Comparisons between In-Check DIAL® and PF810® in evaluation and training inspiratory capacity for using dry powder inhalers.

BACKGROUND: Dry powder inhalers (DPIs) rely on both internal resistance and patients' inspiratory capacity for effective operation. Optimal inspiratory technique is crucial for DPI users. This study assessed the accuracy and repeatability of two available devices, PF810® and In-Check DIAL®, and analyzed their measurement errors and consistency in detecting inspiratory capacity. METHODS: The accuracy and repeatability of peak inspiratory flow (PIF) and forced inspiratory vital capacity (FIVC) against various internal resistances of the two devices were assessed using standard waveforms generated by a breathing simulator. The agreement of PIF measurements between the two devices in healthy volunteers and chronic obstructive pulmonary disease (COPD) patients was analyzed with the intraclass correlation coefficient and Bland-Altman graphical analysis. RESULTS: PF810® showed great accuracy and repeatability in measuring PIF, except for square waveforms at the lowest flow rate (20 L/min). In-Check DIAL® exhibited poor accuracy against high resistance levels. In scenarios with no resistance, In-Check DIAL® had significantly smaller measurement errors than PF810®, but larger errors against high resistance levels. The two devices showed excellent agreement (ICC > 0.80, P < 0.05), except for healthy volunteers against medium to high resistance (R3-R5) where the ICC was insignificant. Bland-Altman plots indicated small disagreements between the two devices for both healthy volunteers and COPD patients. CONCLUSIONS: In-Check DIAL® exhibited poor accuracy and larger measurement errors than PF810® when detecting PIFs against higher internal resistances. However, its good performance against lower internal resistances, along with its cost-effectiveness and convenience made it appropriate for primary care. PF810® showed good accuracy and repeatability and could detect additional parameters of inspiratory capacity beyond PIF, though required further studies to confirm its clinical benefits.

NKG2A genetic deletion promotes human primary NK cell anti-tumor responses better than an anti-NKG2A monoclonal antibody.

Natural killer (NK) cells eliminate infected or cancer cells via their cytotoxic capacity. NKG2A is an inhibitory receptor on NK cells and cancer cells often overexpress its ligand HLA-E to evade NK cell surveillance. Given the successes of immune checkpoint blockade in cancer therapy, NKG2A is an interesting novel target. However, anti-NKG2A antibodies have shown limited clinical response. In the pursuit of enhancing NK cell-mediated anti-tumor responses, we devised a Cas9-based strategy to delete KLRC1, encoding NKG2A, in human primary NK cells. Our approach involved electroporation of KLRC1-targeting Cas9 ribonucleoprotein resulting in effective ablation of NKG2A expression. Compared with anti-NKG2A antibody blockade, NKG2AKO NK cells exhibited enhanced activation, reduced suppressive signaling, and elevated expression of key transcription factors. NKG2AKO NK cells overcame inhibition from HLA-E, significantly boosting NK cell activity against solid and hematologic cancer cells. We validated this efficacy across multiple cell lines, a xenograft mouse model, and primary human leukemic cells. Combining NKG2A knockout with antibody coating of tumor cells further enhanced cytotoxicity through ADCC. Thus, we provide a comprehensive comparison of inhibition of the NKG2A pathway using genetic ablation and antibodies and provide novel insight in the observed differences in molecular mechanisms, which can be translated to enhance adoptive NK cell immunotherapy.

Nlp-dependent ER-to-Golgi transport.

The mechanism that maintains ER-to-Golgi vesicles formation and transport is complicated. As one of the adapters, Ninein-like protein (Nlp) participated in assembly and transporting of partial ER-to-Golgi vesicles that contained specific proteins, such as ß-Catenin and STING. Nlp acted as a platform to sustain the specificity and continuity of cargoes during COPII and COPI-coated vesicle transition and transportation through binding directly with SEC31A as well as Rab1B. Thus, we proposed an integrated transport model that particular adapter participated in specific cargo selection or transportation through cooperating with different membrane associated proteins to ensure the continuity of cargo trafficking. Deficiency of Nlp led to vesicle budding failure and accumulation of unprocessed proteins in ER, which further caused ER stress as well as Golgi fragmentation, and PERK-eIF2α pathway of UPR was activated to reduce the synthesis of universal proteins. In contrast, upregulation of Nlp resulted in Golgi fragmentation, which enhanced the cargo transport efficiency between ER and Golgi. Moreover, Nlp deficient mice were prone to spontaneous B cell lymphoma, since the developments and functions of lymphocytes significantly depended on secretory proteins through ER-to-Golgi vesicle trafficking, including IL-13, IL-17 and IL-21. Thus, perturbations of Nlp altered ER-to-Golgi communication and cellular homeostasis, and might contribute to the pathogenesis of B cell lymphoma.

Maize auxin response factor ZmARF1 confers multiple abiotic stresses resistances in transgenic Arabidopsis.

Prolonged exposure to abiotic stresses causes oxidative stress, which affects plant development and survival. In this research, the overexpression of ZmARF1 improved tolerance to low Pi, drought and salinity stresses. The transgenic plants manifested tolerance to low Pi by their superior root phenotypic traits: root length, root tips, root surface area, and root volume, compared to wide-type (WT) plants. Moreover, the transgenic plants exhibited higher root and leaf Pi content and upregulated the high affinity Pi transporters PHT1;2 and phosphorus starvation inducing (PSI) genes PHO2 and PHR1 under low Pi conditions. Transgenic Arabidopsis displayed tolerance to drought and salt stress by maintaining higher chlorophyll content and chlorophyll fluorescence, lower water loss rates, and ion leakage, which contributed to the survival of overexpression lines compared to the WT. Transcriptome profiling identified a peroxidase gene, POX, whose transcript was upregulated by these abiotic stresses. Furthermore, we confirmed that ZmARF1 bound to the auxin response element (AuxRE) in the promoter of POX and enhanced its transcription to mediate tolerance to oxidative stress imposed by low Pi, drought and salt stress in the transgenic seedlings. These results demonstrate that ZmARF1 has significant potential for improving the tolerance of crops to multiple abiotic stresses.

Rhamnogalacturonan lyase 1 (RGL1), as a suppressor of E3 ubiquitin ligase Arabidopsis thaliana ring zinc finger 1 (AtRZF1), is involved in dehydration response to mediate proline synthesis and pectin rhamnogalacturonan-I composition.

Proline metabolism plays a crucial role in both environmental stress responses and plant growth. However, the specific mechanism by which proline contributes to abiotic stress processes remains to be elucidated. In this study, we utilized atrzf1 (Arabidopsis thaliana ring zinc finger 1) as a parental line for T-DNA tagging mutagenesis and identified a suppressor mutant of atrzf1, designated proline content alterative 31 (pca31). The pca31 mutant suppressed the insensitivity of atrzf1 to dehydration stress during early seedling growth. Using Thermal Asymmetric Interlaced-PCR, we found that the T-DNA of pca31 was inserted into the promoter region of the At2g22620 gene, which encodes the cell wall enzyme rhamnogalacturonan lyase 1 (RGL1). Enzymatic assays indicated that RGL1 exhibited rhamnogalacturonan lyase activity, influencing cell wall pectin composition. The decrease in RGL1 gene expression suppressed the transcriptomic perturbation of the atrzf1 mutant. Silencing of the RGL1 gene in atrzf1 resulted in a sensitive phenotype similar to pca31 under osmotic stress conditions. Treatment with mannitol, salt, hydrogen peroxide, and abscisic acid induced RGL1 expression. Furthermore, we uncovered that RGL1 plays a role in modulating root growth and vascular tissue development. Molecular, physiological, and genetic experiments revealed that the positive modulation of RGL1 during abiotic stress was linked to the AtRZF1 pathway. Taken together, these findings establish that pca31 acts as a suppressor of atrzf1 in abiotic stress responses through proline and cell wall metabolisms.

Comprehensive analysis of human monocyte subsets using full-spectrum flow cytometry and hierarchical marker clustering.

Introduction: Exploring monocytes' roles within the tumor microenvironment is crucial for crafting targeted cancer treatments. Methods: This study unveils a novel methodology utilizing four 20-color flow cytometry panels for comprehensive peripheral immune system phenotyping, specifically targeting classical, intermediate, and non-classical monocyte subsets. Results: By applying advanced dimensionality reduction techniques like t-distributed stochastic neighbor embedding (tSNE) and FlowSom analysis, we performed an extensive profiling of monocytes, assessing 50 unique cell surface markers related to a wide range of immunological functions, including activation, differentiation, and immune checkpoint regulation. Discussion: This in-depth approach significantly refines the identification of monocyte subsets, directly supporting the development of personalized immunotherapies and enhancing diagnostic precision. Our pioneering panel for monocyte phenotyping marks a substantial leap in understanding monocyte biology, with profound implications for the accuracy of disease diagnostics and the success of checkpoint-inhibitor therapies. Key findings include revealing distinct marker expression patterns linked to tumor progression and providing new avenues for targeted therapeutic interventions.

Modular Biomimetic Strategy Enables Discovery and SAR Exploration of Oxime Macrocycles as Influenza A Virus (H1N1) Inhibitors.

Although vaccination remains the prevalent prophylactic means for controlling Influenza A virus (IAV) infections, novel structural antivirus small-molecule drugs with new mechanisms of action for treating IAV are highly desirable. Herein, we describe a modular biomimetic strategy to expeditiously achieve a new class of macrocycles featuring oxime, which might target the hemagglutinin (HA)-mediated IAV entry into the host cells. SAR analysis revealed that the size and linker of the macrocycles play an important role in improving potency. Particularly, as a 14-membered macrocyclic oxime, 37 exhibited potent inhibitory activity against IAV H1N1 with an EC50 value of 23 nM and low cytotoxicity, which alleviated cytopathic effects and protected cell survival obviously after H1N1 infection. Furthermore, 37 showed significant synergistic activity with neuraminidase inhibitor oseltamivir in vitro.

Effects of different light intensity on leaf color changes in a Chinese cabbage yellow cotyledon mutant.

Leaf color is one of the most important phenotypic features in horticultural crops and directly related to the contents of photosynthetic pigments. Most leaf color mutants are determined by the altered chlorophyll or carotenoid, which can be affected by light quality and intensity. Our previous study obtained a Chinese cabbage yellow cotyledon mutant that exhibited obvious yellow phenotypes in the cotyledons and the new leaves. However, the underlying mechanisms in the formation of yellow cotyledons and leaves remain unclear. In this study, the Chinese cabbage yellow cotyledon mutant 19YC-2 exhibited obvious difference in leaf color and abnormal chloroplast ultrastructure compared to the normal green cotyledon line 19GC-2. Remarkably, low-intensity light treatment caused turn-green leaves and a significant decrease in carotenoid content in 19YC-2. RNA-seq analysis revealed that the pathways of photosynthesis antenna proteins and carotenoid biosynthesis were significantly enriched during the process of leaf color changes, and many differentially expressed genes related to the two pathways were identified to respond to different light intensities. Remarkably, BrPDS and BrLCYE genes related to carotenoid biosynthesis showed significantly higher expression in 19YC-2 than that in 19GC-2, which was positively related to the higher carotenoid content in 19YC-2. In addition, several differentially expressed transcription factors were also identified and highly correlated to the changes in carotenoid content, suggesting that they may participate in the regulatory pathway of carotenoid biosynthesis. These findings provide insights into the molecular mechanisms of leaf color changes in yellow cotyledon mutant 19YC-2 of Chinese cabbage.

In-depth understanding of the effects of different molecular weight pullulan interacting with protein and starch on dough structure and application properties.

This work clarified the positive effects of pullulan on dough structure and application properties varied with its molecular weight. Pullulan with different molecular weights were introduced into dough system to explore their intervention effects on structural and technological properties of dough as well as physical and digestion properties of biscuits. Results showed that HPL (pullulan with molecule weight of 100- 300 kDa) could increase the intermolecular collisions, prompt the protein aggregation and limit the water migration in dough system, resulting in an integrate, continuous and dense network structure of the gel with strengthened elasticity and weakened extensibility, which caused an increase in biscuit thickness, hardness and crispness. On the contrary, LPL (pullulan with molecule weight of 3- 100 kDa) could go against the formation of stable and elastic dough through breaking down cross-linkage between protein and starch so as to provide biscuits with decreased hardness and crispness during baking. Both HPL and LPL delayed starch pasting and retrogradation process while HPL had the stronger retarding effect on starch digestibility of biscuits than LPL. These findings dedicated to a better understanding of pullulan function in dough system and provide suggestions for fractionation applications of pullulan in food field.

Effects of dextran molecular weight on starch retrogradation and technological properties of Chinese steamed bread: Based on the rubber/glass transition.

From the perspective of rubber/glass transition, this study clarified that the impact of dextran on retarding hardening behavior and slowing starch retrogradation of Chinese Steamed Bread (CSB) depended on its molecular weight and concentration level. Guggenheim-Anderson-de Boer (GAB) model was fitted to explore critical behavior changes in rubber/glass transition of CSB. Incorporation of high molecular weight dextran enhanced the elasticity of dough and porosity of CSB, reduced the aging and hardening degree of CSB at appropriate addition levels. CSB hardness showed a growing tendency during storage, while macromolecular dextran reduced the hardness and retrogradation degree by 22.87 % and 67.53 %. Dextran with high molecular weights lowered the glass transition temperature (Tg) and improved the moisture sorption and molecular mobility of CSB under various relative humidity (RHs) conditions by providing hydrophilic sites or intermolecular space to bind water molecules. Meanwhile, it reinforced the binding between denatured gluten and gelatinized starch. Both of them devoted to starch retrogradation inhibition and stable quality maintenance of CSB. CSB is suggested to maintain stable quality at room temperature with RHs ≤33 % to prevent rubber/glass transition. This work provided theoretical guidance for fractionation application of dextran to regulate the quality and extend the shelf-life of flour products.

Influence of nonalcoholic fatty liver disease on response to antiviral treatment in patients with chronic hepatitis B: A meta-analysis.

BACKGROUND: Although hepatitis B virus infection is the leading cause of chronic liver injury globally, nonalcoholic fatty liver disease (NAFLD) is gradually gaining attention as another major chronic liver disease. The number of patients having chronic hepatitis B (CHB) with concomitant hepatic steatosis has increased. AIM: To analyze the effect of NAFLD on the response to antiviral treatment in patients with CHB. METHODS: Relevant English studies were systematically searched across PubMed, EMBASE, Web of Science, and Cochrane Library until October 2023. Studies in which the treatment outcomes were compared between patients with CHB only and those with CHB and hepatic steatosis were included. RESULTS: Of the 2502 retrieved studies, 11 articles were finally included. Biochemical response until 48 wk (OR = 0.87, 95%CI: 0.50-1.53, P = 0.000) and 96 wk (OR = 0.35, 95%CI: 0.24-0.53, P = 0.24) and virological response until 96 wk (OR = 0.80, 95%CI: 0.43-1.49, P = 0.097) were lower in patients with hepatic steatosis than in patients with CHB alone. CONCLUSION: Hepatic steatosis lowers the biochemical response to antiviral treatment in patients with CHB.

CDK7 in breast cancer: mechanisms of action and therapeutic potential.

Cyclin-dependent kinase 7 (CDK7) serves as a pivotal regulator in orchestrating cellular cycle dynamics and gene transcriptional activity. Elevated expression levels of CDK7 have been ubiquitously documented across a spectrum of malignancies and have been concomitantly correlated with adverse clinical outcomes. This review delineates the biological roles of CDK7 and explicates the molecular pathways through which CDK7 exacerbates the oncogenic progression of breast cancer. Furthermore, we synthesize the extant literature to provide a comprehensive overview of the advancement of CDK7-specific small-molecule inhibitors, encapsulating both preclinical and clinical findings in breast cancer contexts. The accumulated evidence substantiates the conceptualization of CDK7 as a propitious therapeutic target in breast cancer management.

Effects and long-term outcomes of endurance versus resistance training as an adjunct to standard medication in patients with stable COPD: a multicenter randomized trial.

BACKGROUND: Comparisons between endurance training (ET) and resistance training (RT) have produced equivocal findings in chronic obstructive pulmonary disease (COPD) patients. The purpose of our study is to investigate the effectiveness and long-term outcomes of adding ET and RT to conventional medical treatment in patients with COPD. A secondary objective is to investigate the clinical improvements resulting from exercise training in patients with different disease severities. METHODS: The study was a multicenter, prospective trial in people with stable COPD. The cohort was randomized to three groups: individualized medical treatment group (MT), MT + endurance training group (MT + ET) and MT + resistance training group (MT + RT). Exercise was performed 3 times weekly over a 12-week period. The endpoints of exercise capacity, health-related quality of life, COPD symptoms, lung function, and anxiety and depression questionnaires were re-evaluated at baseline, at the completion of the intervention and at 6 and 12-month follow-up. According to the COPD assessment tool offered by GOLD guidelines, patients were stratified into GOLD A and B groups and GOLD C and D groups for further subgroup analysis. RESULTS: The intention-to-treat (ITT) population included 366 patients, 328 of them completed the study protocol over 12 months (the PP-population). There were no significant differences in the primary outcome, quality of life, between patients who underwent medical treatment (MT) alone, MT + endurance training (MT + ET), or MT + resistance training (MT + RT) at the completion of the intervention, 6-, or 12-month follow-up. Additionally, no significant differences were observed between MT, MT + RT, or MT + ET groups concerning the primary outcome, exercise capacity (3MWD), after initial 3 months of intervention. However, a small statistically significant difference was noted in favor of MT + ET compared to MT + RT at 12 months (ITT: Δ3MWD in ET vs RT = 5.53 m, 95% confidence interval: 0.87 to 13.84 m, P = 0.03) (PP: Δ3MWD in ET vs RT = 7.67 m, 95% confidence interval: 0.93 to 16.27 m, P = 0.04). For patients in the GOLD C and D groups, improvement in quality of life following ET or RT was significantly superior to medical intervention alone. Furthermore, upon completion of the exercise regimen, RT exhibited a greater improvement in anxiety compared to ET in these patients (ITT: ΔHAD-A at 3-month: RT = -1.63 ± 0.31 vs ET = -0.61 ± 0.33, p < 0.01) (PP: ΔHAD-A at 3-month: RT = -1.80 ± 0.36 vs ET = -0.75 ± 0.37, p < 0.01). CONCLUSIONS: Our study presents evidence of the beneficial effects of ET and RT in combination with standard medical treatment, as well as the long-term effects over time after the intervention. While the statistically significant effect favoring ET over RT in terms of exercise capacity was observed, it should be interpreted cautiously. Patients in severe stages of COPD may derive greater benefits from either ET or RT and should be encouraged accordingly. These findings have implications for exercise prescription in patients with COPD. TRIAL REGISTRATION: ChiCTR-INR-16009892 (17, Nov, 2016).

Contribution of small airway inflammation to the development of COPD.

BACKGROUND: Little attention has been paid to the pathophysiological changes in the natural history of chronic obstructive pulmonary disease (COPD). The destructions of the small airways were visualized on thoracic micro-computed tomography scan. We investigated whether small airway inflammation (SAI) was the risk for the development of COPD. METHODS: A total of 1062 patients were enrolled and analyzed in the study. The partitioned airway inflammation was determined by exhaled nitric oxide (NO) of FnNO, FeNO50, FeNO200, and calculated CaNOdual. Both FeNO200 and CaNOdual were compared to detect the promising predictor for peripheral airway/alveolar inflammation in COPD. The correlation between exhaled NO and white cell classification was evaluated to determine the inflammation type during the development of COPD. RESULTS: Exhaled NO levels (FnNO, FeNO50, FeNO200, and CaNOdual) were the highest in the COPD group compared with all other groups. Furthermore, compared with controls, exhaled NO levels (FeNO50, FeNO200, and CaNOdual) were also significantly higher in the emphysema, chronic bronchitis, and smoking groups. FeNO200 was found to be a promising predictor for peripheral airway/alveolar inflammation (area under the curve [AUC] of the receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.841) compared with CaNOdual (AUC ROC = 0.707) in COPD. FeNO200 was the main risk factor (adjusted odds ratio, 2.191; 95% CI, 1.797-2.671; p = 0.002) for the development of COPD. The blood eosinophil and basophil levels were correlated with FeNO50 and FeNO200. CONCLUSION: The complete airway inflammations were shown in COPD, whereas SAI was the main risk factor for the development of COPD, which might relate to eosinophil and basophil levels.

Sensitive detection of herbicide residues using field-amplified sample injection coupled with electrokinetic supercharging in flow-gated capillary electrophoresis.

Residues of glyphosate (GlyP) and its major degradation product, aminomethylphosphonic acid (AMPA), widely exist in the water system and plant products and thus are also present in the bodies of animals and humans. Although no solid evidence has been obtained, the concern about the cancer risk of GlyP is persistent. The measurement of GlyP and AMPA in trace levels is often needed but lacks readily available analytical approaches with detection sensitivity, accuracy and speed. This study aims to develop a simple and robust technique for the sensitive detection of GlyP and AMPA residues in a surface water system with flow-gated capillary electrophoresis (CE). Experimentally, water samples were first fluorogenically derivatized with 4-fluoro-7-nitrobenzofurazan (NBD-F) in a low-conductivity buffer at room temperature, and the mixture was injected and concentrated in the capillary based on field-amplified sample injection (FASI) coupled with electrokinetic supercharging (EKS). This scheme included a step of sample buffer injection upon electroosmotic pumping, where negatively charged analytes were electrophoretically rejected, followed by automatic voltage reversal for FASI-EKS. The detection sensitivity was improved by 296, 444, and 861 times for glufosinate (GluF), AMPA, and GlyP, respectively. The proposed method was validated in terms of accuracy, precision, limits of detection (LODs), and linearity. The LODs were estimated to be 50.0 pM, 5.0 pM, and 10.0 pM for GluF, AMPA, and GlyP, respectively. Its application was demonstrated by measuring GluF and AMPA in water samples collected from a local water system. This study provides an effective approach for the online preconcentration of negatively charged analytes, thus enabling the sensitive detection of herbicide residues in water samples. The method can also be applied to analyze other samples, including biological fluids and plant products, upon appropriate sample preparation such as solid phase extraction of analytes.

ZmARF1 positively regulates low phosphorus stress tolerance via modulating lateral root development in maize.

Phosphorus (P) deficiency is one of the most critical factors for plant growth and productivity, including its inhibition of lateral root initiation. Auxin response factors (ARFs) play crucial roles in root development via auxin signaling mediated by genetic pathways. In this study, we found that the transcription factor ZmARF1 was associated with low inorganic phosphate (Pi) stress-related traits in maize. This superior root morphology and greater phosphate stress tolerance could be ascribed to the overexpression of ZmARF1. The knock out mutant zmarf1 had shorter primary roots, fewer root tip number, and lower root volume and surface area. Transcriptomic data indicate that ZmLBD1, a direct downstream target gene, is involved in lateral root development, which enhances phosphate starvation tolerance. A transcriptional activation assay revealed that ZmARF1 specifically binds to the GC-box motif in the promoter of ZmLBD1 and activates its expression. Moreover, ZmARF1 positively regulates the expression of ZmPHR1, ZmPHT1;2, and ZmPHO2, which are key transporters of Pi in maize. We propose that ZmARF1 promotes the transcription of ZmLBD1 to modulate lateral root development and Pi-starvation induced (PSI) genes to regulate phosphate mobilization and homeostasis under phosphorus starvation. In addition, ZmERF2 specifically binds to the ABRE motif of the promoter of ZmARF1 and represses its expression. Collectively, the findings of this study revealed that ZmARF1 is a pivotal factor that modulates root development and confers low-Pi stress tolerance through the transcriptional regulation of the biological function of ZmLBD1 and the expression of key Pi transport proteins.

Arabidopsis thaliana ubiquitin-associated protein 2 (AtUAP2) functions as an E4 ubiquitin factor and negatively modulates dehydration stress response.

E4, a ubiquitin (Ub) chain assembly factor and post-translational modification protein, plays a key role in the regulation of multiple cellular functions in plants during biotic or abiotic stress. We have more recently reported that E4 factor AtUAP1 is a negative regulator of the osmotic stress response and enhances the multi-Ub chain assembly of E3 ligase Arabidopsis thaliana RING Zinc Finger 1 (AtRZF1). To further investigate the function of other E4 Ub factors in osmotic stress, we isolated AtUAP2, an AtUAP1 homolog, which interacted with AtRZF1, using pull-down assay and bimolecular fluorescence complementation analysis. AtUAP2, a Ub-associated motif-containing protein, interacts with oligo-Ub5, -Ub6, and -Ub7 chains. The yeast functional complementation experiment revealed that AtUAP2 functions as an E4 Ub factor. In addition, AtUAP2 is localized in the cytoplasm, different from AtUAP1. The activity of AtUAP2 was relatively strongly induced in the leaf tissue of AtUAP2 promoter-ß-glucuronidase transgenic plants by abscisic acid, dehydration, and oxidative stress. atuap2 RNAi lines were more insensitive to osmotic stress condition than wild-type during the early growth of seedlings, whereas the AtUAP2-overexpressing line exhibited relatively more sensitive responses. Analyses of molecular and physiological experiments showed that AtUAP2 could negatively mediate the osmotic stress-induced signaling. Genetic studies showed that AtRZF1 mutation could suppress the dehydration-induced sensitive phenotype of the AtUAP2-overexpressing line, suggesting that AtRZF1 acts genetically downstream of AtUAP2 during osmotic stress. Taken together, our findings show that the AtRZF1-AtUAP2 complex may play important roles in the ubiquitination pathway, which controls the osmotic stress response in Arabidopsis.

Application of Machine Learning and Deep EfficientNets in Distinguishing Neonatal Adrenal Hematomas From Neuroblastoma in Enhanced Computed Tomography Images.

Background: The aim of the study was to employ a combination of radiomic indicators based on computed tomography (CT) imaging and machine learning (ML), along with deep learning (DL), to differentiate between adrenal hematoma and adrenal neuroblastoma in neonates. Methods: A total of 76 neonates were included in this retrospective study (40 with neuroblastomas and 36 with adrenal hematomas) who underwent CT and divided into a training group (n = 38) and a testing group (n = 38). The regions of interest (ROIs) were segmented by two radiologists to extract radiomics features using Pyradiomics package. ML classifications were done using support vector machine (SVM), AdaBoost, Extra Trees, gradient boosting, multi-layer perceptron (MLP), and random forest (RF). EfficientNets was employed and classified, based on radiometrics. The area under curve (AUC) of the receiver operating characteristic (ROC) was calculated to assess the performance of each model. Results: Among all features, the least absolute shrinkage and selection operator (LASSO) logistic regression selected nine features. These radiomics features were used to construct radiomics model. In the training cohort, the AUCs of SVM, MLP and Extra Trees models were 0.967, 0.969 and 1.000, respectively. The corresponding AUCs of the test cohort were 0.985, 0.971 and 0.958, respectively. In the classification task, the AUC of the DL framework was 0.987. Conclusion: ML decision classifiers and DL framework constructed from CT-based radiomics features offered a non-invasive method to differentiate neonatal adrenal hematoma from neuroblastoma and performed better than the clinical experts.