Ferrostatin­1 alleviates liver injury via decreasing ferroptosis following ricin toxin poisoning in rat.

Ricin is a highly toxic plant toxin that can cause multi-organ failure, especially liver dysfunction, and is a potential bioterrorism agent. Despite the serious public health challenge posed by ricin, effective therapeutic for ricin-induced poisoning is currently unavailable. Therefore, it is important to explore the mechanism of ricin poisoning and develop appropriate treatment protocols accordingly. Previous studies have shown that lipid peroxidation and iron accumulation are associated with ricin poisoning. Ferroptosis is an iron-dependent form of cell death caused by excessive accumulation of lipid peroxide. The role and mechanism of ferroptosis in ricin poisoning are unclear and require further study. We investigated the effect of ferroptosis on ricin-induced liver injury and further elucidated the mechanism. The results showed that ferroptosis occurred in the liver of ricin-intoxicated rats, and Ferrostatin­1 could ameliorate hepatic ferroptosis and thus liver injury. Ricin induced liver injury by decreasing hepatic reduced glutathione and the protein level of glutathione peroxidase 4 and Solute Carrier Family 7 Member 11, increasing iron, malondialdehyde and reactive oxygen species, and mitochondrial damage, whereas Ferrostatin­1 pretreatment increased hepatic reduced glutathione and the protein level of glutathione peroxidase 4 and Solute Carrier Family 7 Member 11, decreased iron, malondialdehyde, and reactive oxygen species, and ameliorated mitochondrial damage, thereby alleviated liver injury. These results suggested that ferroptosis exacerbated liver injury after ricin poisoning and that inhibition of ferroptosis may be a novel strategy for the treatment of ricin poisoning.

DNA-induced assembly of biocatalytic nanocompartments for sensitive and selective aptasensing of aflatoxin B1.

Enzyme cascade with high specificity and catalytic efficiency has significant applications for developing efficient bioanalysis methods. In this work, a sensitive and selective aptasensor was constructed based on the DNA-induced assembly of biocatalytic nanocompartments. Different from the conventional co-immobilization in one pot, the cascade enzymes of glucose oxidase (GOX) and horseradish peroxidase (HRP) were separately encapsulated in ZIF-90 nanoparticles. After conjugating complementary DNA or aptermer on enzyme@ZIF-90, DNA hybridization drove enzyme@ZIF-90 connected into clusters or linked on other DNA modified biocatalytic nanocompartment (such as invertase loaded Fe3O4@SiO2). Owing to the shortened distance between enzymes, the catalytic efficiency of connected clusters was significantly enhanced. However, the specifically interaction between the substrate molecule and aptermer sequence would lead to the disassembly of DNA duplexes, resulting in the gradual "switching-off" of cascade reactions. With aflatoxin B1 (AFB1) as the model substrate, the compartmentalized three-enzyme nanoreactors showed good analytical performance in the linear range from 0.01 ng mL-1 to 50 ng mL-1 with a low detection limit (3.3 pg mL-1). In addition, the proposed aptasensor was applied to detect AFB1 in corn oil and wheat powder samples with total recoveries ranging from 94 % to 109 %. As a result, this DNA-induced strategy for enzyme cascade nanoreactors opens new avenues for stimuli-responsive applications in biosensing.

Subintimal recanalization for non-acute occlusion of intracranial vertebral artery in an emergency endovascular procedure: A case report.

BACKGROUND: Endovascular recanalization of non-acute intracranial artery occlusion is technically difficult, particularly when the microwire enters the subintima. Although the subintimal tracking and re-entry technique has been well established in the endovascular treatment of coronary artery occlusion, there is limited experience with its use in intracranial occlusion due to anatomical variations and a lack of dedicated devices. CASE SUMMARY: A 74-year-old man was admitted to the hospital two days after experiencing acute weakness in both lower extremities, poor speech, and dizziness. After admission, imaging revealed acute ischemic stroke and non-acute occlusion of bilateral intracranial vertebral arteries (ICVAs). On the fourth day of admission, the patient's condition deteriorated and an emergency endovascular recanalization of the left ICVA was performed. During this procedure, a microwire was advanced in the subintima of the vessel wall and successfully reentered the distal true lumen. Two stents were implanted in the subintima. The patient's Modified Rankin Scale was 1 at three months postoperatively. CONCLUSION: We present a technical case of subintimal recanalization for non-acute ICVA occlusion in an emergency endovascular procedure. However, we emphasize the necessity for caution when applying the subintimal tracking approach in intracranial occlusion due to the significant dangers involved.

[Retracted] microRNA­363­3p inhibits cell growth and invasion of non­small cell lung cancer by targeting HMGA2.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the data shown for the Transwell cell migration and invasion assays in Figs. 2C and 4C were strikingly similar to data appearing in different form in another article by different authors at a different research institution. Owing to the fact that the contentious data in the above article were under consideration for publication elsewhere at a similar time to when it was submitted to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive any reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 2712­2718, 2018; DOI: 10.3892/mmr.2017.8131].

Molecule characterization of chemosensory and metabolism-related genes in the proboscis of Athetis lepigone.

Introduction: The moth species Athetis lepigone (Möschler) (Lepidoptera: Noctuidae), which has recently been identified as a pest of summer maize (Zea mays L.) in China, has demonstrated a rapid proliferation with in the Huang-Huai-Hai Plain region since its initial discovery in Hebei Province in 2005. It has become a prevalent pest of corn crops, and its ability to adapt quickly to its surroundings is currently being investigated. One of the key characteristics of its siphoning mouthparts is not only the feeding apparatus itself but also the chemosensory organs that enable the detection of chemical signals from the surrounding environment. However, there is a lack of comprehensive research on the genes responsible for chemosensory and metabolic mechanisms in the proboscises of male and female A. lepigone adults. Methods: In this study, we utilized transcriptome analysis to identify a total of fifty chemosensory genes from six distinct families, including 19 odorant-binding proteins (OBPs), 22 chemosensory proteins (CSPs), one co-receptor (Orco), six odorant receptors (ORs), four ionotropic receptors (IRs), and two sensory neuron membrane proteins (SNMPs) in the proboscis. Notably, seven OBPs, two CSPs, and one OR were discovered for the first time. Additionally, fourteen genes related to metabolism, including cytochrome P450 (CYPs) and carboxylesterases (CXEs), were also identified. Furthermore, a qualitative analysis was conducted on the relative transcript levels of eight related genes. The expression of 21 annotated chemosensory and metabolic genes was compared between A. lepigone adults and larvae using qRT-PCR, revealing tissue specificity. The majority of genes exhibited predominant expression in the antennae and proboscis during the adult stage, while showing slight expression in the combination of sixth-instar larval head oral appendages (maxilla, labium, and antenna) and pheromone gland-ovipositors of female adults. Results/discussion: Our study points to a new pest control strategies that these newly discovered genes have the potential to serve as targets for enhancing future pest control, including mating disruption and the use of food attractants. And it would be advantageous to ascertain the distribution of chemosensory gene expression and gain insights into the functionalities of these genes, thereby establishing a novel theoretical framework for the advancement of eco-friendly pesticides and efficient pest management strategies in the future.

Antibacterial Activity and Components of the Methanol-Phase Extract from Rhizomes of Pharmacophagous Plant Alpinia officinarum Hance.

The rhizomes of Alpinia officinarum Hance (known as the smaller galangal) have been used as a traditional medicine for over 1000 years. Nevertheless, little research is available on the bacteriostatic activity of the herb rhizomes. In this study, we employed, for the first time, a chloroform and methanol extraction method to investigate the antibacterial activity and components of the rhizomes of A. officinarum Hance. The results showed that the growth of five species of pathogenic bacteria was significantly inhibited by the galangal methanol-phase extract (GMPE) (p < 0.05). The GMPE treatment changed the bacterial cell surface hydrophobicity, membrane fluidity and/or permeability. Comparative transcriptomic analyses revealed approximately eleven and ten significantly altered metabolic pathways in representative Gram-positive Staphylococcus aureus and Gram-negative Enterobacter sakazakii pathogens, respectively (p < 0.05), demonstrating different antibacterial action modes. The GMPE was separated further using a preparative high-performance liquid chromatography (Prep-HPLC) technique, and approximately 46 and 45 different compounds in two major component fractions (Fractions 1 and 4, respectively) were identified using ultra-HPLC combined with mass spectrometry (UHPLC-MS) techniques. o-Methoxy cinnamaldehyde (40.12%) and p-octopamine (62.64%) were the most abundant compounds in Fractions 1 and 4, respectively. The results of this study provide data for developing natural products from galangal rhizomes against common pathogenic bacteria.

Comparative proteomics and secretomics revealed virulence, and coresistance-related factors in non O1/O139 Vibrio cholerae recovered from 16 species of consumable aquatic animals.

Vibrio cholerae can cause pandemic cholera in humans. The bacterium resides in aquatic environments worldwide. Identification of risk factors of V. cholerae in aquatic products is imperative for assuming food safety. In this study, we determined virulence-associated genes, cross-resistance between antibiotics and heavy metals, and genome fingerprinting profiles of non O1/O139 V. cholerae isolates (n = 20) recovered from 16 species of consumable aquatic animals. Secretomes and proteomes of V. cholerae with distinct genotypes and phenotypes were obtained by using two-dimensional gel electrophoresis (2D-GE) and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques. Comparative secretomic analysis revealed 4 common and 45 differential extracellular proteins among 20 V. cholerae strains, including 13 virulence- and 8 resistance-associated proteins. A total of 21,972 intracellular proteins were identified, and comparative proteomic analysis revealed 215 common and 913 differential intracellular proteins, including 22 virulence- and 8 resistance-associated proteins. Additionally, different secretomes and proteomes were observed between V. cholerae isolates of fish and shellfish origins. A number of novel proteins with unknown function and strain-specific proteins were also discovered in the V. cholerae isolates. SIGNIFICANCE: V. cholerae can cause pandemic cholera in humans. The bacterium is distributed in aquatic environments worldwide. Identification of risk factors of V. cholerae in aquatic products is imperative for assuming food safety. Non-O1/O139 V. cholerae has been reported to cause sporadic cholera-like diarrhea and bacteremia diseases, which indicates virulence factors rather than the major cholera toxin (CT) exist. This study for the first time investigated proteomes and secretomes of non-O1/O139 V. cholerae originating from aquatic animals. This resulted in the identification of a number of virulence and coresistance-related factors, as well as novel proteins and strain-specific proteins in V. cholerae isolates recovered from 16 species of consumable aquatic animals. These results fill gaps for better understanding of pathogenesis and resistance of V. cholerae, and also support the increasing need for novel diagnosis and vaccine targets against the leading waterborne pathogen worldwide.

Combining targeted sequencing and ultra-low-pass whole-genome sequencing for accurate somatic copy number alteration detection.

This study investigated the feasibility of combining targeted sequencing and ultra-low-pass whole-genome sequencing (ULP-WGS) for improved somatic copy number alteration (SCNA) detection, due to its role in tumorigenesis and prognosis. Cerebrospinal fluid and matched blood samples were obtained from 29 patients with brain metastasis derived from lung cancer. Samples were subjected to targeted sequencing (genomic coverage: 300 kb) and 2×ULP-WGS. The SCNA was detected by the CTLW_CNV, Control-FreeC, and CNVkit methods and their accuracy was analyzed. Eighteen tumor samples showed consistent SCNA results between the three methods, while a small fraction of samples resulted in different SCNA estimations. Further analysis indicated that consistency of SCNA highly correlated with the difference of baseline depth (normalized depth of regions without SCNA events) estimation between methods. Conflict Index showed that CTLW_CNV significantly improved the accuracy of SCNA detection through precise baseline depth estimation. CTLW_CNV combines targeted sequencing and ULP-WGS for improved SCNA detection. The improvement in detection accuracy is mainly due to a refined baseline depth estimation, guided by single-nucleotide polymorphism allele frequencies within the deeply sequenced region (targeted sequencing). This method is especially suitable for tumor samples with biased aneuploidy, a previously under-estimated genomic characteristic across different cancer types.

Screening key lncRNAs for human lung adenocarcinoma based on machine learning and weighted gene co-expression network analysis.

BACKGROUND: Lung adenocarcinoma (LUAD) accounts for a significant proportion of lung cancer and there have been few diagnostic and therapeutic targets for LUAD due to the lack of specific biomarker. The aim of this study was to identify key long non-coding RNAs (lncRNAs) for LUAD. METHODS: The lncRNA and mRNA expression profiles of a large group of patients with LUAD were obtained from The Cancer Genome Atlas (TCGA). The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified. The optimal diagnostic lncRNA biomarkers for LUAD were identified by using feature selection procedure and classification model. We established classification models including random forests, decision tree and support vector machine to distinguish LUAD and normal tissues. The lncRNAs-mRNAs co-expression networks and module identification were established by weighted gene co-expression network analysis (WGCNA). Functional annotation of pink and green modules was performed. The expression of selected DElncRNAs were validated by qRT-PCR. RESULTS: A total of 1364 DEmRNAs (468 down-regulated and 896 up-regulated mRNAs) and 260 DElncRNAs (88 down-regulated and 172 up-regulated lncRNAs) between LUAD and normal tissue were obtained. LANCL1-AS1, MIR3945HG, LINC01270, RP5-1061H20.4, BLACAT1, LINC01703, CTD-2227E11.1 and RP1-244F24.1 were identified as optimal diagnostic lncRNA biomarkers for LUAD. The area under curve (AUC) of the random forests model, decision tree model and SVM model were 0.999, 0.937 and 0.999, and the specificity and sensitivity of the three model were 98.3% and 99.8%, 93.2% and 99% and 100% and 98.4%, respectively. Co-expression networks analysis showed that RP11-389C8.2, CTD-2510F5.4 and TMPO-AS1 were co-expressed with 44, 242 and 241 mRNAs, respectively. Cell cycle, DNA replication and p53 signaling pathway were three significantly enriched pathways. The qRT-PCR results were consistent with our integrated analysis, generally. The GSE32863 and GSE104854 validation was consistent with our integrated analysis, generally. CONCLUSION: Our study identified eight DElncRNAs as potential diagnostic biomarkers of LUAD. Functional annotation of green module provided new evidences for exploring the precise roles of lncRNA in LUAD.

microRNA-363-3p inhibits cell growth and invasion of non­small cell lung cancer by targeting HMGA2.

Lung cancer is the second most common cancer and is the leading cause of cancer-related death worldwide. For decades, increasing evidence revealed that microRNAs may contribute to non­small cell lung cancer (NSCLC) carcinogenesis and progression and could provide novel therapeutic targets for treatments of patients with NSCLC. Accumulated studies indicate that microRNA (miR)­363­3p serves important roles in tumorigenesis and tumor development; however, the role of miR­363­3p in NSCLC is still unclear. The current study reported that miR­363­3p exhibited reduced expression in NSCLC tissues and cell lines. Reduced miR­363­3p expression was correlated with tumor node metastasis classification and distant metastasis of NSCLC patients. Notably, miR­363­3p re­expression significantly suppressed cell proliferation and invasion of NSCLC. Furthermore, bioinformatics analysis, luciferase reporter assay, reverse transcription­quantitative polymerase chain reaction and western blotting indicated that (high mobility group AT-hook 2) HMGA2 was a direct target gene of miR­363­3p. HMGA2 was increased in NSCLC tissues and inversely associated with HMGA2 expression. Moreover, HMGA2 underexpression had similar effects to miR­363­3p overexpression in NSCLC cells. Thus, the current study suggested that miR­363­3p may act as a tumor suppressor in NSCLC and that the miR­363­3p could be investigated as a therapeutic target for the patients with this disease.

Endogenous microRNA-424 predicts clinical outcome and its inhibition acts as cancer suppressor in human non-small cell lung cancer.

PURPOSE: We examined the expression, clinical correlation and functional mechanisms of endogenous microRNA-424 (miR-424) in human non-small cell lung cancer (NSCLC). METHODS: Expression pattern of endogenous miR-424 was examined by qRT-PCR in clinical samples obtained from 233 NSCLC patients. Correlations between differential miR-424 expression level (low vs. high) and NSCLC patients' clinicopathological parameters or survival were statistically examined. In in vitro NSCLC H596 and SW900 cells, miR-424 was either upregulated or downregulation by lentiviral transduction. Their effects on cancer cell viability, proliferation, and cell-cycle transition were also examined. RESULTS: MiR-424 expression was not different between NSCLC tumors and healthy lung tissues. However, it is much upregulated in NSCLC tumors associated with patients at advanced clinical stages. Statistical analyses demonstrated that high endogenous miR-424 expression in NSCLC tumors was significantly correlated with patients' advanced clinical stages, aggressive tumor metastasis, and short survival. In addition, Cox regression model predicted that endogenous miR-424 might be an independent prognostic marker in NSCLC. In in vitro NSCLC cell lines, miR-424 downregulation had a significant suppressing effect on cancer proliferation and G1 to S phase cell-cycle transition. On the other hand, miR-424 upregulation had no effect on NSCLC in vitro. CONCLUSION: High endogenous miR-424 expression in tumors may predict poor prognosis of patients with NSCLC. Inhibiting endogenous miR-424 may also serve an effective cancer suppressor in NSCLC.

MicroRNA-320 was downregulated in non-small cell lung cancer and inhibited cell proliferation, migration and invasion by targeting fatty acid synthase.

The expression and functions of microRNA (miR)-320 have been previously investigated in various types of cancer. However, to the best of our knowledge, no previous studies have investigated miR-320 in human lung cancer. The current study determined the expression, biological functions and molecular mechanisms of miR­320 in human lung cancer. The expression level of miR­320 in human non­small cell lung cancer (NSCLC) and normal adjacent tissue samples (NATs), NSCLC cell lines and non­tumorigenic bronchial epithelial cells was measured by reverse transcription­quantitative polymerase chain reaction. Following transfection with miR­320 mimics, 3­(4,5­dimethylthiazol­2­yl)­2,5­diphenyltetrazolium bromide, cell migration and cell invasion assays, western blot analysis and luciferase assay were performed in human NSCLC cell lines. The results demonstrated that miR­320 was significantly downregulated in NSCLC tissue samples and cell lines compared with NATs and a control cell line, respectively. Statistical analysis demonstrated that expression of miR­320 was significantly associated with the TNM classification and metastasis. It was also observed that miR­320 inhibited cell growth, migration and invasion in NSCLC cells. Additionally, the present study provided evidence that miR­320 may directly target fatty acid synthase. These results suggest that miR­320 may serve as a therapeutic biomarker of NSCLC in the future.

Haze is an important medium for the spread of rotavirus.

This study investigated whether the rotavirus infection rate in children is associated with temperature and air pollutants in Hangzhou, China. This study applied a distributed lag non-linear model (DLNM) to assess the effects of daily meteorological data and air pollutants on the rotavirus positive rate among outpatient children. There was a negative correlation between temperature and the rotavirus infection rate. The impact of temperature on the detection rate of rotavirus presented an evident lag effect, the temperature change shows the greatest impact on the detection rate of rotavirus approximate at lag one day, and the maximum relative risk (RR) was approximately 1.3. In 2015, the maximum cumulative RR due to the cumulative effect caused by the temperature drop was 2.5. Particulate matter (PM) 2.5 and PM10 were the primary air pollutants in Hangzhou. The highest RR of rotavirus infection occurred at lag 1-1.5 days after the increase in the concentration of these pollutants, and the RR increased gradually with the increase in concentration. Based on the average concentrations of PM2.5 of 53.9 µg/m(3) and PM10 of 80.6 µg/m(3) in Hangzhou in 2015, the cumulative RR caused by the cumulative effect was 2.5 and 2.2, respectively. The current study suggests that temperature is an important factor impacting the rotavirus infection rate of children in Hangzhou. Air pollutants significantly increased the risk of rotavirus infection, and dosage, lag and cumulative effects were observed.

Permanent neonatal diabetes mellitus in China.

BACKGROUND: Permanent neonatal diabetes mellitus (PNDM) is a rare disease, which is defined as the onset of diabetes before the age of 6 months with persistence through life. Infants with KCNJ11 or ABCC8 genetic mutations may respond to oral sulfonylurea therapy. Currently, there are limited studies about the genetic analysis and long-term follow-up of PNDM. CASE PRESENTATION: We report four cases of PNDM. None of the infants or their parents had INS, KCNJ11, or ABCC8 genetic mutations. One infant underwent continuous subcutaneous insulin infusion (CSII) and the other infants underwent multiple injections of insulin (MII). In these infants, PNDM persisted from 35 months to 60 months of follow-up. Three infants maintained fairly stable blood sugar levels, and one infant had poor sugar control. CONCLUSIONS: We suggest that all of the infants with PNDM should undergo genetic evaluation. For infants without KCNJ11 and ABCC8 genetic mutations, oral sulfonylurea should not be considered as treatment. CSII is a useful method for overcoming the difficulties of diabetes, and it may also improve the quality of life of both infants and their parents.