Effects of Boride Orientation and Si Content on High-Temperature Oxidation Resistance of Directionally Solidified Fe–B Alloys

In this work, the as-cast directionally solidified (DS) Fe–B alloys with various Si contents and different boride orientation were designed and fabricated, and the as-cast microstructures and static oxidation behaviors of the DS Fe–B alloys were investigated extensively. The as-cast microstructure of the DS Fe–B alloys consists of the well-oriented Fe₂B columnar grains and α-Fe, which are strongly refined by Si addition. The oxidation interface of the scales in the DS Fe–B alloy with 3.50 wt.% Si demonstrates an obvious saw-tooth shaped structure and is embedded into the alternating distributed columnar layer structures of the DS Fe–B alloy with oriented Fe₂B and α-Fe matrix, which is beneficial to improve the anti-peeling performance of the oxide film compared with lower amounts of Si addition in DS Fe–B alloys with oriented Fe₂B [002] orientation parallel to the oxidation direction (i.e., oxidation diffusion direction, labeled as Fe₂B_// sample). In the DS Fe–B alloys with oriented Fe₂B [002] orientation vertical to the oxidation direction (i.e., labeled as Fe₂B_⊥ sample), due to the blocking and barrier effect of laminated-structure boride, Si is mainly enriched in the lower part of the oxide film to form a dense SiO₂ thin layer adhered to layered boride. As a result, the internal SiO₂ thin layer plays an obstructed and shielded role in oxidation of the substrate, which hinders the further internal diffusion of oxygen ions and improves the anti-oxidation performance of the Fe₂B_⊥ sample, making the average anti-oxidation performance better than that of the Fe₂B_// sample.     

Physicochemical Properties of Water-Based Copolymer and Zeolite Composite Sustained-Release Membrane Materials

A nitrogen fertilizer slow-release membrane was proposed using polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), epoxy resin, and zeolite as raw materials. The effects of the water-based copolymer (PVA:PVP) solution ratio A (A₁–A₄) and zeolite amount B (B₁–B₄) on the water absorption rate (XS), water permeability (TS), fertilizer permeability (TF), tensile strength (KL), elongation at break (DSL), and viscosity (ND) of the membrane were explored using the swelling method, a self-made device, and a universal testing machine. The optimal combination of the water-based copolymer and zeolite amount was determined by the coefficient-of-variation method. The results show that the effects of the decrease in A on KL and the increase in B on KL and DSL are promoted first and then inhibited. DSL and ND showed a negative response to the A decrease, whereas XS, TS, and TF showed a positive response. The effect of increasing B on ND, TS, and TF showed a zigzag fluctuation. In the condition of A₁–A₃, XS showed a negative response to the B increase, whereas in the condition of A₄, XS was promoted first and then inhibited. Adding PVP and zeolite caused the hydroxyl stretching vibration peak of PVA at 3300 cm⁻¹ to widen; the former caused the vibration peak to move to low frequencies, and the latter caused it to move to high frequencies. The XRD pattern shows that the highest peak of zeolite is located at 2θ = 7.18° and the crystallization peak of the composite membrane increases with the rise in the proportion of zeolite. Adding PVP made the surface of the membrane smooth and flat, and adding a small amount of zeolite improved the mechanical properties of the membrane and exhibited good compatibility with water-based copolymers. In the evaluation model of the physicochemical properties of sustained-release membrane materials, the weight of all indicators was in the following order: TF > ND > TS > KL > XL > DSL. The optimal membrane material for comprehensive performance was determined to be A₂B₃.     

Inter-Fighting between Influenza A Virus NS1 and β-TrCP: A Novel Mechanism of Anti-Influenza Virus

Influenza A virus (IAV) prevents innate immune signaling during infection. In our previous study, the production of pro-inflammatory cytokines was associated with Cullin-1 RING ligase (CRL1), which was related to NF-κB activation. However, the underlying mechanism is unclear. Here, an E3 ligase, β-transducin repeat-containing protein (β-TrCP), was significantly downregulated during IAV infection. Co-IP analysis revealed that non-structural 1 protein (NS1) interacts with β-TrCP. With co-transfection, an increase in NS1 expression led to a reduction in β-TrCP expression, affecting the level of IκBα and then resulting in repression of the activation of the NF-κB pathway during IAV infection. In addition, β-TrCP targets the viral NS1 protein and significantly reduces the replication level of influenza virus. Our results provide a novel mechanism for influenza to modulate its immune response during infection, and β-TrCP may be a novel target for influenza virus antagonism.     

Prospects of Probiotic Adjuvant Drugs in Clinical Treatment

In modern society, where new diseases and viruses are constantly emerging, drugs are still the most important means of resistance. However, adverse effects and diminished efficacy remain the leading cause of treatment failure and a major determinant of impaired health-related quality of life for patients. Clinical studies have shown that the disturbance of the gut microbial structure plays a crucial role in the toxic and side effects of drugs. It is well known that probiotics have the ability to maintain the balance of intestinal microecology, which implies their potential as an adjunct to prevent and alleviate the adverse reactions of drugs and to make medicines play a better role. In addition, in the past decade, probiotics have been found to have excellent prevention and alleviation effects in drug toxicity side effects, such as liver injury. In this review, we summarize the development history of probiotics, discuss the impact on drug side effects of probiotics, and propose the underlying mechanisms. Probiotics will be a new star in the world of complementary medicine.     

Bone Safety Profile of Steroidal Aromatase Inhibitor in Comparison to Nonsteroidal Aromatase Inhibitors in Postmenopausal Women with Breast Cancer: A Network Meta-Analysis

Background and ObjectivesAromatase inhibitors (AIs) provide an alternative to tamoxifen as an adjuvant therapy for postmenopausal patients with breast cancer (BC). Large trials resulted better outcomes with AIs. Adjuvant therapy with AIs reduced the risk of relapse compared with tamoxifen. Systemic therapies for BC can interfere with bone turnover, either by affecting gonadal steroid hormone production or by inhibiting peripheral aromatization into estrogen. We aimed to evaluate the safety profile of bone-related events by comparing 3 AIs with tamoxifen and a placebo.MethodsThe Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were used for network meta-analyses (NMAs). Searches were performed using PubMed, Embase/Medline, Cochrane, and Ovid databases. Randomized controlled trials comparing tamoxifen and placebo or other AIs to steroidal or nonsteroidal AIs in patients with BC reporting bone-related safety events were included in NMA. NMA in a Bayesian approach was performed using R software (ver 3.2), Gemtc package.ResultsSeventeen studies reporting 4 different bone-related endpoints were included. Although there was no statistical significance, treatment with exemestane lowered the incidence of bone pain (odds ratio [OR] vs. anastrozole and letrozole: 0.63, 0.54), fracture episodes (OR vs. anastrozole and letrozole: 0.84, 0.80), and osteoporosis (OR vs. anastrozole and letrozole: 0.85, 0.73) compared with letrozole and anastrozole. Reduction in bone mineral density was lesser in exemestane than in anastrozole (mean reduction in hip: 1.05; lumbar spine: 1.25). Treatment ranking with the surface under the cumulative ranking curve showed that exemestane was found to reduce the incidence of bone-related adverse events.ConclusionA lower incidence of bone-related safety events was observed in patients treated with exemestane.     

Establishment of a novel prognostic prediction model through bioinformatics analysis for prostate cancer based on ferroptosis-related genes and its application in immune cell infiltration

BackgroundFerroptosis-related genes (FRGs) play vital roles in survival and prognosis of prostate cancer (PCa) patients. We establish a ferroptosis-related prediction model through bioinformatics analysis for overall survival (OS) and disease-free survival (DFS), so as to evaluate the clinical survival status through the characteristics of immune cell infiltration (ICI), which could provide information for treatment monitoring.MethodsAt first, 268 FRGs were obtained from previous studies. Differentially expressed FRGs were identified based on The Cancer Genome Atlas (TCGA) database, and FRG enrichment analysis was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We then performed univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to establish OS- and DFS-related prognostic prediction models. The association of the model and clinicopathological features was further analyzed. Subsequently, unique genomic signatures of immune cell subsets were obtained through the KEGG database. Based on specific genes associated with ferroptosis and their association with ICI, immune infiltration was assessed in patients in different risk groups.ResultsWe constructed an OS- and an DFS-prognostic model through bioinformatics analysis. The predicted values of OS and DFS-related models were higher in T3–4 than in T1–2 (P=0.0057, P<0.001), and the predicted value of the DFS model in N0 stage was higher than that in N1 stage (P=0.0136). Results of Single-sample gene set enrichment analysis (ssGSEA) on the basis of the KEGG dataset showed p53 signaling being the most enriched signal in the high-risk group, while endocytosis was the most enriched signal in the low-risk group. M2 macrophages (P=0.007) and neutrophils (P=0.024) were enriched in the high-risk group, and CD4-activated memory T cells were significantly accumulated in the low-risk group (P=0.017).ConclusionsThe OS- and DFS-related model based on FRGs and ICI create new insights into the disease state assessment of PCa patients., which may aid in the development of individualized and precise treatment in the future.     

Fusobacterium nucleatum induces excess methyltransferase‐like 3‐mediated microRNA‐4717‐3p maturation to promote colorectal cancer cell proliferation

Fusobacterium nucleatum infection plays vital roles in colorectal cancer (CRC) progression. Overexpression of microRNA‐4717‐3p (miR‐4717) was reported to be upregulated in F. nucleatum positive CRC tissues, however, the underlying mechanism is unknown. In this study, we found that miR‐4717 promoted CRC cell proliferation in vitro and growth of CRC in vivo following F. nucleatum infection. MicroRNA‐4717 suppressed the expression of mitogen‐activated protein kinase kinase 4 (MAP2K4), a tumor suppressor, by directly targeting its 3′‐UTR. Furthermore, we confirmed that methyltransferase‐like 3 (METTL3)‐dependent m⁶A methylation could methylate primary (pri)‐miR‐4717, which further promoted the maturation of pri‐miR‐4717, and METTL3 positively regulated CRC cell proliferation through miR‐4717/MAP2K4 pathways. In conclusion, F. nucleatum‐induced miR‐4717 excessive maturation through METTL3‐dependent m⁶A modification promotes CRC cell proliferation, which provides a potential therapeutic target and diagnostic biomarker for CRC.