Realization of mouse brain imaging and manipulation through scalp and skull.

Cortical visualization is essential to understand the dynamic changes in brain microenvironment under physiopathological conditions. However, the turbid scalp and skull severely limit the imaging depth and resolution. Existing cranial windows require invasive scalp excision and various subsequent skull treatments. Non-invasive in vivo imaging of skull bone marrow, meninges, and cortex through scalp and skull with high resolution yet remains a challenge. In this work, a non-invasive trans-scalp/skull optical clearing imaging window is proposed for cortical and calvarial imaging, which is achieved by applying a novel skin optical clearing reagent. The imaging depth and resolution are greatly enhanced in near infrared imaging and optical coherence tomography imaging. Combining this imaging window with adaptive optics, we achieve the visualization and manipulation of the calvarial and cortical microenvironment through the scalp and skull using two-photon imaging for the first time. Our method provides a well-performed imaging window and paves the way for intravital brain studies with the advantages of easy-operation, convenience and non-invasiveness.

A Portable Wireless Intelligent Nanosensor for 6,7-Dihydroxycoumarin Analysis with A Black Phosphorene and Nano-Diamond Nanocomposite-Modified Electrode.

In this work, a novel portable and wireless intelligent electrochemical nanosensor was developed for the detection of 6,7-dihydroxycoumarin (6,7-DHC) using a modified screen-printed electrode (SPE). Black phosphorene (BP) nanosheets were prepared via exfoliation of black phosphorus nanoplates. The BP nanosheets were then mixed with nano-diamond (ND) to prepare ND@BP nanocomposites using the self-assembly method, achieving high environmental stability. The nanocomposite was characterized by SEM, TEM, Raman, XPS and XRD. The nanocomposite was used for the modification of SPE to improve its electrochemical performances. The nanosensor displayed a wide linear range of 0.01-450.0 µmol/L with a low detection limit of 0.003 µmol/L for 6,7-DHC analysis. The portable and wireless intelligent electrochemical nanosensor was applied to detect 6,7-DHC in real drug samples by the standard addition method with satisfactory recoveries, which extends the application of BP-based nanocomposite for electroanalysis.

Students Can (Mostly) Recognize Effective Learning, So Why Do They Not Do It?

Cognitive psychology research has emphasized that the strategies that are effective and efficient for fostering long-term retention (e.g., interleaved study, retrieval practice) are often not recognized as effective by students and are infrequently used. In the present studies, we use a mixed-methods approach and challenge the rhetoric that students are entirely unaware of effective learning strategies. We show that whether being asked to describe strategies used by poor-, average-, and high-performing students (Study 1) or being asked to judge vignettes of students using different strategies (Study 2), participants are generally readily able to identify effective strategies: they were able to recognize the efficacy of explanation, pretesting, interpolated retrieval practice, and even some interleaving. Despite their knowledge of these effective strategies, they were still unlikely to report using these strategies themselves. In Studies 2 and 3, we also explore the reasons why students might not use the strategies that they know are effective. Our findings suggest that interventions to improve learners' strategy use might focus less on teaching them about what is effective and more on increasing self-efficacy, reducing the perceived costs, and establishing better habits.

Preparation and Application of Electrochemical Horseradish Peroxidase Sensor Based on a Black Phosphorene and Single-Walled Carbon Nanotubes Nanocomposite.

To design a new electrochemical horseradish peroxidase (HRP) biosensor with excellent analytical performance, black phosphorene (BP) nanosheets and single-walled carbon nanotubes (SWCNTs) nanocomposites were used as the modifier, with a carbon ionic liquid electrode (CILE) as the substrate electrode. The SWCNTs-BP nanocomposite was synthesized by a simple in situ mixing procedure and modified on the CILE surface by the direct casting method. Then HRP was immobilized on the modified electrode with Nafion film. The electrocatalysis of this electrochemical HRP biosensor to various targets was further explored. Experimental results indicated that the direct electrochemistry of HRP was realized with a pair of symmetric and quasi-reversible redox peaks appeared, which was due to the presence of SWCNTs-BP on the surface of CILE, exhibiting synergistic effects with high electrical conductivity and good biocompatibility. Excellent electrocatalytic activity to trichloroacetic acid (TCA), sodium nitrite (NaNO2), and hydrogen peroxide (H2O2) were realized, with a wide linear range and a low detection limit. Different real samples, such as a medical facial peel solution, the soak water of pickled vegetables, and a 3% H2O2 disinfectant, were further analyzed, with satisfactory results, further proving the potential practical applications for the electrochemical biosensor.

In-situ growth of nitrogen-doped carbonized polymer dots on black phosphorus for electrochemical DNA biosensor of Escherichia coli O157: H7.

Sensitive and accurate detection technology for pathogenic bacteria is of great social and economic significance in foodborne disease and food safety. In this paper, a novel portable electrochemical DNA biosensor for the detection of specific DNA sequence of Escherichia coli (E. coli) O157: H7 was constructed. To enhance the performance of the electrochemical sensor, a functionalized nitrogen-doped carbonized polymer dots in-situ grown on few-layer black phosphorus (N-CPDs@FLBP) was synthesized and used as the modifier on the surface of screen-printed electrode. Combining gold nanoparticles as immobilization matrix and methylene blue as electrochemical indicator, the analytical performance of this electrochemical DNA biosensor was evaluated using standard complementary ssDNA sequence in the linear concentration range from 1.0 × 10-19 to 1.0 × 10-6 mol/L with a low detection limit as 3.33 × 10-20 mol/L (3 σ). Furthermore, the portable electrochemical DNA biosensor was proposed based on polymerase chain reaction amplification for the detection of the E. coli O157: H7 genomic DNA from chicken meat, which verified the feasibility for practical samples detection. The research has great theoretical and practical significance for the development of electrochemical biosensor of pathogenic bacteria.

The pharmacokinetics of oral trazpiroben (TAK-906) after organic anion transporting polypeptide 1B1/1B3 inhibition: A phase I, randomized study.

Trazpiroben is a dopamine D2 /D3 receptor antagonist under development for the treatment of gastroparesis. This phase I, open-label, randomized, two-way crossover study (NCT04121078) evaluated the effect of single-dose intravenous rifampin, a potent inhibitor of the organic anion transporting polypeptides (OATPs) 1B1 and 1B3, on the pharmacokinetics and safety of trazpiroben in healthy adults. The utility of coproporphyrin (CP) I and CPIII as biomarkers of OATP inhibition was also assessed. Overall, 12 participants were enrolled and randomized (1:1) into one of two treatment sequences (AB and BA). Participants received either a single oral dose of trazpiroben 25 mg (treatment A) or a single oral dose of trazpiroben 25 mg immediately after a single 30-min intravenous infusion of rifampin 600 mg (treatment B). After a washout period of at least 7 days, participants received the other treatment. Geometric mean area under the curve from time 0 extrapolated to infinity (AUC∞ ) and maximum serum concentration (Cmax ) of plasma trazpiroben were higher in participants receiving treatment B than those receiving treatment A (AUC∞ , 168.5 vs. 32.68 ng*h/ml; Cmax , 89.62 vs. 14.37 ng/ml); corresponding geometric mean ratios (90% confidence interval) showed 5.16 (4.25-6.25) and 6.24 (4.62-8.42)-fold increases in these parameters, respectively. In this study, trazpiroben was confirmed as a substrate of OATP1B1/1B3, and therefore co-administration of trazpiroben with moderate to strong inhibitors of OATP1B1/1B3 is not recommended. This is also the first assessment of the utility of CPI and CPIII as endogenous biomarkers of OATP1B1/1B3 inhibition after a single intravenous dose of rifampin.

Evaluation of the pharmacokinetics of trazpiroben (TAK-906) in the presence and absence of the proton pump inhibitor esomeprazole.

Trazpiroben, a dopamine D2 /D3 receptor antagonist under development to treat gastroparesis, displays decreasing solubility with increasing pH. This single-sequence, open-label, two-period, crossover study evaluated the effect of esomeprazole, a proton pump inhibitor that raises gastric pH, on the single-dose pharmacokinetics, safety, and tolerability of trazpiroben in healthy adults (NCT03849690). In total, 12 participants were enrolled and entered period 1 (days 1-3), receiving a single oral dose of trazpiroben 25 mg on day 1. After a 4-day washout, participants then entered period 2 (days 8-13) and received esomeprazole 40 mg once daily on days 8-12, with a single oral dose of trazpiroben 25 mg co-administered 1 h post esomeprazole dosing on day 11. Geometric mean area under the curve from time 0 extrapolated to infinity (AUC∞ ) and maximum plasma concentration (Cmax ) values were generally similar when trazpiroben was administered alone versus alongside esomeprazole (AUC∞ , 44.03 vs. 38.85 ng h/ml; Cmax , 19.76 vs. 17.24 ng/ml). Additionally, the associated geometric mean ratio (GMR; co-administration: administration alone) 90% confidence intervals (CIs) suggested no clinically meaningful difference between treatment groups (AUC∞ , GMR 0.88, 90% CI 0.78-1.00; Cmax , 0.87, 90% CI 0.70-1.09). Mean apparent first-order terminal elimination half-life values were similar between treatments, illustrating co-administration with esomeprazole had minimal effect on trazpiroben elimination. Trazpiroben was well-tolerated in healthy adults following administration alone and alongside esomeprazole, with no clinically relevant adverse events reported. The lack of evidence of any clinically meaningful drug-drug interaction supports the co-administration of esomeprazole with trazpiroben.

The Regulation of let-7c-5p on the Biological Characteristics of Lung Adenocarcinoma Cells by Targeting AURKB.

To study the modulatory mechanism of let-7c-5p on the biological characteristics of lung adenocarcinoma (LUAD) cells by targeting AURKB. Differentially expressed genes (DEGs) were screened by bioinformatics analysis. CCK-8, colony formation, scratch healing, Transwell, and flow cytometry assays were employed to test biological functions of LUAD cells. Western Blot was undertaken to assay the protein level of AURKB, and qRT-PCR was undertaken to test AURKB mRNA and let-7c-5p expression. Dual-luciferase reporter gene method was applied to detect the interaction between AURKB and let-7c-5p. Let-7c-5p was much likely to target AURKB expression. Let-7c-5p was poorly expressed in LUAD cells and suppressed AURKB. Silencing AURKB or overexpressing let-7c-5p both could suppress proliferation, migration, and invasion and stimulate apoptosis, while overexpressing the two simultaneously could reverse such effect. Forced expression of let-7c-5p inhibited proliferation, migration, and invasion and accelerated apoptosis of LUAD cells by inhibiting AURKB, which may provide a new way to understand the malignant progression of LUAD.

Systematic analysis of brain and skull ischemic injury expression profiles reveals associations of the tumor immune microenvironment and cell death with ischemic stroke.

Background: Previous studies have shown that stroke is a potential first sign of neoplasia, but the relationship between stroke and cancer remains unclear. As a complex brain disease, ischemic stroke involves cell death and immunity. Thus, it is necessary to investigate the association of the tumor immune microenvironment and cell death with ischemic stroke. Methods: We established a photothrombosis-induced ischemic injury model in mouse brain and skull. Subsequently, we sequenced the whole transcriptome of the injured mouse brain and skull and analyzed the expression profiles. To investigate the association of stroke with cell death and cancer, we systematically performed gene set enrichment analysis in pan-cell death (i.e., apoptosis, cuproptosis, ferroptosis, necroptosis, and pyroptosis) and the cancer hallmark pathways. The time-dependent immune cell abundance variations after ischemic injury were estimated. Furthermore, pan-cancer genomic and prognostic analyses of the ischemic injury-related gene sets were also performed. Results: In this study, we found that there exist temporal and spatial differences in the gene expression patterns of both the brain and skull with ischemic injury. The skull ischemic injury-induced changes in the brain transcriptome were particularly great, but could recover in a short period, while the skull transcriptome variation resulting from brain ischemic injury was long-lasting. In addition, the expression of the genes related to ischemic injury was also associated with pan-cell death and the cancer hallmark pathways. The changes in the abundance of immune cells indicate that brain ischemic injury may disrupt the immune microenvironment for a longer time, while the skull can balance the stability of the immune microenvironment better. Moreover, the brain ischemic injury-related gene sets were highly correlated with a variety of tumors, particularly glioblastoma multiforme (GBM), kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and uveal melanoma (UVM), which carry a greater mortality risk after stroke. Conclusion: This systematic analysis not only helps in the understanding of the changes in the gene expression profiles of both the brain and skull with ischemic injury but also reveals the association of the tumor immune microenvironment and cell death with ischemic stroke.

A histone H3K4me1-specific binding protein is required for siRNA accumulation and DNA methylation at a subset of loci targeted by RNA-directed DNA methylation.

In plants, RNA-directed DNA methylation (RdDM) is a well-known de novo DNA methylation pathway that involves two plant-specific RNA polymerases, Pol IV and Pol V. In this study, we discovered and characterized an RdDM factor, RDM15. Through DNA methylome and genome-wide siRNA analyses, we show that RDM15 is required for RdDM-dependent DNA methylation and siRNA accumulation at a subset of RdDM target loci. We show that RDM15 contributes to Pol V-dependent downstream siRNA accumulation and interacts with NRPE3B, a subunit specific to Pol V. We also show that the C-terminal tudor domain of RDM15 specifically recognizes the histone 3 lysine 4 monomethylation (H3K4me1) mark. Structure analysis of RDM15 in complex with the H3K4me1 peptide showed that the RDM15 tudor domain specifically recognizes the monomethyllysine through an aromatic cage and a specific hydrogen bonding network; this chemical feature-based recognition mechanism differs from all previously reported monomethyllysine recognition mechanisms. RDM15 and H3K4me1 have similar genome-wide distribution patterns at RDM15-dependent RdDM target loci, establishing a link between H3K4me1 and RDM15-mediated RdDM in vivo. In summary, we have identified and characterized a histone H3K4me1-specific binding protein as an RdDM component, and structural analysis of RDM15 revealed a chemical feature-based lower methyllysine recognition mechanism.

Organic pollutants in sedimentary microplastics from eastern Guangdong: Spatial distribution and source identification.

Microplastics have a strong affinity for potentially toxic organic pollutants such as polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs). Since 2005, the International Pellet Watch used plastic pellets to monitor hydrophobic organic contaminants in marine environments. We examined the spatial distribution and sources of 16 PAHs and eight OCPs on microplastics (pellets, fragments, and foam) collected from eastern Guangdong beaches with the goal of evaluating the feasibility of exclusively using pellets in global monitoring of hydrophobic organic contaminants. The ∑PAH and ∑OCP concentrations ranged from 11.2 to 7710 ng g-1 and 2.2-1970 ng g-1, respectively. Although inter-site and regional differences were insignificant in fragments and foam, regional differences were observed in ∑OCP concentrations on pellets samples collected at the estuary mouth and the distributary (p < 0.05). No regional difference in ∑PAH concentration on microplastics was observed, except between fragments from the remote beach and those from the distributary (p = 0.015) and the estuary mouth (p = 0.015). The compositional profiles of PAHs revealed that PAHs with 2-4 rings were more dominant than those with >4 rings. Considering low molecular weight PAHs are less hydrophobic and more toxic; the results suggest low molecular weight PAHs may pose a significant risk to marine organisms. This study shows that the International Pellet Watch could offer critical data on source and transport of microplastic-associated OCPs but may overlook critical vehicles of PAHs in coastal environments such as foam.

Adverse effect of paternal hepatitis B virus infection on clinical pregnancy after frozen-thawed embryo transfer.

PURPOSE: This study aimed to determine the effect of paternal hepatitis B virus (HBV) infection on reproductive outcomes of couples undergoing frozen-thawed embryo transfer (FET). METHODS: This retrospective cohort study included FET cycles performed between January 2014 and March 2017 in couples with a hepatitis B surface antigen (HBsAg)-positive male partner and an HBsAg-negative female partner, which was categorized as HBsAg group. The FET cycles underwent by couples with both HBsAg-negative partners were randomly selected as controls. The primary outcome was clinical pregnancy. RESULTS: A total of 117 FET cycles, comprising 39 in the HBsAg group and 78 in the control group, were included. Couples with HBsAg-positive male partners had significantly lower clinical pregnancy rate (17.9 vs 41.0%, P = 0.013), lower implantation rate (11.1 vs 24.5%, P = 0.014), and lower live birth rate (12.8 vs 30.8%, P = 0.034) compared with the control group. Moreover, the multivariate logistic regression analysis showed that paternal HBV infection was negatively associated with clinical pregnancy (odds ratio = 0.297, 95% confidence interval 0.108-0.817, P = 0.019). The miscarriage rate was not significantly different between the two groups (28.6 vs 25.0%, P = 1.000). CONCLUSIONS: Paternal HBV infection resulted in a lower frequency of clinical pregnancy after FET, a difference that was probably attributed to a detrimental effect of HBV on the ability of embryos to survive freezing and thawing.

Assisted Hatching in Couples with Advanced Maternal Age: A Systematic Review and Meta-analysis.

This systematic review aimed to evaluate the efficacy and safety of assisted hatching (AH) performed in couples with advanced maternal age. We searched for randomized controlled trials (RCTs) in electronic databases, including MEDLINE, EMBASE and CENTRAL (from inception to January 2018); in addition, we hand-searched the reference lists of included studies and similar reviews. We included RCTs comparing AH versus no treatment (control). The meta-analysis was performed by RevMan 5.3 software. The search retrieved 943 records and 8 RCTs were included, comprising 870 cycles (n=440 for AH, and n=430 for control). There was no significant difference in the rates of live birth (RR 0.88, 95% CI 0.65 to 1.18, 3 RCTs, n=427, I2=0%), clinical pregnancy (RR 1.00, 95% CI 0.83 to 1.19, 8 RCTs, n=870, I2=22%), implantation (RR 1.07, 95% CI 0.83 to 1.39, 4 RCTs, n=1359, I2=0%), miscarriage (RR 1.13, 95% CI 0.66 to 1.94, 2 RCTs, n=116, I2=0%) and multiple pregnancy (RR 0.89, 95% CI 0.31 to 2.52, 1 RCT, n=97, I2=not applicable) between the treatment group and control group. No reasonable conclusions could be drawn regarding reproductive outcomes after AH in patients with advanced maternal age due to the small sample pooled in meta-analyses. Studies of high methodological quality and with adequate power are necessary to further investigate the value of AH in assisted conception of those patients.

Gaussian-Based Smooth Dielectric Function: A Surface-Free Approach for Modeling Macromolecular Binding in Solvents.

Conventional modeling techniques to model macromolecular solvation and its effect on binding in the framework of Poisson-Boltzmann based implicit solvent models make use of a geometrically defined surface to depict the separation of macromolecular interior (low dielectric constant) from the solvent phase (high dielectric constant). Though this simplification saves time and computational resources without significantly compromising the accuracy of free energy calculations, it bypasses some of the key physio-chemical properties of the solute-solvent interface, e.g., the altered flexibility of water molecules and that of side chains at the interface, which results in dielectric properties different from both bulk water and macromolecular interior, respectively. Here we present a Gaussian-based smooth dielectric model, an inhomogeneous dielectric distribution model that mimics the effect of macromolecular flexibility and captures the altered properties of surface bound water molecules. Thus, the model delivers a smooth transition of dielectric properties from the macromolecular interior to the solvent phase, eliminating any unphysical surface separating the two phases. Using various examples of macromolecular binding, we demonstrate its utility and illustrate the comparison with the conventional 2-dielectric model. We also showcase some additional abilities of this model, viz. to account for the effect of electrolytes in the solution and to render the distribution profile of water across a lipid membrane.