Search

Herein, we used alkali metal to catalyze the hydroboration of amides, and hence provide a new route for the reduction of the amides. And we conducted a study of the mechanism of the reduction of primary amide by carrying out control experimental reactions.

False Base Station (FBS) attack has been a severe security problem for the cellular network since 2G era. During handover, the user equipment (UE) periodically receives state information from surrounding base stations (BSs) and uploads it to the source BS. The source BS compares the uploaded signal power and shifts UE to another BS that can provide the strongest signal. An FBS can transmit signal with the proper power and attract UE to connect to it. In this paper, based on the 3GPP standard, a Precheck Sequence-based Detection (PSD) Scheme is proposed to secure the transition of legal base station (LBS) for UE. This scheme first analyzes the structure of received signals in blocks and symbols. Several additional symbols are added to the current signal sequence for verification. By designing a long table of symbol sequence, every UE which needs handover will be allocated a specific sequence from this table. The simulation results show that the performance of this PSD Scheme is better than that of any existing ones, even when a specific transmit power is designed for FBS.

Cervical neuroblastic tumors (NTs) are rare but less aggressive cancer with an above-average survival rate. Little has been published regarding the management and surgical outcomes of patients with cervical NTs based on pathology category. This study compared and identified the preoperative characteristics of cervical NTs in different pathology categories and evaluated the outcomes of patients undergoing surgical resection.Upon the institutional review board's approval, a retrospective chart review was performed at Beijing Children's Hospital from April 2013 to August 2020. Demographics of patients, imaging data, lab test results, operation details and outcomes were recorded and analyzed.Of 32 cervical NTs, 24(80%) were classified as neuroblastoma (NB) /ganglioneuroblastoma-nodular (GNBn) and 8(20%) as ganglioneuroblastoma-intermixed (GNBi)/ ganglioneuroma (GN). Patients with GNBi/GN were older than those with NB/GNBn (44.5 months (IQR 16-81) vs 9 months (IQR 1-47); P = 0.001). GNBi/GN patients presented more frequently with stage 1 disease compared with NB/GNBn patients (100% vs. 29.2%, P = 0.001), less frequently with tumor-related symptoms (0% vs. 70.8%, P = 0.001), artery encased tumor (0% vs. 41.7%, P = 0.035), and surgical complications (25% vs. 70.8%, P = 0.038). GNBi/GN patients were also less likely to show elevated neuron specific enolase (NSE) (12.5% vs. 79.2%, P = 0.002).Cervical NB/GNBn and GNBi/GN patients had distinct characteristic clinical presentations and surgical outcomes. For children with features suggestive of benign disease (older age, asymptomatic, normal serum tumor markers) and no artery image-defined risk factors (IDRFs), upfront resection can be considered.

Manli Li,1 Xiaoli Ma,1 Chendi Mai,1 Zhiru Fan,1 Yangyang Wang,2 Yankai Ren1 1Department of Physiology, Sanquan College of Xinxiang Medical University, Xinxiang, People’s Republic of China; 2Ningxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical University, Yinchuan, People’s Republic of ChinaCorrespondence: Yankai Ren, Department of Physiology, Sanquan College of Xinxiang Medical University, Xinxiang, People’s Republic of China, Email renyankai@sqmc.edu.cn Yangyang Wang, Ningxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical University, Yinchuan, People’s Republic of China, Email yang1275990@163.comObjective: In order to determine research hotspots and prospective directions, this work used VOSviewer and CiteSpace to assess the current state of insular epilepsy research.Methods: We looked for pertinent research about insular epilepsy published between the first of January 2000 and the thirtieth of April 2022 in the Web of Science Core Collection (WoSCC) database. CiteSpace and VOSviewer were used to build a knowledge atlas by analyzing authors, institutions, countries, keywords with citation bursts, keyword clustering, keyword co-occurrence, publishing journals, reference co-citation patterns, and other factors.Results: A total of 305 publications on insular epilepsy were found. Nguyen DK had the most articles published (37), whereas Mauguière F and Isnard J had the highest average number of citations/publications (39.37 and 38.09, respectively). The leading countries and institutions in this field were the United States (82 papers) and Université de Montréal (40 papers). Authors, countries, and institutions appear to be actively collaborating. Hot topics and research frontiers included surgical treatment, functional network connectivity, and the application of neuroimaging methods to study insular epilepsy.Conclusion: In summary, the most influential articles, authors, journals, organizations, and countries on the subject of insular epilepsy were determined by this analysis. This study investigated the area of insular epilepsy research and forecasted upcoming trends using co-occurrence and evolution methods.Keywords: visualization analysis, insular epilepsy, CiteSpace, VOSviewer, bibliometrics

Objective. Gastroesophageal adenocarcinoma (GEA) is a high deadly and heterogeneous cancer. RNA N6-methyladenosine (m6A) modification plays a non-negligible role in shaping individual tumour microenvironment (TME) characterizations. However, the landscape and relationship of m6A modification patterns and TME cell infiltration features remain unknown in GEA. Methods. In this study, we examined the TME of GEA using assessments of the RNA-sequencing data focusing on the distinct m6A modification patterns from the public databases. Intrinsic patterns of m6A modification were evaluated for associations with clinicopathological characteristics, underlying biological pathways, tumour immune cell infiltration, oncological outcomes, and treatment responses. The expression of key m6A regulators and module genes was validated by qRT-PCR analysis. Results. We identified two distinct m6A modification patterns of GEA (cluster 1/2 subgroup), and correlated two subgroups with TME cell-infiltrating characteristics. Cluster 2 subgroup correlates with a poorer prognosis, downregulated PD-1 expression, higher risk scores, and distinct immune cell infiltration. In addition, PPI and WGCNA network analysis were integrated to identify key module genes closely related to immune infiltration of GEA to find immunotherapy markers. COL4A1 and COL5A2 in the brown module were significantly correlated to the prognosis, PD-1/L1 and CTLA-4 expression of GEA patients. Finally, a prognostic risk score was constructed using m6A regulator-associated signatures that represented an independent prognosis factor for GEA. Interestingly, COL5A2 expression was linked to the response to anti-PD-1 immunotherapy, m6A regulator expression, and risk score. Conclusion. Our work identified m6A RNA methylation regulators as an important class of players in the malignant progression of GEA and were associated with the complexity of the TME. COL5A2 may be the potential biomarker which contributes to predicting the response to anti-PD-1 immunotherapy and patients’ prognosis.

Nitrogen-rich compounds have attracted significant fundamental and practical interest owing to their ability to accommodate diverse nitrogen-bonding patterns and their feasibility as high-energy-density materials. Herein, we examine a wide range of chemical compositions in the compressed Ga-N system using first-principles structural search and experimental preparation using a laser-heated diamond anvil cell. Our investigations have theoretically identified three thermodynamically stable stoichiometries─GaN

Trimethylamine N-oxide (TMAO) and phenylacetylglutamine (PAGln) are associated with acute myocardial infarction (AMI) and type 2 diabetes mellitus (T2DM). This study developed and validated a simple method firstly for simultaneously quantifying serum TMAO and PAGln using liquid chromatography-tandem mass spectrometry (LC-MS/MS).Serum samples from patients with T2DM, AMI, and healthy subjects were analyzed using a new LC-MS/MS method to evaluate TMAO and PAGln levels. Statistical analyses were performed to evaluate TMAO and PAGln distributions among different groups.Retention and separation of the two metabolites were achieved within 5 min. For both analytes, the assay was linear in a 0.02-10 µg/mL range, with 0.99 average linear correlation coefficients, and quantification limit values of approximately 0.010 µg/mL. The average recoveries of TMAO and PAGln were 96.3 % and 96.4 %, respectively. The intra-run and total coefficient variations were 3.5-4.8 % and 3.9-5.7 % respectively for TMAO; and 4.0-5.1 % and 4.6-6.3 % respectively for PAGln. TMAO and PAGln showed a moderate correlation (P 0.001) and their levels in patients with T2DM were significantly higher than those in healthy individuals (P 0.001). TMAO levels were higher in patients with T2DM than in patients with AMI (P 0.01). Patients with AMI had higher PAGln levels than healthy individuals (P 0.05). After adjusting for sex and age, the top tertile of PAGln was positively correlated with T2DM and AMI while that of TMAO was positively correlated with T2DM.Overall, a robust isotope dilution LC-MS/MS method was established, which may be beneficial for assessing the association between two metabolites with AMI and T2DM.

Objectives Measurement of the serum levels of vitamin B12 (VB12) is key for evaluating VB12 deficiency-dependent anemia. Immunoassay, the major method for determining VB12, tends to give false-normal results because of the presence of anti-intrinsic factor (IF-Ab) or other factors such as heterophilic antibodies et al. This study aimed to develop a liquid chromatography tandem mass spectrometry (LC-MS/MS) method that is helpful for distinguish false normal VB12 results measured by the immunoassay. Methods Different forms of VB12 were derivatized into CN-B12, which was collected through solid-phase extraction and analyzed via LC-MS/MS. 236 serum samples were measured both by LC-MS/MS and immunoassay, results were compared, and the IF-Ab effect was evaluated. Results The LC-MS/MS assay afforded a linear slope from 20 to 4,000 pmol/L for CN-B12. OH-VB12, methyl-VB12, and CoA-VB12 showed recovery within 89.3–109.5%. The intra-assay CV of VB12 was 2.6–4.1%, whereas the total CV was 9.3–9.8%. Passing–Bablok regression between LC-MS/MS and immunoassay results showed that the slope was 1.085 and the intercept was −15.691. The Bland–Altman plot showed that the mean difference and difference% were −34.6 pmol/L and 0.3%, respectively. Inter-rater agreement analysis showed that the linear weighted kappa value was 0.885, implying good agreement between the two methods. However, two samples were falsely elevated and one sample was falsely normal in the immunoassay compared with LC-MS/MS. The LC-MS/MS method helped in the distinction of false-normal VB12 results shown by the immunoassay. Conclusions The VB12 LC-MS/MS method can be used as an arbiter of clinically discordant immunoassay results.

HBV nucleos(t)ide reverse transcriptase inhibitors (NrtIs) do not completely suppress HBV replication. Previous reports indicate persistent viremia during NrtI treatment despite HBV DNA being undetectable. HBV core inhibitors may enhance viral suppression when combined with NrtIs. This phase II trial (NCT03576066) evaluated the efficacy and safety of the investigational core inhibitor, vebicorvir (VBR), in virologically- suppressed patients on NrtIs.Non-cirrhotic, NrtI-suppressed patients with chronic HBV were randomised to VBR 300 mg once daily or matching placebo (PBO) for 24 weeks. Treatment was stratified by hepatitis B e antigen (HBeAg) status. The primary endpoint was change from Baseline in serum HBeAg or hepatitis B surface antigen (HBsAg) after 24 weeks.Of 73 patients enrolled, 47 were HBeAg positive and 26 were HBeAg negative. In HBeAg-positive and -negative patients, there were no differences in the change from Baseline at Week 24 for HBsAg or HBeAg. Using a novel, high-sensitivity assay to detect HBV DNA, a greater proportion of patients with detectable HBV DNA at Baseline achieved undetectable HBV DNA at Week 24 in the VBR+NrtI vs. PBO+NrtI group. In HBeAg-positive patients, a greater change from Baseline in HBV pregenomic (pg)RNA was observed at Week 24 with VBR+NrtI vs. PBO+NrtI. Treatment-emergent adverse events (TEAEs) in VBR+NrtI patients included upper respiratory tract infection, nausea, and pruritus. No serious adverse events, Grade 4 TEAEs, or deaths were reported.In this 24-week study, VBR+NrtI demonstrated a favourable safety and tolerability profile. While there were no significant changes in viral antigen levels, enhanced viral suppression was demonstrated by greater changes in DNA and pgRNA with the addition of VBR compared to NrtI alone.NCT03576066.Core inhibitors represent a novel approach for the treatment of chronic hepatitis B virus (HBV) infection, with mechanisms of action distinct from existing treatments. In this study, vebicorvir added to existing therapy reduced HBV replication to a greater extent than existing treatment and was generally safe and well tolerated.

The Chinese medicine of Cannabis sativa fruit is called “Hemp Seed” or “Cannabis Kernel.” It is calm, sweet, and has the function of moistening the intestines and treating dry stool. The flower is called “Ma Bo,” and it treats evil wind, amenorrhea, and forgetfulness. After the extraction of active ingredient from Cannabis sativa, its treatment activity against acute coronary artery was determined and the detailed mechanism was also examined. First of all, ELISA was exploited to investigate the release of inflammatory cytokines in plasma. After that, via utilizing real time RT-PCR, the activation for the signaling pathway of NF-κB existing in endothelial cell could be identified after the specific treatment. For the Cannabis sativa, its complete chloroplast genome was analyzed through Illumina pair-end sequencing. According to neighbor-joining (NJ) phylogenetic analysis, the Humulus lupulus and Cannabis sativa come together and become the sisters of other associated species.

Objective. Esophageal squamous-cell carcinoma (ESCC) is an aggressive malignant tumor, accounting for more than 90% of esophageal cancers. However, treatments such as surgical resection, radiotherapy, and chemotherapy are unable to achieve ideal clinical outcomes. The purpose of this study was to explore the effects of COQ10B on proliferation, apoptosis, migration, and invasion of esophageal squamous-cell carcinoma (ESCC) cells. Methods. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of COQ10B in ESCC and normal tissues and in ESCC cell lines (KYSE-150 and TE-1). MTT assay and flow cytometry were applied to investigate the effects of COQ10B shRNA lentivirus (LV-shCOQ10B) on ESCC cell proliferation and apoptosis, respectively. The effect of COQ10B silencing on ESCC cell migration and invasion was determined by wound healing assay and transwell invasion assay, respectively. Results. The expression of COQ10B mRNA in ESCC tissues was higher than that in surrounding tissues. The decreased COQ10B level in KYSE-150 and TE-1 cells by LV-shCOQ10B could inhibit cell proliferation, promote cell apoptosis, and reduce the ability of invasion and migration (all P < 0.05 ). Conclusion. COQ10B was highly expressed in human ESCC tissues. COQ10B silencing contributed to the inhibition of proliferation, invasion, and migration of ESCC cells and the promotion of cell apoptosis, suggesting COQ10B may be a potential molecular target for the diagnosis and treatment of ESCC.

The paper constructs an evolutionary game model on dynamic alliance of engineering project and analyzes the process of the game. Finally, it is concluded that the expected return, risk and alliance resources are the important factors that affect dynamic alliance of engineering project. On the basis, a solution of dynamic alliance is proposed to accelerate the development of the construction.

Background Regular sleep is very important for human health; however, the short-term and long-term effects of nightshift with sleep deprivation and disturbance on human metabolism, such as oxidative stress, have not been effectively evaluated based on a realistic cohort. We conducted the first long-term follow-up cohort study to evaluate the effect of nightshift work on DNA damage. Methods We recruited 16 healthy volunteers (aged 33 ± 5 years) working night shifts at the Department of Laboratory Medicine at a local hospital. Their matched serum and urine samples were collected at four time points: before, during (twice), and after the nightshift period. The levels of 8-oxo-7,8-dihydroguanosine (8-oxoG) and 8-oxo-7,8-dihydro-2’-deoxyguanosine (8-oxodG), two important nucleic-acid damage markers, were accurately determined based on a robust self-established LC‒MS/MS method. The Mann–Whitney U or Kruskal–Wallis test was used for comparisons, and Pearson’s or Spearman’s correlation analysis was used to calculate the correlation coefficients. Results The levels of serum 8-oxodG, estimated glomerular filtration rate-corrected serum 8-oxodG, and the serum-to-urine 8-oxodG ratio significantly increased during the nightshift period. These levels were significantly higher than pre-nightshift work level even after 1 month of discontinuation, but no such significant change was found for 8-oxoG. Moreover, 8-oxoG and 8-oxodG levels were significantly positively associated with many routine biomarkers, such as total bilirubin and urea levels, and significantly negatively associated with serum lipids, such as total cholesterol levels. Conclusion The results of our cohort study suggested that working night shifts may increase oxidative DNA damage even after a month of discontinuing nightshift work. Further studies with large-scale cohorts, different nightshift modes, and longer follow-up times are needed to clarify the short- and long-term effects of night shifts on DNA damage and find effective solutions to combat the negative effects.

Background Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, which is highly prone to bone marrow (BM) metastasis. BM can monitor early signs of mild disease and metastasis. Existing biomarkers are insufficient for the diagnosis and treatment of NB. Bromodomain PHD finger transcription factor (BPTF) is an important subunit of the chromatin-remodeling complex that is closely associated with tumors. Here, we evaluated whether BPTF in BM plays an important role in predicting NB progression, and explore the molecular mechanism of BPTF in NB. Methods The clinical relevance of the BPTF was predicted in the GEO (GSE62564) and TARGET database. The biological function of BPTF in NB was investigated by constructing cell lines and employing BPTF inhibitor AU1. Western blot was used to determine the changes of BPTF, TFAP4, PI3K/AKT signaling and Epithelial-mesenchymal transition (EMT) related markers. A total of 109 children with newly diagnosed NB in Beijing Children's Hospital from January 2018 to March 2021 were included in this study. RT-PCR was used to measure the BPTF and TFAP4 expression in BM. The cut-off level was set at the median value of BPTF expression levels. Results Databases suggested that BPTF expression was higher in NB and was significantly associated with stage and grade. Proliferation and migration of NB cells were slowed down when BPTF was silenced. Mechanistically, TFAP4 could positively regulate BPTF and promotes EMT process through activating the PI3K/AKT signaling pathway. Moreover, detection of the newly diagnosed BM specimens showed that BPTF expression was significantly higher in high-risk group, stage IV group and BM metastasis group. Children with high BPTF at initial diagnosis were considered to have high risk for disease progression and recurrence. BPTF is an independent risk factor for predicting NB progression. Conclusions A novel and convenient BPTF-targeted humoral detection that can prompt minimal residual and predict NB progression in the early stages of the disease were identified. BPTF inhibitor AU1 is expected to become a new targeted drug for NB therapy. It’s also reveal previously unknown mechanisms of BPTF in NB cell proliferation and metastasis through TFAP4 and PI3K/AKT pathways.

Background To summarize the characteristics and treatment, and analyze the prognosis of large number of infants with retinoblastoma (RB) in China through a multicenter, 10-year retrospective analysis. Methods The data of RB infants were collected from multiple centers. The characteristics and survival prognosis were analyzed. The overall survival (OS) rate was estimated by the Kaplan–Meier method. Multivariate Cox survival analysis was to evaluate the independent risk factors affecting the prognosis of RB infants. Results A total of 373 RB infants (202 boys and 171 girls) were included, the median age was 6.22 months (10 days to 11.93 months). The median follow-up time of RB infants was 18.4 (1.02–122.81 months). After excluding the lost to follow-up cases, the OS rate was 97.7% (345/353). Kaplan–Meier survival analysis indicated that 9 cases died and the median survival time was not reached. Univariate analysis of prognostic factors revealed eye affected, presenting signs, left eye stage and recurrence to be poor prognostic factors for OS rate in RB infants (all P P = 0.048) was an independent factor for prognosis of infants with RB. The median survival time of infants underwent chemotherapy + intra-arterial chemotherapy (IAC) + enucleation + vitrectomy was the longest than other treatments (n = 9, 47.64 months, OS = 100%, all P Conclusion Recurrence is an independent factor for prognosis of RB infants, which still needs attention after treatment. Early screening, comprehensive treatments and follow-up of patients may lead to improvements of prognosis of RB infants.

Excessive phosphate content input into natural water can lead to the waste of resource and eutrophication. Biochar is a kind of low-cost adsorbents. However, its adsorption capacity for phosphate is low. In order to solve this problem, Fe compounds modified fly ash/cotton stalk biochar composites (Fe-FBC) were prepared through co-pyrolyzed fly ash and cotton stalk at 800oC, followed by infiltration of FeSO4 solution. The samples were characterized by Scanning electron microscopy, Brunauer-Emmett-Teller, X-ray diffraction, Fourier-transform infrared spectroscopy, and zeta potential. After modification, the hydrophilicity and polarity of Fe-FBC increased. In addition, the pore volume, specific surface area, and surface functional groups were significantly improved. The adsorption process of Fe-FBC for phosphate in water can be well fitted by the pseudo-second-order kinetic and Sips isotherm adsorption model, with a maximum adsorption capacity of 47.91 mg/g. Fe-FBC maintained a high adsorption capacity in the pH range of 3–10. The coexisting anions (NO3-, SO42-, and Cl-) had negligible effects on phosphate adsorption. The adsorption mechanisms of Fe-FBC include electrostatic attraction, ligand exchange, surface complexation, ion exchange, chemical precipitation and hydrogen bonding. Moreover, the desorption dynamic process of phosphate was investigated, indicating that the phosphate-saturated Fe-FBC could use as slow-release phosphate fertilizer. This study proposed a potentially environmental protection and recycling economy approach, which consists of recycling resources and treating wastes with wastes.

Stem-cell-based therapy is very promising for Alzheimer’s disease (AD), yet has not become a reality. A critical challenge is the transplantation microenvironment, which impacts the therapeutic effect of stem cells. In AD brains, amyloid-beta (Aβ) peptides and inflammatory cytokines continuously poison the tissue microenvironment, leading to low survival of grafted cells and restricted efficacy. It is necessary to create a growth-supporting microenvironment for transplanted cells. Recent advances in AD studies suggest that the asparaginyl endopeptidase (AEP) is a potential intervention target for modifying pathological changes. We here chose APP/PS1 mice as an AD model and employed pharmacological inhibition of the AEP for one month to improve the brain microenvironment. Thereafter, we transplanted neural stem cells (NSCs) into the hippocampus and maintained therapy for one more month. We found that inhibition of AEPs resulted in a significant decrease of Aβ, TNF-α, IL-6 and IL-1β in their brains. In AD mice receiving NSC transplantation alone, the survival of NSCs was at a low level, while in combination with AEP inhibition pre-treatment the survival rate of engrafted cells was doubled. Within the 2-month treatment period, implantation of NSCs plus pre-inhibition of the AEP significantly enhanced neural plasticity of the hippocampus and rescued cognitive impairment. Neither NSC transplantation alone nor AEP inhibition alone achieved significant efficacy. In conclusion, pharmacological inhibition of the AEP ameliorated brain microenvironment of AD mice, and thus improved the survival and therapeutic efficacy of transplanted stem cells.

Background: A historical controlled study method to compare the effectiveness of laser engraved personalized nasal cannula fixation devices with conventional cut nasal patches for fixing nasogastric tubes after esophageal cancer surgery. Methods: One hundred and twenty-four patients with indwelling nasal catheters for esophageal cancer surgery in a tertiary care hospital in Lanzhou were selected as study subjects and divided into control and observation groups according to the historical control study method, with 62 patients in each group. The control group used conventionally cut nasal patches to fix the nasal ducts, and the observation group used laser-engraved personalized nasal patches to fix the nasal ducts. The rate of catheter displacement or slippage under the fixation device, the number of rolled edges and replacement of nasal patches, nasal medical device related pressure injury and pre-injury condition, medical adhesive related skin injury, and patient comfort condition were observed in both groups. Results: The rate of nasal catheter displacement in the observation group was lower than that in the control group (P < 0.05). The number of rolled edges and replacement of nasal patches in the observation group were lower than those in the control group (P < 0.05). The incidence of nasal mucosal indentation, nasal pain, and medical adhesive-related skin lesions in the observation group was lower than that in the control group (P < 0.05). The physiological level of comfort of patients in the observation group was better than that in the control group (P < 0.05). Conclusion: Laser engraved personalized nasal cannula fixation devices have better clinical value than conventional cut nasal patches. It can reduce the incidence of clinical nasal catheter displacement, the frequency of rolled edges and replacement of nasal patches, reduce the incidence of nasal medical device related pressure injuries and medical adhesive related skin injuries, and increase patient comfort.

Background: Immunotherapy has brought new hope to gastric cancer (GC) patients. Exploring the immune infiltration pattern in GC and the key molecules is critical for optimizing the efficacy of immunotherapy. Aldo-keto reductase family 1 member B10 (AKR1B10) is an inflammatory regulator and is closely related to the prognosis of patients with GC. However, the function of AKR1B10 in GC remains unclear. Methods: In this study, the CIBERSORT algorithm was used to analyze the immune infiltration pattern in 373 samples in the Cancer Genome Atlas (TCGA) database. Differentially expressed genes (DEGs) were seared by combing the TCGA database and the Gene Expression Omnibus (GEO) database, and the key molecule AKR1B10 was identified by weighted gene coexpression network analysis (WGCNA). The biological functions of AKR1B10 in stomach adenocarcinoma (STAD) were investigated in vitro. Results: Macrophage polarization was the main immune infiltration pattern in GC, and the state of macrophage polarization was closely related to the pathological grading of GC and the clinical stage of patients. AKR1B10, MUC5AC, TFF2, GKN1, and PGC were significantly downregulated in GC tissues. Low AKR1B10 expression induced M2 macrophage polarization and promoted the malignant phenotype of GC. Conclusion: M2 macrophage polarization is the main immune infiltration pattern in GC. Low AKR1B10 expression induces M2 macrophage polarization and promotes the malignant transformation of GC.

Background Helicobacterpylori (H. pylori) infection causes aberrant DNA methylation and contributes to the risk of gastric cancer (GC). Guanine nucleotide-binding protein subunit beta-4 (GNB4) is involved in various tumorigenic processes. We found an aberrant methylation level of GNB4 in H. pylori-induced GC in our previous bioinformatic analysis; however, its expression and underlying molecular mechanisms are poorly understood. Methods The expression, underlying signaling pathways, and clinical significance of GNB4 were analyzed in a local cohort of 107 patients with GC and several public databases. H. pylori infection was induced in in vitro and in vivo models. Methylation-specific PCR, pyrosequencing, and mass spectrometry analysis were used to detect changes in methylation levels. GNB4, TET1, and YAP1 were overexpressed or knocked down in GC cell lines. We performed gain- and loss-of-function experiments, including CCK-8, EdU, colony formation, transwell migration, and invasion assays. Nude mice were injected with genetically manipulated GC cells, and the growth of xenograft tumors and metastases was measured. Real-time quantitative PCR, western blotting, immunofluorescence, immunohistochemistry, chromatin immunoprecipitation, and co-immunoprecipitation experiments were performed to elucidate the underlying molecular mechanisms. Results GNB4 expression was significantly upregulated in GC and correlated with aggressive clinical characteristics and poor prognosis. Increased levels of GNB4 were associated with shorter survival times. Infection with H. pylori strains 26695 and SS1 induced GNB4 mRNA and protein expression in GC cell lines and mice. Additionally, silencing of GNB4 blocked the pro-proliferative, metastatic, and invasive ability of H. pylori in GC cells. H. pylori infection remarkably decreased the methylation level of the GNB4 promoter region, particularly at the CpG#5 site (chr3:179451746–179451745). H. pylori infection upregulated TET1 expression via activation of the NF-κB. TET binds to the GNB4 promoter region which undergoes demethylation modification. Functionally, we identified that GNB4 induced oncogenic behaviors of tumors via the Hippo–YAP1 pathway in both in vitro and in vivo models. Conclusions Our findings demonstrate that H. pylori infection activates the NF-κB-TET1-GNB4 demethylation-YAP1 axis, which may be a potential therapeutic target for GC.

BackgroundMulberry (Morus alba) fruits of the woody mulberry tree (family: Moraceae Morus) is a type of mulberry fruit grown in the southern Xinjiang region,which polysaccharides have antioxidant and liver protective effects.This article further preliminary study on the protective effects of mulberry polysaccharide (MP) on liver.MethodsA detection kit was used to assess serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver malondialdehyde (MDA), superoxide dismutase (SOD) and other indicators. Liver tissue sections were stained with hematoxylin and eosin (H&E) and observed under a microscope. The entire endogenous metabolite profiling was acquired via metabolomics strategy using gas chromatography-mass spectrometry (GC-MS) to assess the underlying protective mechanisms of MPs. ResultsResults indicated that MPs exerted a hepatoprotective effect on acute liver injury by decreasing serum ALT and AST levels, hepatic MDA, and restored hepatic SOD glutathione peroxidase (GSH-Px) activities. A total of 33 possible endogenous metabolites associated with lipid, glucose, and energy metabolism including amino acids, sugars, and fatty acids, were found.Conclusions The results of the present study provide a reference for elucidating the protective mechanisms of MPs against acute liver injury.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), particularly eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), play a very important role in human health. Channel catfish (Ictalurus punctatus) is one of the leading freshwater aquaculture species in the USA, but has low levels of EPA and DHA compared to some fish such as salmon. To improve EPA and DHA content, a modification of the n-3 PUFA biosynthetic pathway was achieved through the insertion of an elovl2 transgene isolated from masu salmon (Oncorhynchus masou) driven by a carp β-actin promoter using a two-hit by gRNA and two oligos with a targeting plasmid (2H2OP) CRISPR/Cas9 approach. Integration rate of the transgene was high (37.5%) and detected in twelve different tissues of P

Supplementary Figure 3 from Identification of LIV1, a Putative Zinc Transporter Gene Responsible for HDACi-Induced Apoptosis, Using a Functional Gene Screen Approach

Data Supplement from Synergistic Killing Effect between Vorinostat and Target of CD146 in Malignant Cells

Supplementary Figure 1 from Identification of LIV1, a Putative Zinc Transporter Gene Responsible for HDACi-Induced Apoptosis, Using a Functional Gene Screen Approach

Histone deacetylase inhibitors (HDACi) show promise as a novel class of antitumoral agents and have shown the ability to induce apoptosis of tumor cells. To gain a better understanding of the action of HDACi, we conducted a functional gene screen approach named suppression of mortality by antisense rescue technique to identify the key genes responsible for the tumor-selective killing trichostatin A. Over 20 genes associated with HDACi-induced mortality were identified. One of the confirmed positive hits is LIV1, a putative zinc transporter. LIV1 is significantly induced by treatment with HDACi in a number of tumor cells, but not in normal cells. Knockdown of LIV1 suppressed apoptosis induced by HDACi in tumor cells. Although HDACi induced a slight increase in the free intracellular zinc concentration, knockdown of LIV1 significantly enhanced the intracellular zinc level, which was associated with resistance to apoptosis. On the other hand, pretreatment of the cells with a specific zinc chelator TPEN reversed the apoptosis resistance conferred by knockdown of LIV1. However, the biological effects of TPEN were abolished by addition of physiologic concentrations of zinc. Taken together, the present study identifies LIV1 as a critical mediator responsible for HDACi-induced apoptosis. The effect of LIV1 is, at least in part, mediated by affecting intracellular zinc homeostasis, which may be related to alteration of the catalytic activity of the Caspase 3 and expression of some BCL-2 family genes. As such, these findings highlight a novel mechanism underlying the action of HDACi that could be potentially useful in the clinical setting. [Mol Cancer Ther 2009;8(11):3108–16]

Supplementary Figure 5 from Identification of LIV1, a Putative Zinc Transporter Gene Responsible for HDACi-Induced Apoptosis, Using a Functional Gene Screen Approach

Purpose:Although histone deacetylase inhibitors (HDACi) are emerging as a new class of anticancer agents, one of the most significant concerns is that interactions with a wide array of substrates using these agents might initiate both therapeutic and undesired protective responses. Here, we sought to identify the potential protective reactions initiated by HDACi and determine whether targeting these reactions would enhance the antitumoral activity of HDACi.Experimental Design:Gene expression profiles were analyzed by cDNA microarray in Molt-4 cells before and after treatment of vorinostat. Induction of CD146 by vorinostat was examined in a wide range of tumors and nonmalignant cells. AA98, an anti-CD146 monoclonal antibody, was used to target CD146 function. Synergistic antitumoral and antiangiogenic effects between AA98 and vorinostat were examined both in vitro and in vivo. The potential effect of combined AA98 and vorinostat treatment on the AKT pathway was determined by Western blotting.Results:The induction of CD146 is a common phenomenon in vorinostat-treated cancer but not in nonmalignant cells. Targeting of CD146 with AA98 substantially enhanced vorinostat-induced killing via the suppression of activation of AKT pathways in cancer cells. Moreover, AA98 in combination with vorinostat significantly inhibited angiogenesis. In vivo, AA98 synergized with vorinostat to inhibit tumor growth and metastasis.Conclusion:The present study provided the first evidence that an undesired induction of CD146 could serve as a protective response to offset the antitumor efficacy of vorinostat. On the other hand, targeting CD146 in combination with vorinostat could be exploited as a novel strategy to more effectively kill cancer cells. Clin Cancer Res; 16(21); 5165–76. ©2010 AACR.

Supplementary Figure 2 from Identification of LIV1, a Putative Zinc Transporter Gene Responsible for HDACi-Induced Apoptosis, Using a Functional Gene Screen Approach

Supplementary Figure 4 from Identification of LIV1, a Putative Zinc Transporter Gene Responsible for HDACi-Induced Apoptosis, Using a Functional Gene Screen Approach

Background Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma with poor prognosis in children. The 5-year survival rate for early RMS has improved, whereas it remains unsatisfactory for advanced patients. Urine can rapidly reflect changes in the body and identify low-abundance proteins. Early screening of tumor markers through urine in RMS allows for earlier treatment, which is associated with better outcomes. Methods RMS patients under 18 years old, including those newly diagnosed and after surgery, were enrolled. Urine samples were collected at the time points of admission and after four cycles of chemotherapy during follow-up. Then, a two-stage workflow was established. (1) In the discovery stage, differential proteins (DPs) were initially identified in 43 RMS patients and 12 healthy controls (HCs) using a data-independent acquisition method. (2) In the verification stage, DPs were further verified as biomarkers in 54 RMS patients and 25 HCs using parallel reaction monitoring analysis. Furthermore, a receiver operating characteristic (ROC) curve was used to construct the protein panels for the diagnosis of RMS. Gene Ontology (GO) and Ingenuity Pathway Analysis (IPA) software were used to perform bioinformatics analysis. Results A total of 251 proteins were significantly altered in the discovery stage, most of which were enriched in the head, neck and urogenital tract, consistent with the most common sites of RMS. The most overrepresented biological processes from GO analysis included immunity, inflammation, tumor invasion and neuronal damage. Pathways engaging the identified proteins revealed 33 common pathways, including WNT/β-catenin signaling and PI3K/AKT signaling. Finally, 39 proteins were confirmed as urinary biomarkers for RMS, and a diagnostic panel composed of 5 candidate proteins (EPS8L2, SPARC, HLA-DRB1, ACAN, and CILP) was constructed for the early screening of RMS (AUC: 0.79, 95%CI = 0.66 ~ 0.92). Conclusions These findings provide novel biomarkers in urine that are easy to translate into clinical diagnosis of RMS and illustrate the value of global and targeted urine proteomics to identify and qualify candidate biomarkers for noninvasive molecular diagnosis.

Adipose tissue (AT) is considered as a regional immune organ and plays an important role in the anti-infection immune response. However, the function and mechanism of chicken AT in response to secondary immune response remain poorly understood. Here, we used mRNA and microRNA (miRNA) sequencing technology to survey the transcriptomic landscape of chicken abdominal adipose tissue (AAT) during the first and second immunization with Newcastle disease virus (NDV) vaccine, and carried out bioinformatics analysis, such as Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis, protein–protein interaction (PPI) analysis, and miRNA–mRNA integrated analysis. The results indicated that chicken AAT actively responded to the secondary immune response. DNA replication and cytoskeleton regulation as the regulatory functions of immune activation changed significantly, and weakened lipid metabolism was an effective strategy for the secondary immunity. Mechanically, the regulatory network between the differentially expressed miRNAs (DEMs) and their targeted differentially expressed genes (DEGs), such as miR-206/miR-499-5p-nuclear receptor subfamily 4 group A member 3 (NR4A3)/methylsterol monooxygenase 1 (MSMO1) pathway, was one of the potential key mechanisms by which AAT responded to the secondary immune response. In conclusion, regional immunity of chicken AT responds to secondary immunity by promoting immune activation and weakening lipid metabolism, and this study can instruct future research on antiviral strategy.