Accelerated infected wound healing by probiotic-based living microneedles with long-acting antibacterial effect.

Delays in infected wound healing are usually a result of bacterial infection and local inflammation, which imposes a significant and often underappreciated burden on patients and society. Current therapies for chronic wound infection generally suffer from limited drug permeability and frequent drug administration, owing to the existence of a wound biofilm that acts as a barrier restricting the entry of various antibacterial drugs. Here, we report the design of a biocompatible probiotic-based microneedle (MN) patch that can rapidly deliver beneficial bacteria to wound tissues with improved delivery efficiency. The probiotic is capable of continuously producing antimicrobial substances by metabolizing introduced glycerol, thereby facilitating infected wound healing through long-acting antibacterial and anti-inflammatory effects. Additionally, the beneficial bacteria can remain highly viable (>80 %) inside MNs for as long as 60 days at 4 °C. In a mouse model of Staphylococcus aureus-infected wounds, a single administration of the MN patch exhibited superior antimicrobial efficiency and wound healing performance in comparison with the control groups, indicating great potential for accelerating infected wound closure. Further development of live probiotic-based MN patches may enable patients to better manage chronically infected wounds.

Traffic accident duration prediction using multi-mode data and ensemble deep learning.

Predicting the duration of traffic accidents is a critical component of traffic management and emergency response on expressways. Traffic accident information is inherently multi-mode data in terms of data types. However, most existing studies focus on single-mode data, and the influence of multi-mode data on the prediction performances of models has been the subject of only very limited quantitative analysis. The present work addresses these issues by proposing a heterogeneous deep learning architecture employing multi-modal features to improve the accuracy of predictions for traffic accident durations on expressways. Firstly, six unique data modes are obtained based on the structured data and the text data. Secondly, a hybrid deep learning approach is applied to build classification models with reduced prediction error. Finally, a rigorous analysis of the influence for multi-mode data on the accident duration prediction performances is conducted using a variety of deep learning models. The proposed method is evaluated using survey data collected from an expressway monitoring system in Shaanxi Province, China. The experimental results show that Word2Vec-BiGRU-CNN is a suitable and better model using text features for traffic accident duration prediction, as the F1-score is 0.3648. This study confirms that the newly established structured features extracted from text data substantially enhance the prediction effects of deep learning algorithms. However, these new features were a detriment to the prediction effects of conventional machine learning algorithms. Accordingly, these results demonstrate that the processing and extraction of text features is a complex issue in the field of traffic accident duration prediction.

Self-Implantable Core-Shell Microneedle Patch for Long-Acting Treatment of Keratitis via Programmed Drug Release.

Bacteria-induced keratitis is a major cause of corneal blindness in both developed and developing countries. Instillation of antibiotic eyedrops is the most common management of bacterial keratitis but usually suffers from low bioavailability (i.e., <5%) and frequent administration, due to the existence of corneal epithelial barrier that prevents large and hydrophilic drug molecules from entering the cornea, and the tear film on corneal surface that rapidly washes drug away from the cornea. Here, a self-implantable core-shell microneedle (MN) patch with programmed drug release property to facilitate bacterial keratitis treatment is reported. The pH-responsive antimicrobial nanoparticles (NPs), Ag@ZIF-8, which are capable of producing antibacterial metal ions in the infected cornea and generating oxidative stress in bacteria, are loaded in the dissolvable core, while the anti-angiogenic drug, rapamycin (Rapa), is encapsulated in the biodegradable shell, thereby enabling rapid release of Ag@ZIF-8 NPs and sustained release of Rapa after corneal insertion. Owing to the programmed release feature, one single administration of the core-shell MN patch in a rat model of bacterial keratitis, can achieve satisfactory antimicrobial activity and superior anti-angiogenic and anti-inflammation effects as compared to daily topical eyedrops, indicating a great potential for the infectious keratitis therapy in clinics.

Design, optimization, and evaluation for a long-time-released transdermal microneedle delivery system containing estradiol.

Transdermal drug delivery systems (TDDS) have drawbacks such as poor absorption, low blood concentration, and delayed effects. Dissolving microneedle has sharp tips and short length, which overcome patients' pain and improve transdermal efficiency but has low mechanical strength and drug loading capacity. This study thereby proposes a microemulsion-encapsulated and long-time-released transdermal microneedle (MN) delivery system with estradiol (Es) as the model drug. The microemulsion (ME) was optimized by utilizing the pseudo-ternary phase diagram and D-optimal mixture design. The estradiol microemulsion-encapsulated microneedle (Es-ME-MN) was optimized by Box-Behnken design and prepared by freeze-thaw method. The Es-ME-MN obtained was characterized and evaluated through a large variety of studies. Es-ME-MN had sufficient mechanical strength to pierce skin and was safe enough, the length of which was 600 µm, and the Es content was 177.12 ± 0.72 µg/patch without drug-excipient chemical interaction. In vitro permeation study showed that Es-ME-MN has a higher transdermal efficiency and lower retention capacity than commercial estradiol patch and conventional MN. Es plasma concentration began to increase at 3 h and remained at 12.98-23.52 ng/mL until 72 h by pharmacokinetic experiments in the Es-ME-MN group. Es-ME-MN rapidly achieves effective blood concentrations through needle puncture and microemulsion delivery and maintains blood concentrations through the baseplate long-time release. Microemulsion-encapsulated, organic solvent-free, and long-time-released transdermal microneedle will make progress and provide a new idea for transdermal delivery of lipophilic drugs.

WITHDRAWN: Long-time-released Transdermal Microneedle Delivery System.

The article has been withdrawn at the request of the authors of the journal "Current Drug Delivery", Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused. The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Construction and optimization of ecological security network in the Shule River Basin, China.

Construction and optimization of ecological security network is an efficient way to ensure regional ecological security and achieve sustainable development. Based on the morphological spatial pattern analysis method, circuit theory and other methods, we constructed the ecological security network of the Shule River Basin. The PLUS model was used to predict the land use change in 2030, with the aim to explore the current ecological protection direction and propose reasonable optimization strategies. The results showed that there were 20 ecological sources in the Shule River Basin, with a total area of 15774.08 km2, accounting for 12.3% of the total area of study area. The ecological sources were mainly distributed in the south part of the study area. A total of 37 potential ecological corridors were extracted, including 22 important ecological corridors, which showed the overall spatial characteristics of vertical distribution. Meanwhile, 19 ecological pinch points and 17 ecological obstacle points were identified. We predicted that the expansion of construction land would continue to squeeze the ecological space by 2030, and identified 6 warning areas of ecological protection space to effectively avoid conflicts between ecological protection and economic development. After optimization, 14 new ecological sources and 17 stepping stones were added, and the circuitry, ratio of line to node and connectivity index of the ecological security network increased by 18.3%, 15.5%, and 8.2% respectively compared with those before optimization, forming a structurally stable ecological security network. The results could provide scientific basis for ecological security network optimization and ecological restoration.

Modelling the combined effects of photoperiod and temperature on diapause induction in Apolygus lucorum (Meyer-Dür) across different latitudes.

BACKGROUND: The green mirid bug Apolygus lucorum is a dominant pest species on multiple crops over a wide area in northern China. However, the combined effect of photoperiod and temperature on diapause induction in this species across different latitudes is not clear. Thus, the combined effects of temperature (17-29 °C) and photoperiod (11:13 h to 15:9 h light/dark) on diapause induction for seven geographic populations, collected at latitudes between 30.47°N and 38.30°N, were investigated. RESULTS: A model, I = (15 - p)/(30 - p - 1.923(t - 16)1/2 + 0.4499 t - 0.015 L - 19.5389) was established to predict diapause incidence (I) using photophase (p), temperature (t) and latitude (L). In most cases, the diapause incidence predicted by the model was within or close to the 95% confidence interval estimated from independently observed field data. CONCLUSION: Diapause incidence in A. lucorum was influenced nonlinearly by temperature and photoperiod across different latitudes. The model established in this study is valid for predicting diapause incidence in this pest over a wide area in northern China, and thus can be incorporated into an areawide population dynamic model of this pest. © 2020 Society of Chemical Industry.

Effect of Water on Survival and Development of Diapausing Eggs of Apolygus lucorum (Hemiptera: Miridae).

The green mirid bug Apolygus lucorum is a regional pest of multiple crops in northern China, and the survival and development of diapausing eggs during winter plays an important role in the population dynamics of this species. The effect of water on the survival and development of A. lucorum eggs was investigated using laboratory-induced diapause. Diapausing eggs were exposed to various humidity regimes under three conditions: (1) termination of diapause with exposure to warm long-day (WLD) conditions (i.e., 26 ± 1°C and 75 ± 5% relative humidity (RH) under a photoperiod of 16 hours light and 8 hours dark), (2) termination of diapause by chilling at 4°C, or (3) during the post-diapause stage, i.e., from transfer to WLD conditions after chilling, until the hatching of nymphs. The results indicate that water availability is crucial for the post-diapause resumption of development of A. lucorum. However, exposure to excessive moisture was detrimental, as indicated by a decrease in diapause termination rate and a prolonged pre-hatching period of diapausing eggs, compared to limited moisture conditions. This implies that both too dry and too humid environmental conditions would suppress survival and postpone hatching of overwintered A. lucorum eggs, and might explain why this pest has not caused severe damage in either southern or western China where the respective climates are very humid or dry.

Establishment of an artificial diet for successive rearing of Apolygus lucorum (Hemiptera: Miridae).

The plant bug Apolygus lucorum (Meyer-Dür) is a major pest on Bt cotton and multiple crops in northern China. A modified NI artificial diet called T7 was developed to rear this pest for 10 successive generations both individually and in groups. This T7 diet was similar in components and preparation process to the NI diet used for Lygus hesperus in North America, but was comprised of more whole chicken eggs, soybean lecithin, and Vanderzant vitamin mixture, and less brewer's yeast, wheat germ, lima bean meal, soy flour, and sugars than NI diet. While being reared individually on T7 diet, A. lucorum nymphs had a developmental duration of approximately 12 d and survival rate of approximately 80%, which was not significantly different from that on green beans. While being reared in groups, nymphal survival rate was above 81% (indeed above 90% for the first four generations), the weight of adults was heavier than on green beans and the average fecundity had a logistic increase through generations. The replacement rate of A. lucorum populations was expected to be approximately 29 times per generation while being reared at a density of 100 nymphs per box (20 x 12 x 7 cm). This is the first successful artificial diet reported for rearing A. lucorum and is superior to green beans. The diet offers an economic means for producing natural enemies for biological control of this pest on Bt cotton. The possibility of further improvement of the present artificial diet is also discussed.