Transcription factor ZmDof22 enhances drought tolerance by regulating stomatal movement and antioxidant enzymes activities in maize (Zea mays L.).

KEY MESSAGE: The Dof22 gene encoding a deoxyribonucleic acid binding with one finger in maize, which is associated with its drought tolerance. The identification of drought stress regulatory genes is essential for the genetic improvement of maize yield. Deoxyribonucleic acid binding with one finger (Dof), a plant-specific transcription factor family, is involved in signal transduction, morphogenesis, and environmental stress responses. In present study, by weighted correlation network analysis (WGCNA) and gene co-expression network analysis, 15 putative Dof genes were identified from maize that respond to drought and rewatering. A real-time fluorescence quantitative PCR showed that these 15 genes were strongly induced by drought and ABA treatment, and among them ZmDof22 was highly induced by drought and ABA treatment. Its expression level increased by nearly 200 times after drought stress and more than 50 times after ABA treatment. After the normal conditions were restored, the expression levels were nearly 100 times and 40 times of those before treatment, respectively. The Gal4-LexA/UAS system and transcriptional activation analysis indicate that ZmDof22 is a transcriptional activator regulating drought tolerance and recovery ability in maize. Further, overexpressed transgenic and mutant plants of ZmDof22 by CRISPR/Cas9, indicates that the ZmDof22, improves maize drought tolerance by promoting stomatal closure, reduces water loss, and enhances antioxidant enzyme activity by participating in the ABA pathways. Taken together, our findings laid a foundation for further functional studies of the ZmDof gene family and provided insights into the role of the ZmDof22 regulatory network in controlling drought tolerance and recovery ability of maize.

Performance evaluation of quantitative material decomposition in slow kVp switching dual-energy CT.

BACKGROUND: Slow kVp switching technique is an important approach to realize dual-energy CT (DECT) imaging, but its performance has not been thoroughly investigated yet. OBJECTIVE: This study aims at comparing and evaluating the DECT imaging performance of different slow kVp switching protocols, and thus helps determining the optimal system settings. METHODS: To investigate the impact of energy separation, two different beam filtration schemes are compared: the stationary beam filtration and dynamic beam filtration. Moreover, uniform tube voltage modulation and weighted tube voltage modulation are compared along with various modulation frequencies. A model-based direct decomposition algorithm is employed to generate the water and iodine material bases. Both numerical and physical experiments are conducted to verify the slow kVp switching DECT imaging performance. RESULTS: Numerical and experimental results demonstrate that the material decomposition is less sensitive to beam filtration, voltage modulation type and modulation frequency. As a result, robust material-specific quantitative decomposition can be achieved in slow kVp switching DECT imaging. CONCLUSIONS: Quantitative DECT imaging can be implemented with slow kVp switching under a variety of system settings.

Developments of Fms-like Tyrosine Kinase 3 Inhibitors as Anticancer Agents for AML Treatment.

BACKGROUND: FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated gene in acute myeloid leukemia. As a receptor tyrosine kinase (RTK), FLT3 plays a role in the proliferation and differentiation of hematopoietic stem cells. As the most frequent molecular alteration in AML, FLT3 has drawn the attention of many researchers, and a lot of small molecule inhibitors targeting FLT3 have been intensively investigated as potential drugs for AML therapy. METHODS: In this paper, PubMed and SciFinder® were used as a tool; the publications about "FLT3 inhibitor" and "Acute myeloid leukemia" were surveyed from 2014 to the present with an exclusion of those published as patents. RESULTS: In this study, the structural characterization and biological activities of representative FLT3 inhibitors were summarized. The major challenges and future directions for further research are discussed. CONCLUSION: Recently, numerous FLT3 inhibitors have been discovered and employed in FLT3-mutated AML treatment. In order to overcome the drug resistance caused by FLT3 mutations, screening multitargets FLT3 inhibitors has become the main research direction. In addition, the emergence of irreversible FLT3 inhibitors also provides new ideas for discovering new FLT3 inhibitors.

An emerging strategy: probiotics enhance the effectiveness of tumor immunotherapy via mediating the gut microbiome.

The occurrence and progression of tumors are often accompanied by disruptions in the gut microbiota. Inversely, the impact of the gut microbiota on the initiation and progression of cancer is becoming increasingly evident, influencing the tumor microenvironment (TME) for both local and distant tumors. Moreover, it is even suggested to play a significant role in the process of tumor immunotherapy, contributing to high specificity in therapeutic outcomes and long-term effectiveness across various cancer types. Probiotics, with their generally positive influence on the gut microbiota, may serve as effective agents in synergizing cancer immunotherapy. They play a crucial role in activating the immune system to inhibit tumor growth. In summary, this comprehensive review aims to provide valuable insights into the dynamic interactions between probiotics, gut microbiota, and cancer. Furthermore, we highlight recent advances and mechanisms in using probiotics to improve the effectiveness of cancer immunotherapy. By understanding these complex relationships, we may unlock innovative approaches for cancer diagnosis and treatment while optimizing the effects of immunotherapy.

Sex-specific alterations in visual properties induced by single prolonged stress model.

Patients with post-traumatic stress disorder (PTSD) exhibit sex differences in symptomology, with women more likely to report higher rates of intrusive and avoidance symptoms than men, underscoring the need for sex-informed approaches to research and treatment. Our study delved into the sex-specific aspects of stress-induced visual impairments using the single prolonged stress (SPS) model, a partially validated rodent model for PTSD. Male SPS mice exhibit heightened optimal spatial frequency (SF) of primary visual cortex (V1) neurons, while female counterparts exhibit decreased optimal temporal frequency (TF) of V1 neurons. This phenomenon persisted until the 29th day after SPS modeling, and it may be the physiological basis for the observed increase in visual acuity in male SPS mice in visual water task. Furthermore, our study found that corticotropin-releasing factor receptor 1 regulated optimal TF and optimal SF of V1 in mice, but did not exhibit sex differences. These findings indicated that severe stress induces sex-specific effects on visual function.

Identification of the Maize PP2C Gene Family and Functional Studies on the Role of ZmPP2C15 in Drought Tolerance.

The protein phosphatase PP2C plays an important role in plant responses to stress. Therefore, the identification of maize PP2C genes that respond to drought stress is particularly important for the improvement and creation of new drought-resistant assortments of maize. In this study, we identified 102 ZmPP2C genes in maize at the genome-wide level. We analyzed the physicochemical properties of 102 ZmPP2Cs and constructed a phylogenetic tree with Arabidopsis. By analyzing the gene structure, conserved protein motifs, and synteny, the ZmPP2Cs were found to be strongly conserved during evolution. Sixteen core genes involved in drought stress and rewatering were screened using gene co-expression network mapping and expression profiling. The qRT-PCR results showed 16 genes were induced by abscisic acid (ABA), drought, and NaCl treatments. Notably, ZmPP2C15 exhibited a substantial expression difference. Through genetic transformation, we overexpressed ZmPP2C15 and generated the CRISPR/Cas9 knockout maize mutant zmpp2c15. Overexpressing ZmPP2C15 in Arabidopsis under drought stress enhanced growth and survival compared with WT plants. The leaves exhibited heightened superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APX), and catalase (CAT) activities, elevated proline (Pro) content, and reduced malondialdehyde (MDA) content. Conversely, zmpp2c15 mutant plants displayed severe leaf dryness, curling, and wilting under drought stress. Their leaf activities of SOD, POD, APX, and CAT were lower than those in B104, while MDA was higher. This suggests that ZmPP2C15 positively regulates drought tolerance in maize by affecting the antioxidant enzyme activity and osmoregulatory substance content. Subcellular localization revealed that ZmPP2C15 was localized in the nucleus and cytoplasm. Yeast two-hybrid (Y2H) and bimolecular fluorescence complementation (BiFC) experiments demonstrated ZmPP2C15's interaction with ZmWIN1, ZmADT2, ZmsodC, Zmcab, and ZmLHC2. These findings establish a foundation for understanding maize PP2C gene functions, offering genetic resources and insights for molecular design breeding for drought tolerance.

Emergence of colistin-resistant Stenotrophomonas maltophilia with high virulence in natural aquatic environments.

The presence of Stenotrophomonas maltophilia in aquatic environments poses great health risks to immunocompromised individuals because of its multidrug resistance and resultant high mortality. However, a significant gap exists in the isolation and understanding of colistin-resistant S. maltophilia in aquatic environments. In this study, nine colistin-resistant S. maltophilia strains isolated from natural lakes were explored, and their phylogenetic relationship, biofilm formation, virulence, and antibiotic resistance profiles and underlying genetic determinants were assessed. After genome analysis, besides known multi-locus sequence typing (MLST) of ST532, new assigned ST965 and ST966 which phylogenetically clustered into soil isolates were found firstly. All the isolates exhibited resistance to multiple antibiotics, including aminoglycosides, beta-lactams, tetracyclines, and even colistin, with the highest minimum inhibitory concentration (MIC) against colistin reaching 640 mg/L. Comparative genomic analysis revealed aph(3')-Iic, blaL1, tetT, phoP, mcr-3, arnA, pmrE, and efflux pump genes as the genetic determinants underlying this multidrug resistance. Notably, the biofilm-forming capacities of the newly discovered ST965 and ST966 isolates were significant stronger than those of the known ST532 isolates (p < 0.01), resulting in the death of over 50 % of the Galleria mellonella population within 1 day of injection. The ST965 isolates demonstrated the highest virulence against G. mellonella, followed by the ST966 isolates and ST532 isolates which was phylogenetically clustered with clinical isolates, indicating that the novel S. maltophilia strains of ST965 and ST966 may pose considerable health risks to humans. Our findings provide insights into colistin-resistant S. maltophilia in aquatic environments and raise concerns about the health risks posed by the newly assigned sequence types of colistin-resistant S. maltophilia with potential high virulence in natural aquatic environments.

Establishing a novel inflammatory bowel disease prediction model based on gene markers identified from single nucleotide variants of the intestinal microbiota.

The intestinal microbiota is a crucial environmental factor in the development of inflammatory bowel disease (IBD). The abundance of Faecalibacterium prausnitzii is significantly decreased in IBD patients, which is used as a biomarker for IBD diagnosis. However, this can be observed in both IBD and colorectal cancer, which would confound the diagnostic results. Thus, we first established a new model for predicting Crohn's disease (CD) with high precision according to gene characteristics based on single nucleotide variants (SNVs). Next, five gene markers belonging to two species, F. prausnitzii and Eubacterium rectale, that were enriched in the CD group were obtained to build a CD prediction model, and high accuracy in distinguishing the CD and control groups was observed in the discovery (area under curve [AUC] = 91.13%) and validation cohorts (AUC = 79.55%). The model still maintained high accuracy after expanding the healthy cohort (AUC = 89.75%). High disease specificity in distinguishing CD and CRC groups (AUC = 95.74%) was also proven. This study establishes a novel diagnostic method for predicting IBD that also provides unprecedented insight for the early, painless diagnosis of other non-communicable diseases.