To prepare a topical formulation of bimatoprost (BIM) with high skin permeability, we designed a solvent mixture system composed of ethanol, diethylene glycol monoethyl ether, cyclomethicone, and butylated hydroxyanisole, serving as a volatile solvent, nonvolatile co-solvent, spreading agent, and antioxidant, respectively. The ideal topical BIM formulation (BIM–TF#5) exhibited 4.60-fold higher human skin flux and a 529% increase in dermal drug deposition compared to BIM in ethanol. In addition, compared to the other formulations, BIM–TF#5 maximally activated human dermal papilla cell proliferation at a concentration of 5 μM BIM, equivalent to 10 μM minoxidil. Moreover, BIM–TF#5 (0.3% [w/w] BIM) significantly promoted hair regrowth in the androgenic alopecia mouse model and increased the area covered by hair at 10 days by 585% compared to the vehicle-treated mice, indicating that entire telogen area transitioned into the anagen phase. Furthermore, at day 14, the hair weight of mice treated with BIM–TF#5 (5% [w/w] BIM) was 8.45- and 1.30-fold greater than in the 5% (w/w) BIM in ethanol and 5% (w/v) minoxidil treated groups, respectively. In the histological examination, the number and diameter of hair follicles in the deep subcutis were significantly increased in the BIM–TF#5 (0.3 or 5% [w/w] BIM)-treated mice compared to the mice treated with vehicle or 5% (w/w) BIM in ethanol. Thus, our findings suggest that BIM–TF#5 is an effective formulation to treat scalp alopecia, as part of a novel therapeutic approach involving direct prostamide F2α receptor-mediated stimulation of dermal papilla cells within hair follicles.
Two-dimensional (2D) MXenes are promising as electrode materials for energy storage, owing to their high electronic conductivity and low diffusion barrier. Unfortunately, similar to most 2D materials, MXene nanosheets easily restack during the electrode preparation, which degrades the electrochemical performance of MXene-based materials. A novel synthetic strategy is proposed for converting MXene into restacking-inhibited three-dimensional (3D) balls coated with iron selenides and carbon. This strategy involves the preparation of Fe 2 O 3 @carbon/MXene microspheres via a facile ultrasonic spray pyrolysis and subsequent selenization process. Such 3D structuring effectively prevents interlayer restacking, increases the surface area, and accelerates ion transport, while maintaining the attractive properties of MXene. Furthermore, combining iron selenides and carbon with 3D MXene balls offers many more sites for ion storage and enhances the structural robustness of the composite balls. The resultant 3D structured microspheres exhibit a high reversible capacity of 410 mAh g ⁻¹ after 200 cycles at 0.1 A g ⁻¹ in potassium-ion batteries, corresponding to the capacity retention of 97% as calculated based on 100 cycles. Even at a high current density of 5.0 A g ⁻¹ , the composite exhibits a discharge capacity of 169 mAh g ⁻¹ .
Background: Antisocial personality disorder (ASPD) incurs a high cost to society due to the high risk of violent and nonviolent offenses associated with this personality disorder, thus making the examination of the etiology and the onset of ASPD an important public health concern. Method: The present study consisted of five waves of data collection of the Harlem Longitudinal Development Study (N = 674). In the Cox proportional hazard model, latent multiple substance use trajectories from mid-adolescence to emerging adulthood (mean age 14 to mean age 24) were used as a predictor for the onset of ASPD during emerging adulthood to the mid-thirties (mean age 24 to mean age 36). The control variables were gender, ethnicity, problem behaviors, and victimization. Results: In the multiple Cox proportional hazard model, the high (HR = 2.74, p < 0.001) and the increasing frequency of (HR = 2.55, p < 0.001) use on alcohol, cigarette, and cannabis latent trajectory groups were associated with an increased hazard of ASPD onset as compared with the no or low frequency of use on alcohol, cigarette, and cannabis latent trajectory group after controlling for demographic factors and earlier problem behaviors as well as victimization. Conclusions: The implications of this study for the prediction of adult ASPD onset time may focus on the early use of alcohol, cigarette, and cannabis from mid adolescence to emerging adulthood.
Efforts to map atomic-scale chemistry at low doses with minimal noise using electron microscopes are fundamentally limited by inelastic interactions. Here, fused multi-modal electron microscopy offers high signal-to-noise ratio (SNR) recovery of material chemistry at nano- and atomic-resolution by coupling correlated information encoded within both elastic scattering (high-angle annular dark-field (HAADF)) and inelastic spectroscopic signals (electron energy loss (EELS) or energy-dispersive x-ray (EDX)). By linking these simultaneously acquired signals, or modalities, the chemical distribution within nanomaterials can be imaged at significantly lower doses with existing detector hardware. In many cases, the dose requirements can be reduced by over one order of magnitude. This high SNR recovery of chemistry is tested against simulated and experimental atomic resolution data of heterogeneous nanomaterials.
Transition metal dichalcogenides have attracted renewed interest for use as thermoelectric materials owing to their tunable bandgap, moderate Seebeck coefficient, and low thermal conductivity. However, their thermoelectric parameters such as Seebeck coefficient, electrical conductivity, and thermal conductivity are interdependent, which is a drawback. Therefore, it is necessary to find a way to adjust one of these parameters without affecting the other parameters. In this study, we investigated the effect of helium ion irradiation on MoSe 2 thin films with the objective of controlling the Seebeck coefficient and electrical conductivity. At the optimal irradiation dose of 10 ¹⁵ cm ⁻² , we observed multiple enhancements of the power factor resulting from an increase in the electrical conductivity, with slight suppression of the Seebeck coefficient. Raman spectroscopy, X-ray diffraction, and transmission electron microscopy analyses revealed that irradiation-induced selenium vacancies played an important role in changing the thermoelectric properties of MoSe 2 thin films. These results suggest that helium ion irradiation is a promising method to significantly improve the thermoelectric properties of two-dimensional transition metal dichalcogenides. Graphical Abstract Effect of He ⁺ irradiation on thermoelectric properties of MoSe 2 thin films.
We present a single-step, room-temperature synthesis of fluorescent organosilica nanobeads (FOS NBs). The FOS NBs were synthesized under aqueous conditions using (3-aminopropyl)triethoxysilane (APTES) as the silicon source in the presence of l -ascorbic acid (L-AA). In the APTES/L-AA/water ternary phase, the hydrolysis and condensation reaction of APTES occurred under acidic conditions to form spherical FOS NBs with an average diameter of 426.8 nm. FOS NBs exhibit excellent colloidal stability in aqueous media. The formation of FOS NBs was complete within a 10 min reaction time, which indicates potential for large-scale mass-production synthesis of luminescent colloidal NBs. The FOS NBs exhibited blue photoluminescence (PL) under UV excitation in the absence of an additional high temperature calcination process or with the incorporation of any fluorophores. This phenomenon is attributed to the presence of carbon-containing defects, which act as luminescent centers formed by the reaction between amino groups in the APTES and l -ascorbic acid reductant. Finally, the results of a cytotoxicity test and cellular uptake experiments revealed that the FOS NBs showed potential as optical contrast agents for bioimaging. Graphical Abstract
In this study, we investigated the effects of dicaffeoylquinic acid derivatives, including 1,4-di-O-caffeoylquinic acid (1,4-DCQA), 3,4-di-O-caffeoylquinic acid (3,4-DCQA), 3,5-di-O-caffeoylquinic acid (3,5-DCQA), 4,5-di-O-caffeoylquinic acid (4,5-DCQA), and 1,5-di-O-caffeoylquinic acid (1,5-DCQA) on glucose-stimulated insulin secretion (GSIS) activity and α-glucosidase activity were compared in rat INS-1 pancreatic β-cells. The α-glucosidase inhibitory activities of dicaffeoylquinic acid derivatives were as follows: 1,4-DCQA > 1,5-DCQA > 3,4-DCQA > 4,5-DCQA > 3,5-DCQA. In INS-1 cells, dicaffeoylquinic acid derivatives showed no cytotoxic effect at any concentration (2.5–10 μM). In addition, the GSIS activities of dicaffeoylquinic acid derivatives were as follows: 4,5-DCQA > 3,4-DCQA > 1,4-DCQA > 3,5-DCQA > 1,5-DCQA. Treatment of INS-1 cells with 4,5-DCQA resulted in a marked increase in protein expression of extracellular signal-regulated protein kinases (ERK), insulin receptor substrate-2 (P-IRS-2), Akt, phosphoinositide 3-kinase (P-PI3K), and pancreatic and duodenal homeobox-1 (PDX-1), which might be related to its GSIS activity in INS-1 cells. These findings indicate that the location of the dicaffeoyl functional group influences the anti-diabetic activity of quinic acid.
Prime editing can induce a desired base substitution, insertion, or deletion in a target gene using reverse transcriptase after nick formation by CRISPR nickase. In this study, we develop a technology that can be used to insert or replace external bases in the target DNA sequence by linking reverse transcriptase to the Francisella novicida Cas9, which is a CRISPR-Cas9 ortholog. Using FnCas9(H969A) nickase, the targeting limitation of existing Streptococcus pyogenes Cas9 nickase [SpCas9(H840A)]-based prime editing is dramatically extended, and accurate prime editing is induced specifically for the target genes in human cell lines.
The purpose of the present study was to explore the effects of wearing knee guards on skin blood flow and skin pressure during dynamic soccer motions. Twenty-one male subjects participated in the following two experimental conditions: wearing knee guards (KG) and no knee guards (Control). Subjects performed several consecutive soccer motions along with a standing position between each motion. Skin blood flow and skin pressure on the thigh, knee, and calf were monitored. The results showed that skin pressure had the greatest value in a sitting position for both the KG condition and Control, but the smallest during instep kicking and switching directions (P < 0.001). The rear calf had the greatest skin pressure for the KG condition (P < 0.001), while the side knee showed the greatest for the Control (P < 0.001). Normalized skin blood flow based on values from their standing position was the greatest during the jump motion among the various soccer motions. Interestingly, skin blood flow decreased by wearing the knee guards on the front thigh and calf (r = − 0.859; r = − 0.835; P < 0.001), while the blood flow increased on the side knee (r = 0.295, P < 0.001). Subjects felt greater skin pressure sensation during the jump motion and switching directions than other soccer positions/motions (P < 0.001). These results indicate that the knee guards result in relatively lighter pressure for dynamic motions (e.g., kick, switching directions, or jump) than for static positions (e.g., sitting or standing), and the skin blood flows for the thigh, knee, and calf are redistributed by wearing the knee guards, especially during jumping.
Automated formulation of sketches from face photos has seen successive growth since the work of Wang and Tang in recent years. Each new methodology is, however, able to partially achieve its objective of sketch synthesis while using pairs of photos and viewed sketches as a training medium. The viewed sketches are also used as a testing medium to determine the success of those methodologies. Resulting sketches do not fully capture all features of the training photos and viewed sketches. Their similarity value to respective sketch is also around 30 – 50%. One technique may produce sketches with sharp edges, but they do not bear completeness of facial features. Another technique produces sketches with the completeness of facial elements, but they are not well-focused. Second limitation of existing techniques is attributable to face-recognition procedure which is used as a validation step for these methodologies. Face-recognition process with help of synthesized sketches delivers reliable results over datasets with a limited diversity of age, ethnicity, and light intensities. We propose a novel and cost-effective approach to fuse resulting sketches of two test techniques. The two techniques are merged to yield a better sketch containing well-defined features, sharp contours, and less noise. Secondly, fusion suppresses limitations of the component methodologies reaching the resulting sketch. To test this idea of combining sketch-synthesis methods, we experiment with the most basic techniques of image fusion including simple (arithmetic), PCA, and Wavelet based fusions. The proposed setup considered FCN (complete features but less sharpness) and Fast-RSLCR (sharp edges but missing contours) as candidate techniques. It is tested on two datasets namely CUFS and CUFSF. Second dataset incorporates variations of age, ethnicity, light intensities, and slightly deformed features between photos and viewed sketches. Our results indicate achievement of 60.29% SSIM score (enhancement by 3.84%) and 79.03% face-recognition score (enhancement by 5.62%) as compared to Fast-RSLCR.
Nitrocellulose (NC) membranes, as porous paper-like substrates with high protein-binding capabilities, are very popular in the field of point-of-care immunoassays. However, generating robust hydrophobic structures in NC membranes to fabricate microfluidic paper-based analytical devices (μPADs) remains a great challenge. At present, the main method relies on an expensive wax printer. In addition, NC membranes very easy to adhere during the printing process due to electrostatic adsorption. Herein, we developed a facile, fast and low-cost strategy to fabricate μPADs in NC membranes by screen-printing polyurethane acrylate (PUA) as a barrier material for defining flow channels and reaction zones. Moreover, hydrophobic barriers based on UV-curable PUA can resist various surfactant solutions and organic solvents that are generally used in immunoassays and biochemical reactions. To validate the feasibility of this PUA-based NC membrane for immunoassays in point-of-care testing (POCT), we further designed and assembled a rotational paper-based analytical device for implementing a multiplexed enzyme-linked immunosorbent assay (ELISA) in a simple manner. Using the proposed device under the optimal conditions, alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA) could be identified, with limits of detection of 136 pg/mL and 174 pg/mL, respectively, which are below the threshold values of these two cancer biomarkers for clinical diagnosis. We believe that this reliable device provides a promising platform for the diagnosis of disease based on ELISA or other related bioassays in limited settings or remote regions.
Background A targeted co-administration system of docetaxel (DTX) and curcumin (CUR) using a PEG-modified RIPL peptide (IPLVVPLRRRRRRRRC)-conjugated nanostructured lipid carrier (P/R-NLC) was constructed to exert synergistic anticancer effects against chemoresistant breast cancer. Results DTX- or CUR-loaded NLCs and P/R-NLCs were prepared using the solvent emulsification–evaporation method. NLCs showed homogeneous spherical morphology with nano-sized dispersion (< 210 nm) with zeta potential varying from − 16.4 to − 19.9 mV. DTX or CUR was successfully encapsulated in the NLCs: encapsulation efficiency (> 95%); drug loading (8 − 18%). All NLC formulations were stable for 4 weeks under the storage conditions at 4 °C. Drug release was diffusion-controlled, revealing the best fit to the Higuchi equation. DTX- or CUR-loaded formulations showed dose-dependent cytotoxicity. The DTX/CUR combination (1:3 w/w) in P/R-NLC formulations exhibited the strongest synergism in both MCF7 and MCF7/ADR cells with combination index values of 0.286 and 0.130, respectively. Co-treatment with DTX- or CUR-P/R-NLCs increased apoptosis in both cell lines exhibited the superior synergistic inhibitory effect on MCF7/ADR three-dimensional spheroids. Finally, in OVCAR3-xenografted mouse models, co-treatment with DTX- or CUR-loaded P/R-NLCs significantly suppressed tumor growth compared to the other treatment groups. Conclusions Co-administration of DTX/CUR (1:3 w/w) using P/R-NLCs induced a synergistic effect against chemoresistant cancer cells. Graphical Abstract
This study proposed a strategy for effectively diminishing the carrier concentration in Cu2Te by introducing graphene sheets. Based on thermoelectric property measurements and single parabolic band modeling, the incorporated graphene effectively reduced the carrier concentration, not only enhancing the thermoelectric performance of the Cu2Te/graphene composite but also substantially improving its figure of merit up to ∼1.47 at 1000 K, which is 268% higher than that of pristine Cu2Te. This study gives an insight into the control of carrier concentration and thermoelectric properties in Cu2Te, and it could be extended to other copper chalcogenides for excellent thermoelectrics.
Background Endocrine-disrupting chemicals (EDCs) interfere with physiological function by mimicking or blocking hormones; these chemicals enter the human body through various materials used in food packaging, among other routes. Thyroid hormones (THs) are very important hormones that control various basic physiological functions. Results In a previous study, we developed a TH agonist transactivation (TA) assay based on the A549 cell line. However, the assay using A549 showed some limitations, since it required 4 days to yield results and showed low sensitivity to the natural form of human triiodothyronine (T3). Therefore, in this study, we have developed a more sensitive TH TA assay based on a HeLa cell line to screen potential TH agonists. We evaluated the TH agonist activity of 17 chemicals, 5 of which showed TH agonist activity. Conclusions In conclusion, in comparison with the previously developed TA assay, the assay using HeLa cells provided greater accuracy, sensitivity, and specificity, yielding more detailed results for TH agonist chemicals in less time.
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