STING mediates LPS-induced acute lung injury by regulating ferroptosis.

The pathogenesis of acute lung injury is not fully understood. Stimulator of interferon genes (STING) and ferroptosis have been implicated in various pathological and physiological processes, including acute lung injury (ALI). However, the relationship between STING and ferroptosis in lipopolysaccharide (LPS)-induced ALI is unclear. We found that LPS stimulation activated STING and ferroptosis. Furthermore, STING knockout and ferroptosis inhibitor alleviated lung inflammation and epithelial cell damage. Also, STING knockout reduced inflammation injury and ferroptosis. Notably, the ferroptosis inducer reversed the alleviation of inflammation caused by STING knockout. These results show that STING participates in the inflammation injury of ALI by regulating ferroptosis. Results also showed that p-STAT3 levels increased after STING knockout, suggesting that STING negatively regulates STAT3 activation. Besides, STAT3 inhibitor aggravated ferroptosis after STING knockout, indicating that STING regulates ferroptosis through STAT3 signaling. In conclusion, STING mediates LPS-induced ALI by regulating ferroptosis, indicating that STING and ferroptosis may be new targets for ALI treatment.

Identification of Novel FZD4 Mutations in Familial Exudative Vitreoretinopathy and Investigating the Pathogenic Mechanisms of FZD4 Mutations.

Purpose: The purpose of this study is to report five novel FZD4 mutations identified in familial exudative vitreoretinopathy (FEVR) and to analyze and summarize the pathogenic mechanisms of 34 of 96 reported missense mutations in FZD4. Methods: Five probands diagnosed with FEVR and their family members were enrolled in the study. Ocular examinations and targeted gene panel sequencing were conducted on all participants. Plasmids, each carrying 29 previously reported FZD4 missense mutations and five novel mutations, were constructed based on the selection of mutations from each domain of FZD4. These plasmids were used to investigate the effects of mutations on protein expression levels, Norrin/ß-catenin activation capacity, membrane localization, norrin binding ability, and DVL2 recruitment ability in HEK293T, HEK293STF, and HeLa cells. Results: All five novel mutations (S91F, V103E, C145S, E160K, C377F) responsible for FEVR were found to compromise Norrin/ß-catenin activation of FZD4 protein. After reviewing a total of 34 reported missense mutations, we categorized all mutations based on their functional changes: signal peptide mutations, cysteine mutations affecting disulfide bonds, extracellular domain mutations influencing norrin binding, transmembrane domain (TM) 1 and TM7 mutations impacting membrane localization, and intracellular domain mutations affecting DVL2 recruitment. Conclusions: We expanded the spectrum of FZD4 mutations relevant to FEVR and experimentally demonstrated that missense mutations in FZD4 can be classified into five categories based on different functional changes.

Characterization of a novel heterozygous frameshift variant in NDP gene that causes familial exudative vitreoretinopathy in female patients.

Familial exudative vitreoretinopathy (FEVR) is a severe inherited disease characterized by defective retinal vascular development. With genetic and clinical heterogeneity, FEVR can be inherited in different patterns and characterized by phenotypes ranging from moderate visual defects to complete vision loss. This study was conducted to unravel the genetic and functional etiology of a 4-month-old female FEVR patient. Targeted gene panel and Sanger sequencing were utilized for genetic evaluation. Luciferase assays, western blot, quantitive real-time PCR, and immunocytochemistry were performed to verify the functional defects in the identified candidate variant. Here, we report a 4-month-old girl with bilateral retinal folds and peripheral avascularization, and identified a novel frameshift heterozygous variant c.37dup (p.Leu13ProfsTer13) in NDP. In vitro experiments revealed that the Leu13ProfsTer13 variant led to a prominent decrease in protein levels instead of mRNA levels, resulting in compromised Norrin/ß-catenin signaling activity. Human androgen receptor assay further revealed that a slight skewing of X chromosome inactivation could partially cause FEVR. Thus, the pathogenic mechanism by which heterozygous frameshift or nonsense variants in female carriers cause FEVR might largely result from a loss-of-function variant in one X chromosome allele and a slightly skewed X-inactivation. Further recruitment of more FEVR-affected females carrying NDP variants and genotype-phenotype correlation analysis can ultimately offer valuable information for the prognosis prediction of FEVR.

Deciphering a crucial dimeric interface governing Norrin dimerization and the pathogenesis of familial exudative vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disease that could cause blindness. It has been established that Norrin forms dimers to activate ß-catenin signaling, yet the core interface for Norrin dimerization and the precise mechanism by which Norrin dimerization contributes to the pathogenesis of FEVR remain elusive. Here, we report an NDP variant, c.265T>C (p.Phe89Leu), that interrupted ß-catenin signaling by disrupting Norrin dimerization. Structural and functional analysis revealed that the Phe-89 of one Norrin monomer interacts with Pro-98, Ser-101, Arg-121, and Ile-123 of another, forming two core symmetrical dimerization interfaces that are pivotal for the formation of a "hand-by-arm" dimer. Intriguingly, we proved that one of the two core symmetrical interfaces is sufficient for dimerization and activation of ß-catenin signaling, with a substantial contribution from the Phe-89/Pro-98 interaction. Further functional analysis revealed that the disruption of both dimeric interfaces eliminates potential binding sites for LRP5, which could be partially restored by over-expression of TSPAN12. In conclusion, our findings unveil a core dimerization interface that regulates Norrin/LRP5 interaction, highlighting the essential role of Norrin dimerization on ß-catenin signaling and providing potential therapeutic avenues for the treatment of FEVR.

The structure correspondence hypothesis predicts how word and sentence in language correlate with term and principle in mathematics.

The association between language and mathematics is an important debated topic. Here, we proposed a structure correspondence hypothesis to explain under what conditions language and mathematics are closely related. According to the hypothesis, there would be an association when they have equivalent structure. One hundred and fifty high school students were recruited to finish mathematical and language tests at the element level (i.e., geometric term processing and word analogy) and at the low-dimensional combination level (i.e., geometric principle processing and sentence completion) as well as the tests to measure cognitive covariates (general intelligence and spatial processing). After controlling for age, gender and cognitive covariates, geometric term processing and word analogy were closely correlated, and geometric principle processing and sentence completion were significantly correlated. No other correlations were found. The results support the structure correspondence hypothesis and provide a new perspective of structure of language and verbalized mathematics for the relation between language and mathematics.

Different cognitive mechanisms used for solving open and closed math problems.

Problem-solving skills are very important in our daily life. Almost all problem-solving studies have addressed the cognitive correlates of solving closed problems, but only limited studies have investigated the cognitive mechanisms of solving open problems. The current study aimed to systematically examine differences between the cognitive mechanisms used for solving open and closed problems. In total, the abilities of 142 high school students to solve open and closed problems were assessed, as were a series of general cognitive abilities as controlled variates. Analogical reasoning uniquely contributed to solving both open and closed math problems, after controlling for age, gender, and inductive reasoning. Reactive cognitive flexibility (measured using the Wisconsin card sorting test) and spatial working memory uniquely correlated only with solving open and closed math problems, respectively. These findings suggest that the cognitive processes used to solve open and closed math problems differ. Open and closed math problems appear to require more reactive cognitive flexibility for generation and more memory for retrieval, respectively.

A clinical decision support system to predict the efficacy for EGFR-TKIs based on artificial neural network.

BACKGROUND: The efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) was affected by numerous factors. In the study, we developed and validated an artificial neural network (ANN) system based on clinical characteristics and next-generation sequencing (NGS) to support clinical decisions. METHODS: A multicenter retrospective non-interventional study was conducted. 240 patients from three hospitals with advanced non-small cell lung cancer (NSCLC) and EGFR mutation were tested by NGS before the first treatment. All patients received formal EGFR-TKIs treatment. Five different models were individually trained to predict the efficacy of EGFR-TKIs based on one medical center with 188 patients. Two independent cohorts from other medical centers were collected for external validation. RESULTS: Compared with logistic regression, four machine learning methods showed better predicting abilities for EGFR-TKIs. The inclusion of NGS tests improved the predictive power of models. ANN performed best on the dataset with mutations TP53, RB1, PIK3CA, EGFR mutation sites, and tumor mutation burden (TMB). The prediction accuracy, recall and AUC were 0.82, 0.82, and 0.82, respectively in our final model. In the external validation set, ANN still showed good performance and differentiated patients with poor outcomes. Finally, a clinical decision support software based on ANN was developed and provided a visualization interface for clinicians. CONCLUSION: This study provides an approach to assess the efficacy of NSCLC patients with first-line EGFR-TKI treatment. Software is developed to support clinical decisions.

Simultaneous enrichment optimization of glycopeptides and phosphopeptides with the highly hydrophilic DZMOF-FDP.

Protein glycosylation and phosphorylation play essential roles in biological systems. The crosstalk of both glycosylation and phosphorylation on one protein represents an unveiled biological function. To realize the analyses of both glycopeptides and phosphopeptides, a simultaneous enrichment method of N-glycopeptides, mono-phosphopeptides and multi-phosphopeptides was developed based on a multi-functional dual-metal centered zirconium metal-organic framework that provided multiple interactions for HILIC, IMAC, and MOAC for glycopeptides and phosphopeptides. Based on a careful optimization of sample loading and elution conditions for the simultaneous enrichment of glycopeptides and phosphopeptides with the zirconium metal-organic framework, a total of 1011 N-glycopeptides derived from 410 glycoproteins and 1996 phosphopeptides including 741 multi-phosphopeptides derived from 1189 phosphoproteins could be identified from a HeLa cell digest. The simultaneous enrichment approach for glycopeptides and mono-/multi-phosphopeptides demonstrates the great potential of the combined interactions for HILIC, IMAC, and MOAC in integrated post-translational modification proteomics research.

Moderate-Intensity Intermittent Training Alters the DNA Methylation Pattern of PDE4D Gene in Hippocampus to Improve the Ability of Spatial Learning and Memory in Aging Rats Reduced by D-Galactose.

(1) Background: Aging is the main risk factor for most neurodegenerative diseases, and the inhibition of Phosphodiesterase 4(PDE4) is considered a potential target for the treatment of neurological diseases. The purpose of this study was to investigate the inhibitory effect of moderate-intensity intermittent training (MIIT) on PDE4 in the hippocampus of rats with D-galactose (D-gal)-induced cognitive impairment, and the possible mechanism of improving spatial learning and memory. (2) Methods: the aging rats were treated with D-Gal (150 mg/kg/day, for 6 weeks). The aging rats were treated with MIIT for exercise intervention (45 min/day, 5 days/week, for 8 weeks). The Morris water maze test was performed before and after MIIT to evaluate the spatial learning and memory ability, then to observe the synaptic ultrastructure of the hippocampus CA1 region, to detect the expression of synaptic-related protein synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), and to detect the expression of PDE4 subtypes, cAMP, and its signal pathway protein kinase A (PKA)/cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF), and the PDE4 methylation level. (3) Results: we found that MIIT for 8 weeks alleviated the decline in spatial learning and memory ability, and improved the synaptic structure of the hippocampus and the expression of synaptic protein SYP and PSD95 in D-Gal aging rats. To elucidate the mechanism of MIIT, we analyzed the expression of PDE4 isoforms PDE4A/PDE4B/PDE4D, cAMP, and the signaling pathway PKA/CREB/BDNF, which play an important role in memory consolidation and maintenance. The results showed that 8 weeks of MIIT significantly up-regulated cAMP, PKA, p-CREB, and BDNF protein expression, and down-regulated PDE4D mRNA and protein expression. Methylation analysis of the PDE4D gene showed that several CG sites in the promoter and exon1 regions were significantly up-regulated. (4) Conclusions: MIIT can improve the synaptic structure of the hippocampus CA1 area and improve the spatial learning and memory ability of aging rats, which may be related to the specific regulation of the PDE4D gene methylation level and inhibition of PDE4D expression.

Language Ability Accounts for Ethnic Difference in Mathematics Achievement.

The mathematics achievement of minority students has always been a focal point of educators in China. This study investigated the differences in mathematics achievement between Han and minority pupils to determine if there is any cognitive mechanism that can account for the discrepancy. We recruited 236 Han students and 272 minority students (including Uygur and Kazak) from the same primary schools. They were tested on mathematics achievement, language abilities, and general cognitive abilities. The results showed that Han pupils had better mathematics achievement scores and better Chinese language ability than minority students. After controlling for age, gender, and general cognitive abilities, there were still significant differences in mathematics achievement between Han and minority students. However, these differences disappeared after controlling for language ability. These results suggest that the relatively poor levels of mathematics achievement observed in minority students is related to poor Chinese language skills.

Serum tumor markers for the prediction of concordance between genomic profiles from liquid and tissue biopsy in patients with advanced lung adenocarcinoma.

BACKGROUND: The concordance between mutations detected from plasma and tissue is critical for treatment choices of patients with advanced lung adenocarcinoma. METHODS: We prospectively analyzed the association of the serum tumor markers with the concordance between blood and tissue genomic profiles from 185 patients with advanced lung adenocarcinoma. The concordance was defined according to 3 criteria. Class 1 included all targetable driver mutations in 8 genes; class 2 included class 1 mutations plus mutations in KRAS, STK11, and TP53; class 3 included class 2 mutations plus tumor mutation burden (TMB) status. RESULTS: Collectively, 150 out of 185 patients had mutations in both tissue and plasma samples, while one patient was mutation-negative for both, resulting a concordance of 81.6%. The concordance rate for class 1 mutations was 80%, and 65% and 69% for class 2 and class 3, respectively. Carbohydrate antigen 19-9 (CA19-9) or cytokeratin 19 (CYFRA21-1) levels higher than the normal upper limit predicted the concordance of tissue and blood results in class 1 (P=0.005, P=0.011), class 2 (P=0.011, P<0.001), and class 3 (P=0.001, P=0.014). In class 1, the cutoff values of CA19-9 were 30, 36, and 284 U/mL to reach the concordance thresholds of 90%, 95%, and 100%, respectively (P=0.032, P=0.003, P=0.043). For CYFRA21-1, the cutoff values were 6, 18, and 52 µg/L (P=0.005, P=0.051, P=0.354). In class 2, the cutoff values for CYFRA21-1 were 18, 22, and 52 µg/L (P=0.001, P=0.001, P=0.052). In class 3, the cutoff values for CA19-9 were 36, 39, and 85 U/mL (P=0.003, P=0.001, P=0.008). For CYFRA21-1, the cutoff values were 22, 52, and 52 µg/L (P=0.900, P>0.99, P>0.99). When the sum score for 4 serum tumor markers was greater than 35, both class 1, class 2, and class 3 reached a predictive threshold of 90%. CONCLUSIONS: Serum tumor markers can be used as easy and practical clinical predictors of concordance in mutation profiles between blood and tissue samples from patients with advanced lung adenocarcinoma.

Is cardia cancer a special type of gastric cancer? A differential analysis of early cardia cancer and non-cardia cancer.

Background: The prognosis of early cardia cancer and non-cardia cancer is still controversial. It is difficult to collect a large number of cases with complete information in clinical practice. Our study was aimed to identify the differences in clinicopathological characteristics and outcomes of early cardia gastric cancer and non-cardia gastric cancer. Methods: All cases analyzed were from Surveillance, Epidemiology, and End Results database. The data of the patients with early gastric cancer from 2004 to 2010 was retrospectively analyzed. Patients were distributed to cardia cancer group and non-cardia cancer group. Univariate and multivariate analyses were performed to examine differences between groups. The competitive risk model was made to compare the association with cardia cancer and non-cardia cancer about the causes of death. Propensity score matching (PSM) was performed to reduce the bias. Results: We found that cardia cancer was more common in male patients and the White than that in non-cardia cancer at early stage, signet ring cell carcinoma was more common in non-cardia cancer, and the differentiation of non-cardia cancer was worse. Univariate analysis showed that age, marital status, race, tumor location, histology, grade, stage, and operation or not can determine the prognosis. And the prognosis of patients with cardia cancer was worse than that of non-cardia cancer, according to lymph node metastasis and the depth of tumor invasion. Multivariate analysis showed cardia cancer was an independent prognostic factor for poor prognosis. After PSM, cardia cancer still exhibited poor prognosis. Conclusions: At early stage, cardia cancer had a poor prognosis compared with non-cardia cancer. The prevention and treatment of early cardia cancer need to be seriously treated.

Breast metastasis from EGFR/ALK negative lung adenocarcinoma: A case report.

INTRODUCTION: Lung adenocarcinoma is the most common type of lung cancer. Distant metastasis of lung adenocarcinoma often occurs in multiple organs. The common metastasis sites of lung cancer include the lungs, brain, bones, adrenal glands, and lymph nodes; however, breast metastasis is rare. PATIENT CONCERNS: In this report, we describe a case of breast metastasis from lung adenocarcinoma. A 55-year-old woman reported left breast pain for more than 1 month. DIAGNOSIS: Based on imaging, pathological examination, and immunohistochemical examination, the diagnosis of breast metastasis from lung adenocarcinoma was confirmed. Epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement were not detected by next-generation sequencing. INTERVENTIONS: The patient was treated with six courses of a combination of albumin-bound paclitaxel, cisplatin, and bevacizumab over 21 days. OUTCOMES: After six cycles of palliative chemotherapy, her left breast pain and swelling subsided; in addition, her serum CA12-5, CYFRA, and CEA levels normalized by April 2019. PR status was evaluated as per the RECIST 1.1 criteria. The patient developed brain metastases 3 months later and died due to multiple organ failure. CONCLUSION: The possibility of breast metastasis should be considered in patients with existing malignant tumors and breast pain. Clinical and imaging examinations are helpful for diagnosis, and pathological and immunohistochemical analyses are the most important diagnostic tools.

A new clinical prognostic nomogram for liver cancer based on immune score.

BACKGROUND: Increased attention is being paid to the relationship between the immune status of the tumor microenvironment and tumor prognosis. The application of immune scoring in evaluating the clinical prognosis of liver cancer patients has not yet been explored. This study sought to clarify the association between immune score and prognosis and construct a clinical nomogram to predict the survival of patients with liver cancer. METHODS: A total of 346 patients were included in our analysis datasets downloaded from The Cancer Genome Atlas (TCGA) dataset. A Cox proportional-hazards regression model was used to estimate the adjusted hazard ratios (HRs). A nomogram was built based on the results of multivariate analysis and was subjected to bootstrap internal validation. The predictive accuracy and discriminative ability were measured by the concordance index (C-index) and the calibration curve. Through the functional analysis of differential expression of genes with different immune scores, the target genes were screened out. RESULTS: In comparison with patients with low immune scores, those with intermediate and high immune scores had significantly improved survival time [HR and 95% confidence interval (CI): 0.54 (0.30-0.97) and 0.51 (0.27-0.97), respectively]. The C-index for survival time prediction was 0.66 (95% CI: 0.60-0.71). The calibration plot for the probability of survival at three or five years showed good agreement between prediction by the nomogram and actual observations. The top 10 hub genes were CXCL8(chemokine (C-X-C motif) ligand 8), SYK(spleen tyrosine kinase), CXCL12(chemokine (C-X-C motif) ligand 12), CXCL10 (chemokine (C-X-C motif) ligand10), CXCL1(chemokine (C-X-C motif) ligand1), CCL5(chemokine (C-C motif) ligand 5), CCL20(chemokine (C-C motif) ligand 20), LCK, CXCL11(chemokine (C-X-C motif) ligand 11), CCR5(chemokine (C-C motif) receptor 5). More importantly, we found that the high expression of CXCL8 and CXCL1 were related to the prognosis. CONCLUSIONS: High and/or intermediate immune scores are significantly correlated with better survival time in patients with liver cancer. Moreover, nomograms for predicting prognosis may help to estimate the survival of patients. We also propose that CXCL8 and CXCL1 may be a potential therapeutic target for liver cancer treatment.

Methylation-Driven Genes Identified as Novel Prognostic Indicators for Thyroid Carcinoma.

BACKGROUND: Aberrant DNA methylation plays an crucial role in tumorigenesis through regulating gene expression. Nevertheless, the exact role of methylation in the carcinogenesis of thyroid cancer and its association with prognosis remains unclear. The purpose of this study is to explore the DNA methylation-driven genes in thyroid cancer by integrative bioinformatics analysis. METHODS: The transcriptome profiling data and DNA methylation data of thyroid cancer were downloaded from The Cancer Genome Atlas (TCGA) database. The methylmix R package was used to screen DNA methylation-driven genes in thyroid cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to annotate the function of methylation-driven genes. Univariate Cox regression analyses was performed to distinguish prognosis-related methylation-driven genes. Multivariate Cox regression analyses was utilized to build a prognostic multi-gene signature. A survival analysis was carried out to determine the individual prognostic significance of this multi-gene signature. RESULTS: A total of 51 methylation-driven genes were identified. The functional analysis indicated that these genes were significantly enriched in diverse biological processes (BP) and pathways related to the malignancy processes. Four of these genes (RDH5, TREM1, BIRC7, and SLC26A7) were selected to construct the risk evaluation model. Patients in the low-risk group had an conspicuously better overall survival (OS) than those in high-risk group (p < 0.001). The area under the receiver operating characteristic (ROC) curve for this model was 0.836, suggesting a good specificity and sensitivity. Subsequent survival analysis revealed that this four-gene signature served as an independent indicator for the prognosis of thyroid cancer. Moreover, the prognostic signature was well validated in a external thyroid cancer cohort. CONCLUSION: We identified methylation-driven genes in thyroid cancer with independent prognostic value, which may offer new insight into molecular mechanisms of thyroid cancer and provide new possibility for individualized treatment of thyroid cancer patients.

Treatment strategies for metastatic gastric cancer: chemotherapy, palliative surgery or radiotherapy?

Aim: This study explored whether chemotherapy combined with palliative surgery and/or radiotherapy is a possible treatment for metastatic gastric cancer. Materials & methods: Patients were divided into groups according to treatments. COX models were used to explore prognostic factors. Kaplan-Meier models and log-rank tests were used to analyze outcomes. Outcomes were analyzed before and after propensity score matching. Results: Chemotherapy combined with gastrectomy or metastasectomy prolongs the survival time compared with chemotherapy alone (p < 0.05). Chemotherapy combined with gastrectomy plus metastasectomy and/or radiation therapy also prolongs the survival time (p < 0.05). Conclusion: Chemotherapy combined with gastrectomy could be a more effective treatment for metastatic gastric cancer. Chemotherapy combined with gastrectomy plus metastasectomy and/or radiation therapy could also be a promising treatment.

Omethoate induces pharyngeal cancer cell proliferation and G1/S cell cycle progression by activation of Akt/GSK-3ß/cyclin D1 signaling pathway.

Omethoate is a broad category of organophosphorous pesticides (OPs) and has toxic effects on human health under long-term, low-dose exposure. However, the role of omethoate in cancer development remains elusive. The incidence of global head and neck squamous cell carcinomas (HNSCC) has markedly increased in recent years. Thus, we examined whether omethoate induced the proliferation of FaDu cells (a cell line of HNSCC) and if so, what the underlying mechanism was. The study revealed that omethoate induced FaDu cell growth in a dose- and time-dependent manner. Omethoate stimulated FaDu cell proliferation was mainly due to enhancing the G1 to S phase transition by flow cytometry analysis. We also found that omethoate up-regulated cyclin D1, a key gene controlling the G1-S transition. Furthermore, we showed that omethoate was capable of activating the Akt/GSK-3ß signaling pathway. Blockage of Akt by siRNA or small molecule inhibitor significantly suppressed omethoate-induced cyclin D1 expression and cell proliferation. Collectively, these findings demonstrated for the first time that omethoate could induce the pharyngeal cancer cell proliferation by activation of the Akt/GSK-3ß/cyclin D1 signaling pathway.

Enhanced performance and microbial community analysis of bioelectrochemical system integrated with bio-contact oxidation reactor for treatment of wastewater containing azo dye.

Feasibility and superiority of the bioelectrochemical system integrated with biocontact oxidation (BES-BCO) for degradation and/or mineralization of azo dyes have been confirmed. In this study, the effects of hydraulic retention time (HRT), applied voltage, and dissolved oxygen (DO) concentration at the bioanode on the performance of BES-BCO and traditional BES were investigated. Using the response surface methodology, the optimum values of HRT, applied voltage, and DO concentration at the bioanode of BES-BCO were investigated to obtain the maximum decolouration and COD removal efficiency and minimum specific energy consumption (SEC). The microbial community structure in BES-BCO was studied for analyzing the change following the introduction of oxygen. The optimised solution was an applied voltage of 0.59V, HRT of 12h, and DO concentration of 0.96mg/L at the bioanode. Under such conditions, the DE, COD removal efficiency, and SEC values were 94.62±0.63%, 89.12±0. 32%, and 687.57±3.86J/g, respectively. In addition, after changing from BES to BES-BCO, the bacterial community structure of the bioanode underwent significant changes. Several aerobic aniline-degrading bacteria and anode-respiration bacteria (ARB) were found to dominate the community of the anode biofilm. The results showed that the removal of azo dye degradation by-products was closely correlated with the o-bioanode and the BCO bacterial community structure.

miR-125b regulates the drug-resistance of breast cancer cells to doxorubicin by targeting HAX-1.

MircroRNAs (miRNAs) are considered as essential regulators in the tumorigenesis and chemoresistance of multiple cancer types. In the present study, it was demonstrated that the expression levels of miR-125b were significantly downregulated in the tissues of patients with breast cancer (BC), as well as the BC cell lines in vitro. To study the association between chemoresistance and miR-125b in BC, doxorubicin (DOX)-resistant MCF-7 (MCF-7/R) cells were established, and gain- and loss-of-function experiments were performed. It was demonstrated that the overexpression of miR-125b increased the sensitivity of MCF-7/R cells to DOX. Furthermore, it was revealed that the sensitization of miR-125b mimics to DOX-induced cell death was regulated by the hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) vector and HAX-1 small interfering RNA. These results emphasized the notable function of miR-125b and its target of HAX-1 in regulating DOX-resistance. In addition, it was demonstrated that the miR-125b mimics promoted the loss of the mitochondrial membrane potential and the generation of reactive oxygen species induced by DOX treatment in MCF-7/R cells. These data suggest that the miR-125b-HAX-1-mitochondria pathway has a notable function in the treatment of DOX-resistant BC cells, which may provide a novel target for the chemotherapy of BC.

HES5 promotes cellular proliferation of non-small cell lung cancer through STAT3 signaling.

HES5 is a transcription factor activated downstream of the Notch pathway and regulates cell differentiation in multiple tissues. Disruption of its normal expression has been associated with developmental diseases and cancer. But its role in non-small cell lung cancer (NSCLC) remains elusive. Western blot analysis and immunohistochemistry assays demonstrated that HES5 expression was frequently increased in NSCLC tumor tissues and cell lines. Moreover, immunohistochemistry analysis revealed that upregulation of HES5 expression was positively correlated with a more invasive tumor phenotype and poor prognosis. Immunoprecipitation assay indicated that HES5 directly interacted with STAT3. In addition, depletion of HES5 resulted in inhibited phosphorylation of STAT3 and decreased expression of the downstream genes. In vitro studies, using serum starvation-refeeding experiment and HES5-siRNA transfection assay demonstrated that HES5 expression promoted proliferation of NSCLC cells, while HES5 knockdown caused growth arrest of cell cycle at G0/G1 phase, decreased rate of colony formation and alleviated cellular apoptosis. Taken together, out data have delineated that HES5 might contribute to the proliferation of NSCLC by STAT3 signaling.