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Size-dependent phagocytosis is a well-characterized phenomenon in monocytes and macrophages. However, this size effect for preferential gene delivery to these important cell targets has not been fully exploited because commonly adopted stabilization methods for electrostatically complexed nucleic acid nanoparticles, such as PEGylation and charge repulsion, typically arrest the vehicle size below 200 nm. Here, we bridge the technical gap in scalable synthesis of larger submicron gene delivery vehicles by electrostatic self-assembly of charged nanoparticles, facilitated by a polymer structurally designed to modulate internanoparticle Coulombic and van der Waals forces. Specifically, our strategy permits controlled assembly of small poly(ß-amino ester)/messenger ribonucleic acid (mRNA) nanoparticles into particles with a size that is kinetically tunable between 200 and 1,000 nm with high colloidal stability in physiological media. We found that assembled particles with an average size of 400 nm safely and most efficiently transfect monocytes following intravenous administration and mediate their differentiation into macrophages in the periphery. When a CpG adjuvant is co-loaded into the particles with an antigen mRNA, the monocytes differentiate into inflammatory dendritic cells and prime adaptive anticancer immunity in the tumor-draining lymph node. This platform technology offers a unique ligand-independent, particle-size-mediated strategy for preferential mRNA delivery and enables therapeutic paradigms via monocyte programming.
Subject(s)
Monocytes , Nanoparticles , RNA, Messenger , Monocytes/metabolism , Nanoparticles/chemistry , RNA, Messenger/genetics , RNA, Messenger/metabolism , Animals , Mice , Humans , Polyelectrolytes/chemistry , Macrophages/metabolism , Polyamines/chemistry , Particle Size , Cell Differentiation , Gene Transfer Techniques , Dendritic Cells/metabolism , Static Electricity , PolymersABSTRACT
Carbon (C), nitrogen (N), and phosphorus (P) are essential nutrients that promote plant growth and development and maintain the stability of ecosystem structure and function. Analyzing the C, N, and P characteristics of plant leaves aids in understanding the plant's nutrient status and nutrient limitation. Seasonal water-level fluctuations in riparian zones lead to various ecological problems, such as reduced biodiversity and decreased ecosystem stability. Therefore, comprehending the stoichiometric characteristics of riparian zone plants and their nutrient response to plant traits is important for a deeper insight into riparian zone forest ecosystems. This study analyzed the C, N, and P contents of the leaves of 44 woody plants in the riparian zone of the Dahuofang Reservoir to investigate the stoichiometric characteristics of C, N, and P of trees in the region. The results showed that the average C content of the leaves in woody plants was 446.9 g kg-1; the average N content was 28.42 g kg-1; and the average P content was 2.26 g kg-1. Compared to global and regional scales, woody plants in the riparian zone of the Dahuofang Reservoir exhibited higher N and P contents but lower N:P ratios. Compared to other riparian zones, woody plant leaves in the riparian zone of Dahuofang Reservoir had relatively high N content and N:P ratios. Variations in plant stoichiometric characteristics across different life forms were minimal, with only tree leaf P content significantly lower than its in shrubs. There was no significant correlation between leaf C, N, and P in woody plants, while specific leaf area showed a negative correlation with leaf C content. Trees in the riparian zone have high leaf N and P content and are primarily N-limited during the growing season. This study reveals the stoichiometric characteristics of leaves of woody plants in the riparian zone, which can contribute to an in-depth understanding of leaf stoichiometric patterns and the factors influencing them among plant life types in the riparian zone.
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OBJECTIVE: To investigate the association of quadriceps strength with the presence of knee pain. DESIGN: This cross-sectional study was based on data from the 1999-2000 to 2001-2002 National Health and Nutrition Examination Survey. SETTING: This was a community-based study. PARTICIPANTS: This study included 2619 adults with complete data for knee pain, quadriceps strength, and covariates. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Self-reported knee pain. RESULTS: This study included 2619 individuals, 1287 (52.66%) of whom were women and 1543 (81.66%) identified as Non-Hispanic White. The mean ±standard deviation age was 62.48±9.71 years. After adjusting for covariates, the odds of knee pain decreased with every 20 N/m increase in quadriceps strength (odds ratio, 0.87; 95% confidence interval, 0.81-0.94). Individuals in the upper quartile of quadriceps strength had lower odds of knee pain than those in the lower quartile (Q4 vs Q1 [reference]: odds ratio, 0.28, 95% confidence interval, 0.15-0.52; Ptrend=.006). Nonlinear analyses indicated L-shaped associations for knee pain. The subgroup analyses showed no significant interactions, except for sex (Pinteraction=.046). The significance of the sex interaction indicated a correlation exclusively in women. CONCLUSIONS: The results demonstrated an inverse association between quadriceps strength and the presence of knee pain. The subgroup analysis by sex showed that this inverse relationship was statistically significant in the women but not in the men subgroup.
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Background: The novel coronavirus disease 2019 (COVID-19) pandemic spread worldwide and brought unprecedented challenges to healthcare systems. Healthcare workers experienced tremendous pressure and psychological issues. Methods: A cross-sectional online survey was conducted from January 2022 to April 2022 among healthcare workers in Anyang, Henan Province, China. Insomnia, anxiety, depression, post-traumatic stress disorder (PTSD), and problematic internet use (PIU) were evaluated. Logistic regression analyses were used to explore the factors that were associated with mental health problems. Results: A total of 242 participants (mean [SD] age, 34.7 [6.6] years, 187 female [77.3 %]) were included in the study. The prevalence of symptoms of insomnia, anxiety, depression, PTSD and PIU during the COVID-19 pandemic in China was 53.7 %, 100.0 %, 7.0 %, 20.3 %, and 19.4 %, respectively. Participants who smoked, used sedative-hypnotic drugs and may need psychological assistance were at a higher risk for mental health problems. Respondents who were older than 45 years and were married displayed a lower risk of insomnia and PTSD, respectively. Conclusions: Mental health symptoms are pervasive among healthcare workers in specialized COVID-19 hospitals during the outbreak. Risk factors include smoking, sedative-hypnotic drug use, and the need for psychological assistance, while protective factors include age and marital status. Developing social media platforms and providing psychological assistance may be effective interventions for healthcare workers.
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The growth and quality of medicinal plants depend heavily on environmental variables. The quality of Rubia cordifolia, an important medicinal plant, is determined by the two main secondary metabolites of the root, purpurin and mollugin. However, their relationship with environmental factors has not been studied. In this study, the purpurin and mollugin contents of R. cordifolia roots from different sampling sites in China were measured using ultra-high-performance liquid chromatography, and the correlations between the two secondary metabolites and environmental variables were analyzed. The results showed that there were significant differences in the contents of purpurin and mollugin in the roots of R. cordifolia at different sampling points. The content of purpurin ranged from 0.00 to 3.03 mg g-1, while the content of mollugin ranged from 0.03 to 10.09 mg g-1. The quality of R. cordifolia in Shanxi, Shaanxi and Henan border areas and southeastern Liaoning was higher. Liaoning is expected to become a R. cordifolia planting area in Northeast China. Correlation and regression analysis revealed that the two secondary metabolites were affected by different environmental factors, the two secondary metabolites contents were positively correlated with longitude and latitude, and negatively correlated with soil nutrients. In addition, higher temperature and shorter sunshine duration facilitated the synthesis of purpurin. Annual precipitation might be the main factor limiting the quality of R. cordifolia because it had opposite effects on the synthesis of two major secondary metabolites. Therefore, this study is of great significance for the selection of R. cordifolia planting areas and the improvement of field planting quality.
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The appearance of dried fruit clearly influences the consumer's perception of the quality of the product but is a subtle and nuanced characteristic that is difficult to quantitatively measure, especially online. This paper describes a method that combines several simple strategies to assess a suitable surrogate for the elusive quality using imaging, combined with multivariate statistics and machine learning. With such a convenient tool, this study also shows how one can vary the pretreatments and drying conditions to optimize the resultant product quality. Specifically, an image batch processing method was developed to extract color (hue, saturation, and value) and morphological (area, perimeter, and compactness) features. The accuracy of this method was verified using data from a case study experiment on the pretreatment of hot-air-dried kiwifruit slices. Based on the extracted image features, partial least squares and random forest models were developed to satisfactorily predict the moisture ratio (MR) during drying process. The MR of kiwifruit slices during drying could be accurately predicted from changes in appearance without using any weighing device. This study also explored determining the optimal drying strategy based on appearance quality using principal component analysis. Optimal drying was achieved at 60 °C with 4 mm thick slices under ultrasonic pretreatment. For the 70 °C, 6 mm sample groups, citric acid showed decent performance.
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Hydrogen peroxide (H2O2) is a signaling molecule that has the capacity to control a variety of biological processes in organisms. Cancer cells release more H2O2 during abnormal tumor growth. There has been a considerable amount of interest in utilizing H2O2 as a biomarker for the diagnosis of cancer tissue. In this study, an electrochemical sensor for H2O2 was constructed based on 3D reduced graphene oxide (rGO), MXene (Ti3C2), and multi-walled carbon nanotubes (MWCNTs) composite. Three-dimensional (3D) rGO-Ti3C2-MWCNTs sensor showed good linearity for H2O2 in the ranges of 1-60 µM and 60 µM-9.77 mM at a working potential of -0.25 V, with sensitivities of 235.2 µA mM-1 cm-2 and 103.8 µA mM-1 cm-2, respectively, and a detection limit of 0.3 µM (S/N = 3). The sensor exhibited long-term stability, good repeatability, and outstanding immunity to interference. In addition, the modified electrode was employed to detect real-time H2O2 release from cancer cells and cancer tissue ex vivo.
Subject(s)
Biosensing Techniques , Electrodes , Graphite , Hydrogen Peroxide , Nanotubes, Carbon , Neoplasms , Nanotubes, Carbon/chemistry , Graphite/chemistry , Humans , Neoplasms/diagnosis , Electrochemical Techniques , Limit of DetectionABSTRACT
Electrocatalytic semihydrogenation of alkynols presents a sustainable alternative to conventional thermal methodologies for the high-value production of alkenols. The design of efficient catalysts with superior catalytic and energy efficiency for semihydrogenation poses a significant challenge. Here, we present the application of an electron-divergent Cu3Pd alloy-based heterojunction in promoting the electrocatalytic semihydrogenation of alkynols to alkenols using water as the proton source. The tunable electron divergence of Cuδ- and Pdδ+, modulated by rectifying contact with nitrogen-rich carbons, enables the concerted binding of active H species from the Volmer step of water dissociation and the C≡C bond of alkynols on Pdδ+ sites. Simultaneously, the pronounced electron divergence of Cu3Pd facilitates the universal adsorption of OH species from the Volmer step and alkynols on the Cuδ- sites. The electron-divergent dual-center substantially boosts water dissociation and inhibition of completing hydrogen evolution to give a turnover frequency of 2412 h-1, outperforming the reported electrocatalysts' value of 7.3. Moreover, the continuous production of alkenols at industrial-related current density (-200 mA cm-2) over the efficient and durable Cu3Pd-based electrolyzer could achieve a cathodic energy efficiency of 45 mol kW·h-1, 1.7 times the bench-marked reactors, promising great potential for sustainable industrial synthesis.
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Fungal infections maintain a close relation with the body's immune function. In this study, three series of benzazole compounds were designed as dual-target (PD-L1/CYP51) inhibitors using the skeleton splicing approach; their molecular structures were synthesized and evaluated accordingly. Among them, the compounds 9a-2, 12a-2, and 12b-1 exhibited potent antifungal activity and dual-target inhibition ability. Especially, the compound 12a-2 simultaneously exerted excellent bifunctional effects of fungal inhibition and immune activation. Moreover, a layered double hydroxide (LDH) carrier was also successfully constructed based on an infection microenvironment to improve the bioavailability and the targeting of compound 12a-2. This significantly accelerated the recovery process of deep and shallow fungal infections. In conclusion, this study expanded the development horizon of antifungal drugs and provided a novel drug delivery route for treating fungal infections.
Subject(s)
Antifungal Agents , Drug Design , Microbial Sensitivity Tests , Antifungal Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Humans , Structure-Activity Relationship , Animals , Mice , Drug Carriers/chemistry , Molecular Structure , Candida albicans/drug effects , 14-alpha Demethylase Inhibitors/pharmacology , 14-alpha Demethylase Inhibitors/chemical synthesis , 14-alpha Demethylase Inhibitors/chemistry , Molecular Docking SimulationABSTRACT
BACKGROUND: Major depressive disorder (MDD) is treated primarily using antidepressant drugs, but clinical effects may be delayed for weeks to months. This study investigated the efficacy of brief therapeutic sleep deprivation (TSD) for inducing rapid improvements in MDD symptoms. METHODS: From November 2020 to February 2023, 54 inpatients with MDD were randomly allocated to TSD and Control groups. The TSD group (23 cases) remained awake for 36 h, while the Control group (31 cases) maintained regular sleep patterns. All participants continued regular drug therapy. Mood was assessed using the 24-item Hamilton Depression Scale (HAMD-24) at baseline and post-intervention in both groups. In the TSD group, the Visual Analogue Scale (VAS) was utilized to evaluate subjective mood during and after the intervention. Cognitive function was assessed at baseline and post-intervention using the Montreal Cognitive Assessment (MoCA). Objective sleep parameters were recorded in the TSD group by polysomnography. The follow-up period spanned one week. RESULTS: HAMD-24 scores did not differ between groups at baseline or post-intervention. However, the clinical response rate was 34.8 % higher in the TSD group on day 3 post-intervention compared to the Control group (3.2 %), but not sustained by day 7. Moreover, responders demonstrated a faster improvement in the VAS score during TSD than non-responders (p = 0.047). There were no significant differences in MoCA scores or objective sleep parameters between the groups. LIMITATIONS: Small sample size and notable attrition rate. CONCLUSIONS: Therapeutic sleep deprivation can rapidly improve MDD symptoms without influencing sleep parameters or cognitive functions. Assessment of longer-term effects and identification of factors predictive of TSD response are warranted.
Subject(s)
Depressive Disorder, Major , Sleep Deprivation , Humans , Depressive Disorder, Major/therapy , Depressive Disorder, Major/drug therapy , Female , Male , Sleep Deprivation/complications , Adult , Middle Aged , Treatment Outcome , Psychiatric Status Rating Scales , Polysomnography , Affect , Antidepressive Agents/therapeutic useABSTRACT
Asthenozoospermia (AZS) is a prevalent contributor to male infertility, characterized by a substantial decline in sperm motility. In recent years, large-scale studies have explored the interplay between the male reproductive system's microecology and its implications for reproductive health. Nevertheless, the direct association between seminal microecology and male infertility pathogenesis remains inconclusive. This study used 16S rDNA sequencing and multi-omics analysis to conduct a comprehensive investigation of the seminal microbial community and metabolites in AZS patients. Patients were categorized into four distinct groups: Normal, mild AZS (AZS-I), moderate AZS (AZS-II), and severe AZS (AZS-III). Microbiome differential abundance analysis revealed significant differences in microbial composition and metabolite profiles within the seminal plasma of these groups. Subsequently, patients were classified into a control group (Normal and AZS-I) and an AZS group (AZS-II and AZS-III). Correlation and cross-reference analyses identified distinct microbial genera and metabolites. Notably, the AZS group exhibited a reduced abundance of bacterial genera such as Pseudomonas, Serratia, and Methylobacterium-Methylorubrum in seminal plasma, positively correlating with core differential metabolite (hexadecanamide). Conversely, the AZS group displayed an increased abundance of bacterial genera such as Uruburuella, Vibrio, and Pseudoalteromonas, with a negative correlation with core differential metabolite (hexadecanamide). In vitro and in vivo experiments validated that hexadecanamide significantly enhanced sperm motility. Using predictive metabolite-targeting gene analysis and single-cell transcriptome sequencing, we profiled the gene expression of candidate target genes PAOX and CA2. Protein immunoblotting techniques validated the upregulation protein levels of PAOX and CA2 in sperm samples after hexadecanamide treatment, enhancing sperm motility. In conclusion, this study uncovered a significant correlation between six microbial genera in seminal plasma and the content of the metabolite hexadecanamide, which is related to AZS. Hexadecanamide notably enhances sperm motility, suggesting its potential integration into clinical strategies for managing AZS, providing a foundational framework for diagnostic and therapeutic advancements.
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As a positional and geometrical isomer of linoleic acid, trans 10, cis 12 conjugated linoleic acid (t10c12-CLA) reduces white fat by reducing food intake, modulating lipid metabolism, and stimulating energy expenditure. However, the t10c12-CLA products are mostly mixtures, making it difficult to obtain accurate results. Studies are needed to investigate the effects of pure t10c12-CLA on animals and humans. In this study, we used the biallelic transgenic (tg) mice, which could produce t10c12-CLA itself, to investigate the effects of pure t10c12-CLA on female reproductive ability. The results showed that the body and relative ovary weights had no significant difference between tg and wild-type (wt) littermates at ages 3 or 10 weeks. While the fecundity test found that tg mice had a significantly longer first litter time (32.0 ± 4.70 days vs. 21.3 ± 2.31 days, P<0.05), and a significantly lower number of litters (4.75 ± 2.75 vs. 6.67 ± 0.57, P<0.05) when compared with wt mice during continuous mating within seven months. Hormone profiles showed that serum estradiol levels did not change in tg mice; however, significantly (P<0.05) decreased progesterone and increased prostaglandin E2 levels were observed in tg mice compared with those of wt mice. Hematoxylin-eosin staining showed no pathological characteristics in tg ovaries, except for the increased atresia follicles (P<0.05). Moreover, the tg mice had a significantly more extended diestrus period than the wt mice (48.4 ± 6.38% vs. 39.6 ± 3.81%, P<0.05). In summary, t10c12-CLA could affect serum progesterone and prostaglandin E2 levels, lead to a disordered estrus cycle, and impact the reproductive performance of female mice. This study provided theoretical and biosafety recommendations for applying t10c12-CLA in female mammals.
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Faced with increasingly serious fungal infections and drug resistance issues, three different series of novel dual-target (programmed death ligand 1/14 α-demethylase) compounds were constructed through the fragment combination pathway in the study. Their chemical structures were synthesized, characterized, and evaluated. Among them, preferred compounds 10c-1, 17b-1, and 18b-2 could efficiently exert their antifungal and antidrug-resistant fungal ability through blocking ergosterol biosynthesis, inducing the upregulation of reactive oxygen species level, and triggering apoptosis. Especially, compound 18b-2 exhibited the synergistic function of fungal inhibition and immune activation. Moreover, the covalent organic framework carrier was also generated based on the acidic microenvironment of fungal infection to improve the bioavailability and targeting of preferred compounds; this finally accelerated the body's recovery rate.
Subject(s)
Antifungal Agents , Antifungal Agents/pharmacology , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Humans , Animals , Microbial Sensitivity Tests , Structure-Activity Relationship , Reactive Oxygen Species/metabolism , Apoptosis/drug effects , 14-alpha Demethylase Inhibitors/pharmacology , 14-alpha Demethylase Inhibitors/chemistry , 14-alpha Demethylase Inhibitors/chemical synthesis , Mycoses/drug therapy , Mice , Candida albicans/drug effects , Ergosterol/metabolism , Molecular StructureABSTRACT
BACKGROUND: A complex interaction and mutual influence exists among landscapes, cultures, and landraces, with rice culture being a typical embodiment of this relationship. The conservation of landraces operates alongside preserving traditional practices. The Xishuangbanna region stands out as a hub for the genetic diversity of landraces, boasting rich genetic resources. Despite the diverse rice resources in this region, a comprehensive and systematic study has not been undertaken. METHODS: From October to November 2023, we collected rice landraces under the on-farm conservation in 18 townships including Menghai, Mengla and Jinghong in Xishuangbanna. Employing semi-structured interviews and various methods, we investigated factors influencing the preservation and loss of rice landraces in the region. Statistical analysis was applied to the agronomic traits of collected local rice, encompassing indica or japonica, glutinous or non-glutinous, grain shape, and hull color as second category traits. The second category included quantitative traits like thousand grain weight and grain length. Rice diversity among different regions, traits, and ethnic groups was assessed using the Shannon-Wiener index. Additionally, clustering analysis via the UPGMA method depicted the distribution characteristics of the resources. RESULTS: A total of 70 rice landraces were collected in the Xishuangbanna region, each exhibiting distinct characteristics. Differences were observed across regions, trait, naming, and ethnic groups. Diversity analysis revealed that Mengla had the highest diversity, followed by Menghai, while Jinghong exhibited the lowest diversity. The second category of traits displayed broader diversity than the first, with the Dai people's glutinous rice showcasing greater diversity than other ethnic groups. Cluster analysis categorized the 70 samples into seven groups at a genetic distance of 1.15. Ethnobotanical interviews emphasized the rapid loss of rice landraces resources in Xishuangbanna, with indigenous ethnic cultures playing a vital role in the conservation of rice landraces. Dai traditions, in particular, played a crucial role in protecting glutinous rice resources, showcasing a mutual dependence between Dai culture and glutinous rice. CONCLUSIONS: The rich natural environment and diverse ethnic cultures in Xishuangbanna have given rise to various rice landraces. The Dai, primary cultivators of glutinous rice with higher diversity, intertwine their traditional ethnic culture with the conservation of glutinous rice resources. At the same time, the preserving glutinous rice resources promotes the inheritance of Dai ethnic culture. However, rice landraces are facing the risk of loss. Hence, collecting and documenting rice landraces is crucial. Encourage local communities to sustain and expand their cultivation, promoting on-farm conservation. These measures contribute valuable germplasm and genes for rice breeding and serve as a means of cultural preservation.
Subject(s)
Conservation of Natural Resources , Ethnobotany , Oryza , China , Oryza/genetics , Oryza/growth & development , Humans , FarmsABSTRACT
Stem cell paracrine has shown potential application in skin wound repair and photoaging treatment. Our previous study demonstrated that miR-1246-overexpressing Exosomes (OE-EXs) isolated from adipose-derived stem cells (ADSCs) showed superior photo-protecting effects on UVB-induced photoaging than that of the vector, however, the underlying mechanism was unclear. The simultaneous bioinformatics analysis indicated that miR-1246 showed potential binding sites with GSK3ß which acted as a negative regulator for autophagy. This study was aimed to explore whether OE-EXs ameliorate skin photoaging by activating autophagy via targeting GSK3ß. The results demonstrated that OE-EXs significantly decreased GSK3ß expression, enhanced autophagy flux and autophagy-related proteins like LC3II, while suppressed p62 expression. Meanwhile, OE-EXs markedly reversed the levels of intracellular ROS, MMP-1, procollagen type I and DNA damage in human skin fibroblasts caused by UVB irradiation, but the ameliorating effects were significantly inhibited when 3-Methyladenine (3-MA) was introduced to block the autophagy pathway. Further, OE-EXs could reverse UVB-induced wrinkles, epidermal hyperplasia, and collagen fibers reduction in Kunming mice, nevertheless, the therapeutical effects of OE-EXs were attenuated when it was combinative treated with 3-MA. In conclusion, OE-EXs could cure UVB induced skin photoaging by activating autophagy via targeting GSK3ß.
Subject(s)
Autophagy , Exosomes , Glycogen Synthase Kinase 3 beta , MicroRNAs , Skin Aging , Ultraviolet Rays , Animals , Skin Aging/radiation effects , Glycogen Synthase Kinase 3 beta/metabolism , Mice , Exosomes/metabolism , Humans , MicroRNAs/metabolism , MicroRNAs/genetics , Fibroblasts/metabolism , Cells, CulturedABSTRACT
OBJECTIVE: Although Endovascular Thrombectomy (EVT) significantly improves the prognosis of Acute Ischemic Stroke (AIS) patients with large vessel occlusion, the mortality rate remains higher. This study aimed to construct and validate a nomogram for predicting 90-day all-cause mortality in AIS patients with large vessel occlusion and who have undergone EVT. METHODS: AIS patients with large vessel occlusion in the anterior circulation who underwent EVT from May 2017 to December 2022 were included. 430 patients were randomly split into a training group (N=302) and a test group (N=128) for the construction and validation of our nomogram. In the training group, multivariate logistic regression analysis was performed to determine the predictors of 90-day all-cause mortality. The C-index, calibration plots, and decision curve analysis were applied to evaluate the nomogram performance. RESULTS: Multivariate logistic regression analysis revealed neurological deterioration during hospitalization, age, baseline National Institutes of Health Stroke Scale (NIHSS) score, occlusive vessel location, malignant brain edema, and Neutrophil-to-lymphocyte Ratio (NLR) as the independent predictors of 90-day all-cause mortality (all p ≤ 0.039). The C-index of the training and test groups was 0.891 (95%CI 0.848-0.934) and 0.916 (95% CI: 0.865-0.937), respectively, showing the nomogram to be well distinguished. The Hosmer-Lemeshow goodness-of-fit test revealed the p-values for both the internal and external verification datasets to be greater than 0.5. CONCLUSION: Our nomogram has incorporated relevant clinical and imaging features, including neurological deterioration, age, baseline NIHSS score, occlusive vessel location, malignant brain edema, and NLR ratio, to provide an accurate and reliable prediction of 90-day all-cause mortality in AIS patients undergoing EVT.
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Cadmium (Cd) pollution in soil poses a global concern due to its serious impacts on human health and ecological security. In plants, tremendous efforts have been made to identify some key genes and pathways in Cd stress responses. However, studies on the roles of epigenetic factors in response to Cd stress were still limited. In the study, we first gain insight into the gene expression dynamics for maize seedlings under 0â¯h, 12â¯h, and 72â¯hâ¯Cd stress. As a result, six distinct groups of genes were identified by hierarchical clustering and principal component analysis. The key pathways associated with 12â¯hâ¯Cd stress were protein modifications including protein ubiquitination, signal transduction by protein phosphorylation, and histone modification. Whereas, under 72â¯h stress, main pathways were involved in biological processes including phenylalanine metabolism, response to oxygen-containing compounds and metal ions. Then to be noted, one of the most highly expressed genes at 12â¯h under Cd treatment is annotated as histone demethylases (ZmJMJ20). The evolutionary tree analysis and domain analysis showed that ZmJMJ20 belonged to the JmjC-only subfamily of the Jumonji-C (JmjC) family, and ZmJMJ20 was conserved in rice and Arabidopsis. After 72â¯h of Cd treatment, the zmjmj20 mutant created by EMS treatment manifested less severe chlorosis/leaf yellowing symptoms compared with wild-type plants, and there was no significant difference in Fv/Fm and φPSII value before and after Cd treatment. Moreover, the expression levels of several photosynthesis-related down-regulated genes in EMS mutant plants were dramatically increased compared with those in wild-type plants at 12â¯h under Cd treatment. Our results suggested that ZmJMJ20 plays an important role in the Cd tolerance response pathway and will facilitate the development of cultivars with improved Cd stress tolerance.
Subject(s)
Cadmium , Gene Expression Profiling , Gene Expression Regulation, Plant , Soil Pollutants , Stress, Physiological , Zea mays , Zea mays/genetics , Zea mays/drug effects , Cadmium/toxicity , Soil Pollutants/toxicity , Stress, Physiological/drug effects , Gene Expression Regulation, Plant/drug effects , Histone Demethylases/genetics , Histone Demethylases/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Seedlings/drug effects , Seedlings/geneticsABSTRACT
Ultrasound switchable fluorescence (USF) imaging, a hybrid imaging technology that combines the advantages of both fluorescence sensitivity and acoustic resolution in centimeter-deep tissue, has great potential for biomedical different applications. A camera-based USF imaging system reveals its capability of capturing both spatial and temporal dynamics of the USF signal in tissue. In this study, various algorithms were explored to enhance the spatial resolution and signal-to-noise ratio (SNR) of USF images, utilizing temporal and spatial information from a camera-based time-domain USF imaging system. The correlation method proved effective in boosting SNR, while the ascending-slope-weighted method enhanced spatial resolution. Additionally, the spatially back-projection method significantly improved spatial resolution in silicone phantoms. The results underscore the advantages of incorporating temporal and spatial information from USF signals.
Subject(s)
Optical Imaging , Phantoms, Imaging , Signal-To-Noise Ratio , Optical Imaging/instrumentation , Optical Imaging/methods , Image Processing, Computer-Assisted/methods , Algorithms , UltrasonographyABSTRACT
The inherent characteristics of cellulose-derived aerogels, such as their natural abundance and environmental friendliness, make them highly interesting. However, its significant shrinkage before and after the supercritical drying procedure and low mechanical strength limit its potential application. Here, we propose a strategy to prepare cellulose diacetate aerogels (CDAAs) with low drying shrinkage, exceptional thermal insulation, and superior mechanical strength. The low drying shrinkage (radial drying shrinkage of 1.4%) of CDAAs is attributed to their relative strong networking skeletons, which are greatly formed by tert-butanol solvent exchange in exerting the interaction of reducing the surface tension force. In this case, CDAAs are eventually endowed with the low bulk density of 0.069 g cm-3 as well. Additionally, as-prepared CDAAs possess an abundant three-dimensional networking structure whose pore size is concentrated in the diameter range of ~50 nm, and the result above is beneficial for improving the thermal insulation performance (thermal conductivity of 0.021 W m-1 K-1 at ambient environmental and pressure conditions). On the other hand, the optimal compressive stresses of CDAAs at 3% and 5% strain are 0.22 and 0.27 MPa respectively, indicating a mechanically well robustness. The above evidence demonstrates indeed the exceptional thermal insulation and superior compressive properties of CDAAs. This work may provide a new solution for developing a kind of high-performance cellulose-derived aerogel in the future.
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BACKGROUND: Concurrent chemo-radiotherapy (CCRT) is the preferred non-surgical treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Unfortunately, some patients respond poorly, which leads to inappropriate or excessive treatment and affects patient survival. To accurately predict the response of ESCC patients to CCRT, we developed classification models based on the clinical, serum proteomic and radiomic data. METHODS: A total of 138 ESCC patients receiving CCRT were enrolled in this study and randomly split into a training cohort (n = 92) and a test cohort (n = 46). All patients were classified into either complete response (CR) or incomplete response (non-CR) groups according to RECIST1.1. Radiomic features were extracted by 3Dslicer. Serum proteomic data was obtained by Olink proximity extension assay. The logistic regression model with elastic-net penalty and the R-package "rms" v6.2-0 were applied to construct classification and nomogram models, respectively. The area under the receiver operating characteristic curves (AUC) was used to evaluate the predictive performance of the models. RESULTS: Seven classification models based on multi-omics data were constructed, of which Model-COR, which integrates five clinical, five serum proteomic, and seven radiomic features, achieved the best predictive performance on the test cohort (AUC = 0.8357, 95 % CI: 0.7158-0.9556). Meanwhile, patients predicted to be CR by Model-COR showed significantly longer overall survival than those predicted to be non-CR in both cohorts (Log-rank P = 0.0014 and 0.027, respectively). Furthermore, two nomogram models based on multi-omics data also performed well in predicting response to CCRT (AUC = 0.8398 and 0.8483, respectively). CONCLUSION: We developed and validated a multi-omics based classification model and two nomogram models for predicting the response of ESCC patients to CCRT, which achieved the best prediction performance by integrating clinical, serum Olink proteomic, and radiomic data. These models could be useful for personalized treatment decisions and more precise clinical radiotherapy and chemotherapy for ESCC patients.