Everolimus inhibits hepatoblastoma by inducing autophagy-dependent ferroptosis.

Everolimus, a known inhibitor of the mammalian target of rapamycin (mTOR), has shown uncertain efficacy in treating hepatoblastoma. This study delves into the potential anti-hepatoblastoma properties of everolimus and its intricate relationship with autophagy and ferroptosis, both in vitro and in vivo. In vivo, tumor tissue from hepatoblastoma patient and human hepatoblastoma cell line HuH-6 were xenografted into nude mice to establish xenograft models for observing the effect of everolimus on tumor growth. In vitro, HuH-6 cells were cultured to evaluate the anti-hepatoblastoma activity of everolimus. Transmission electron microscopy and microtubule-associated proteins 1 light chain 3 (LC3), beclin 1, and p62 protein expressions were employed to investigate autophagy. Additionally, indicators of cell apoptosis, reactive oxygen species (ROS) and proteins associated with ferroptosis were measured to evaluate ferroptosis. The results demonstrate that everolimus treatment effectively induced the formation of autophagosomes in hepatoblastoma cells, upregulated the LC3II/I ratio and beclin 1 expression, and downregulated p62 expression, indicating an enhanced autophagy level both in vitro and in vivo. Furthermore, everolimus treatment induced cell apoptosis, increased ROS level, elevated concentrations of malondialdehyde, 4-hydroxynonenal, and iron content, while reducing the ratio of glutathione/oxidized glutathione, and downregulating the protein expression of glutathione peroxidase 4 and solute carrier family 7 member 11, suggesting its ability to induce ferroptosis in hepatoblastoma cells. Importantly, the induction of ferroptosis by everolimus was significantly reversed in the presence of autophinib, an autophagy inhibitor, indicating the autophagy-dependent of everolimus-induced ferroptosis. Taken together, these findings suggest that everolimus holds promise as an effective anti-hepatoblastoma drug, with its mechanism of action potentially involving the induction of autophagy-dependent ferroptosis in hepatoblastoma cells.

Patent vitellointestinal duct with ileal prolapse in a newborn: A case report and literature review.

RATIONALE: Patent vitellointestinal duct is the most common omphalomesenteric duct anomaly to present with symptoms. PATIENT CONCERNS: A 10-day-old child presented with increase in the size of a polypoidal lesion into a large, "Y"-shaped reddish, prolapsing lesion, discharging gaseous, and fecal matter at her umbilicus. A laparoscopic exploration was performed, followed by wedge resection and anastomosis. No complications occurred during postoperative follow-up. DIAGNOSES: A patent vitellointestinal duct with ileal prolapse. INTERVENTIONS: The resection of extended intraperitoneal intestinal tube was performed. OUTCOMES: During the follow-up 3 months after surgery, the umbilical cord of the child healed well after surgery. LESSONS: Timely surgical treatment can minimize the occurrence of complications, and the overall prognosis is good after surgery.

Simultaneous Expression of Chicken Granulocyte Monocyte Colony-Stimulating Factor and the Hemagglutinin-Neuraminidase Epitope of the Virulent Newcastle Disease Virus Genotype VII C22 Strain in a Functional Synthetic Recombinant Adenovirus as a Genotype-Matched Vaccine with Potential Antiviral Activity.

When it comes to the prevention of clinical signs and mortality associated with infection of the Newcastle disease virus (NDV), vaccination has been very effective. However, recent evidence has proven that more highly virulent strains are emerging that bypass existing immune protection and pose a serious threat to the global poultry industry. Here, a novel rescued adenovirus 5-coexpressed chicken granulocyte monocyte colony-stimulating factor (ChGM-CSF) bio-adjuvant and C22-hemagglutinin-neuraminidase (HN) boosted chickens' immunological genetic resistance and thus improved the immunological effectiveness of the critical new-generation vaccine in vitro and in vivo. Accordingly, the hemagglutination inhibition (HI) titers (log2) of the recombinant adenovirus (rAdv)-ChGM-CSF-HN-immunized chickens had greater, more persistent, and longer-lasting NDV-specific antibodies than the La Sota and rAdv-HN-inoculated birds. Moreover, humoral and adaptive immunological conditions were shown to be in harmony after rAdv-ChGM-CSF-HN inoculation and uniformly enhanced the expression of alpha interferon (IFN-α), IFN-ß, IFN-γ, interleukin-1ß (IL-1ß), IL-2, IL-16, IL-18, and IL-22. Postchallenge, the control challenge (CC), wild-type adenovirus (wtAdv), and rAdv-ChGM-CSF groups developed unique NDV clinical manifestations, significant viral shedding, high tissue viral loads, gross and microscopic lesions, and 100% mortality within 7 days. The La Sota, rAdv-HN, and rAdv-ChGM-CSF-HN groups were healthy and had 100% survival rates. The rAdv-ChGM-CSF-HN group swiftly regulated and stopped viral shedding and had lower tissue viral loads than all groups at 5 days postchallenge (dpc). Thus, the antiviral activity of ChGM-CSF offered robust immune protection in the face of challenge and reduced viral replication convincingly. Our advance innovation concepts, combining ChGM-CSF with a field-circulating strain epitope, could lead to the development of a safe, genotype-matched, universal transgenic vaccine that could eradicate the disease globally, reducing poverty and food insecurity. IMPORTANCE We studied the biological characterization of the developed functional synthetic recombinant adenoviruses, which showed a high degree of safety, thermostability, and genetic stability for up to 20 passages. It was demonstrated through both in vitro and in vivo testing that the immunogenicity of the proposed vaccine, which uses the T2A peptide from the Thosea asigna virus capsid protein supported by glycine and serine, helps with efficiency to generate a multicistronic vector, enables expression of two functional proteins in rAdv-ChGM-CSF-HN, and is superior to that of comparable vaccines. Additionally, adenovirus can be used to produce vaccines matching the virulent field-circulating strain epitope. Because there is no preexisting human adenoviral immunity detected in animals, the potency of adenoviral vaccines looks promising. Also, it ensures that the living vector does not carry the resistance gene that codes for the kanamycin antibiotic. Accordingly, a human recombinant adenoviral vaccine that has undergone biological improvements is beneficial and important.

9-Butyl-Harmol Exerts Antiviral Activity against Newcastle Disease Virus through Targeting GSK-3ß and HSP90ß.

The paramyxoviruses represent a large family of human and animal pathogens that cause significant health and economic burdens worldwide. However, there are no available drugs against the virus. ß-carboline alkaloids are a family of naturally occurring and synthetic products with outstanding antiviral activities. Here, we examined the antiviral effect of a series of ß-carboline derivatives against several paramyxoviruses, including Newcastle disease virus (NDV), peste des petits ruminants virus (PPRV), and canine distemper virus (CDV). Among these derivatives, 9-butyl-harmol was identified as an effective antiviral agent against these paramyxoviruses. Further, a genome-wide transcriptome analysis in combination with target validation strategies reveals a unique antiviral mechanism of 9-butyl-harmol through the targeting of GSK-3ß and HSP90ß. On one hand, NDV infection blocks the Wnt/ß-catenin pathway to suppress the host immune response. 9-butyl-harmol targeting GSK-3ß dramatically activates the Wnt/ß-catenin pathway, which results in the boosting of a robust immune response. On the other hand, NDV proliferation depends on the activity of HSP90. The L protein, but not the NP protein or the P protein, is proven to be a client protein of HSP90ß, rather than HSP90α. 9-butyl-harmol targeting HSP90ß decreases the stability of the NDV L protein. Our findings identify 9-butyl-harmol as a potential antiviral agent, provide mechanistic insights into the antiviral mechanism of 9-butyl-harmol, and illustrate the role of ß-catenin and HSP90 during NDV infection. IMPORTANCE Paramyxoviruses cause devastating impacts on health and the economy worldwide. However, there are no suitable drugs with which to counteract the viruses. We determined that 9-butyl-harmol could serve as a potential antiviral agent against paramyxoviruses. Until now, the antiviral mechanism of ß-carboline derivatives against RNA viruses has rarely been studied. Here, we found that 9-butyl-harmol exerts dual mechanisms of antiviral action, with its antiviral activities being mediated by two targets: GSK-3ß and HSP90ß. Correspondingly, the interaction between NDV infection and the Wnt/ß-catenin pathway or HSP90 is demonstrated in this study. Taken together, our findings shed light on the development of antiviral agents against paramyxoviruses, based on the ß-carboline scaffold. These results present mechanistic insights into the polypharmacology of 9-butyl-harmol. Understanding this mechanism also deepens the host-virus interaction and reveals new drug targets for anti-paramyxoviruses.

Development of a digital imaging analysis system to evaluate the treatment response in superficial infantile hemangiomas.

Superficial infantile hemangiomas (IH) are benign vascular tumors common in children characterized by bright red "strawberry" lesions on the skin. In order to optimize the treatment for this disease, there is a need to develop objective tools to assess treatment response. Since a color change in the lesion is a good indicator of treatment response, we have developed a digital imaging system to quantify the values of red, green, and blue (RGB) difference and RGB ratio between the tumor and normal tissue to take into account the variations in color between different skin types. The efficacy of the proposed system in assessing treatment response in superficial IH was evaluated in relation to established visual and biochemical tools used to grade hemangiomas. As the treatment progressed, the RGB ratio was almost 1, while the RGB difference was close to 0, which indicates a good response to treatment. There was a strong correlation between the RGB score and the other visual grading systems. However, the correlation between the RGB scoring system and the biochemical method was weak. These findings suggest that the system can be used clinically to objectively and accurately evaluate disease progression and treatment response in patients diagnosed with superficial IH.

Thin-wall hollow porous cystic-like graphitic carbon nitride with awakened n→π* electronic transitions and exceptional structural features for superior photocatalytic degradation of sulfamethoxazole.

Effective photoexcitation and carrier migration are the essential aspects to strengthen semiconductor-engaged redox reaction. Herein, a three-dimensional thin-wall hollow porous cystic-like g-C3N4 (HPCN) with curved layer edge was successfully fabricated via a non-template thermal-condensation strategy. The construction of unique distorted structure can evoke the hard-to-activate n→π* electronic transition to some extent, broadening the absorption spectrum to 800 nm. And benefiting from the multiple reflections of incident light, the effective photoactivation can be further achieved. Moreover, the thin-wall porous framework can shorten the diffusion distance and accelerate migration of photogenerated charge, favouring interfacial redox reactions. The optimized HPCN1.0 demonstrated an excellent photocatalytic degradation of SMX under blue-LED light irradiation, which was dramatically superior to that of pristine g-C3N4 (CN, 11.4 times). Ultimately, in consideration of reactions under several influencing factors with four different water samples, we demonstrated that the HPCN photocatalyst could be utilized far more productively for the elimination of SMX under real-world aqueous conditions. This work provides a straightforward approach for the removal of SMX and has immense potential to contribute to global scale environmental remediation.

Study on Influencing Factors of High-Temperature Basic Characteristics of Iron Ore Powder and Optimization of Ore Blending.

In order to explore the reasonable ore blending of low-silicon magnetite in sintering, it I necessary to realize the efficient utilization of low-silicon ore, further reduce cost, and increase yield. In this study, based on the high-temperature basic characteristics of iron ore powder used in the experiment, sinter pot tests were carried out with different low-silicon ore ratios, and the microstructure of the sinter was observed by scanning electron microscopy (SEM) and energy spectrum analysis (EDS) to determine the optimal matching law of low-silicon ore. The result showed that SiO2, Al2O3, and burning loss in iron ore powder composition were positively correlated with its assimilation, whereas MgO and basicity R2 were negatively correlated with the assimilation of iron ore powder. When the ratio of low-silicon ore was not more than 35%, increasing the ratio of hematite improved the liquid production and increased the production of acicular calcium ferrite. Therefore, the optimization of ore blending based on assimilation can improve the quality of sinter and strengthen the sintering process. This study has certain reference significance for the industrial production of low-silica sintering.

Activation of peracetic acid via Co3O4 with double-layered hollow structures for the highly efficient removal of sulfonamides: Kinetics insights and assessment of practical applications.

Sulfonamides (SAs) have been of ecotoxicological concern for ambient ecosystems due to their widespread application in the veterinary industry. Herein, we developed a powerful advanced oxidation peracetic acid (PAA) activation process for the remediation of SAs by Co3O4 with double-layered hollow structures (Co3O4 DLHSs). Systematic characterization results revealed that the polyporous hollow hierarchical structure endows Co3O4 DLHSs with abundant active reaction sites and enhanced mass transfer rate, which were conducive for improving the PAA activation efficiency. Laser flash photolysis experiment and mechanism studies indicated that organic radical species were dominant reactive species for SAs removal. The present system is also highly effective under natural water matrices and trace SAs concentration (20 µg/L) condition. More importantly, the chlorella acute toxicity of the SAs solution was eliminated during mineralization process, supporting this catalytic system may be efficaciously applied for the remediation of SAs contamination in ambient waterways.

Amlodipine removal via peroxymonosulfate activated by carbon nanotubes/cobalt oxide (CNTs/Co3O4) in water.

Amlodipine (AML) is an effective drug that has been widely used for hypertension and angina. However, AML is frequently detected in aqueous environments, posing potential risks to human and ecological health. In this study, the degradation of AML via peroxymonosulfate (PMS) activated by CNTs/Co3O4 was investigated. CNTs/Co3O4 was prepared via a facile method, and multiple characterizations suggested that Co3O4 were uniformly dispersed on the surface of MWCNTs-COOH. Experimental results indicated that complete removal of 10 µM AML was achieved within 30 min by using 2 mg/L CNTs/Co3O4 and 4 µM PMS at 25 °C in PBS buffered solution (pH 7.0). The observed pseudo-first-order rate constant was calculated to be 0.1369 min-1. Interestingly, the presence of 100 mM Cl- resulted in a slight enhancement of AML removal rate from 0.0528 to 0.0642 min-1. The addition of 100 mM HCO3-, 5 mg/L Pony Lake fulvic acid (PLFA), or Suwannee River humic acid (SRHA) retarded AML degradation by 15.5, 0.7, and 1.6 times, respectively. As per the quenching experiments, SO4⦁- rather than ⦁OH were verified to be the dominant reactive oxygen species (ROS). Additionally, ten major intermediates were identified using TOF-LC-MS and three associated reaction pathways including ether bond broken, H-abstraction, and hydroxylation were proposed. We outlook these findings to advance the feasibility of organic contaminants removal via CNTs/Co3O4 + PMS systems that have extremely low-level PMS.

Determining the geographical origin of flaxseed based on stable isotopes, fatty acids and antioxidant capacity.

BACKGROUND: Flaxseed is an economically important oilseed crop whose geographic origin is of significant interest to producers and consumers because every region may exhibit particular quality characteristics. The lipid/fatty acid method of determining the geographic origin of flaxseed has not been found to be adequate. RESULTS: To improve the discrimination rate and the geographical traceability of this crop, the chemical profiles of the flaxseed samples were characterized via lipids/fatty acids, stable isotopes, and antioxidant capacity. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were also performed. A satisfactory discrimination rate of 98.6% was obtained after combining fatty acids, stable isotopes, and antioxidant capacity to trace the origin of flaxseed from five regions in northern China. CONCLUSION: This study provides an effective method for distinguishing the geographic origin of flaxseed. © 2021 Society of Chemical Industry.

Enhanced Bio-Barcode Immunoassay Using Droplet Digital PCR for Multiplex Detection of Organophosphate Pesticides.

A bio-barcode immunoassay based on droplet digital polymerase chain reaction (ddPCR) was developed to simultaneously quantify triazophos, parathion, and chlorpyrifos in apple, cucumber, cabbage, and pear. Three gold nanoparticle (AuNP) probes and magnetic nanoparticle (MNP) probes were prepared, binding through their antibodies with the three pesticides in the same tube. Three groups of primers, probes, templates, and three antibodies were designed to ensure the specificity of the method. Under the optimal conditions, the detection limits (expressed as IC10) of triazophos, parathion, and chlorpyrifos were 0.22, 0.45, and 4.49 ng mL-1, respectively. The linear ranges were 0.01-20, 0.1-100, and 0.1-500 ng mL-1, and the correlation coefficients (R2) were 0.9661, 0.9834, and 0.9612, respectively. The recoveries and relative standard deviations (RSDs) were in the ranges of 75.5-98.9 and 8.3-16.7%. This study provides the first insights into the ddPCR for the determination of organophosphate pesticides. It also laid the foundation for high-throughput detection of other small molecules.

The application of whole-course nursing in patients undergoing emergency PCI and its impact on cardiac function.

OBJECTIVE: To implement whole-course care in patients undergoing emergency percutaneous coronary intervention and investigate its impact on cardiac function. METHODS: This study included 88 acute myocardial infarction patients undergoing percutaneous coronary intervention. These patients were randomly divided into the control group (n=44, which underwent routine care) and the experimental group (n=44, which underwent whole-course care). The cardiac function, physiological states, quality of life, complications, and the patient satisfaction with the care were compared between the two groups. RESULTS: Compared with before the surgery, the left ventricular ejection fractions and the cardiac output in both groups at discharge were increased, while the left ventricular end-systolic diameters and left ventricular end-diastolic diameters were decreased (all P<0.05). In addition, the changes in the experimental group were greater than they were in the control group (all P<0.05). The HAMA and HAMD scores in the two groups at discharge were decreased compared with before the surgeries, but the GQOLI-74 scores in all aspects were increased (all P<0.05). Similarly, the changes in the experimental group were greater than those in the control group (all P<0.05). The incidence of postoperative complications in the experimental group was lower than it was in the control group, and the satisfaction with care was higher than it was in the control group (both P<0.05). CONCLUSIONS: The whole-course care of AMI patients undergoing PCI can significantly relieve their negative emotions, improve their cardiac function, increase their quality of life, and reduce their incidences of complications.

A sensitive bio-barcode immunoassay based on bimetallic Au@Pt nanozyme for detection of organophosphate pesticides in various agro-products.

Organophosphate pesticides (OPs) are often used as insecticides and acaricides in agriculture, thus improving yields. OP residues may pose a serious threat, duetoinhibitionof the enzymeacetylcholinesterase(AChE). Therefore, a competitive bio-barcode immunoassay was designed for simultaneous quantification of organophosphate pesticide residues using AuNP signal amplification technology and Au@Pt catalysis. The AuNP probes were labelled with antibodies and corresponding bio-barcodes (ssDNAs), MNP probes coated with ovalbumin pesticide haptens and Au@Pt probes functionalized with the complementary ssDNAs were then prepared. Subsequently, pesticides competed with MNP probes to bind the AuNP probes. The recoveries of the developed assay were ranged from 71.26 to 117.47% with RSDs from 2.52 to 14.52%. The LODs were 9.88, 3.91, and 1.47 ng·kg-1, for parathion, triazophos, and chlorpyrifos, respectively. The assay was closely correlated with the data obtained from LC-MS/MS. Therefore, the developed method has the potential to be used as an alternative approach for detection of multiple pesticides.

Development and validation of psychological status questionnaire for parents of infantile hemangiomas.

BACKGROUND: Infantile hemangioma (IH) is the most frequent benign tumor of infancy which impacts the psychological status of parents of affected children. Parental psychological status has a significant effect on the therapeutic effect and long-term prognosis of IH children. However, no standard questionnaires had been established previously to assess the psychological status of Chinese parents of children with IH. METHODS: This study prospectively developed and validated a psychological status instrument for the assessment of parents of patients with IH and to identify clinical features with effects on the psychological status. A total of 350 parents completed the 35-item Psychologic Status Questionnaire for parents of Infantile Hemangiomas (IH-PSQ) and provided demographic information. The IH-PSQ was refined via item analysis, validity analysis (including exploratory factor analysis and criterion-related validity) and reliability analysis (including internal consistency reliability, split half reliability, and test-retest reliability). RESULTS: The dimensionality of the items was evaluated using factor analysis, with results suggesting 5 factors: anxiety, depression, psychological imbalance, disease shame, and disease fear. The final instrument consists of 4 scales with a total of 23 items. Construct validity was demonstrated and IH-PSQ showed good internal coherence (Cronbach's α: 0.957), good split half reliability (0.971), and good test-retest reliability (correlation coefficient: 0.967). The correlation coefficient between the Self-Rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) of children with IH was 0.874 and 0.754, respectively. Multiple linear regression analysis found that some characteristics will affect the score of IH-PSQ. CONCLUSIONS: The IH-PSQ contains 5 dimensions and 23 entries, and with good reliability and validity, can objectively and effectively evaluate the psychological status of IH parents. Certain clinical characteristics of IH families, including parents' own factors (including their monthly income and cultural level) and disease-related factors of affected children (including the duration of illness, tumor size, with or without complications, single or multiple, whether being treated or not), were associated with a greater impact on IH-PSQ.

Cyclooxygenase-2 Facilitates Newcastle Disease Virus Proliferation and Is as a Target for Canthin-6-One Antiviral Activity.

Cyclooxygenase-2 (COX-2), one of the mediators of inflammation in response to viral infection, plays an important role in host antiviral defense system. But its role in Newcastle disease virus (NDV) proliferation process remains unclear. This study revealed that inhibition of COX-2 could benefit NDV proliferation and overexpression of COX-2 dose-dependently suppressed NDV proliferation. Overexpression of COX-2 also showed inhibitory effect on NDV-induced endoplasmic reticulum (ER)-stress and autophagy, also promoted the expression of antiviral genes. However, prostaglandin E2 (PGE2), the major product of COX-2, had indistinctive effects on NDV proliferation. At variant time point post viral infection, a tight regulation pattern of COX-2 by NDV was observed. Using inhibitors and siRNA against signaling molecules, the nuclear factor-κB (NF-κB) and melanoma differentiation-associated gene 5 (MDA5) were identified as critical factors for NDV induced COX-2 expression. Nonetheless, at late stage of NDV proliferation, substantial suppression of COX-2 protein synthesis could be detected, accompanied by a decrease in mRNA half-life. Furthermore, three C ring-truncated canthin-6-one analogs were used to activate COX-2 expression and showed inhibitory effect on NDV proliferation with the effective concentrations on µM level. Taken together, these results illustrated a novel NDV-regulated cellular mechanism and indicated that COX-2 is an important regulator of NDV proliferation which can serve as a potential target for anti-NDV agents.

Host CARD11 Inhibits Newcastle Disease Virus Replication by Suppressing Viral Polymerase Activity in Neurons.

Host factors play multiple essential roles in the replication and pathogenesis of mammalian neurotropic viruses. However, the cellular proteins of the central nervous system (CNS) involved in avian neurotropic virus infection have not been completely elucidated. Here, we employed a gene microarray to identify caspase recruitment domain-containing protein 11 (CARD11), a lymphoma-associated scaffold protein presenting brain-specific upregulated expression in a virulent neurotropic Newcastle disease virus (NDV)-infected natural host. Chicken primary neuronal cells infected with NDV appeared slightly syncytial and died quickly. CARD11 overexpression inhibited viral replication and delayed cytopathic effects; conversely, depletion of CARD11 enhanced viral replication and cytopathic effects in chicken primary neuronal cells. The inhibition of viral replication by CARD11 could not be blocked with CARD11-Bcl10-MALT1 (CBM) signalosome and NF-κB signaling inhibitors. CARD11 was found to interact directly with the viral phosphoprotein (P) through its CC1 domain and the X domain of P; this X domain also mediated the interaction between P and the viral large polymerase protein (L). The CARD11 CC1 domain and L competitively bound to P via the X domain that hindered the P-L interaction of the viral ribonucleoprotein (RNP) complex, resulting in a reduction of viral polymerase activity in a minigenome assay and inhibition of viral replication. Animal experiments further revealed that CARD11 contributed to viral replication inhibition and neuropathology in infected chicken brains. Taken together, our findings identify CARD11 as a brain-specific antiviral factor of NDV infection in avian species.IMPORTANCE Newcastle disease virus (NDV) substantially impacts the poultry industry worldwide and causes viral encephalitis and neurological disorders leading to brain damage, paralysis, and death. The mechanism of interaction between this neurotropic virus and the avian central nervous system (CNS) is largely unknown. Here, we report that host protein CARD11 presented brain-specific upregulated expression that inhibited NDV replication, which was not due to CARD11-Bcl10-MALT1 (CBM) complex-triggered activation of its downstream signaling pathways. The inhibitory mechanism of viral replication is through the CARD11 CC1 domain, and the viral large polymerase protein (L) competitively interacts with the X domain of the viral phosphoprotein (P), which hampers the P-L interaction, suppressing the viral polymerase activity and viral replication. An in vivo study indicated that CARD11 alleviated neuropathological lesions and reduced viral replication in chicken brains. These results provide insight into the interaction between NDV infection and the host defense in the CNS and a potential antiviral target for viral neural diseases.

EYA1 mutations leads to Branchio-Oto syndrome in two Chinese Han deaf families.

OBJECTIVES: Branchio-Oto (BO) syndrome is one of the common syndromic forms of hearing loss. In this study, we aimed to characterize the clinical and genetic features of BO syndrome in two Chinese Han deaf families. METHODS: The auditory and other BO-related clinical features of Family 1809 and Family 1974 were summarized. Targeted next-generation sequencing in 144 known deafness genes was performed in the probands. Co-segregation of the pathogenic mutations and the phenotype was confirmed by Sanger sequencing in the family members. RESULTS: Interfamilial and intrafamilial variations can be observed in the clinical phenotypes of BO syndrome in Family 1809 and 1974. A novel c.1493_1494insAT (p.Ile498PhefsTer*3) mutation and a previous reported c.967-2A>G mutation in EYA1 were identified as the pathogenic cause in Family 1974 and 1809, respectively. CONCLUSION: Our results supported the heterogeneity of the genetic and phenotypic spectrum of BO syndrome. The recurrent c.967-2A>G in different ethnical groups suggested that it is a hot-spot mutation.

Newcastle disease virus selectively infects dividing cells and promotes viral proliferation.

Newcastle disease virus (NDV) can select cells to infect, but the mechanism of its cell selectivity has not been comprehensively investigated. Here, we use HeLa cells to establish that NDV can selectively infect cells at the single-cell level. We labeled proliferating cells with 5'-bromo-2-deoxyuridine (BrdU) and examined the colocalization of BrdU with NDV in cells to clarify the relationships between NDV infection and cell proliferation. Receptors at the plasma membrane mediate NDV entry into host cells. We labeled sialic acid receptor isoforms, compared their densities between different cell types and measured the sialic acid receptor densities in different cell phases. Our results suggest that NDV displays host tropism to HeLa cells compared to BHK cells and that the differences in the receptor isoform expression patterns between cell types contribute to the selection of HeLa by NDV. At the single-cell level, the dynamics of receptor expression changes during different cell phases contributing to the selection of cells in S/G2 phase for NDV infection. Furthermore, cell proliferation benefits viral replication, and enhanced virus replication leads to increased damage to cells. The elucidation of the mechanisms underlying host cell selection by NDV may help in the screening and characterizing of additional candidate oncolytic virus strains.

A highly selective electrochemical sensor based on molecularly imprinted polypyrrole-modified gold electrode for the determination of glyphosate in cucumber and tap water.

An electrochemical sensor based on molecularly imprinted polypyrrole (MIPPy) was developed for selective and sensitive detection of the herbicide glyphosate (Gly) in cucumber and tap water samples. The sensor was prepared via synthesis of molecularly imprinted polymers on a gold electrode in the presence of Gly as the template molecule and pyrrole as the functional monomer by cyclic voltammetry (CV). The sensor preparation conditions including the ratio of template to functional monomers, number of CV cycles in the electropolymerization process, the method of template removal, incubation time, and pH were optimized. Under the optimal experimental conditions, the DPV peak currents of hexacyanoferrate/hexacyanoferrite changed linearly with Gly concentration in the range from 5 to 800 ng mL-1, with a detection limit of 0.27 ng mL-1 (S/N = 3). The sensor was used to detect the concentration of Gly in cucumber and tap water samples, with recoveries ranging from 72.70 to 98.96%. The proposed sensor showed excellent selectivity, good stability and reversibility, and could detect the Gly in real samples rapidly and sensitively. Graphical abstract Schematic illustration of the experimental procedure to detect Gly using the MIPPy electrode.

Characterization of genotype IX Newcastle disease virus strains isolated from wild birds in the northern Qinling Mountains, China.

This study was conducted to evaluate the virulence and evolution of genotype IX Newcastle disease virus (NDV) isolates obtained from wild birds in the northern Qinling Mountains of China. Five isolates were obtained from 374 larynx and cloacae swabs, which were collected from multiple asymptomatic wild bird species from August 2008 to July 2011, and were subsequently characterized by pathotype and genotype. Deduced amino acid sequences revealed that all five NDV isolates exhibited velogenic fusion protein cleavage sites motif (112)R-R-Q-R-R-F(117), shared as high as 99.8-99.9 % homology with each other, and varied in pathotype by intracerebral pathogenicity indices (ICPI) of 0.425-1.638. Phylogenetic analysis showed that all five isolates were clustered to genotype IX NDV. This is the first study to confirm multiple asymptomatic wild bird species as natural carriers of virulent genotype IX NDV. A novel NDV isolate from the Spotted-necked Dove (family Columbidae) exhibited discordance between its lentogenic ICPI and its virulent proteolytic cleavage site motif (112)R-R-Q-R-R-F(117). Although the five isolates underwent several amino acid mutations in the fusion protein, evidence of continuous evolutionary divergence did exist in the genotype IX NDV, which was always regarded as a conservative genotype.