TFAP2A downregulation mediates tumor-suppressive effect of miR-8072 in triple-negative breast cancer via inhibiting SNAI1 transcription.

BACKGROUND: Triple-negative breast cancer (TNBC) represents a highly aggressive subset of breast malignancies characterized by its challenging clinical management and unfavorable prognosis. While TFAP2A, a member of the AP-2 transcription factor family, has been implicated in maintaining the basal phenotype of breast cancer, its precise regulatory role in TNBC remains undefined. METHODS: In vitro assessments of TNBC cell growth and migratory potential were conducted using MTS, colony formation, and EdU assays. Quantitative PCR was employed to analyze mRNA expression levels, while Western blot was utilized to evaluate protein expression and phosphorylation status of AKT and ERK. The post-transcriptional regulation of TFAP2A by miR-8072 and the transcriptional activation of SNAI1 by TFAP2A were investigated through luciferase reporter assays. A xenograft mouse model was employed to assess the in vivo growth capacity of TNBC cells. RESULTS: Selective silencing of TFAP2A significantly impeded the proliferation and migration of TNBC cells, with elevated TFAP2A expression observed in breast cancer tissues. Notably, TNBC patients exhibiting heightened TFAP2A levels experienced abbreviated overall survival. Mechanistically, TFAP2A was identified as a transcriptional activator of SNAI1, a crucial regulator of epithelial-mesenchymal transition (EMT) and cellular proliferation, thereby augmenting the oncogenic properties of TFAP2A in TNBC. Moreover, miR-8072 was unveiled as a negative regulator of TFAP2A, exerting potent inhibitory effects on TNBC cell growth and migration. Importantly, the tumor-suppressive actions mediated by the miR-8072/TFAP2A axis were intricately associated with the attenuation of AKT/ERK signaling cascades and the blockade of EMT processes. CONCLUSIONS: Our findings unravel the role and underlying molecular mechanism of TFAP2A in driving tumorigenesis of TNBC. Targeting the TFAP2A/SNAI1 pathway and utilizing miR-8072 as a suppressor represent promising therapeutic strategies for treating TNBC.

GmHXK2 promotes the salt tolerance of soybean seedlings by mediating AsA synthesis, and auxin synthesis and distribution.

BACKGROUND: Salt is an important factor that affects crop productivity. Plant hexokinases (HXKs) are key enzymes in the glycolytic pathway and sugar signaling transduction pathways of plants. In previous studies, we identified and confirmed the roles of GmHXK2 in salt tolerance. RESULTS: In this study, we analyzed the tissue-specific expression of GmHXK2 at different growth stages throughout the plant's life cycle. The results showed that GmHXK2 was expressed significantly in all tissues at vegetative stages, including germination and seedling. However, no expression was detected in the pods, and there was little expression in flowers during the later mature period. Arabidopsis plants overexpressing the GmHXK2 (OE) had more lateral roots. The OE seedlings also produced higher levels of auxin and ascorbic acid (AsA). Additionally, the expression levels of genes PMM, YUC4/YUC6/YUC8, and PIN/LAX1,LAX3, which are involved respectively in the synthesis of AsA and auxin, as well as polar auxin transport, were upregulated in OE plants. This upregulation occurred specifically under exogenous glucose treatment. AtHKT1, AtSOS1, and AtNHX1 were up-regulated in OE plants under salt stress, suggesting that GmHXK2 may modulate salt tolerance by maintaining ion balance within the cells and alleviating damage caused by salt stress. Additionally, we further confirmed the interaction between GmHXK2 and the protein GmPMM through yeast two-hybridization and bimolecular fluorescence complementation assays, respectively. CONCLUSION: The expression of GmHXK2 gene in plants is organ-specific and developmental stage specific. GmHXK2 not only regulates the synthesis of AsA and the synthesis and distribution of auxin, but also promotes root elongation and induces lateral root formation, potentially enhancing soil water absorption. This study reveals the crosstalk between sugar signaling and hormone signaling in plants, where GmHXK2 acts as a glucose sensor through its interaction with GmPMM, and sheds light on the molecular mechanism by which GmHXK2 gene is involved in salt tolerance in plants.

Co-inoculation of Soybean Seedling with Trichoderma asperellum and Irpex laceratus Promotes the Absorption of Nitrogen and Phosphorus.

Soybean are one of the main oil crops in the world. The study demonstrated that co-inoculation with Trichoderma asperellum (Sordariomycetes, Hypocreomycetidae) and Irpex laceratus (Basidiomycota, Polyporales) isolated from Kosteletzkya virginica can promote the growth of soybean seedlings. The two fungi were found to produce various enzymes, including cellulase, amylase, laccase, protease, and urease. Upon inoculation, T. asperellum mainly colonized within the phloem of the roots in soybean seedlings, while I. laceratus mainly in the xylem and phloem of the roots. Physiological parameters, such as plant height, root length, and fresh weight, were significantly increased in soybean seedlings co-inoculated with T. asperellum and I. laceratus. Moreover, the expression of key genes related to N and P absorption and metabolism was also increased, leading to improved N and P utilization efficiency in soybean seedlings. These results indicate that the two fungi may have complementary roles in promoting plant growth, co-inoculation with T. asperellum and I. laceratus can enhance the growth and nutrient uptake of soybean. These findings suggest that T. asperellum and I. laceratus have the potential to be used as bio-fertilizers to improve soybean growth and yield.

Overexpression of KvCHX Enhances Salt Tolerance in Arabidopsis thaliana Seedlings.

The CHX (cation/H+ exchanger) family plays an important role in the transmembrane transport of cation/H+ in plants. The aim of this study was to identify and functionally analyze the KvCHX gene in the halophyte Kosteletzkya virginica to investigate its role in regulating the K+/Na+ ratio under salinity tolerance. Based on a partial gene sequence of EST from K. virginica, the full-length DNA sequence of the KvCHX gene was obtained using genome walking technology. Structural analysis and phylogenetic relationship analysis showed that the KvCHX gene was closely related to the AtCHX17 gene. The KvCHX overexpression vector was successfully constructed and transformed into Arabidopsis via floral dipping. Arabidopsis seedlings overexpressing KvCHX showed an enhanced tolerance to salt stress compared with wild-type plants. Transgenic Arabidopsis seedlings grew better under K+ deficiency than WT. The results showed that KvCHX could promote the uptake of K+, increase the ratio of K+/Na+, and promote the growth of plants under K+ deficiency and treatment with NaCl solution. KvCHX is involved in K+ transport and improves plant salt tolerance by coordinating K+ acquisition and homeostasis.

Factors Associated With Psychological Wellbeing in Home Care Older Adults With Alzheimer's Disease: A Longitudinal Analysis.

The long-term symptoms associated with Alzheimer's disease pose significant challenges to the psychological wellbeing of patients. This longitudinal study aims to analyze the effects of socioeconomic factors and physical health factors on the psychological wellbeing of older patients diagnosed with Alzheimer's disease (AD) receiving home care, as well as the moderating role of aging and care support in influencing their psychological wellbeing. Data from the Health and Retirement Study (N = 628 older Alzheimer's patients) were analyzed using pooled ordinary least squares fixed-effects models. Findings suggest that Alzheimer's patients' psychological wellbeing was significantly affected by factors including cohabitation, gender, assistance frequency, age, education, and daily activity challenges, with assistance and increasing age mitigating some daily difficulties. The findings underline the multifactorial nature of psychological wellbeing among older Alzheimer's patients in home care and the critical role of social and physical health determinants in shaping these outcomes.

Deep reinforcement learning in radiation therapy planning optimization: A comprehensive review.

PURPOSE: The formulation and optimization of radiation therapy plans are complex and time-consuming processes that heavily rely on the expertise of medical physicists. Consequently, there is an urgent need for automated optimization methods. Recent advancements in reinforcement learning, particularly deep reinforcement learning (DRL), show great promise for automating radiotherapy planning. This review summarizes the current state of DRL applications in this field, evaluates their effectiveness, and identifies challenges and future directions. METHODS: A systematic search was conducted in Google Scholar, PubMed, IEEE Xplore, and Scopus using keywords such as "deep reinforcement learning", "radiation therapy", and "treatment planning". The extracted data were synthesized for an overview and critical analysis. RESULTS: The application of deep reinforcement learning in radiation therapy plan optimization can generally be divided into three categories: optimizing treatment planning parameters, directly optimizing machine parameters, and adaptive radiotherapy. From the perspective of disease sites, DRL has been applied to cervical cancer, prostate cancer, vestibular schwannoma, and lung cancer. Regarding types of radiation therapy, it has been used in HDRBT, IMRT, SBRT, VMAT, GK, and Cyberknife. CONCLUSIONS: Deep reinforcement learning technology has played a significant role in advancing the automated optimization of radiation therapy plans. However, there is still a considerable gap before it can be widely applied in clinical settings due to three main reasons: inefficiency, limited methods for quality assessment, and poor interpretability. To address these challenges, significant research opportunities exist in the future, such as constructing evaluators, parallelized training, and exploring continuous action spaces.

Lactobacillus reuteri JCM 1112 ameliorates chronic acrylamide-induced glucose metabolism disorder via the bile acid-TGR5-GLP-1 axis and modulates intestinal oxidative stress in mice.

Acrylamide (AA) is a toxic food contaminant that has been reported to cause glucose metabolism disorders (GMD) at high doses. However, it is unclear whether chronic low-dose AA can induce GMD and whether probiotics can alleviate AA-induced GMD. Here, C57BL/6N mice were orally administered with 5 mg per kg bw AA for 10 weeks, followed by another 3 weeks of glucagon-like peptide-1 (GLP-1) analogue (dulaglutide) treatment. Chronic low-dose AA exposure increased the blood glucose level and decreased serum insulin and GLP-1 levels, whereas dulaglutide treatment decreased the blood glucose level and increased the serum insulin level in AA-exposed mice. Then, mice were administered with AA or AA + INT-777 (Takeda G-protein-coupled receptor 5 (TGR5) agonist) for 10 weeks. INT-777 treatment reversed AA-induced downregulation of ileal TGR5 and proglucagon (PG) gene expression and decreased the serum GLP-1 level. These findings indicated that chronic low-dose AA induced GMD via inhibiting the TGR5-GLP-1 axis. Finally, mice were administered with AA for 10 weeks, followed by another 3 weeks of Lactobacillus reuteri JCM 1112 supplementation. L. reuteri supplementation significantly increased serum glucose, insulin and GLP-1 levels, upregulated ileal TGR5 and PG gene expression, and effectively restored the imbalance of bile acid (BA) metabolism in AA-exposed mice, demonstrating that L. reuteri ameliorates chronic AA-induced GMD via the BA-TGR5-GLP-1 axis. In addition, L. reuteri significantly enhanced ileal superoxide dismutase and catalase activities and total antioxidant capacity, thereby preventing chronic AA-induced oxidative stress. Our research provides new insights into the GMD toxicity of chronic low-dose AA and confirms the role of probiotics in alleviating AA-induced GMD.

All-optical interrogation of brain-wide activity in freely swimming larval zebrafish.

We introduce an all-optical technique that enables volumetric imaging of brain-wide calcium activity and targeted optogenetic stimulation of specific brain regions in unrestrained larval zebrafish. The system consists of three main components: a 3D tracking module, a dual-color fluorescence imaging module, and a real-time activity manipulation module. Our approach uses a sensitive genetically encoded calcium indicator in combination with a long Stokes shift red fluorescence protein as a reference channel, allowing the extraction of Ca2+ activity from signals contaminated by motion artifacts. The method also incorporates rapid 3D image reconstruction and registration, facilitating real-time selective optogenetic stimulation of different regions of the brain. By demonstrating that selective light activation of the midbrain regions in larval zebrafish could reliably trigger biased turning behavior and changes of brain-wide neural activity, we present a valuable tool for investigating the causal relationship between distributed neural circuit dynamics and naturalistic behavior.

UFObow: A single-wavelength excitable Brainbow for simultaneous multicolor ex-vivo and in-vivo imaging of mammalian cells.

Brainbow is a genetic cell-labeling technique that allows random colorization of multiple cells and real-time visualization of cell fate within a tissue, providing valuable insights into understanding complex biological processes. However, fluorescent proteins (FPs) in Brainbow have distinct excitation spectra with peak difference greater than 35 nm, which requires sequential imaging under multiple excitations and thus leads to long acquisition times. In addition, they are not easily used together with other fluorophores due to severe spectral bleed-through. Here, we report the development of a single-wavelength excitable Brainbow, UFObow, incorporating three newly developed blue-excitable FPs. We have demonstrated that UFObow enables not only tracking the growth dynamics of tumor cells in vivo but also mapping spatial distribution of immune cells within a sub-cubic centimeter tissue, revealing cell heterogeneity. This provides a powerful means to explore complex biology in a simultaneous imaging manner at a single-cell resolution in organs or in vivo.

Characterization key genes of Arabidopsis seedlings in response to ß-caryophyllene, eugenol using combined transcriptome and WGCN analysis.

Weeds present a significant challenge to high crop yield and quality. In our study, we investigated the phytotoxic activity of ß-caryophyllene (BCP) and eugenol, which are natural allelopathic chemical compounds, on Arabidopsis seedlings. We found that these compounds inhibited the growth of Arabidopsis thaliana plants. When either BCP or eugenol was applied, it led to decrease in the content of cell wall components such as lignin, cellulose, hemicellulose, and pectin; and increase in the levels of endogenous hormones like ETH, ABA, SA, and JA in the seedlings. Through transcriptome profiling, we identified 7181 differentially expressed genes (DEGs) in the roots and shoots that were induced by BCP or eugenol. The genes involved in the synthesis of lignin, cellulose, hemicellulose, and pectin were down-regulated, whereas genes related to synthesis and signal transduction of ABA, ETH, SA, and JA were up-regulated. However, genes related to IAA synthesis and signal transduction were found to be down-regulated. Furthermore, we characterized 24 hub genes using Weighted Correlation Network Analysis (WGCNA). Among them, the identified 16 genes in response to BCP was primarily associated with hypoxia stress, while 8 genes induced by eugenol were linked to inhibition of cell division. Our results suggested that BCP and eugenol had ability to target multiple genes to inhibit growth and development of Arabidopsis plants. Therefore, they can serve as excellent candidates for natural biological herbicides.

Facilitators and Barriers of HPV Vaccine Acceptance, Initiation, and Completion among LGBTQ Community in the U.S.: A Systematic Review.

Objective: This study aims to identify facilitators and barriers of Human Papillomavirus (HPV) vaccine acceptance, initiation, and completion among LGBTQ (lesbian, gay, bisexual, trans, and queer) individuals. Method: A systematic review of qualitative and quantitative studies on HPV vaccine acceptance, initiation, and completion from 2006 to June 15, 2020 was performed in each database. Results: Twenty-six studies focusing on HPV vaccination among LGBTQ individuals were reviewed. Conclusions: Knowledge of HPV vaccine and healthcare providers' recommendations were identified as facilitators to receive HPV vaccinate, while high co-pay cost and concerns of the effectiveness and safety were identified as barriers.