An inflammation-responsive double-layer microneedle patch could be responsively degraded by atopic dermatitis specific inflammatory factor MMP to release loaded Vitamin D3 for recurrent AD therapy.
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Seeking a potent therapeutic strategy for alleviating atopic dermatitis (AD) attack and preventing its recurrence is highly desired but remains challenging in clinical practice. Here, we propose an inflammation-responsive double-layer microneedle (IDMN) patch in situ delivering VD3 for recurrent AD therapy. IDMN comprises the backing layer part and the double-layer microneedle part, in which the inner layer is gelatin methacryloyl (GelMA) loaded with VD3 while the outer layer is composed of hyaluronic acid (HA). Introduction of the HA backing layer and outer layer around the GelMA tips can not only provide sufficient mechanical strength to penetrate into hardened AD skin with minimal invasiveness, but also exert a strong moisturizing effect after being rapidly dissolved. The inner layer of GelMA is degraded by the matrix metalloproteinase (MMP) in a dose dependent manner, which is secreted according to the disease progression of AD. The responsive degradation of GelMA tips result in corresponding release of VD3 to treat AD, triggering negative feedback against GelMA degradation. The IDMN administration on AD-bearing mice reveals efficient “curing” performances (including suppress erythema, scaling and lichenification, reduce epidermal thickness, inhibit mast cells infiltration, and down-regulate inflammatory factor secretion), which are basically realized through synergistic effect of the released VD3 and the dissolved HA molecules. Importantly, the residual tips of IDMN with VD3 are retained in the skin after the first AD relief, showing promising “warning” ability to inhibit the recurrence of AD. Hence, the developed IDMN patch is expected to be one of the excellent candidates for AD therapy and other relapsing diseases in clinical fields.
A persistent enigma is the rarity of polyploidy in animals, compared to its prevalence in plants. Although animal polyploids are thought to experience deleterious genomic chaos during initial ...polyploidization and subsequent rediploidization processes, this hypothesis has not been tested. We provide an improved reference-quality de novo genome for allotetraploid goldfish whose origin dates to ~15 million years ago. Comprehensive analyses identify changes in subgenomic evolution from asymmetrical oscillation in goldfish and common carp to diverse stabilization and balanced gene expression during continuous rediploidization. The homoeologs are coexpressed in most pathways, and their expression dominance shifts temporally during embryogenesis. Homoeolog expression correlates negatively with alternation of DNA methylation. The results show that allotetraploid cyprinids have a unique strategy for balancing subgenomic stabilization and diversification. Rediploidization process in these fishes provides intriguing insights into genome evolution and function in allopolyploid vertebrates.
A simple hydration model is used here by taking the composition of the cement and the initial water: cement ratio (w/c) into account explicitly. Its conceptual basis is a combination of the Avrami ...equation and Bentz's model based on simple spatial considerations. In this model, the
Avrami equation determines the initial reaction, and Bentz's model describes the following hydration stage. The model favors engineers for it relies on one experimental parameter and has a reliable approximation in the practice.
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•Co3O4 nanopartices transform into nanoflakes driven by an electric field.•Morphologically transformed Co3O4 boosts the high yield of atomic H* and •OH.•Co3O4 cathode ...electrochemically degrades Thiamphenicol in wide pH window.•Co3O4 cathode is feasible and ultra-stable in dealing with actual water.
Degradation of halogenated organic compounds using the electro-reduction process is a promising approach for advanced water treatment. In this work, antiferromagnetic Co3O4 nanoparticles were first loaded on a uniform anodic porous TiO2 surface through a hydrothermal strategy, then subjected to an electrochemical reduction, which transform from nanoparticle-shape to interconnected nanoflakes. Compared with the pristine Co3O4 nanoparticles, the morphologically transformed Co3O4 cathode features a porous interface with amorphous Co(OH)2 and CoOOH shell, which favors the generation of abundant •OH radicals along with lower overpotential for reducing H+ to H*. On account of the plentiful radicals and self-supporting nature, the resulting Co3O4 cathode retains high activity for efficiently degrading Thiamphenicol in water, even after 10 h run, demonstrating remarkable durability. Moreover, it is adaptable in a wide pH window of 3 to 10, and effectual when the initial Thiamphenicol concentration increases from 0.5 to 50 mg/L regardless of the water background (tap water, lake water, or river water). This study delivers a profound cognition about the dynamic behaviors of Co3O4-based electrocatalysts applied in eliminating halogenated antibiotics.
Few studies focused on the effects of iron on characterizing alterations of metabolic processes in neonatal piglets. In the present study, 16 neonatal piglets were randomly assigned to two groups. In ...the first group piglets were given an intramuscularly injection of iron dextran at 150 mg as a positive control (CON) and the second group were not supplemented with iron as a negative control for iron deficiency (ID). At day 8, iron status, serum biochemical parameters, serum metabolome, hepatic histology, and hepatic expression of genes for the metabolism were analyzed. Results indicated that piglets without iron supplementation had significantly reduced iron values and increased blood urea nitrogen concentrations at day 8 (p < 0.05). Analysis of serum metabolome revealed that concentrations of serum lysine, leucine, tyrosine, methionine, and cholesterol were significantly decreased while concentrations of 3-Methyldioxyindole, chenodeoxycholate acid, indoleacetic acid, icosadienoic acid, phenylpyruvic acid, pantothenic acid, ursocholic acid, and cholic acid were significantly increased in iron deficient piglets (p < 0.05). Furthermore, expressions of cyp7a1 and the urea cycle enzyme (ornithinetranscarbamoylase and argininosuccinate synthetase) were significantly increased in iron deficient pigs (p < 0.05). The present experimental results indicated that neonatal piglets without iron supplementation drop to borderline anemia within 8 days after birth. Iron deficiency led to a series of metabolic changes involved in tyrosine metabolism, phenylalanine metabolism, bile secretion, primary bile acid biosynthesis, steroid biosynthesis, and upregulated activities of the urea cycle enzymes in the liver of neonatal piglets, suggesting early effects on metabolic health of neonatal piglets.
The quantum-dot cellular automata (QCA) present great promising advantages for emerging nano logic circuits. However, feedback design in QCA sequential circuit is often a big problem. Especially in ...line feedback shift registers (LFSR), each feedback loop consists of at least a modulo-2 adder and a trigger unit, which is hard to implement using the conventional methods. Given the importance of LFSR in communication systems, a design methodology with QCA is proposed in this work. At first, a new structure is presented to be used in every single feedback LFSR since it can make the feedback loop consume only one clock cycle of delay. Subsequently, quantitative criteria are presented to judge whether any multi-feedback LFSR can be directly designed using the proposed structure. LFSR that cannot satisfy the criteria are supposed to be transformed to their equivalent forms. We verify any LFSR can be transformed to the type of single feedback, according to the theorem of searching the monic and irreducible polynomials over Galois field GF (2). The step-by-step method of transforming multi-feedback into single feedback is given on the consideration of all kinds of cases. Further, two other simple transforming methods are presented to cope with the exponential growth of clock delay in the multi-to-single transforming method. The most remarkable advantage of this series of methods is to keep from introducing undesired bits into the payload data flowing in the sequential circuits.
Rheumatoid arthritis (RA) is a common chronic disease dominated by inflammatory synovitis, which is characterized with hyperplastic synovium, up-regulated matrix metalloproteinase (MMP) expression, ...hypoxic joint cavity and excessive reactive oxygen species (ROS) accumulation. Such local adverse microenvironment in RA joints further exacerbates the infiltration of synovial inflammatory cells, especially M1-type macrophages. Regulating intra-articular pathological conditions, eliminating excess M1 macrophages or converting them to an anti-inflammatory M2 phenotype may break the vicious progression circle. Herein, we develop a multi-stimulus responsive lipogel as effective platform to relieve RA symptoms and promote articular cartilage recovery via reversing its inflammatory microenvironment. The injectable lipogel is fabricated by loading polydopamine nanoparticles and methotrexate into a thermosensitive gel, and intra-articularly injected to form the therapeutic depot (PDA/MTX@TSG) in situ. The gel degrades slowly under esterase hydrolysis, and maintains sustained drug release in physiological conditions. Meanwhile, it can 1) induce a reversible gel-sol phase transition upon mild photothermal treatment (external NIR light control), and 2) specifically respond to MMP-rich RA microenvironment (internal enzymatic hydrolysis effect). Such stimulus-responsive system can deliver therapeutic components in a controllable manner, and significantly reverse adverse inflammatory microenvironment of RA joints through ROS eliminating, hypoxia alleviating, and M1-M2 macrophage polarization effects. Animal experiments indicate that observable RA relief and joint repair are realized after a single lipogel injection combined with NIR irradiation. Our study highlights the importance of altering local RA microenvironment via anti-inflammatory macrophage polarization, and therefore presents a potent therapeutic strategy for RA treatment in clinical intervention.
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Abstract Background Medical school learning environment (MSLE) has a holistic impact on students’ psychosomatic health, academic achievements, and personal development. Students in different grades ...perceive MSLE in different ways. Thus, it is essential to investigate the specific role of student’s grade in the perception of MSLE. Methods Using the Johns Hopkins Learning Environment Scale (JHLES) as a quantification instrument for the perception level of MSLE, 10,901 medical students in 12 universities in China were categorized into low or high JHLES group according to their questionnaires. We investigated the relationship between student’s grade and JHLES category by univariate analysis employing Pearson Chi-square test and Welch’s ANOVA. Then multivariable logistic regression analysis confirmed the predictive efficacy of student’s grade. A nomogram concerning the prediction of low JHLES score probability in medical students was also constructed. Results A significant difference between two JHLES categories among students in different grades was observed ( p < 0.001), with the proportion of the high JHLES group dominating in grade 1, 5, and the graduate subgroups ( p < 0.001). The mean JHLES score declined especially in the third and fourth graders compared to freshmen ( p < 0.001), while the mean score among the fifth graders had a remarkable rebound from the third graders ( p < 0.001). Most imperatively, identified by multivariable logistic regression analysis, students in grade 3 (OR = 1.470, 95% CI = 1.265–1.709, p < 0.001) and 4 (OR = 1.578, 95% CI = 1.326–1.878, p < 0.001) perceived more negatively than freshmen. The constructed nomogram provided a promising prediction model for student’s low JHLES score probability, with accuracy, accordance, and discrimination (area under the curve (AUC) = 0.627). Conclusion The student’s grade was a significant influencing factor in medical students’ perception of MSLE. The perceptions among the third and fourth graders got worse, probably due to the worrying changes in various aspects of MSLE during that period. The relevant and appropriate interventions to improve medical students’ perceptions are urgently needed.
Dysarthria is common in movement disorders, such as Wilson's disease (WD), Parkinson's disease, or Huntington's disease. Dysarthria severity assessment is often indispensable for the management of ...these diseases. However, such assessment is usually labor‐intensive, time‐consuming, and expensive. To seek efficient and cost‐effective solutions for dysarthria assessment, an artificial intelligence (AI)‐powered acoustic analysis system is proposed and its performance in a valuable sample of WD, an ideal disease model with mainly mixed dysarthria, is verified. A test‐retest reliability analysis yields excellent reproducibility in the acoustic measures (mean intraclass correlation coefficient ICC = 0.81). Then, a system for dysarthria assessment is trained with WD patients (n = 65) and sex‐matched healthy controls (n = 65) using a machine learning approach. The system achieves reasonable performance in evaluating dysarthria severity with either stepwise classification or regression (all areas under the curve >80%; mean absolute error = 6.25, r = 0.79, p < 0.0001). The diadochokinesis and sustained phonation tasks contribute the most to prediction, and the corresponding acoustic features can provide significant and independent contributions. The present study demonstrates the feasibility and good performance of the AI‐powered acoustic analysis framework, offering the potential to facilitate early screening and subsequent management of dysarthria.
Dysarthria severity assessment is often indispensable in diagnosing, treating, and rehabilitating movement disorders. The study proposes an interpretable artificial intelligence‐powered acoustic analysis system in the clinical decision support system framework and discovers some biomarkers sensitive enough to dysarthria with good retest reliability. The framework provides an efficient and effective decision‐support tool for clinics to diagnose, assess, and monitor dysarthria early.
Biological data are generated at unprecedentedly exponential rates, posing considerable challenges in big data deposition, integration and translation. The BIG Data Center, established at Beijing ...Institute of Genomics (BIG), Chinese Academy of Sciences, provides a suite of database resources, including (i) Genome Sequence Archive, a data repository specialized for archiving raw sequence reads, (ii) Gene Expression Nebulas, a data portal of gene expression profiles based entirely on RNA-Seq data, (iii) Genome Variation Map, a comprehensive collection of genome variations for featured species, (iv) Genome Warehouse, a centralized resource housing genome-scale data with particular focus on economically important animals and plants, (v) Methylation Bank, an integrated database of whole-genome single-base resolution methylomes and (vi) Science Wikis, a central access point for biological wikis developed for community annotations. The BIG Data Center is dedicated to constructing and maintaining biological databases through big data integration and value-added curation, conducting basic research to translate big data into big knowledge and providing freely open access to a variety of data resources in support of worldwide research activities in both academia and industry. All of these resources are publicly available and can be found at http://bigd.big.ac.cn.
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