Value of the NF-κB signalling pathway and the DNA repair gene PARP1 in predicting distant metastasis after breast cancer surgery.

The DNA repair gene PARP1 and NF-κB signalling pathway affect the metastasis of breast cancer by influencing the drug resistance of cancer cells. Therefore, this study focused on the value of the DNA repair gene PARP1 and NF-κB pathway proteins in predicting the postoperative metastasis of breast cancer. A nested case‒control study was performed. Immunohistochemical methods were used to detect the expression of these genes in patients. ROC curves were used to analyse the predictive effect of these factors on distant metastasis. The COX model was used to evaluate the effects of PARP1 and TNF-α on distant metastasis. The results showed that the expression levels of PARP1, IKKß, p50, p65 and TNF-α were significantly increased in the metastasis group (P < 0.001). PARP1 was correlated with IKKß, p50, p65 and TNF-α proteins (P < 0.001). There was a correlation between IKKß, p50, p65 and TNF-α proteins (P < 0.001). ROC curve analysis showed that immunohistochemical scores for PARP1 of > 6, IKKß of > 4, p65 of > 4, p50 of > 2, and TNF-α of > 4 had value in predicting distant metastasis (SePARP1 = 78.35%, SpPARP1 = 79.38%, AUCPARP1 = 0.843; Sep50 = 64.95%, Spp50 = 70.10%, AUCp50 = 0.709; SeTNF-α = 60.82%, SpTNF-α = 69.07%, AUCTNF-α = 0.6884). Cox regression analysis showed that high expression levels of PARP1 and TNF-α were a risk factor for distant metastasis after breast cancer surgery (RRPARP1 = 4.092, 95% CI 2.475-6.766, P < 0.001; RRTNF-α = 1.825, 95% CI 1.189-2.799, P = 0.006). Taken together, PARP1 > 6, p50 > 2, and TNF-α > 4 have a certain value in predicting breast cancer metastasis, and the predictive value is better when they are combined for diagnosis (Secombine = 97.94%, Spcombine = 71.13%).

Inflammatory cytokines and oral lichen planus: a Mendelian randomization study.

Background: Inflammatory cytokines have long been considered closely related to the development of oral lichen planus (OLP), and we further explored the causal relationship between the two by Mendelian randomization (MR) method. Methods: We performed bidirectional MR analyses by large genome-wide association studies (GWAS). The data included a large-scale OLP dataset, as well as datasets of 41 inflammatory cytokines. All data were obtained from the University of Bristol database, which includes 41 inflammatory cytokines, and the GWAS Catalog database, which includes 91 inflammatory cytokines. OLP data were obtained from the Finngen database, which includes 6411 cases and 405770 healthy controls. We used the inverse variance weighted (IVW) method, MR-Egger method, weighted median method, simple mode method and weighted mode method to analyze the causal relationship between inflammatory cytokines and OLP, and we also combined with sensitivity analysis to further verify the robustness of the results. We performed a meta-analysis of positive or potentially positive results for the same genes to confirm the reliability of the final results. Results: We primarily used the IVW analysis method, corrected using the Benjamin Hochberg (BH) method. When p<0.00038 (0.05/132), the results are significantly causal; when 0.00038

Exploring the prognostic value of S100A11 and its association with immune infiltration in breast cancer.

Breast cancer (BC) is a severe danger to women's lives and health globally. S100A11 is aberrantly expressed in many carcinomas and serves a crucial function in cancer development. However, the role of S100A11 in BC is unclear. In this study, we utilized multiple databases and online tools, including the TCGA database, cBioPortal, and STRING, to evaluate the significance of S100A11 in BC prognosis and immune infiltration. We found that S100A11 was considerably more abundant in BC tissues. Survival analysis indicated that individuals with S100A11 high expression of BC had shorter overall survival. Multivariate Cox regression analysis revealed that high S100A11 expression independently influenced the poor outcome of patients with BC (HR = 1.738, 95%CI 1.197-2.524). Our nomogram incorporating five factors, including S100A11, age, clinical stage, N, and M, was developed to anticipate the survival probability in BC prognosis. The model demonstrated good consistency and accuracy. Furthermore, the mutation rete of S100A11 was 14%. Survival analysis suggested that breast cancer patients with S100A11 mutation had a worse prognosis. KEGG pathway enrichment analysis revealed that S100A11 may be mainly involved in the IL-17 signaling pathway. Finally, we discovered a correlation between S100A11 expression and immune cell infiltration on BC. S100A11 expression was positively associated with 17 immune checkpoint-related genes. In conclusion, this study indicates that S100A11 may contribute to a worse prognosis for BC and potentially has a significant impact through its influence on immune cell infiltration and the IL-17 signaling pathway.

Long non-coding RNA and the tumor microenvironment: Prospects for clinical applications in breast cancer.

Breast cancer has surpassed lung cancer as the number one cancer worldwide, and invasion and metastasis are still the main causes of death in breast cancer patients. The tumor microenvironment (TME) is an important site for the growth of tumor cells nourished by vascular networks, and various components of the TME interact strongly with cancer cells and are one of the important mechanisms of tumor progression and metastasis. In recent years, many studies have reported that long non-coding RNAs (LncRNAs) are involved in the formation of TME and influence the process of tumorigenesis and metastasis. This paper reviews the basic characteristics and functional roles of LncRNA in breast cancer TME and introduces the various mechanisms of LncRNA in breast cancer microenvironment that induce breast cancer development and metastasis in three directions: immune cells, non-immune cells, and extracellular matrix in TME, providing potential biomarkers or therapeutic targets for clinical practice.

6-Mercaptopurine potently inhibits recruitment of SHP2 by phosphorylated PD-1 to inhibit PD-1 signalling and enhance T cell function.

Antibody inhibitors that block PD-1/PD-L1 interaction have been approved for oncological clinics, yielding impressive treatment effects. Small molecules inhibiting PD-1 signalling are at various stages of development, given that small molecular drugs are expected to outperform protein drugs in several ways. Currently, a significant portion of these small molecular inhibitors achieve this purpose by binding to a limited region of the PD-L1 protein, thereby limiting the choice of chemical structures. Alternative strategies for developing small-molecular PD-1 inhibitors are urgently needed to broaden the choice of chemical structures. Here, we report that 6-mercaptopurine (6-MP) inhibits PD-1 signalling, activates T cell function in vitro and in vivo and shrinks tumours by activating cytotoxic T cells. Mechanistically, 6-MP potently inhibited PD-1 signalling by blocking the recruitment of SHP2 by PD-1. Considering that 6-MP is a chemotherapeutic agent already approved by the FDA for childhood leukaemia, our work revealed a novel anti-tumour mechanism for this drug and suggests that 6-MP warrants further clinical evaluation for other tumour types.

In vivo genome-wide CRISPR screening identifies ZNF24 as a negative NF-κB modulator in lung cancer.

Systemic identification of tumor suppressor genes (TSGs) and elucidation of their signaling provide a new angle for understanding of tumorigenesis, which is important for developing successful treatment for lung cancer patients. In our current work, we conducted an in vivo screen for lung cancer TSGs through CRISPR/Cas9 mediated knockout of genes at genome-wide scale. We found that ZNF24 was a potent and clinically relevant TSG of lung cancer. Ectopic expression of ZNF24 arrested lung cancer cells in S phase. Mechanistically, ZNF24 bound to promoter region of P65 to negatively regulate its transcription and thereby the signaling activity of NF-κB pathway. This signaling cascade is clinically relevant. Importantly, we found that combinational inhibition of KRAS, NF-κB, and PD-1 effectively shrank autochthonous KrasG12D/ZNF24-/- lung cancers in transgenic mouse model. Our current work thus revealed an important role played by loss of function of ZNF24 in lung tumorigenesis and shed new light in precision medicine for a portion of lung cancer patients.

Facile hydrothermal synthesis of layered 1T' MoTe2 nanotubes as robust hydrogen evolution electrocatalysts.

Layered transition metal dichalcogenides (TMDs), such as molybdenum ditelluride (MoTe2), have attracted much attention because of their novel structure-related physicochemical properties. In particular, semi-metallic-phase MoTe2 (1T') is considered as a competitive candidate for low-cost electrocatalysts for water splitting. However, there are few reports on the simple hydrothermal synthesis of MoTe2 nanostructures compared with other layered TMDs. In this study, a facile one-step hydrothermal process was developed for the fabrication of layered MoTe2, in which uniform nanotubes with a few layers of 1T' MoTe2 were fabricated at a lower temperature for the first time. The as-obtained MoTe2 nanotubes were fully characterized using different techniques, which revealed their structure and indicated the presence of layered 1T' nanocrystals. The efficient activity of MoTe2 nanotubes for the electrocatalytic hydrogen evolution reaction (HER) in 0.5 M H2SO4 was demonstrated by the small Tafel slope of 54 mV/dec-1 and endurable ability, which is attributed to the abundant active sites and remarkable conductivity of 1T' MoTe2 with a few-layer feature. This provides a facile method for the design and construction of efficient layered MoTe2 based electrocatalysts.

Vitamin A and vitamin D deficiencies exacerbate symptoms in children with autism spectrum disorders.

Objectives: This study was designed to investigate the vitamin A (VA) and vitamin D (VD) levels in children with autism spectrum disorders (ASD) and to determine whether co-deficiency of VA and VD exacerbates clinical symptoms in autistic children. Methods: The Autism Behavior Checklist, Childhood Autism Rating Scale (CARS), and Social Responsiveness Scale (SRS) were used to assess the symptoms of 332 children diagnosed as ASD. And the Gesell Developmental Scale (GDS) was used to evaluate neurodevelopment in children with ASD. Anthropometric measurement and questionnaire results were compared for all autistic children and 197 age- and gender-matched control children. Serum retinol levels were detected with high-performance liquid chromatography, and serum levels of 25-OH vitamin D were measured with an immunoassay method in the two groups. Results: The ZHA, ZWA, and ZBMIA of the children with ASD were significantly lower than those of the control children. Furthermore, higher proportions of children with picky eating, resistance to new foods, and eating problems were observed in the ASD group when compared with the control group. Serum retinol and 25-OH vitamin D levels in autistic children were significantly lower than those in the control children. Additionally, VA and VD co-deficiency impacts more on the symptoms and development in autistic children. Conclusions: We found that children with autism have more VA and VD deficiencies than control children, and VA and VD co-deficiency may exacerbate the symptoms of children with ASD.

Novel Single-Crystal Hollandite K1.46Fe0.8Ti7.2O16 Microrods: Synthesis, Double Absorption, and Magnetism.

Novel multifeatured hollandite K1.46Fe0.8Ti7.2O16 (KFTO) was synthesized by a simple hydrothermal method. Magnetic KFTO microrods were well controlled to long rectangular rods with pyramid-shaped tops. A KFTO growth mechanism was proposed on the basis of examining phase and morphology of the samples acquired at different reaction times. The KFTO morphology was confirmed by the calculated surface energies. The UV-vis diffuse reflectance spectra of KFTO microrods showed double absorption with band gaps of 2.01 and 2.16 eV, which was further confirmed by photoluminescence. First-principles studies revealed that the double absorption and magnetic properties originate from the d-d transitions of Fe3+ under the crystal field. The magnetic property could be applied in ferromagnetic semiconductor devices and the double absorption could be applied in visible-light harvesting. This work highlights the multifunctional KFTO microrods with low cost and environmental friendliness.

Plasmon-enhanced photocatalytic activity of Na0.9Mg0.45Ti3.55O8 loaded with noble metals directly observed with scanning Kelvin probe microscopy.

The noble metals Au, Ag and Pt were loaded onto Na0.9Mg0.45Ti3.55O8 (NMTO) using a chemical bath deposition method devised in our recent work for the first time. The composite photocatalysts exhibit more effective photodegradation of methylene blue, due to the Schottky barrier built between NMTO and noble metal. Hot electrons generated during localized surface plasmon processes in metal nanoparticles transfer to the semiconductor, manifesting as a depression of surface potential directly detectable by scanning Kelvin probe microscopy. The key factor responsible for the improved ability of semiconductor-based photocatalysts is charge separation. The most effective weight concentrations of Au, Ag and Pt loaded onto NMTO were found to be 5.00%, 12.6% and 5.55% respectively. NMTO loaded with noble metals shows good photostability and recyclability for the degradation of methylene blue. A possible mechanism for the photodegradation of methylene blue over NMTO loaded with noble metals is proposed. This work highlights the potential application of NMTO-based photocatalysts, and provides an effective method to detect localized surface plasmons.

One-step synthesis of NiTe2 nanorods coated with few-layers MoS2 for enhancing photocatalytic activity.

A facile one-step hydrothermal process was developed for fabrication of three-dimensional hierarchical NiTe2@MoS2 heterostructures. A few layers of MoS2 uniformly grew on the NiTe2 nanorods, possessing a higher surface area. The strategy was extended to CoTe2@MoS2 heterostructures with a few layers of MoS2. The photocatalytic activities of the heterostructures were evaluated by the photodegradation of methylene blue. The composites show strong adsorption ability and much better photocatalytic efficiency in comparison with pure MoS2 microflowers and NiTe2 nanorods. Especially, the NiTe2@MoS2 heterostructure with 40 wt% of MoS2 presents the highest performance in photocatalytic degradation of dye molecules, which is attributed to the formation of hierarchical network between NiTe2 nanorods and MoS2 nanosheets. And the possible mechanism of the enhanced photocatalytic activities was discussed.

Novel magnetic properties of CoTe nanorods and diversified CoTe2 nanostructures obtained at different NaOH concentrations.

CoTe and CoTe2 nanorods with average diameter of 100 nm were synthesized by a simple hydrothermal process, and different CoTe2 nanostructures were obtained by changing the NaOH concentration. CoTe nanorods exhibit weak ferromagnetism while CoTe2 nanorods present paramagnetic behavior. Different magnetic behaviors occur in the other CoTe2 nanostructures due to Na+ entrance into CoTe2 crystals. A first-principles study on Na-doped CoTe2 confirms the magnetic characteristics.

Experimental research on the mechanical properties of porcine iris.

Quantification of the mechanical properties of the iris is necessary to assess the clinical significance of passive iris deformation, which has been suggested as a mechanism for angle closure glaucoma. The animal model simulating the total pupillary block was developed to simulate angle closure glaucoma, and experiments were performed on isolated porcine irises, deformation of the iris was captured when changing the pressure difference between the posterior and anterior chamber. A simple mechanical model was used to account for the geometry of the experiment. The relationship between the area strain (delta) and the pressure differences between the posterior and anterior chamber (P') is described as delta=b(0)+b(1)LnP'. Furthermore the radial 2D elastic mechanics parameter was calculated. The average 2D elastic mechanics parameter of porcine iris was found to be 5.3N/m in the radial direction and 24.7N/m in azimuthal direction. Experimental results provide reliable theoretical and experimental base for explanation of the blindness caused by Glaucoma.

Experimental research on the biomechanical properties of the rabbit iris.

OBJECTIVE: To qualify the mechanical properties of the iris during its passive deformation under the condition of glaucoma. MATERIAL AND METHODS: Experiments simulating the total pupillary block was performed on isolated rabbit irises to determine the passive mechanical behavior of the intact iris. RESULTS: The relationship between the area strain(delta) and the pressure of posterior chamber relative to the anterior chamber(P') was obtained: (P1) was obtained P'+b eb1 delta.