ZBTB20 suppresses tumor growth in glioblastoma through activating the TET1/FAS/caspase­3 pathway.

Zinc finger and BTB domain containing 20 (ZBTB20) is a key transcription repressor that regulates multiple physiological and pathophysiological processes. Thus far, the role of ZBTB20 in glioblastoma (GBM), a World Health Organization grade IV glioma, remains unclear. In the present study, the expression profile data of ZBTB20 in GBM tissues from public databases was analyzed. It was found that ZBTB20 expression in GBM tissues was significantly lower than that measured in lower grade glioma tissues. Furthermore, patients with GBM with lower ZBTB20 expression were associated with a shorter overall survival time. Gain- and loss-of-function experiments in GBM cells were also performed. The results demonstrated that ZBTB20 overexpression decreased GBM cell proliferation, while ZBTB20 knockdown significantly enhanced it. Cell cycle analysis showed the ZBTB20 overexpression may have inhibited proliferation through cell cycle arrest at the G2/M phase, while ZBTB20 knockdown increased the percentages of cells in both the S phase and G2/M phase. Ten-eleven translocation 1 (TET1) is an important tumor suppressor involved in the formation of various types of tumor, and it was upregulated in ZBTB20-overexpressing GBM cells. It was further demonstrated that ZBTB20 activated the TET1/FAS/caspase-3 pathway. The results of the present study therefore indicated the potential role of ZBTB20 as a tumor suppressor and therapeutic target for GBM.

Rhetorical strategies in Chinese and English talk show humor: a comparative analysis.

Humor is a kind of cognitive psychology activity, and it is diverse among individuals. One of the main characteristics of talk shows is to produce humorous discourse to make the audience laugh; however, rare studies have made a deeper comparative investigation on the rhetorical strategies in different language humorous utterances. Therefore, the current study adopted a mixed method of sequential explanatory design to identify the types of rhetorical strategies in the monolog verbal humor of Chinese and English talk shows, examine their similarities and differences. Two hundred monolog samples from 2016 to 2022, which consisted of 100 monologs of Chinese talk shows (CTS) and 100 monologs of English talk shows (ETS), were downloaded from the internet as language corpus. Berger's theory was adopted to identify the types of rhetorical strategies. Based on the obtained findings, this study found that both language talk show hosts use a variety type of rhetorical strategies to produce humorous discourse. The comparison of similarities and differences revealed that the most frequently used rhetorical strategies in both talk shows were almost similar (e.g., satire, exaggeration, facetiousness, and ridicule), but the percentage of usage of these various rhetorical strategies in both talk shows was slightly different. Interestingly, misunderstanding occurred 20 times in CTS but was not found in ETS. Meanwhile, simile and personification were used more often in ETS. Conclusively, this study contributes valuable insights on the use of different types of rhetorical strategies to create verbal humor in different language contexts.

Relationship Between Resilience, Social Support, Existential Well-Being and Negative Emotions in Cervical Cancer Patients: a Mediation Analysis.

Background: The patients of cervical cancer have more negative emotions and lower quality of life. The aim of this study was to explore the relationships between existential well-being (EWB), social support, resilience, negative emotions in patients with cervical cancer, and to examine whether resilience mediates the associations between EWB or social support and negative emotions. Material and methods: This study enrolled patients with cervical cancer who were treated at the Tianjin Medical University Cancer Institute and Hospital in China during 2012-2019. The Hospital Anxiety and Depression Scale (HADS), the Resilience Scale of 14 items (RS-14) and the McGill Quality of Life Questionnaire (MQOL) were utilized to assess patient's anxiety, depression, resilience, social support and EWB via telephone. Spearman's correlation analyses were used to assess bivariate correlations, and mediation analyses were applied to examine whether resilience mediated the relationship between social support or EWB and negative emotions. Results: A total of 150 (92.0%) out of 163 eligible patients completed the questionnaires. EWB and social support were negatively correlated with anxiety (r=-0.560 and r=-0.561) and depression (r=-0.508 and r=-0.526), and positively correlated with resilience (r=0.691 and r=0.652). Resilience was negatively associated with anxiety (r=-0.545) and depression (r=-0.505). Negative direct effects of social support on anxiety and EWB on anxiety and depression were statistically significant (P<0.05). Resilience played a partial mediating role in the relationship between EWB and depression (ß=-0.085, 95%CI: -0.150 to -0.020), accounting for 37.12% of the total effect. It also served as a partial mediator in the association between EWB and anxiety (ß=-0.061, 95%CI: -0.107 to -0.015), explaining 34.46% of the overall effect. Additionally, resilience partially mediated the connection between social support and depression (ß=-0.173, 95%CI: -0.312 to -0.053), explicating 57.48% of the total effect. Conclusions: A combination of existential, supportive and resilient interventions may help reduce psychological distress and improve quality of life among cervical cancer patients, thereby promoting both physical and psychological health.

Vitamin D and Its Receptors in Cervical Cancer.

Several studies have investigated the relationship between vitamin D (VD) and its receptors (VDR) and the risk of cervical cancer. However, the underlying mechanisms that underpin these associations remain incompletely comprehended. In this review, we analyzed the impacts of VD and VDR on cervical cancer and related mechanisms, and discussed the effects of VD, calcium, and other vitamins on cervical cancer. Our literature research found that VD, VDR and their related signaling pathways played indispensable roles in the occurrence and progression of cervical cancer. Epidemiological studies have established associations between VD, VDR, and cervical cancer susceptibility. Current studies have shown that the inhibitory effect of VD and VDR on cervical cancer may be attributed to a variety of molecules and pathways, such as the EAG potassium channel, HCCR-1, estrogen and its receptor, p53, pRb, TNF-α, the PI3K/Akt pathway, and the Wnt/ß-catenin pathway. This review also briefly discussed the association between VDR gene polymorphisms and cervical cancer, albeit a comprehensive elucidation of this relationship remains an ongoing research endeavor. Additionally, the potential ramifications of VD, calcium, and other vitamins on cervical cancer has been elucidated, yet further exploration into the precise mechanistic underpinnings of these potential effects is warranted. Therefore, we suggest that further studies should focus on explorations into the intricate interplay among diverse molecular pathways and entities, elucidation of the mechanistic underpinnings of VDR polymorphic loci changes in the context of HPV infection and VD, inquiries into the mechanisms of VD in conjunction with calcium and other vitamins, as well as investigations of the efficacy of VD supplementation or VDR agonists as part of cervical cancer treatment strategies in the clinical trials.

Effect of lactic acid bacteria by different concentrations of copper based on non-target metabolomic analysis.

Copper (Cu) is an essential element for mammals, but excess intake can have detrimental health consequences. However, Cu is no longer present in the "Limit of Contaminants in Foods" promulgated in 2022. The potential impact of different Cu (II) concentrations on human health remains unclear. In this study, a strain of lactic acid bacteria (LAB), namely, Lactiplantibacillus plantarum CICC 23121 (L23121), was selected as a prebiotic indicator strain to indirectly assess the effects of food-limited Cu (II) concentrations (issued by Tolerance limit of copper in foods in 1994) on the functions of intestinal microbes. We used non-target metabolomics, automatic growth curve detector, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) to investigate the effects of Cu (II) on L23121. The study revealed shows that the 50% minimum inhibitory concentration (MIC50) of Cu (II) for most lactic acid bacteria was 4 mg/L. At low Cu (II) concentrations (≤ 4 mg/L), the pentose phosphate pathway and pyrimidine metabolism of the lactic acid bacteria were affected, resulting in a decrease in the content of beneficial secondary metabolites and a significant decrease in the cell activity. As Cu (II) concentrations increase (≥ 6 mg/L), the key amino acid and lipid metabolisms were affected, leading to the inhibition of growth and primary metabolite production of the bacteria. Under high concentration of Cu (II) (6 mg/L), the surface adhesion of the bacteria was distorted and covered with significantly large particles, and the functional groups of the cells were significantly shifted. As a probiotic, the abundance of lactic acid bacteria in the intestine is significantly reduced, which will inevitably seriously damage intestinal homeostasis. Thus, to protect human intestinal microbes' health, it is recommended to limit the concentration of Cu in food to less than 4 mg/L.

Epigenetic mechanisms of Müller glial reprogramming mediating retinal regeneration.

Retinal degenerative diseases, characterized by retinal neuronal death and severe vision loss, affect millions of people worldwide. One of the most promising treatment methods for retinal degenerative diseases is to reprogram non-neuronal cells into stem or progenitor cells, which then have the potential to re-differentiate to replace the dead neurons, thereby promoting retinal regeneration. Müller glia are the major glial cell type and play an important regulatory role in retinal metabolism and retinal cell regeneration. Müller glia can serve as a source of neurogenic progenitor cells in organisms with the ability to regenerate the nervous system. Current evidence points toward the reprogramming process of Müller glia, involving changes in the expression of pluripotent factors and other key signaling molecules that may be regulated by epigenetic mechanisms. This review summarizes recent knowledge of epigenetic modifications involved in the reprogramming process of Müller glia and the subsequent changes to gene expression and the outcomes. In living organisms, epigenetic mechanisms mainly include DNA methylation, histone modification, and microRNA-mediated miRNA degradation, all of which play a crucial role in the reprogramming process of Müller glia. The information presented in this review will improve the understanding of the mechanisms underlying the Müller glial reprogramming process and provide a research basis for the development of Müller glial reprogramming therapy for retinal degenerative diseases.

Copper-based biological alloys and nanocomposites for enzymatic catalysis and sensing applications.

Copper (Cu) is an inexpensive transition metal on Earth, exhibiting high catalytic activity due to its rich d-electron configuration and variable oxidation states. Cu-based biological alloys and nanocomposites have emerged as a prominent research area. Under specific synthesis conditions, alloys or nanocomposites formed by Cu with other metals demonstrate excellent enzyme-like and sensing activities. These advanced materials offer significant advantages over artificial enzymes in enzymatic applications, including high stability, simple synthesis, flexible catalytic performance, and ease of preservation. In addition, various types of sensors have been designed based on the unique electrochemical properties exhibited by these alloys and nanocomposites as well as their specific reactions with the target substances. These sensors possess advantages such as stability, high efficiency, a broad detection range, low detection limits, and high sensitivity. In this review, we summarize the current research status of Cu-based biological alloys and nanocomposites in enzyme-like applications and sensing applications. Based on this, we introduce the diverse enzyme-like activities exhibited by Cu-based nanozymes prepared under different synthesis conditions and their applications in areas such as biosensing, cancer treatment, and antibacterial therapy. Furthermore, we provide an overview of the applications of Cu-based alloys and nanocomposites in the field of sensing based on their enzyme-like activity or chemical activities. These sensors have been widely employed in biomedical detection, environmental hazardous substance monitoring, and food safety testing. Challenges and prospects faced by Cu-based alloys and nanocomposites are also highlighted for future works.

Characteristics of culprit intracranial plaque without substantial stenosis in ischemic stroke using three-dimensional high-resolution vessel wall magnetic resonance imaging.

Background and aims: We aim to analyze the difference in quantitative features between culprit and non-culprit intracranial plaque without substantial stenosis using three-dimensional high-resolution vessel wall MRI (3D hr-vw-MRI). Methods: The patients with cerebral ischemic symptoms of the unilateral anterior circulation were recruited who had non-stenotic intracranial atherosclerosis (<50%) confirmed by computed tomographic angiographic (CTA) or magnetic resonance angiography (MRA). All patients underwent 3D hr-vw MRI within 1 month after symptom onset. 3D hr-vw-MRI characteristics, including wall thickness, plaque burden, enhancement ratio, plaque volume and intraplaque hemorrhage, and histogram features were analyzed based on T2-, precontrast T1-, and post-contrast T1-weighted images. Univariate and multivariate logistic regression analysis were used to identify key determinates differentiating culprit and non-culprit plaques and to calculate the odds ratios (ORs) with 95% confidence intervals (CIs). Results: A total of 150 plaques were identified, of which 133 plaques (97 culprit and 36 non-culprit) were in the middle cerebral artery, three plaques (all culprit) were in the anterior cerebral artery (ACA) and 14 (11 culprit and three non-culprit) were in the internal carotid artery (ICA). Of all the quantitative parameters analyzed, plaque volume, maximum wall thickness, minimum wall thickness, plaque burden, enhancement ratio, coefficient of variation of the most stenotic site, enhancement ratio of whole culprit plaque in culprit plaques were significantly higher than those in non-culprit plaques. Multivariate logistic regression analysis found that plaque volume [OR, 1.527 (95% CI, 1.231-1.894); P < 0.001] and enhancement ratio of whole plaque [OR, 1.095 (95% CI, 1.021-1.175); P = 0.011] were significantly associated with culprit plaque. The combination of the two features obtained a better diagnostic efficacy for culprit plaque with sensitivity and specificity (0.910 and 0.897, respectively) than each of the two parameters alone. Conclusion: 3D hr-vw MRI features of intracranial atherosclerotic plaques provided potential values over prediction of ischemic stroke patients with non-stenotic arteries. The plaque volume and enhancement ratio of whole plaque of stenosis site were found to be effective predictive parameters.

Status quo of the public's knowledge of probiotics based on video-sharing platforms.

BACKGROUND: Probiotics have been deemed multipotent and unprecedentedly applied in the health field recently. However, there are challenges in promoting credible and reliable resources while avoiding misinformation regarding probiotics for the public. METHODS: This study analysed 400 eligible probiotic-related videos selected from YouTube, and the three most popular video-sharing platforms (Bilibili, Weibo and TikTok) in China. Video retrieval was performed on September 5th, 2022. GQS and tailored DISCERN tool assess each video's quality, usage, and reliability. A comparative analysis of videos from different sources was carried out. RESULTS: The identity distribution of probiotic video-producers was predominantly experts (n = 202, 50.50%), followed by amateurs (n = 161, 40.25%) and health-related institutions (n = 37, 9.25%). The videos' content category mainly discussed the function of probiotics (n = 120, 30%), the way to choose suitable products (n = 81, 20.25%), and the methods for taking probiotics (n = 71, 17.75%).The overall quality of videos was moderate (3/5 point) assessed by GQS, while the usage (1/6 point) and reliability (2/5 point) detailing probiotics assessed by tailored DISCERN tool were poor. The attitude of probiotic video-producers was primarily positive (n = 323, 80.75%), followed by neutral (n = 52, 13.00%) and negative (n = 25, 6.25%) (P < 0.001). CONCLUSIONS: The current study showed that videos on social media platforms publicise important information including the concepts, usage, and precautions of probiotics to the public. But the overall quality of uploaded videos about probiotics was unsatisfactory. More efforts are needed to improve the higher-quality content of probiotic-related online videos and better propagate probiotic knowledge to the public in the future.

Adsorption abilities and mechanisms of Lactobacillus on various nanoplastics.

As a new type of pollutants, nanoplastics (NPs), which are easily ingested by humans from food wraps, salt, drinking water, have been widely detected in various water environments, and are a threat to human health. It is therefore urgent to develop an efficient method to remove NPs from the diet or relief its harm. In the present study, the possibility of a well-known human probiotic, lactic acid bacteria (LAB), was evaluated to remove NPs from food as an absorbent. The results indicated that LAB from infant feces could efficiently absorb three types NPs, i.e. polypropylene (PP), polyethylene (PE), and polyvinyl chloride (PVC) with the adsorption rates of PP > PE > PVC (PP 78.57%, PE 71.59%, PVC 66.57%) and the Nile red-stained NPs being aggregated on the surfaces of Lactobacillus cells. The smaller the particle size, the stronger the ability of NP adsorption on the cell surface. The hydrophobicity of NPs and bacterial cells affected the adsorption process. The measurement of adsorption rates of different cell components indicated that the overall adsorption effect of cell was better than that of individual cell component. The results of molecular dynamics analysis revealed that adsorption was mainly caused by electrostatic interactions, van der Waals forces, and hydrogen bonds. The hydrophobic interaction was also involved in adsorption process. Overall, this research may provide new information for developing new strategies for NPs removal in intestinal environment.

Isolated middle cerebral artery stenosis caused by syphilitic vasculitis.

BACKGROUND: Syphilitic vasculitis (SV) is rare and difficult to be diagnosed. High-resolution vessel wall magnetic resonance imaging (HR-VWI) might be valuable in the diagnosis by differentiating SV from other vessel wall pathologies. METHODS: We report a rare case with severe isolated middle cerebral artery (MCA) stenosis and cerebral infarction, which was evaluated by serial HR-VWI. RESULTS: A 46-year-old woman presented with an acute infarct in the left basal ganglia and severe isolated stenosis in left middle cerebral artery (MCA). Cerebrospinal fluid (CSF) analysis was performed and the findings were consistent with neurosyphilis diagnosis. The MCA stenosis was also suspected to be the result of SV. HR-VWI revealed the evidence of concentric thickening and circular uniform enhancement of the arterial wall. After two cycles of anti-syphilis treatment, subsequent HR-VWI showed that the MCA stenosis was reduced significantly except slight enhancement of the arterial wall, which confirmed that the SV caused the isolated MCA stenosis. CONCLUSIONS: HR-VWI could be an important diagnostic tool for isolated middle cerebral artery stenosis caused by SV, which could serve as a biomarker for assessing the response to anti-syphilis treatment in the future.

Bioinspired Pd-Cu Alloy Nanoparticles as Accept Agent for Dye Degradation Performances.

Dye degradation is a key reaction in organic decomposition production through electron donor transferring. Palladium (Pd) is the best-known element for synthesis Pd-based catalyst, the surface status determines the scope of relative applications. Here we first prepare Pd-Cu alloy nanoparticles (NPs) by co-reduction of Cu(acac)2 (acac = acetylacetonate) and Pd(C5HF6O2)2 in the presence of sodium borohydride (NaBH4) and glutathione (GSH). The obtained Pd-Cu is about ~10 nm with super-hydrophilicity in aqueous mediums. The structural analysis clearly demonstrated the uniform distribution of Pd and Cu element. The colloidal solution keeps stability even during 30 days. Bimetallic Pd-Cu NPs shows biocompatibility in form of cell lines (IMEF, HACAT, and 239 T) exposed to colloidal solution (50 µg mL-1) for 2 days. It shows the catalytic multi-performance for dye degradation such as methyl orange (MO), rhodamine B (RhB), and methylene blue (MB), respectively. The as-synthesized nanoparticles showed one of the best multiple catalytic activities in the industrially important (electro)-catalytic reduction of 4-nitrophenol (4-NP) to corresponding amines with noticeable reduced reaction time and increased rate constant without the use of any large area support. In addition, it exhibits peroxidase-like activity in the 3, 3', 5, 5'-Tetramethylbenzidine (TMB) color test and exhibit obvious difference with previous individual metal materials. By treated with high intensity focused ultrasound filed (HIFU), Pd-Cu NPs might be recrystallized and decreased the diameters than before. The enhancement in catalytic performance is observed obviously. This work expedites rational design and synthesis of the high-hierarchy alloy catalyst for biological and environment-friendly agents.

Diagnostic value of myocardial stress detection based on feature tracking MRI in patients with acute myocardial infarction.

Background: Evaluate the predictive value of myocardial stress measured by magnetic resonance imaging (MRI) on the severity of coronary artery stenosis and acute myocardial infarction (AMI). In the early stage of acute myocardial infarction, many imaging findings are negative, and MRI myocardial stress detection is controversial in the diagnosis of this aspect. Therefore, it is necessary to determine whether MRI myocardial stress can diagnose acute myocardial infarction. Methods: A total of 120 patients were divided into an AMI group and non-AMI group. The AMI group was further divided into a mild group, moderate group, and severe group. The myocardial stress was measured by MRI, compared in each group, the correlation between myocardial stress and coronary artery stenosis rate was analyzed, and coronary artery disease (CAD) compared between patients with AMI, and the relationship between myocardial stress and AMI was observed. Results: Among the 120 patients, there were 77 cases in the AMI group, including 21 cases in the mild group, 40 cases in the moderate group, and 16 cases in the severe group. There were a total of 43 cases in the non-AMI group. Myocardial stress in the AMI group was significantly higher than that in the non-AMI group (P<0.05). The myocardial stress increased gradually in the mild, moderate, and severe AMI groups (P<0.001). Myocardial stress was positively correlated with coronary artery stenosis rate (P<0.001) and CAD (P<0.05). Logistic regression analysis showed that myocardial stress was an independent risk factor for AMI (P<0.05). The sensitivity and specificity of myocardial stress >5.15 mm in the diagnosis of AMI were 83.5%, 68.6% (AUC =0.834), respectively. Acute myocardial infarction is often caused by risk factors such as hyperlipidemia, hypertension and hyperglycemia, as well as vascular stenosis caused by arterial wall malformation, vascular wall inflammation or vasospasm. Conclusions: The MRI measurement of myocardial stress is simple, reliable, and practical to evaluate the degree of coronary artery lesions. Myocardial stress is closely related to AMI and can assist in the diagnosis of AMI.

Metal Cluster Triggered-Assembling Heterogeneous Au-Ag Nanoclusters with Highly Loading Performance and Biocompatible Capability.

In this work, we firstly report the preparation of heterogeneously assembled structures Au-Ag nanoclusters (NCs) as good drug carriers with high loading performance and biocompatible capability. As glutathione-protected Au and Ag clusters self-assembled into porous Au-Ag NCs, the size value is about 1.358 (±0.05) nm. The morphology characterization revealed that the diameter of Au-Ag NCs is approximately 120 nm, as well as the corresponding potential ability in loading performance of the metal cluster triggered-assembling process. Compared with individual components, the stability and loading performance of heterogeneous Au-Ag NCs were improved and exhibit that the relative biocompatibility was enhanced. The exact information about this is that cell viability was approximately to 98% when cells were incubated with 100 µg mL-1 particle solution for 3 days. The drug release of Adriamycin from Au-Ag NCs was carried out in PBS at pH = 7.4 and 5.8, respectively. By simulating in vivo and tumor microenvironment, the release efficiency could reach over 65% at pH = 5.8 but less than 30% at pH = 7.2. Using an ultrasound field as external environment can accelerate the assembling process while metal clusters triggered assembling Au-Ag NCs. The size and morphology of the assembled Au-Ag NCs can be controlled by using different power parameters (8 W, 13 W, 18 W) under ambient atmosphere. Overall, a novel approach is exhibited, which conveys assembling work for metal clusters triggers into heterogeneous structures with porous characteristic. Its existing properties such as water-solubility, stability, low toxicity and capsulation can be considered as dependable agents in various biomedical applications and drug carriers in immunotherapies.

Development of Clinical Risk Scores for Detection of COVID-19 in Suspected Patients During a Local Outbreak in China: A Retrospective Cohort Study.

Objectives: To develop and internally validate two clinical risk scores to detect coronavirus disease 2019 (COVID-19) during local outbreaks. Methods: Medical records were extracted for a retrospective cohort of 336 suspected patients admitted to Baodi hospital between 27 January to 20 February 2020. Multivariate logistic regression was applied to develop the risk-scoring models, which were internally validated using a 5-fold cross-validation method and Hosmer-Lemeshow (H-L) tests. Results: Fifty-six cases were diagnosed from the cohort. The first model was developed based on seven significant predictors, including age, close contact with confirmed/suspected cases, same location of exposure, temperature, leukocyte counts, radiological findings of pneumonia and bilateral involvement (the mean area under the receiver operating characteristic curve [AUC]:0.88, 95% CI: 0.84-0.93). The second model had the same predictors except leukocyte and radiological findings (AUC: 0.84, 95% CI: 0.78-0.89, Z = 2.56, p = 0.01). Both were internally validated using H-L tests and showed good calibration (both p > 0.10). Conclusion: Two clinical risk scores to detect COVID-19 in local outbreaks were developed with excellent predictive performances, using commonly measured clinical variables. Further external validations in new outbreaks are warranted.

Transcriptome analysis reveals the regulatory mechanism by which MdWOX11 suppresses adventitious shoot formation in apple.

Adventitious shoot (AS) regeneration accelerates plant reproduction and genetic transformation. WOX11 is involved in many biological processes, but its regulation of AS regeneration has not been reported. Here, we showed that the genotype and CK/IAA ratio of apple leaves were the key factors that affected their capacity for AS formation. Moreover, the expression level of MdWOX11 was negatively correlated with the capacity for AS formation. Phenotypic analysis of MdWOX11 transgenic plants showed that overexpression of MdWOX11 inhibited AS formation. Endogenous hormone analysis demonstrated that the contents of auxin (IAA), cytokinin (CK), and abscisic acid (ABA) were higher in MdWOX11-RNAi plants than in MdWOX11-OE transgenic plants. We used RNA sequencing to examine the transcriptional responses of genes in MdWOX11-RNAi and MdWOX11-OE transgenic apple plants at different AS stages. We identified 8066 differentially expressed genes and focused our analysis on those involved in the IAA, CK, ABA, and gibberellin (GA) hormone signaling pathways. The expression of genes related to the CK signaling pathway and shoot development was higher in GL-3 than in MdWOX11-OE transgenic plants during the callus and AS emergence stages. However, the expression of MdCKX5 was higher in MdWOX11-OE transgenic plants than in GL3 and MdWOX11-RNAi transgenic plants. Yeast one-hybrid (Y1H) assays, dual-luciferase reporter assays, and ChIP-qPCR showed that MdWOX11 binds to the promoter of MdCKX5, and a dual-luciferase reporter assay showed that MdWOX11 enhanced the promoter activity of MdCKX5. We concluded that MdCKX5 acts downstream of MdWOX11 to control AS formation, and we built a regulatory model of the suppression of AS formation by MdWOX11 in apple.

Utilization of metal or non-metal-based functional materials as efficient composites in cancer therapies.

There has been great progress in cancer treatment through traditional approaches, even though some of them are still trapped in relative complications such as certain side effects and prospective chances of full recovery. As a conventional method, the immunotherapy approach is regarded as an effective approach to cure cancer. It is mainly promoted by immune checkpoint blocking and adoptive cell therapy, which can utilize the human immune system to attack tumor cells and make them necrose completely or stop proliferating cancer cells. Currently however, immunotherapy shows limited success due to the limitation of real applicable cases of targeted tumor environments and immune systems. Considering the urgent need to construct suitable strategies towards cancer therapy, metallic materials can be used as delivery systems for immunotherapeutic agents in the human body. Metallic materials exhibit a high degree of specificity, effectiveness, diagnostic ability, imaging ability and therapeutic effects with different biomolecules or polymers, which is an effective option for cancer treatment. In addition, these modified metallic materials contain immune-modulators, which can activate immune cells to regulate tumor microenvironments and enhance anti-cancer immunity. Additionally, they can be used as adjuvants with immunomodulatory activities, or as carriers for molecular transport to specific targets, which results in the loading of specific ligands to facilitate specific uptake. Here, we provide an overview of the different types of metallic materials used as efficient composites in cancer immunotherapy. We elaborate on the advancements using metallic materials with functional agents as effective composites in synergistic cancer treatment. Some nonmetallic functional composites also appear as a common phenomenon. Ascribed to the design of the composites themselves, the materials' surface structural characteristics are introduced as the drug-loading substrate. The physical and chemical properties of the functional materials emphasize that further research is required to fully characterize their mechanism, showing appropriate relevance for material toxicology and biomedical applications.

A rational synthesis of ultrasmall palladium-based alloys with superhydrophilicity as biocompatible agents and recyclable catalysts.

As essential controlling parameters, the local surface area (size distribution) and polarity property of the surface molecules can determine the catalytic activity and biocompatibility directly. Here, ultrasmall palladium-based alloys (FePd, FePdCo, and FePdCu NCs) were developed to serve as artificial degradation catalysts with superhydrophilicity (SPh), biocompatibility, and reusability, which were referred to as "biocatalysts". As synthesized in aqueous solvent with negative surface potential while dispersing in water medium, because of the surface biological molecules effect. The obtained alloys illustrated a size distribution of about 3.5 nm. Additionally, owing to SPh property, these alloys could be stored in water up to 30 days without any precipitation and retained their monodisperse morphology in colloidal solutions. The cytotoxicity assessment of the alloys by exposing to L-929 cells over 3 days indicated that it maintained cell viability of >80% even up to 390 µg mL-1 (concentration of alloys). Furthermore, they exhibited an obvious enhancement in the catalytic performance for degrading Rhodamine B (RhB) and 4-nitrophenol (4-NP). The recyclable utilization of biocatalysts demonstrates durable stability even after 8 reduction cycles.

Transcriptome analysis reveals that cytokinins inhibit adventitious root formation through the MdRR12-MdCRF8 module in apple rootstock.

Adventitious root (AR) formation is great significance for apple rootstock breeding. Transcriptome analyses were performed with cytokinins (CTKs) signal treatments to analyze the mechanism of AR formation. The results showed that 6-benzyadenine (6-BA) treatment inhibited AR formation. Histological analysis also observed that AR primordium cell formation was significantly suppressed by 6-BA treatment; the ratio of auxin/cytokinins exhibited the lowest values at 1 and 3 day (d) in the 6-BA treatment group. Furthermore, the differentially expressed genes were divided into five categories, including auxin, cytokinins, other hormones, cell cycle, and carbohydrate metabolism pathways. Due to the study of cytokinins signal treatment, it is important to understand the particular module mediated by the cytokinins pathway. The expression level of MdRR12 (a family member of B-type cytokinins-responsive factors) was significantly upregulated at 3 d by 6-BA treatment. Compared to the wild type, the 35S::MdRR12 transgenic tobaccos suppressed AR formation. The promoter sequence of MdCRF8 contains AGATT motif elements that respond to MdRR12. RNA-seq and RT-qPCR assays predicted cytokinins response factor (MdCRF8) to be a downstream gene regulated by MdRR12. The activity of the pro-MdCRF8-GUS promoter was obviously induced by 6-BA treatment and inhibited by lovastatin (Lov) treatment. Yeast one-hybrid, dual-luciferase reporter, and GUS coexpression assays revealed that MdRR12 could directly bind to the MdCRF8 promoter. Additionally, 35S::MdCRF8 transgenic tobaccos also blocked AR growth. Compared to the wild type, 35S::MdRR12 and 35S::MdCRF8 transgenic tobaccos enhanced sensitivity to cytokinins. Thus, we describe that MdRR12 and MdCRF8 function as integrators of cytokinins signals that affect cell cycle- and carbohydrate metabolism-related genes to regulate cell fate transition during AR formation. On the basis of these results, we concluded that the MdRR12-MdCRF8 module is involved in the negative regulation of AR formation in apple rootstock and can potentially be applied in agriculture using genetic approaches.

Hsa_circ_0003204 Knockdown Weakens Ox-LDL-Induced Cell Injury by Regulating miR-188-3p/TRPC6 Axis in Human Carotid Artery Endothelial Cells and THP-1 Cells.

Background: Circular RNAs (circRNAs) are involved in atherosclerosis (AS) development. However, the function and mechanism of circRNA hsa_circ_0003204 (circ_0003204) in carotid artery AS remain unclear. Methods: Oxidized low-density lipoprotein (ox-LDL)-treated human carotid artery endothelial cells (HCtAECs) and THP-1 cells were used as cell models of carotid artery AS. Relative levels of circ_0003204, microRNA-188-3p (miR-188-3p), and transient receptor potential canonical channel 6 (TRPC6) were detected by quantitative reverse transcription-polymerase chain reaction or Western blotting. The targeting relationship between circ_0003204 or TRPC6 and miR-188-3p was assessed via dual-luciferase reporter analysis and RNA immunoprecipitation. Cell proliferation was assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and 5-ethynyl-2'-deoxyuridine (EdU) assay. Cell apoptosis was analyzed via assessing cell caspase-3 activity, apoptosis, and apoptosis-related protein. Inflammatory response was analyzed via analysis of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α). Oxidative stress was assessed via determination of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Results: Circ_0003204 and TRPC6 levels were elevated, and miR-188-3p expression declined in ox-LDL-treated HCtAECs and THP-1 cells. Circ_0003204 could regulate TRPC6 expression via mediating miR-188-3p. Circ_0003204 silencing weakened ox-LDL-induced viability inhibition and apoptosis in HCtAECs, and inflammatory response and oxidative stress in THP-1 cells via regulating miR-188-3p. MiR-188-3p overexpression attenuated ox-LDL-induced injury in HCtAECs and THP-1 cells by targeting TRPC6. Conclusion: Circ_0003204 knockdown mitigated ox-LDL-induced injury in HCtAECs and THP-1 cells via regulating the miR-188-3p/TRPC6 axis, indicating that circ_0003204 might play an important role in carotid artery AS.