Polyoxometalate-Intercalated Tremella-Like CoNi-LDH Nanocomposites for Electrocatalytic Nitrite-Ammonia Conversion.

The electrocatalytic reduction of NO2- (NO2RR) holds promise as a sustainable pathway to both promoting the development of emerging NH3 economies and allowing the closing of the NOx loop. Highly efficient electrocatalysts that could facilitate this complex six-electron transfer process are urgently desired. Herein, tremella-like CoNi-LDH intercalated by cyclic polyoxometalate (POM) anion P8W48 (P8W48/CoNi-LDH) prepared by a simple two-step hydrothermal-exfoliation assembly method is proposed as an effective electrocatalyst for NO2- to NH3 conversion. The introduction of POM with excellent redox ability tremendously increased the electrocatalytic performance of CoNi-LDH in the NO2RR process, causing P8W48/CoNi-LDH to exhibit large NH3 yield of 0.369 mmol h-1 mgcat-1 and exceptionally high Faradic efficiency of 97.0% at -1.3 V vs the Ag/AgCl reference electrode in 0.1 M phosphate buffer saline (PBS, pH = 7) containing 0.1 M NO2-. Furthermore, P8W48/CoNi-LDH demonstrated excellent durability during cyclic electrolysis. This work provides a new reference for the application of POM-based nanocomposites in the electrochemical reduction of NO2- to obtain value-added NH3.

Survival Outcome of Salivary Gland Carcinoma: A 50-Year Retrospective Study With Long-Term Follow-up.

PURPOSE: Salivary gland carcinomas (SGCs) can be classified into more than 20 subtypes with various clinical behaviors. The present study aimed to analyze the clinical and pathological features of SGCs and evaluate their long-term prognosis. METHODS: A retrospective cohort study was performed. This study investigated cases of histologically confirmed SGC at the authors' institution from January 1963 to December 2014. Data on sex, age, site, histopathological diagnosis, tumor-node-metastasis classification, postoperative radiotherapy and/or chemotherapy, local and regional recurrence, and distant metastasis (DM) were collected as covariates. The overall survival (OS) rate was analyzed as the outcome. Kaplan-Meier survival analysis and Cox multivariate analysis were used for survival analysis. The cohort was divided into 2 groups-before and after 1989. The clinicopathological characteristics of the 2 groups were compared using the χ2 test. RESULTS: The cohort included 1,637 patients who met the admission criteria and had a male-to-female ratio of 0.9:1. The median age was 47 years (range, 8 months to 86 years). The median follow-up time was 54 months (range, 1-432 months). The majority of the tumors occurred in the parotid gland (35.3%), followed by the palate gland (25.2%). Adenoid cystic carcinoma was the most common tumor type (34.3%), and mucoepidermoid carcinoma (29%) was the second most common type. In the 1,637 patients, the neck lymph node metastasis rate was 8.7% at the first surgery, and the overall DM rate was 14.1%. The 5-, 10-, and 15-year OS rates of the 1,637 cases were 93.1%, 87.2%, and 79.3%, respectively. Comparative analysis before and after 1989 showed statistically significant differences in sex, site, histologic subtype, T classification, local and regional recurrence rate, and radiotherapy (P < .05), while no significant differences were found in age, N classification, M staging, DM, or chemotherapy. CONCLUSIONS: The OS rates of SGC have improved significantly over the past 30 years. This is attributable to an increase in the proportion of patients diagnosed at the early stage and receiving radiotherapy, as this has led to a reduction in the local and regional recurrence rate and, consequently, an improvement in the survival rates.

AGR2-induced cholesterol synthesis drives lovastatin resistance that is overcome by combination therapy with allicin.

Anterior gradient 2 (AGR2), a protein disulfide isomerase (PDI), is a multifunctional protein under physiological and pathological conditions. In this study we investigated the roles of AGR2 in regulating cholesterol biogenesis, lipid-lowering efficiency of lovastatin as well as in protection against hypercholesterolemia/statin-induced liver injury. We showed that AGR2 knockout significantly decreased hepatic and serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in mice with whole-body or hepatocyte-specific Agr2-null mutant, compared with the levels in their wild-type littermates fed a normal chow diet (NCD) or high-fat diet (HFD). In contrast, mice with AGR2 overexpression (Agr2/Tg) exhibited an increased cholesterol level. Mechanistic studies revealed that AGR2 affected cholesterol biogenesis via activation of AKT/sterol regulatory element-binding protein-2 (SREBP2), to some extent, in a PDI motif-dependent manner. Moreover, elevated AGR2 led to a significant decrease in the lipid-lowering efficacy of lovastatin (10 mg· kg-1· d-1, ip, for 2 weeks) in mice with hypercholesterolemia (hyperCho), which was validated by results obtained from clinical samples in statin-treated patients. We showed that lovastatin had limited effect on AGR2 expression, but AGR2 was inducible in Agr2/Tg mice fed a HFD. Further investigations demonstrated that drug-induced liver toxicity and inflammatory reactions were alleviated in hypercholesterolemic Agr2/Tg mice, suggesting the dual functions of AGR2 in lipid management and hyperCho/statin-induced liver injury. Importantly, the AGR2-reduced lipid-lowering efficacy of lovastatin was attenuated, at least partially, by co-administration of a sulfhydryl-reactive compound allicin (20 mg· kg-1· d-1, ip, for 2 weeks). These results demonstrate a novel role of AGR2 in cholesterol metabolism, drug resistance and liver protection, suggesting AGR2 as a potential predictor for selection of lipid-lowering drugs in clinic.

Transcriptomic study of the mechanism of anoikis resistance in head and neck squamous carcinoma.

BACKGROUND: Normal epithelial cells rapidly undergo apoptosis as soon as they lose contact with the extracellular matrix (ECM), which is termed as anoikis. However, cancer cells tend to develop a resistance mechanism to anoikis. This acquired ability is termed as anoikis resistance. Cancer cells, with anoikis resistance, can spread to distant tissues or organs via the peripheral circulatory system and cause cancer metastasis. Thus, inhibition of anoikis resistance blocks the metastatic ability of cancer cells. METHODS: Anoikis-resistant CAL27 (CAL27AR) cells were induced from CAL27 cells using the suspension culture approach. Transcriptome analysis was performed using RNA-Seq to study the differentially expressed genes (DEGs) between the CAL27ARcells and the parental CAL27 cells. Gene function annotation and Gene Ontology (GO) enrichment analysis were performed using DAVID database. Signaling pathways involved in DEGs were analyzed using Gene Set Enrichment Analysis (GSEA) software. Analysis results were confirmed by reverse transcription PCR (RT-PCR), western blotting, and gene correlation analysis based on the TCGA database. RESULTS: GO enrichment analysis indicated that the biological process (BP) of the DEGs was associated with epidermal development, DNA replication, and G1/S transition of the mitotic cell cycle. The analysis of cellular component (CC) showed that the most significant up-regulated genes were related to extracellular exosome. KEGG Pathway analysis revealed that 23 signaling pathways were activated (p-value ≤ 0.05, FDR q-value ≤ 0.05) and 22 signaling pathways were suppressed (p-value ≤ 0.05, FDR q-value ≤ 0.05). The results from the GSEA indicated that in contrast to the inhibition of EGFR signaling pathway, the VEGF signaling pathway was activated. The VEGF signaling pathway possibly activates STAT3 though induction of STAT3 phosphorylation. Gene correlation analysis revealed that the VEGFA- STAT3-KLF4-CDKN1A signal axis was not only present in head and neck squamous carcinoma (HNSCC) but also two other epithelial-derived carcinomas that highly express VEGFA, including kidney renal clear cell carcinoma (KIRC) and ovarian serous cystadenocarcinoma (OV).

Ghost cell odontogenic carcinoma of the jaws: Report of two cases and a literature review.

BACKGROUND: Ghost cell odontogenic carcinoma (GCOC) is a rare malignant odontogenic epithelial tumor with features of benign calcifying odontogenic cysts. Herein, we report two new cases of GCOC and systematically review the previous literature. CASE SUMMARY: In case 1, a 46-year-old man complained of painless swelling of the right maxilla for 3 years, with a 1-mo history of hemorrhinia in the right nasal cavity. In case 2, a 72-year-old man was referred to our hospital with a chief complaint of painful swelling of the right mandible. Initially, the preliminary diagnoses were ameloblastomas. Thus, the two patients underwent resection of the tumor under general anesthesia. Finally, immunohistochemical examination confirmed the diagnosis of GCOC. The patient in case 1 was followed for 2 years, with no evidence of recurrence. However, the patient in case 2 was lost to follow-up. CONCLUSION: GCOC is a rare malignant odontogenic epithelial tumor with high recurrence. Local extensive resection is necessary for the definitive treatment of GCOC.

Lingual lymph nodes in patients with squamous cell carcinoma of the tongue and the floor of the mouth.

BACKGROUND: The treatment failure for oral squamous cell carcinoma (SCC) frequently takes the form of local and regional recurrences. We investigated the role of lingual lymph nodes (LLNs) in the recurrence of SCC of the tongue and the floor of the mouth. METHODS: A total of 111 patients with SCC of the tongue and the floor of the mouth who received treatment between 2012 and 2017 were included in this study. The patients with lingual lymph nodes that were confirmed to be metastasis on pathological examination were classified into the LNN group. The demographic and clinical data differences between the No-LLN group and the LLN group were compared. Statistical analyses were performed using the Pearson chi-square test RESULTS: The total incidence of LLNs was 17.12% (19/111) and 5 patients (4.5%) demonstrated LLN metastases. All the patients with LLN metastases had a neck lymph node status of N2 classification. The incidence and metastasis of the LLNs were associated with pathological classifications of SCC of the tongue and the floor of the mouth. CONCLUSIONS: LLNs are rare in patients with SCC of the tongue and the floor of the mouth, and they would be ready to be omitted. The dissection of these LLNs would be of benefit to those patients with advanced pathological grade.

Arrestins contribute to amyloid beta-induced cell death via modulation of autophagy and the α7nAch receptor in SH-SY5Y cells.

Amyloid ß-protein (Aß) is believed to contribute to the development of Alzheimer's disease (AD). Here we showed that Aß25-35 rapidly caused activation of autophagy, subsequently leading to reduction of autophagy associated with cellular apoptosis. Further investigation revealed that the accumulation of ß-arrestin 1 (ARRB1) caused by Aß25-35 contributed to the induction of autophagic flux. The depletion of ARRB1 led to decreases in the expression of LC3B, Atg7, and Beclin-1, which are essential for the initiation of autophagy. ARRB1 depletion also reduced downstream ERK activity and promoted Aß25-35-induced cell death. As with ARRB1, transient upregulation of ARRB2 by Aß25-35 was observed after short treatment durations, whereas genetic reduction of ARRB2 caused a marked increase in the expression of the α7nAch receptor at the cell surface, which resulted in partial reversal of Aß25-35-induced cell death. Although expression of both ARRB1 and ARRB2 was reduced in serum from patients with AD, the levels of ARRB1 were much lower than those of ARRB2 in AD. Thus, our findings indicate that ARRB1/2 play different roles in Aß25-35 cytotoxicity, which may provide additional support for exploring the underlying molecular mechanism of AD.

Using UPLC-MS/MS for Characterization of Active Components in Extracts of Yupingfeng and Application to a Comparative Pharmacokinetic Study in Rat Plasma after Oral Administration.

Yupingfeng (YPF), a famous traditional Chinese medicine, which contains a large array of compounds, has been effectually used in health protection. A two-dimensional liquid chromatography (²D-LC) combined with quadrupole time-of-flight mass spectrometry (QTOF-MS) method was firstly established to separate and identify chemical components in YPF. A total of 33 compounds were identified, including 15 constituents (flavonoids and saponins) in Astragali radix; seven constituents (sesquiterpenoids and polysaccharide) in Atractylodis rhizoma; and 11 constituents (chromone and coumarins) in Saposhnikoviae radix. The corresponding fragmentation pathway of typical substances was investigated. Then, seven active constituents (astragaloside, calycosin, formononetin, cimicifugoside, 4-O-beta-d-glucosyl-5-O-methylvisamminol, sec-O-glucosylhamaudol, and atractylenolide II) derived from three medicinal plants were chosen to further investigate the pharmacokinetic behavior of YPF formula using ultrahigh-performance liquid chromatography with triple quadrupole mass spectrometry system. The method was sensitive, accurate and reliable. We also used the area under the plasma concentration-time curve from zero to infinity (AUC0-∞) as weighting factor to make an integrated pharmacokinetic curve. Results show that the constituents of Saposhnikoviae radix have the best absorption and pharmacokinetic behavior and may play important role in leading to the changes of overall therapeutic effects of YPF. Further study is needed to confirm the association between them.