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The effects of heat treatment on the microstructure, mechanical properties and wear resistance of Selective Laser Melting Ti6Al4V alloy were systematically studied. The results show that the as-built part has an acicular α ′ martensite structure. The increase in heat treatment temperature causes the decomposition of acicular α ′ martensite, which leads to the decrease of the hardness of Ti6Al4V alloy. When the heat treatment temperature is 800∘C, the alloy forms an α ′ / α structure, which increases the tensile strength and elongation of the alloy by 12% and 23%, respectively. When the heat treatment reaches above 900∘C, the mechanical properties of the alloy decrease sharply due to the disappearance of the α ′ / α structure, the coarse grains of the α phase, and the increase of the content of the β phase. The tensile strength decreased from 935 MPa to 815 MPa, and the elongation decreased from 8.7% to 3.1%. With the increase of heat treatment temperature, the friction coefficient and wear rate increase linearly, which is opposite to the changing trend of hardness, and the wear mechanism is changed from single abrasive wear to abrasive wear and oxidative wear. This is attributed to the increase in the grain size of the alloy and the increase in the content of the β phase, resulting in a decrease in the overall hardness of the alloy. [ABSTRACT FROM AUTHOR]

Juniperus formosana Hayata (J. formosana) is a commom needlebush cultivar growing in China. Six new compounds (1–6), including four cadinene sesquiterpenoids (1 – 4), one abietane diterpenoid (5), and one β-naphthol derivative (6), along with 18 known compounds (7 – 24) were isolated and identified through phytochemical investigation on the heartwood of J. formosana. The structures of these compounds were fully elucidated by their 1D and 2D NMR, HR-ESI-MS, UV, and IR spectral data analyses. The absolute configurations of compounds 1 , 3 , and 5 were confirmed by experimental and calculated electronic circular dichroism (ECD) data. Moreover, X-ray crystallographic analysis was carried out to characterize the structure of compound 4. The inhibitory effects on the nitric oxide (NO) production of all the isolated compounds were initially examined in RAW264.7 macrophages induced by lipopolysaccharide (LPS). The results showed that compounds 3 and 12 possessed significant inhibitory potency on NO generation with IC 50 values of 3.41 μM and 6.15 μM among the new and known compounds, respectively. The expressions of IL-1β, IL-6, and TNF-α were measured in LPS-stimulated RAW264.7 cells to evaluate the anti-inflammatory effects of compounds 1 – 24. Compounds 1–6 and 9–12 exhibited potent anti-inflammatory effects. Additionally, the expressions of p38, Erk, and IκBα proteins were further determined to explore the anti-inflammatory mechanism of the most potent compounds 3 and 12. Overall, our findings indicate the potential of J. formosana for developing medicine candidates as the treatments of inflammation. [Display omitted] • Chemical investigation of J. formosana yielded six new compounds. • The absolute configuration of compounds has been established by ECD data. • The isolated compounds showed moderate to potent anti-inflammatory activity. • The anti-inflammatory mechanisms of 3 and 12 were discussed. [ABSTRACT FROM AUTHOR]

Objective: To explore the potential clinical and prognostic significance of Homo sapiens solute carrier family 35 member F2 (SLC35F2) in the context of lung adenocarcinoma (LUAD)., Methods: The expression pattern of SLC35F2 in LUAD tissues and normal tissues was analyzed in The Cancer Genome Atlas (TCGA) datasets and validated in 12 pairs of fresh clinical LUAD tissues and their corresponding adjacent normal tissues using quantitative real-time PCR (qRT-PCR) and western blotting. Immunohistochemistry (IHC) was used to assess the protein expression of SLC35F2 in 60 paraffin-embedded LUAD tissues, and its associations with clinicopathological parameters were further examined. The prognostic significance of SLC35F2 mRNA expression was also evaluated using the Kaplan-Meier method, and Cox regression models in LUAD patients from the TCGA database. The potential utility of SLC35F2 as an indicator of recurrence or metastasis was explored through the follow-up of selected clinical LUAD cases. Lastly, gene set enrichment analysis (GSEA) was conducted to investigate the underlying biological mechanisms and signaling pathways., Results: Bioinformatics analysis utilizing the TCGA database indicated that SLC35F2 mRNA exhibited heightened expression in LUAD tissues when compared to normal tissues. These findings were further substantiated through the examination of 12 pairs of clinical LUAD tissues and their corresponding adjacent normal tissues, employing qRT-PCR and western blotting techniques. IHC results from a cohort of 60 LUAD patients demonstrated an up-regulation of SLC35F2 in 38 out of 60 individuals (63.3 %), which exhibited a significant correlation with tumor size, lymph node metastasis, and clinical stage (all P  < 0.05). Both the Kaplan-Meier curve and the Cox proportional hazard analyses indicated a strong association between the up-regulation of SLC35F2 mRNA expression and unfavorable overall survival (OS) in patients with LUAD, as observed in the TCGA datasets ( P  < 0.05). The follow-up findings from select clinical LUAD cases provided evidence that the expression of SLC35F2 could serve as a dependable biomarker for monitoring the recurrence or metastasis. Additionally, the GSEA highlighted the enrichment of apoptosis, adhesion, small cell lung cancer (SCLC), and p53 signaling pathways in the subgroup of LUAD patients with elevated SLC35F2 expression., Conclusion: SLC35F2 exhibited an up-regulated in both mRNA and protein expression, rendering it a valuable independent prognostic indicator for patients diagnosed with LUAD., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

The orphan nuclear receptor Nur77 has been validated as a potential drug target for treating breast cancer. Therefore, focusing on the SAR study of the lead 8b ( K D SPR (Nur77) = 354 nM), we found the active compound ja which exhibited improved Nur77-binding capability ( K D SPR (Nur77) = 91 nM) and excellent antiproliferative activities against breast cancer cell lines. Interestingly, ja acted as a potent and selective Nur77 antagonist, displaying good potency against triple-negative breast cancer (TNBC) cell lines but did not inhibit human normal breast cancer cell line MCF-10A (SI > 20). Exceptionally, ja Nur77-dependently caused mitochondria dysfunction and induced the caspase-dependent apoptosis by mediating the TP53 phosphorylation pathway. Moreover, ja significantly suppressed MDA-MB-231 xenograft tumor growth but had no apparent side effects in mice and zebrafish. Overall, ja demonstrated to be the first Nur77 modulator mediating the TP53 phosphorylation pathway that has the potential as a novel anticancer agent for TNBC.

Ciji-Hua'ai-Baosheng II Formula (CHB-II-F) is a traditional Chinese medical formula that has been shown in clinical practice to relieve side effects of chemotherapy and improve quality of life for cancer patients. In order to understand the mechanism of its protective effects on chemotherapy, mice with transplanted H 22 hepatocellular carcinoma were employed in this study. Ninety-two mice were injected subcutaneously with H 22 HCC cell suspension into the right anterior armpit. After mice were treated with 5-fluorine pyrimidine (5-FU), they were divided into six groups as untreated group, 5-FU group, 5-FU plus Yangzheng Xiaoji Capsule group and three groups of 5-FU plus different concentrations of CHB-II-F. Twenty mice were euthanized after 7 days of treatment in untreated and medium concentration of CHB-II-F groups and all other mice were euthanized after 14 days of treatment. Herbal components/metabolites were analyzed by UPLC-MS. Tumors were evaluated by weight and volume, morphology of light and electron microscope, and cell cycle. Apoptosis were examined by apoptotic proteins expression by western blot. Four major components/metabolites were identified from serum of mice treated with CHB-II-F and they are β-Sitosterol, Salvianolic acid, isobavachalcone, and bakuchiol. Treatment of CHB-II-F significantly increased body weights of mice and decreased tumor volume compared to untreated group. Moreover, CHB-II-F treatment increased tumor cells in G 0 -G 1 transition instead of in S phase. Furthermore, CHB-II-F treatment increased the expression of pro-apoptotic proteins and decreased the expression anti-apoptotic protein. Therefore, CHB-II-F could improve mice general condition and reduce tumor cell malignancy. Moreover, CHB-II-F regulates apoptosis of tumor cells, which could contribute its protective effect on chemotherapy.