Azonia-Naphthalene: A Cationic Hydrophilic Building Block for Stable N-Type Organic Mixed Ionic-Electronic Conductors.

Conjugated polymers that can efficiently transport both ionic and electronic charges have broad applications in next-generation optoelectronic, bioelectronic, and energy storage devices. To date, almost all the conjugated polymers have hydrophobic backbones, which impedes efficient ion diffusion/transport in aqueous media. Here, we design and synthesize a novel hydrophilic polymer building block, 4a-azonia-naphthalene (AN), drawing inspiration from biological systems. Because of the strong electron-withdrawing ability of AN, the AN-based polymers show typical n-type charge transport behaviors. We find that cationic aromatics exhibit strong cation-π interactions, leading to smaller π-π stacking distance, interesting ion diffusion behavior, and good morphology stability. Additionally, AN enhances the hydrophilicity and ionic-electronic coupling of the polymer, which can help to improve ion diffusion/injection speed, and operational stability of organic electrochemical transistors (OECTs). The integration of cationic building blocks will undoubtedly enrich the material library for high-performance n-type conjugated polymers.

Counterion docking: a general approach to reducing energetic disorder in doped polymeric semiconductors.

Molecular doping plays an important role in controlling the carrier concentration of organic semiconductors. However, the introduction of dopant counterions often results in increased energetic disorder and traps due to the molecular packing disruption and Coulomb potential wells. To date, no general strategy has been proposed to reduce the counterion-induced structural and energetic disorder. Here, we demonstrate the critical role of non-covalent interactions (NCIs) between counterions and polymers. Employing a computer-aided approach, we identified the optimal counterions and discovered that NCIs determine their docking positions, which significantly affect the counterion-induced energetic disorder. With the optimal counterions, we successfully reduced the energetic disorder to levels even lower than that of the undoped polymer. As a result, we achieved a high n-doped electrical conductivity of over 200 S cm-1 and an eight-fold increase in the thermoelectric power factor. We found that the NCIs have substantial effects on doping efficiency, polymer backbone planarity, and Coulomb potential landscape. Our work not only provides a general strategy for identifying the most suitable counterions but also deepens our understanding of the counterion effects on doped polymeric semiconductors.

Recent Advances in Zein-Based Nanocarriers for Precise Cancer Therapy.

Cancer has emerged as a leading cause of death worldwide. However, the pursuit of precise cancer therapy and high-efficiency delivery of antitumor drugs remains an enormous obstacle. The major challenge is the lack of a smart drug delivery system with the advantages of biodegradability, biocompatibility, stability, targeting and response release. Zein, a plant-based protein, possesses a unique self-assembly ability to encapsulate anticancer drugs directly or indirectly. Using zein as a nanotherapeutic pharmaceutic preparation can protect anticancer drugs from harsh environments, such as sunlight, stomach acid and pepsin. Moreover, the surface functionalization of zein is easily realized, which can endow it with targeting and stimulus-responsive release capacity. Hence, zein is an ideal nanocarrier for the precise delivery of anticancer drugs. Combined with our previous research experiences, we attempt to review the current state of the preparation of zein-based nanocarriers for anticancer drug delivery. The challenges, solutions and development trends of zein-based nanocarriers for precise cancer therapy are discussed. This review will provide a guideline for precise cancer therapy in the future.

Assessment of different sonographic cervical measures to predict labor induction outcomes: a systematic review and meta-analysis.

Background: Induction of labor (IOL) is a common obstetric approach to start or encourage uterine contractions to achieve a vaginal birth. It is recommended when continuing the pregnancy may be more dangerous for the mother or baby. Different ultrasonographic measures, such as cervical length, have been investigated as possible predictors of the outcomes of IOL. This meta-analysis aimed to assess the accuracy of ultrasound measurements in anticipating successful IOL. Methods: The study conducted a thorough search on three databases (PubMed, Scopus, and Web of Science) until 04 March 2023, to find clinical studies published in English that reported different sonographic cervical measures and their ability to predict IOL outcomes. The chosen studies were stratified based on the type of indicator reported, and a meta-analysis was conducted to determine the best indicator for both successful and failed induction. The risk of bias and concerns about the applicability of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) method. Results: This study analyzed 57 studies with 9,338 patients. Cervical length is moderately effective in predicting successful IOL, with pooled sensitivity (SN) and specificity (SP) of 0.67 and 0.70, respectively. However, cervical length had a pooled SN and SP of 0.70 and 0.61 for predicting failed IOL. The posterior cervical angle was found to have a higher pooled SN and SP of 0.79 and 0.73 for predicting successful IOL. Fetal head-perineum distance demonstrated moderate accuracy with a pooled SN, SP, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve of 0.58, 0.66, 1.95, 0.36, 5.33, and 0.9992, respectively, for predicting successful IOL. Conclusions: Fetal head-perineum distance was the most effective predictor for successful IOL compared to cervical length, which only had a moderate predictive ability. Shortening of cervical length was not a useful indicator for successful IOL. On the other hand, the posterior cervical angle was the most reliable factor for predicting failed induction. The study's findings can aid in developing more effective management strategies for IOL.

Superb microvascular imaging for evaluation of microvascularity in breast nodules compared with conventional Doppler imaging.

Background: Neovascularity visualization in breast nodules is challenging due to the limitations of conventional Doppler imaging methods. This study aims to assess the performance of superb microvascular imaging (SMI) in evaluating the microvascularity of breast nodules (diameter ≤2 cm). The comparison of performances of SMI with color Doppler flow imaging (CDFI) and power Doppler imaging (PDI) was made by using a three-factor scoring system of vascularity. This study also investigated the common features of microvascularity in small malignant nodules on SMI for early differentiating from benign nodules. Methods: Ninety-one female patients (with 125 breast nodules) were enrolled in this retrospective study. All the breast nodules were examined by grayscale ultrasonography (US), CDFI, PDI, and SMI. The number, morphologic features, and distribution of blood vessels were scored to evaluate the nodular vascularity in light of the three-factor scoring system. The diagnostic value of SMI for microvascularity in breast nodules was analyzed and compared with CDFI and PDI. Results: Histological analysis showed 53 malignant and 72 benign nodules. The vascularity grades detected by SMI were significantly different from those of CDFI and PDI (P<0.05). SMI detected 47 grade-IV nodules of the total 125 nodules (37.6%), which was more than those detected by CDFI (10.4%, 13/125) and PDI (12.8%, 16/125), while more grade-I nodules were detected by CDFI (42.4%, 53/125) and PDI (36.8%, 46/125) compared with SMI (21.6%, 27/125). Differences in the vessel number, morphologic features, and distribution between benign and malignant breast nodules were significant on SMI (P<0.05). The vessel number ≥6, penetrating vessels, and a mixed distribution of vessels in peripheral and central nodular tissues were the common features of microvascularity in the grade-IV malignant nodules on SMI, whereas the blood vessels in the benign nodules were straight and branching and peripherally distributed. Conclusions: In comparison with CDFI and PDI, SMI enhances microvascularity detection, depicts the microvascular architecture in breast nodules and has potential in the differential diagnosis of malignant nodules from benign nodules.

Montmorillonite/chitosan nanoparticles as a novel controlled-release topical ophthalmic delivery system for the treatment of glaucoma.

BACKGROUND: To date, the rapid clearance from ocular surface has been a huge obstacle for using eye drops to treat glaucoma, since it has led to the short preocular residence time and low bioavailability. METHODS: The novel nanoparticles (NPs) were designed for topical ophthalmic controlled drug delivery system through intercalating the BH into the interlayer gallery of Na-montmorillonite (Na+Mt) and then further enchasing chitosan nanoparticles. The resulting nanoparticles had a positive charge (+29±0.18 mV) with an average diameter of 460±0.6 nm. RESULTS: In vitro study of drug release profiles suggested controlled release pattern. The irritation experiment analysis on both human immortalized cornea epithelial cell (iHCEC) and chorioallantoic membrane-trypan blue staining (CAM-TBS) showed good tolerance for ocular tissues. It was interestingly found that the nanoparticles could enter into iHCEC from the result of cellular uptake experiment measured by confocal layer scan microscopy (CLSM). Meanwhile, multilayered iHCEC was used to simulate the barrier of corneal epithelial cells for in vivo preocular retention capacity study, which suggested that BH-Mt/CS NPs could prolong the retention time in comparison with BH solution. The ocular pharmacokinetics studied by microdialysis sampling technique showed that AUC0-t and MRT0-t of BH-Mt/CS NPs were 1.99-fold and 1.75-fold higher than those of BH solution, indicating higher bioavailability. Moreover, the study of blood drug concentration, few researchers have reported, showed that low level drug could enter into blood, suggesting lower systematic side effect. Importantly, pharmacodynamics studies suggested that BH-Mt/CS NPs could make a significant decreased intraocular pressure on glaucomatous rabbits. CONCLUSION: Inspired by these advance of montmorillonite/chitosan nanoparticles, we envision that the BH-Mt/CS NPs will be a potential carrier for BH, opening up the possible applications in glaucoma therapy.

Controlled drug delivery for glaucoma therapy using montmorillonite/Eudragit microspheres as an ion-exchange carrier.

BACKGROUND: Glaucoma is a serious eye disease that can lead to loss of vision. Unfortunately, effective treatments are limited by poor bioavailability of antiglaucoma medicine due to short residence time on the preocular surface. MATERIALS AND METHODS: To solve this, we successfully prepared novel controlled-release ion-exchange microparticles to deliver betaxolol hydrochloride (BH). Montmorillonite/BH complex (Mt-BH) was prepared by acidification-intercalation, and this complex was encapsulated in microspheres (Mt-BH encapsulated microspheres [BMEMs]) by oil-in-oil emulsion-solvent evaporation method. The BH loaded into ion-exchange Mt was 47.45%±0.54%. After the encapsulation of Mt-BH into Eudragit microspheres, the encapsulation efficiency of BH into Eudragit microspheres was 94.35%±1.01% and BH loaded into Eudragit microspheres was 14.31%±0.47%. RESULTS: Both Fourier transform infrared spectra and X-ray diffraction patterns indicated that BH was successfully intercalated into acid-Mt to form Mt-BH and then Mt-BH was encapsulated into Eudragit microspheres to obtain BMEMs. Interestingly, in vitro release duration of the prepared BMEMs was extended to 12 hours, which is longer than both of the BH solution (2.5 hours) and the conventional BH microspheres (5 hours). Moreover, BMEM exhibited lower toxicity than that of BH solution as shown by the results of cytotoxicity tests, chorioallantoic membrane-trypan blue staining, and Draize rabbit eye test. In addition, both in vivo and in vitro preocular retention capacity study of BMEMs showed a prolonged retention time. The pharmacodynamics showed that BMEMs could extend the drug duration of action. CONCLUSION: The developed BMEMs have the potential to be further applied as ocular drug delivery systems for the treatment of glaucoma.

A novel ion-exchange carrier based upon liposome-encapsulated montmorillonite for ophthalmic delivery of betaxolol hydrochloride.

As a novel ion-exchange carrier with high surface area and excellent exchangeability, montmorillonite (Mt) was intercalated with betaxolol hydrochloride (BH) to form a nanocomposite and then encapsulated by liposomes (Mt-BH-LPs) for an ophthalmic drug-delivery system. The Mt-BH and Mt-BH-LPs were prepared by an acidification process and ethanol injection combined with ammonium sulfate gradient methods. The successful formation of Mt-BH and Mt-BH-LPs was verified by thermogravimetric analysis, X-ray diffraction, Fourier-transform infrared spectra, and transmission electron microscopy. Mt-BH-LPs possessed the favorable physical characteristics of encapsulation efficiency, drug loading, mean particle size, and ζ-potential. In vitro release studies indicated Mt-BH-LPs effectively maintained a relatively sustained slow release. Immortalized human corneal epithelial cell cytotoxicity, in vivo rabbit eye-irritation tests, and chorioallantoic membrane-trypan blue staining all revealed that Mt-BH-LPs had no obvious irritation on ocular tissues. A new in vitro tear-turnover model, including inserts containing human corneal epithelial cells, was designed to evaluate the precorneal retention time of Mt-BH-LPs. The results showed that Mt-BH-LPs maintained a certain BH concentration in tear fluid for a longer period than the BH solution. In vivo precorneal retention studies also indicated Mt-BH-LPs prolonged drug retention on the ocular surface more than the BH solution. Furthermore, pharmacodynamic studies showed that Mt-BH-LPs had a prolonged effect on decreasing intraocular optical pressure in rabbits. Our results demonstrated that Mt-BH-LPs have potential as an ophthalmic delivery system.