Cavitation-induced particle engulfment via enhancing particle-interface interaction in solidification.

Particle engulfment plays a vital role in the application of particulate reinforced metal matrix composites fabricated by ingot metallurgy. During solidification, particles are nevertheless pushed by an advancing front. As a model system, TiB2p/Al composites were used to investigate the particle engulfment facilitated by acoustic cavitation. The implosion of bubbles drives the particles plunging towards the solid/liquid interface, which increases the engulfment probability. The secondary dendrite arms are refined from 271.2 µm to 98.0 µm as a result of the forced movements of TiB2 particles. Owing to the particle engulfment and dendrite refinement, the composite with ultrasound vibration treatment shows a more rapid work-hardening rate and higher strength.

Dynamic myocardial perfusion computed tomography with mental stress test to detect changes in myocardial microcirculation in patients with anxiety and no obstructive coronary artery disease.

OBJECTIVE: Mental stress can induce myocardial ischemia in patients with anxiety and other psychological disorders. Computed tomography myocardial perfusion imaging (CT-MPI) has the potential to quantitatively diagnose myocardial ischemia. The aim of this study was to measure changes in myocardial microcirculation perfusion (MMP) in patients with anxiety who have angina symptoms/ischemia but no obstructive coronary artery disease (INOCA) using dynamic CT-MPI in combination with a mental stress test. METHODS: Patients with INOCA were divided into five subgroups (none, minimal, mild, moderate, and severe) according to the generalized anxiety disorder scale. Patients underwent dynamic CT-MPI with mental stress testing using a series of the standardized color word/arithmetic stressors. Myocardial blood flow (MBF) during resting and stress phases of CT-MPI was recorded. RESULTS: Fifty-eight patients with 986 segments were included for final analysis. Compared to patients with none, minimal, mild, and moderate anxiety, those with severe anxiety had the largest rate of MBF decrease and the largest MBF decrease value. At the same time, those with no anxiety had the largest rate of MBF increase, the largest MBF increase value (all p < 0.05). As anxiety intensified, the rate of MBF increased and the MBF value increased (r = -0.24, r = -0.27, p < 0.05). Concomitantly, the rate of MBF decreased and the MBF value decreased (r = 0.63, r = 0.43, p < 0.05). CONCLUSIONS: Dynamic CT-MPI with a mental stress test can be used to evaluate MMP in patients with anxiety and INOCA. Mental stress resulted in significant differences in changes in the rate and value of MBF among patients with different anxiety degrees. KEY POINTS: • Dynamic CT-MPI with mental stress test worked well to quantitatively evaluate myocardial microcirculation perfusion in patients with anxiety and INOCA. • The rates of MBF decrease and MBF decrease value were positively correlated with anxiety degree of anxiety patients with INOCA. • MBF change derived from CT-MPI with mental stress test had a good performance to predicting anxiety degree of patients with anxiety and INOCA.

Palliative radiotherapy combined with stent insertion to relieve dysphagia in advanced esophageal carcinoma patients: A systematic review and meta-analysis.

Introduction: Esophageal cancer is one of the most aggressive malignancies with limited treatment options, thus resulting in high morbidity and mortality. For patients with advanced esophageal cancer, the median survival is 3-6 months, with the majority requiring intervention for dysphagia. Objective: To compare the relief of dysphagia in patients with incurable esophageal cancer treated with stenting alone or a combination of stenting and palliative radiotherapy. Methods: The protocol of this study was pre-registered on PROSPERO (CRD42022337481). We searched PubMed, Wan Fang, Cochrane Library, Embase, and Web of Science databases. The literature search, quality assessment, and data extraction were conducted by two reviewers independently. The primary endpoints included median overall survival and dysphagia scores. Bleeding events, stent migration, and pain events were secondary outcomes. The meta-analysis results (the primary and secondary outcomes) were pooled by means of a random-effect model or a fixed-effects model. Results: Nine studies with a total of 851 patients were included in this meta-analysis, consisting of 412 patients in the stenting alone group and 439 patients in the palliative radiotherapy after esophageal cancer stenting (ROCS) group. The ROCS group could significantly improve dysphagia scores (SMD: -0.77; 95% CI: -1.02 to -0.51) and median overall survival (SMD: 1.70; 95% CI: 0.67-2.72). Moreover, there were no significant differences between the two groups in bleeding events, pain events, and stent migration. Conclusion: Patients with dysphagia in advanced esophageal cancer may benefit further from ROCS in median overall survival and dysphagia scores. However, there was no significant advantage in improving bleeding events, pain events, and stent migration. Therefore, it is urgent to find a better therapy to improve adverse events in the future. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022337481.

AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway.

BACKGROUND: Aberrant expression of Aldo-Keto reductase family 1 member B10 (AKR1B10) was associated with tumor size and metastasis of breast cancer in our published preliminary studies. However, little is known about the detailed function and underlying molecular mechanism of AKR1B10 in the pathological process of breast cancer. METHODS: The relationship between elevated AKR1B10 expression and the overall survival and disease-free survival of breast cancer patients was analyzed by Kaplan-Meier Plotter database. Breast cancer cell lines overexpressing AKR1B10 (MCF-7/AKR1B10) and breast cancer cell lines with knockdown of AKR1B10 (BT-20/shAKR1B10) were constructed to analyze the impact of AKR1B10 expression on cell proliferation and migration of breast cancer. The expression levels of AKR1B10 were detected and compared in the breast cancer cell lines and tissues by RT-qPCR, western blot and immunohistochemistry. The proliferation of breast cancer cells was monitored by CCK8 cell proliferation assay, and the migration and invasion of breast cancer cells was observed by cell scratch test and transwell assay. The proliferation- and EMT-related proteins including cyclinD1, c-myc, Survivin, Twist, SNAI1, SLUG, ZEB1, E-cadherin, PI3K, p-PI3K, AKT, p-AKT, IKBα, p-IKBα, NF-κB p65, p-NF-κB p65 were detected by western blot in breast cancer cells. MCF-7/AKR1B10 cells were treated with LY294002, a PI3K inhibitor, to consider the impact of AKR1B10 overexpression on the PI3K/AKT/NF-κB signal cascade and the presence of NF-κB p65 in nuclear. In vivo tumor xenograft experiments were used to observe the role of AKR1B10 in breast cancer growth in mice. RESULTS: AKR1B10 expression was significantly greater in breast cancer tissue compared to paired non-cancerous tissue. The expression of AKR1B10 positively correlated with lymph node metastasis, tumor size, Ki67 expression, and p53 expression, but inversely correlated with overall and disease-free survival rates. Gene Ontology analysis showed that AKR1B10 activity contributes to cell proliferation. Overexpression of AKR1B10 facilitated the proliferation of MCF-7 cells, and induced the migration and invasion of MCF-7 cells in vitro in association with induction of epithelial-mesenchymal transition (EMT). Conversely, knockdown of AKR1B10 inhibited these effects in BT-20 cells. Mechanistically, AKR1B10 activated PI3K, AKT, and NF-κB p65, and induced nuclear translocation of NF-κB p65, and expression of proliferation-related proteins including c-myc, cyclinD1, Survivin, and EMT-related proteins including ZEB1, SLUG, Twist, but downregulated E-cadherin expression in MCF-7 cells. AKR1B10 silencing reduced the phosphorylation of PI3K, AKT, and NF-κB p65, the nuclear translocation of NF-κB p65, and the expression of proliferation- and migration-related proteins in BT-20 cells. LY294002, a PI3K inhibitor, attenuated the phosphorylation of PI3K, AKT, and NF-κB p65, and the nuclear translocation of NF-κB p65. In vivo tumor xenograft experiments confirmed that AKR1B10 promoted breast cancer growth in mice. CONCLUSIONS: AKR1B10 promotes the proliferation, migration and invasion of breast cancer cells via the PI3K/AKT/NF-κB signaling pathway and represents a novel prognostic indicator as well as a potential therapeutic target in breast cancer.

Identification of a Novel Cleavage Site and Confirmation of the Effectiveness of NgAgo Gene Editing on RNA Targets.

Clusters of regularly interspaced short palindromic repeats (CRISPR)/Cas systems have a powerful ability to edit DNA and RNA targets. However, the need for a specific recognition site, protospacer adjacent motif (PAM), of the CRISPR/Cas system limits its application in gene editing. Some Argonaute (Ago) proteins have endonuclease functions under the guidance of 5' phosphorylated or hydroxylated guide DNA (gDNA). The NgAgo protein might perform RNA gene editing at 37 °C, suggesting its application in mammalian cells; however, its mechanisms are unclear. In the present study, the target of NgAgo in RNA was confirmed in vitro and in vivo. Then, an in vitro RNA cleavage system was designed and the cleavage site was verified by sequencing. Furthermore, NgAgo and gDNA were transfected into cells to cleave an intracellular target sequence. We demonstrated targeted degradation of GFP, HCV, and AKR1B10 RNAs in a gDNA-dependent manner by NgAgo both in vitro and in vivo, but no effect on DNA was observed. Sequencing demonstrated that the cleavage sites are located at the 3' of the target RNA which is recognized by 5' sequence of the gDNA. These results confirmed that NgAgo-gDNA cleaves RNA not DNA. We observed that the cleavage site is located at the 3' of the target RNA, which is a new finding that has not been reported in the past.

AKR1B10 protects against UVC-induced DNA damage in breast cancer cells.

The cellular response to DNA damage is crucial for maintaining the integrity and stability of molecular structure. To maintain genome stability, DNA-damaged cells should be arrested so that mutations can be repaired before replication. Although several key components required for this arrest have been discovered, the majority of the pathways are still unclear. Through a number of assays, including cell viability, colony formation, and apotheosis assay, we found that AKR1B10 protected cells from UVC-induced DNA damage. Surprisingly, UVC-induced γH2AX foci and DNA double-strand breaks in the AKR1B10-overexpressing cells were ∼4-5 folds lower than those in the control group. The expression levels of AKR1B10, p53, chk1, chk2, nuclear factor (NF)-κB, and p65 showed dynamic changes in response to UVC irradiation. Our results suggested that AKR1B10 is involved in the pathway of cell cycle checkpoint and NF-κB in DNA damage. Taken together, our results suggest that AKR1B10 is involved in the repair of the DNA double-strand break, which provides a new insight into the role of AKR1B10 in DNA damage repair and indicates a new trail in tumorigenesis and cancer drug resistance.

AKR1B10 confers resistance to radiotherapy via FFA/TLR4/NF-κB axis in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one kind of human head and neck cancers with high incidence in Southern China, Southeast Asia and North Africa. In spite of great innovations in radiation and chemotherapy treatments, the 5-year survival rate is not satisfactory. One of the main reasons is resistance to radiotherapy which leads to therapy failure and recurrence of NPC. The mechanism underlying remains to be fully elucidated. Aldo-keto reductase B10 (AKR1B10) plays a role in the formation and development of carcinomas. However, its role in resistance to radiotherapy of NPC is not clear. In this research, the relationships between AKR1B10 expression and the treatment effect of NPC patients, NPC cell survival, cell apoptosis, and DNA damage repair, as well as the effect and mechanism of AKR1B10 expression on NPC radioresistance were explored. A total of 58 paraffin tissues of NPC patients received radiotherapy were collected including 30 patients with radiosensitivity and 28 patients with radioresistance. The relationships between AKR1B10 expression and the treatment effect as well as clinical characteristics were analyzed by immuno-histochemical experiments, and the roles of AKR1B10 in cell survival, apoptosis and DNA damage repair were detected using the AKR1B10 overexpressed cell models. Furthermore the mechanism of AKR1B10 in NPC radioresistance was explored. Finally, the radioresistance effect of AKR1B10 expression was evaluated by the tumor xenograft model of nude mice and the method of radiotherapy. The results showed AKR1B10 expression level was correlated with radiotherapy resistance, and AKR1B10 overexpression promoted proliferation of NPC cells, reduced apoptosis and decreased cellular DNA damage after radiotherapy. The probable molecular mechanism is that AKR1B10 expression activated FFA/TLR4/NF-κB axis in NPC cells. This was validated by using the TLR4 inhibitor TAK242 to treat NPC cells with AKR1B10 expression, which reduced the phosphorylation of NF-κB. This study suggests that AKR1B10 can induce radiotherapy resistance and promote cell survival via FFA/TLR4/NF-κB axis in NPC, which may provide a novel target to fight against radiotherapy resistance of NPC.

Novel functional fiber loaded with carbon dots for the deep removal of Cr(VI) by adsorption and photocatalytic reduction.

A novel functional fiber (PAN-CDs) loaded with carbon dots (CDs) with excellent photoreduction and adsorption properties for Cr(VI) was prepared via an amidization reaction between the CDs' carboxyl groups and amine groups on polyacrylonitrile (PAN)-based ion exchange fibers, which could completely preserve the fluorescence properties of the CDs. The photoluminescence (PL), photocatalysis and adsorption properties of PAN-CDs were characterized and analyzed. The PAN-CDs possess high adsorption capacity (297.6 mg/g) and excellent kinetic behavior (attaining adsorption equilibrium in 30 min) for Cr(VI) adsorption. Furthermore, the residual Cr(VI) (approximately 3 mg/L) after adsorption could be removed completely by subsequent photoreduction by the PAN-CDs. The Cr-saturated PAN-CDs could be easily separated by filtering and regenerated, with no observable decay of removal efficiency after five regeneration cycles. In addition, due to the PL quenching action of Cr(VI), the PAN-CDs can also be used as sensor for quantitative detection of trace Cr(VI) in aqueous solution.

[AKR1B10 promotes proliferation of breast cancer cells by activating Wnt/ß-catenin pathway].

Objective To investigate the effect of aldosterone reductase family 1 member B10 (AKR1B10) on breast cancer cell proliferation and its mechanism. Methods AKR1B10 was overexpressed in MCF-7 cells and knocked down in BT-20 cells to establish both AKR1B10 overexpression and knockdown cell lines. The effect of AKR1B10 overexpression and knockdown on breast cancer cell proliferation was examined by CCK-8 assay. Real-time quantitative PCR was performed to detect AKR1B10 mRNA levels in breast cancer tissues and paired normal tissues. Western blot analysis was used to determine the protein levels of AKR1B10, ß-catenin, cyclin D1, survivin, c-myc in breast cancer tissues and AKR1B10 overexpression/knockdown breast cancer cell lines. Results The expression of AKR1B10 was higher in breast cancer tissues. With AKR1B10 overexpression in MCF-7 cells, cell proliferation was promoted, and the expression levels of ß-catenin, cyclin D1, c-myc and survivin were elevated. Meanwhile, knockdown of AKR1B10 in BT-20 breast cancer cells reduced cell proliferation and the expression levels of ß-catenin, cyclin D1, c-myc and survivin. Conclusion AKR1B10 is highly expressed in breast cancer and promotes breast cancer cell proliferation by activating Wnt/ß-catenin signaling pathway.