Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhalable Composite Microparticles Containing siRNA-Loaded Lipid-Polymer Hybrid Nanoparticles: Saccharides and Leucine Preserve Aerosol Performance and Long-Term Physical Stability

Thermostable dry powder formulations with high aerosol performance are attractive inhalable solid dosage forms for local treatment of lung diseases. However, preserved long-term physical stability of dry powder inhaler (DPI) formulations is critical to ensure efficient and reproducible delivery to the airways during the shelf life of the drug product. Here, we show that ternary excipient mixtures of the disaccharide trehalose (Tre), the polysaccharide dextran (Dex), and the shell-forming dispersion enhancer leucine (Leu) stabilize siRNA-loaded lipid-polymer hybrid nanoparticles (LPNs) during spray drying into nanocomposite microparticles, and result in inhalable solid dosage forms with high aerosol performance and long-term stability. The stabilizing roles of Tre and Dex were also studied separately by investigating DPI formulations containing binary mixtures of Leu/Tre and Leu/Dex, respectively. DPI formulations containing binary Leu/Dex mixtures were amorphous and displayed preserved long-term physical stability of LPNs and chemical stability of siRNA in accelerated stability studies under exaggerated storage conditions (ambient temperature and relative humidity). In contrast, powders containing binary Leu/Tre mixtures were amorphous, and hence metastable, and were recrystallized after six months of storage. Ternary mixtures of Tre, Leu, and Dex provided the most efficient protection of the LPNs during the spray drying process and prevented recrystallization of amorphous Tre. Hence, in ternary mixtures, Leu, Tre, and Dex have the following functions: the shell-forming Leu functions as a dispersion enhancer and is essential for high aerosol performance, the disaccharide Tre provides LPN protection during manufacturing and storage due to efficient coverage of the LPN surface, and the polysaccharide Dex promotes the formation of porous particles and prevents recrystallization of Tre during long-term storage. Therefore, the use of ternary excipient mixtures composed of Leu, Tre, and Dex, may prevent instability problems of DPI formulations and preserve the aerosol performance during long-term storage, which is essential for effective pulmonary drug delivery.
A New Strategy for Identification of Coal Miners With Abnormal Physical Signs Based on EN-mRMR

Coal miners’ occupational health is a key part of production safety in the coal mine. Accurate identification of abnormal physical signs is the key to preventing occupational diseases and improving miners’ working environment. There are many problems when evaluating the physical health status of miners manually, such as too many sign parameters, low diagnostic efficiency, missed diagnosis, and misdiagnosis. To solve these problems, the machine learning algorithm is used to identify miners with abnormal signs. We proposed a feature screening strategy of integrating elastic net (EN) and Max-Relevance and Min-Redundancy (mRMR) to establish the model to identify abnormal signs and obtain the key physical signs. First, the raw 21 physical signs were expanded to 25 by feature construction technology. Then, the EN was used to delete redundant physical signs. Finally, the mRMR combined with the support vector classification of intelligent optimization algorithm by Gravitational Search Algorithm (GSA-SVC) is applied to further simplify the rest of 12 relatively important physical signs and obtain the optimal model with data of six physical signs. At this time, the accuracy, precision, recall, specificity, G-mean, and MCC of the test set were 97.50%, 97.78%, 97.78%, 97.14%, 0.98, and 0.95. The experimental results show that the proposed strategy improves the model performance with the smallest features and realizes the accurate identification of abnormal coal miners. The conclusion could provide reference evidence for intelligent classification and assessment of occupational health in the early stage.
Sexual Dimorphism in Transcriptional and Functional Glucocorticoid Effects on Mouse Skeletal Muscle

Muscle atrophy is common in patients with increased glucocorticoid exposure. Glucocorticoid effects are often sex-specific, and while different glucocorticoid responses between male and female subjects are reported, it is unclear why this is. In this study, we evaluated the effects of corticosterone and synthetic glucocorticoid treatment on muscle atrophy in male and female mice. We found that corticosterone treatment reduced grip strength in female mice only, whereas muscle mass was reduced in both sexes. Skeletal muscle transcriptional responses to corticosterone treatment were more pronounced and widespread in male mice. Synthetic glucocorticoid treatment reduced grip strength in both sexes, while female mice were more sensitive to muscle atrophy than male mice. To evaluate the role of androgens, chemically-castrated male mice were treated with synthetic glucocorticoids. We observed additively reduced muscle mass, but did not observe any interaction effects. Although sex differences in glucocorticoid responses in skeletal muscle are partly influenced by androgen signaling, further studies are warranted to fully delineate the underlying mechanisms.
Dietary 25-Hydroxyvitamin D3 Supplementation Modulates Intestinal Cytokines in Young Broiler Chickens

Vitamin D signaling is important for intestinal homeostasis. An increase in vitamin D receptors in immune cells can modulate cell phenotype and cytokine secretion. Cytokines regulate both pro- (interleukin 17; IL-17) and anti-inflammatory (IL-10) responses triggered by external stimuli. Inflammation in intestinal tissues can disrupt the structure and the remodeling of epithelial tight junction complexes, thus, compromising the protective barrier. The objective of the study was to determine the impact of dietary supplementation with 25-hydroxycholecalciferol (25OHD3), a hydroxylated metabolite of vitamin D, on intestinal cytokine abundance and epithelial barrier integrity over time in broilers. A randomized complete block design experiment was conducted to evaluate the effect of dietary 25OHD3 inclusion on relative protein expression of the cytokines, IL-17 and IL-10, and tight junction proteins, Zona Occludens 1 (ZO-1), and Claudin-1 (CLD-1), in broiler chicken duodenum and ileum from 3 to 21 days post-hatch. On day 0, male chicks (n = 168) were randomly assigned to raised floor pens. Experimental corn–soybean meal-based treatments were as follows: (1) a common starter diet containing 5,000 IU of D3 per kg of feed (VITD3) and (2) a common starter diet containing 2,240 IU of D3 + 2,760 IU of 25OHD3 per kg of feed (25OHD3) fed from days 0 to 21. On days 3, 6, 9, 12, 15, 18, and 21, 12 birds per treatment were euthanized to collect tissue samples for quantitative, multiplex, and fluorescent Western blot analysis. Target proteins were quantified using Image Quant TL 8.1 and expressed relative to total protein. Feeding 25OHD3 post-hatch decreased ileal IL-10 (anti-inflammatory) protein expression in 21-day-old broilers compared with VITD3 only (P = 0.0190). Broilers fed only VITD3 post-hatch had greater IL-17 (pro-inflammatory) protein expression in the ileum at 18 and 21 days-of-age (P = 0.0412) than those that fed 25OHD3. Dietary inclusion of 25OHD3 lowered the abundance of key inflammatory cytokines in the ileum of young broilers.
Chinese Herbal Medicine Reduces the Risk of Heart Failure in Hypertensive Patients: A Nationwide, Retrospective, Cohort Study

Background Hypertension (HTN) is the leading preventable risk factor for cardiovascular disease worldwide. Patients with HTN are at higher risk for heart failure (HF). The currently available therapeutic approaches for HTN do not always optimally control blood pressure or are not suitable for hypertensive patients who have a higher number of comorbidities. This study aimed to determine whether Chinese herbal medicine (CMH)-based interventions could reduce the risk of HF in hypertensive patients. Methods This retrospective study randomly selected 2 million enrollees from the National Health Insurance Research Database and identified 507,608 patients who were newly diagnosed with HTN in 2000–2017. After 1:1 frequency-matching by age, sex, index year, income, urbanization, duration of HTN, comorbidities and antihypertensive medications, we selected 8,912 eligible patients in each group. During 16 years of follow-up, 380 CHM users and 426 CHM non-users developed HF, representing incidence rates of 6.29 and 7.43 per 1,000 person-years, respectively. Results CHM users had significantly lower HF risk compared with CHM non-users (adjusted HR = 0.85, 95% CI 0.74–0.98). The markedly predominant effect was observed in those receiving CHM products for more than 180 days (adjusted HR = 0.65). The frequently prescribed formula, Jia-Wei-Xiao-Yao-San, and the single herbs Ge Gen, Huang Qi, Du Zhong, Huang Qin, and Chuan Xiong were significantly associated with lower risk of HF. Conclusions This population-based study revealed decreased HF risk in hypertensive patients with CHM use. These findings may provide a reference for HF prevention strategies and support the integration of CHM into clinical intervention programs that provide a favorable prognosis for hypertensive patients.
A Review of Air Conditioning Load Aggregation in Distribution Networks

In the context of global energy transformation, it is particularly important to tap the potential of flexible load on the distribution network side to participate in grid operation. As an important flexible adjustable load in the distribution network, air conditioning loads have typical characteristics of thermal energy storage, rapid response, and flexible scheduling, which is an ideal load resource. Effective and reliable load aggregation technologies for air conditioning load participation are the basis for operation in a power grid. To better understand the current research status of air conditioning load aggregation technologies and make full use of the existing research results to carry out further research, this paper comprehensively reviews the various aggregation technologies being used in distribution networks, including the modeling strategy for air conditioning load aggregation, control strategy, control method, and application analysis. Moreover, future research directions are summarized as a guide to improving the technology of air conditioning load aggregation.
Natural Products from Actinobacteria as a Potential Source of New Therapies Against Colorectal Cancer: A Review

Colorectal cancer (CRC) is a common, and deadly disease. Despite the improved knowledge on CRC heterogeneity and advances in the medical sciences, there is still an urgent need to cope with the challenges and side effects of common treatments for the disease. Natural products (NPs) have always been of interest for the development of new medicines. Actinobacteria are known to be prolific producers of a wide range of bioactive NPs, and scientific evidence highlights their important protective role against CRC. This review is a holistic picture on actinobacter-derived cytotoxic compounds against CRC that provides a good perspective for drug development and design in near future. This review also describes the chemical structure of 232 NPs presenting anti-CRC activity with the being majority of quinones, lactones, alkaloids, peptides, and glycosides. The study reveals that most of these NPs are derived from marine actinobacteria followed by terrestrial and endophytic actinobacteria, respectively. They are predominantly produced by Streptomyces, Micromonospors, Saliniospors and Actinomadura, respectively, in which Streptomyces, as the predominant contributor generating over 76% of compounds exclusively. Besides it provides a valuable snapshot of the chemical structure-activity relationship of compounds, highlighting the presence or absence of some specific atoms and chemical units in the structure of compounds can greatly influence their biological activities. To the best of our knowledge, this is the first comprehensive review on natural actinobacterial compounds affecting different types of CRC. Our study reveals that the high diversity of actinobacterial strains and their NPs derivatives, described here provides a new perspective and direction for the production of new anti-CRC drugs and paves the way to innovation for drugs discovery in the future. The knowledge obtain from this review can help us to understand the pivotal application of actinobacteria in future drugs development.
Vibriosis Outbreaks in Aquaculture: Addressing Environmental and Public Health Concerns and Preventive Therapies Using Gilthead Seabream Farming as a Model System

Bacterial and viral diseases in aquaculture result in severe production and economic losses. Among pathogenic bacteria, species belonging to the Vibrio genus are one of the most common and widespread disease-causing agents. Vibrio infections play a leading role in constraining the sustainable growth of the aquaculture sector worldwide and, consequently, are the target of manifold disease prevention strategies. During the early, larval stages of development, Vibrio species are a common cause of high mortality rates in reared fish and shellfish, circumstances under which the host organisms might be highly susceptible to disease preventive or treatment strategies such as vaccines and antibiotics use, respectively. Regardless of host developmental stage, Vibrio infections may occur suddenly and can lead to the loss of the entire population reared in a given aquaculture system. Furthermore, the frequency of Vibrio–associated diseases in humans is increasing globally and has been linked to anthropic activities, in particular human-driven climate change and intensive livestock production. In this context, here we cover the current knowledge of Vibrio infections in fish aquaculture, with a focus on the model species gilthead seabream (Sparus aurata), a highly valuable reared fish in the Mediterranean climatic zone. Molecular methods currently used for fast detection and identification of Vibrio pathogens and their antibiotic resistance profiles are addressed. Targeted therapeutic approaches are critically examined. They include vaccination, phage therapy and probiotics supplementation, which bear promise in supressing vibriosis in land-based fish rearing and in mitigating possible threats to human health and the environment. This literature review suggests that antibiotic resistance is increasing among Vibrio species, with the use of probiotics constituting a promising, sustainable approach to prevent Vibrio infections in aquaculture.
Long-Term Mild Heat Causes Post-Mitotic Pollen Abortion Through a Local Effect on Flowers

Crop reproductive success is significantly challenged by heatwaves, which are increasing in frequency and severity globally. Heat-induced male sterility is mainly due to aborted pollen development, but it is not clear whether this is through direct or systemic effects. Here, long-term mild heat (LTMH) treatment, mimicking a heatwave, was applied locally to tomato flowers or whole plants and followed up by cytological, transcriptomic, and biochemical analyses. By analyzing pollen viability, LTMH was shown to act directly on the flowers and not via effects on other plant tissue. The meiosis to early microspore stage of pollen development was the most sensitive to LTMH and 3 days of exposure around this period was sufficient to significantly reduce pollen viability at the flower anthesis stage. Extensive cytological analysis showed that abnormalities in pollen development could first be observed after pollen mitosis I, while no deviations in tapetum development were observed. Transcriptomic and biochemical analyses suggested that pollen development suffered from tapetal ER stress and that there was a limited role for oxidative stress. Our results provide the first evidence that heat acts directly on flowers to induce pollen sterility, and that the molecular-physiological responses of developing anthers to the LTMH are different from those to severe heat shock.
The LIM Protein AJUBA is a Potential Oncogenic Target and Prognostic Marker in Human Cancer via Pan-Cancer Analysis

Purpose : The LIM (Lin-11, Isl1, MEC-3) domain protein AJUBA is involved in multiple biological functions, and its aberrant expression is related to the occurrence and progression of various cancers. However, there are no analytical studies on AJUBA in pan-cancer. Methods: We performed a comprehensive pan-cancer analysis and explored the potential oncogenic roles of AJUBA, including gene expression, genetic mutation, protein phosphorylation, clinical diagnostic biomarker, prognosis, and AJUBA-related immune infiltration based on The Cancer Genome Atlas and Genotype-Tissue Expression databases. Results: The results revealed that the expression of AJUBA highly correlated with poor clinical outcomes in patients with different types of cancer. Meanwhile, AJUBA expression was positively correlated with cancer-associated fibroblasts in many human cancers, such as breast invasive carcinoma, colon adenocarcinoma, brain lower-grade glioma, lung adenocarcinoma (LUAD), and ovarian serous cystadenocarcinoma (OV). Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that AJUBA is mainly involved in protein serine/threonine kinase activity, cell–cell junction, covalent chromatin modification, and Hippo signaling pathway. Conclusion: The pan-cancer study reveals the oncogenic roles of AJUBA and provides a comprehensive understanding of the molecular biological genetic information of AJUBA in various tumors.
Understanding the Association Between Intolerance of Uncertainty and Problematic Smartphone Use: A Network Analysis

Background Existing research has demonstrated that intolerance of uncertainty (IU) is associated with problematic smartphone use (PSU). However, little is known about how different IU components such as uncertainty-related beliefs, emotions, and behaviors may impact on different PSU symptoms. Methods Extending previous research, the current study examined the specific associations between IU components and PSU symptoms via a symptom-level network approach. A regularized partial correlation network consisting of different IU components and PSU symptoms was estimated among 1,849 Chinese university students. We examined pathways and influential nodes (i.e. central components/symptoms and bridge components/symptoms) within the IU-PSU network. Results The strongest pathway linking IU and PSU was between emotional reactions to uncertainty and coping-motivated smartphone use. Importantly, emotional reactions toward not having enough information (a reflection of emotional reactions to uncertainty) may act as both a central and a bridge component in maintaining the whole IU-PSU network. Conclusions The results are in line with the I-PACE model and highlight that PSU may be a coping response for negative emotions derived from uncertainty. Finally, the current findings highlight the potential of interventions targeting intolerance of uncertainty for reducing PSU.
Contractile ring composition dictates kinetics of in silico contractility

Constriction kinetics of the cytokinetic ring are expected to depend on dynamic adjustment of ring composition, but the impact of component abundance dynamics on ring constriction is understudied. Computational models generally assume that contractile networks maintain constant composition. To test how compositional dynamics affect constriction kinetics, we first measured F-actin, non-muscle myosin II, septin, and anillin during C. elegans zygotic mitosis. A custom microfluidic device that positioned the cell with the division plane parallel to a light sheet allowed even illumination of the cytokinetic ring. Measured component abundances were implemented in an agent-based 3D model of a membrane-associated contractile ring. With constant network composition, constriction occurred with biologically unrealistic kinetics. Measured changes in component quantities elicited realistic constriction kinetics. Simulated networks were more sensitive to changes in motor and filament amounts, than that of crosslinkers and tethers. Our findings highlight the importance of network composition for actomyosin contraction kinetics. Summary We created a microfluidic device compatible with high numerical aperture light sheet microscopy to measure cytokinetic ring component abundance in the C. elegans zygote. Implementing measured dynamics into our three-dimensional agent-based model of a contractile ring elicited biologically realistic kinetics.
Effect of Maize (Zeal mays) and Soybean (Glycine max) Intercropping on Yield and Root Development in Xinjiang, China

Intercropping is a breakthrough in land-use optimization. This work aimed to study the effects of intercropping patterns on the growth, yield, root morphological characteristics, and interspecific competition of maize and soybean, as well as provide a reference for the development of intercropping patterns of maize and soybean in Northwest China. Three different cropping patterns were designed: monocropping maize, monocropping soybean, and maize-soybean intercropping. Agronomic traits, intercropping indicators such as land equivalent ratio (LER), aggressivity (A), competition ratio (CR), and actual yield loss (AYL), as well as root morphological characteristics were assessed. The results showed that, compared with monocropping, the intercropping maize plant height increased by 6.07–8.40%, and the intercropping soybean plant height increased by 35.27–38.94%; the root length density (RLD) of intercropping maize was higher than that of monocropping maize, the RLD of intercropping soybean was lower than that of monocropping soybean, in the 0–40 cm soil layer the intercropping increased maize RLD by 1.79–7.44% while the soybean RLD was reduced by 3.06–9.46%; the aggressivity of maize was greater than 0 and the competition ratio was greater than 1, which was the dominant species; the maize/soybean land equivalent ratio was 1.18–1.26, which improved the land utilization rate. Therefore, the effect of increasing yield can be achieved by changing the maize and soybean planting method, which is beneficial to the ecological strategy of sustainable development in the northwest region.
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1Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People’s Republic of China; 2Key Laboratory of Reproductive and Genetics, Ministry of Education, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, People’s Republic of China
GANs Powered by Autoencoding — A Theoretic Reasoning

Many recent works integrate GANs with autoen-coding (AE) networks to generate photo-realistic images conditioned on input images. It has been observed empirically that the addition of the AE network, besides generating images under certain condition, helps alleviate the mode missing and instability problems during training. The main objective of this work is not to propose new solutions, but rather we take the ﬁrst attempt in providing theoretical reasoning on why the AE-based GAN structure is able to remedy the mode missing and instability issues. We further show that by adding an adaptive decay variable to the adversarial error, the instability issue caused by competition between the generator and discriminator is largely alleviated. Experimental results on compositional digits, natural images, and faces all show superior performance of autoencoding-based GAN in handling the mode missing and instability problems.