Identification of early events in serrated pathway colorectal tumorigenesis by using digital spatial profiling.

INTRODUCTION: The colorectal serrated pathway involves precursor lesions known as sessile serrated lesions (SSL) and traditional serrated adenomas (TSA). Mutations in BRAF or KRAS are crucial early events in this pathway. Additional genetic and epigenetic changes contribute to the progression of these lesions into high-grade lesions and, eventually, invasive carcinoma. METHODS: We employed digital spatial profiling to investigate the transcriptional changes associated with SSL and TSA. The genes identified are confirmed by immunohistochemical (IHC) staining. Colorectal (CRC) cell lines with CEACAM6 overexpression and knockdown were established to study the roles of CEACAM6 on tumorigenesis of CRC. RESULTS: Ten genes were upregulated in SSL and TSA, and seven were upregulated in both types of lesions. IHC staining confirmed overexpression of CEACAM6, LCN2, KRT19, and lysozyme in SSL and TSA. CEACAM6 expression is an early event in the serrated pathway but a late event in the conventional pathway. Using cell line models, we confirmed that CEACAM6 promotes CRC cells' proliferation, migration, and invasion abilities. CONCLUSION: These results highlight that the transcriptional changes in the early stages of tumorigenesis exhibit relative uniformity. Identifying these early events may hold significant promise in elucidating the mechanisms behind tumor initiation.

Mutations of ribosomal protein genes induce overexpression of catalase in Saccharomyces cerevisiae.

Ribosome assembly defects result in ribosomopathies, primarily caused by inadequate protein synthesis and induced oxidative stress. This study aimed to investigate the link between deleting one ribosomal protein gene (RPG) paralog and oxidative stress response. Our results indicated that RPG mutants exhibited higher oxidant sensitivity than the wild type (WT). The concentrations of H2O2 were increased in the RPG mutants. Catalase and superoxide dismutase (SOD) activities were generally higher at the stationary phase, with catalase showing particularly elevated activity in the RPG mutants. While both catalase genes, CTT1 and CTA1, consistently exhibited higher transcription in RPG mutants, Ctt1 primarily contributed to the increased catalase activity. Stress-response transcription factors Msn2, Msn4, and Hog1 played a role in regulating these processes. Previous studies have demonstrated that H2O2 can cleave 25S rRNA via the Fenton reaction, enhancing ribosomes' ability to translate mRNAs associated with oxidative stress-related genes. The cleavage of 25S rRNA was consistently more pronounced, and the translation efficiency of CTT1 and CTA1 mRNAs was altered in RPG mutants. Our results provide evidence that the mutations in RPGs increase H2O2 levels in vivo and elevate catalase expression through both transcriptional and translational controls.

NOx removal and copper recovery from the leaching process for waste printed circuit boards: performance evaluation and potential environmental impact assessment.

Resource recovery is crucial for small- and medium-sized enterprises to attain a circular economy. The economic benefits of recovering precious metals from electronic waste, such as waste printed circuit boards (WPCBs), are hindered by secondary pollutant emissions from pretreatment processes. This study aims to recover copper from the WPCB acid leaching process and reduce NOx emissions through the use of a high gravity rotating packed bed (RPB). The results indicate that the copper recovery ratio increases to 99.75% through the displacement reaction between iron powder and copper nitrate. The kinetic analysis of copper dissolution was employed to simulate the NOx emissions during acid leaching, with an R-squared value of 0.872. Three oxidants, including H2O2(aq), ClO2(aq), and O3(g), with pH adjusted to different NaOH concentrations, were used to remove NOx. The greatest NOx removal rate was achieved using a 0.06 M NaOH solution, with a removal rate of 91.2% for ozone oxidation at a 152-fold gravity level and a gas-to-liquid (G/L) ratio of 0.83. The gas-side mass transfer coefficients (KGa) for NOx range from 0.003 to 0.012 1/s and are comparable to previous studies. The results of a life cycle analysis indicate that the NOx removal rate, nitric acid recycling rate, and copper recovery rate are 85%, 80%, and 100%, respectively, reducing the environmental impact on the ecosystem, human health, and resource depletion by 10% compared to a scenario with no NOx removal.

Removal of fine particles from IC chip carbonization process in a rotating packed bed: Modeling and assessment.

A high-gravity rotating packed bed (HiGee RPB) is very efficient at removing pollution because it exerts a strong high centrifugal and allows tiny droplets to form, which allows the control of gaseous and particulate air pollution. In this study, fine particles that are removed from integrated circuit (IC) chip carbonization process using a RPB are evaluated under different high gravity factors and liquid-to-gas ratios. The greatest number of particles captured per energy consumption is 17.77 mg kWh-1 in a RPB. This allow greater energy efficiency for the HiGee technology prevents an air-energy nexus. The maximum available particle removal efficiency for a RPB is determined using a response surface model (RSM). 99.5% of particles are removed at a high gravity factor of 262 and a liquid-to-gas ratio of 0.24. A semi-theoretical model is developed to determine the particle removal efficiency individually in packing and cavity zones of the RPB. More particles are removed in a cavity zone than in the packing zone as the high gravity factor increases. An empirical model shows that the particle removal efficiency depends on the operating factors. Finally, a comparison analysis of particulate matter treatment in various types of RPB is used to validate the performance in terms of particle removal using high-gravity technology for different industries.

Particle chain display--an optofluidic electronic paper.

A particle-based display medium and a driving mechanism insensitive to the charge polarity of those particles, based on the transformation of particle chains, are developed for reflective electronic paper displays. Particle chains are formed by dipole-dipole interactions between polarized particles with an appropriate electric field applied across the tested display medium, i.e. the solution that regulates the light in the field of display technology, containing neutral polystyrene (PS) particles dispersed in water. Formation of the particle chains results in a large change in optical transmittance and reflectance of the display medium. The performance of the particle chain displays (PCD) was evaluated according to macroscopic (device), microscopic (particle) and optical (reflectance) points of view. A display medium (thickness 100 µm) containing colored PS particles (3 µm, 2.5% w/v) was polarized to display the fixed images of the directly driven electrodes and programmable images of arrayed (5 × 5) electrodes with electric fields (0.48 MV m(-1) and 0.09 MV m(-1), 500 kHz, respectively). The formation of particle chains under electric fields (0.2 MV m(-1) and 0.4 MV m(-1), 500 kHz) was observed in the microscopic images of a display medium (thickness 100 µm) with fluorescent PS particles (5 µm, 1%). Images recorded with a confocal microscope demonstrated the particle chains. The opacity, a common parameter serving to characterize a display medium, was derived by measuring the reflectance ratio of a black background to a white background of the display medium with varied thickness and particle concentration. The temporal response of a display medium (thickness 50 µm) with black PS particles (3 µm, 5%) was tested. When an electric field (0.6 MV m(-1), 500 kHz) was applied, the reflectance increased twice at the first data point in 0.7 s, attaining a contrast ratio of 2. Application of a voltage (20 s) yielded a contrast ratio of 10. The performance of a tested display medium, composed of simple PS particles and water and driven to form particle chains by polarization, is reported.

Production of Active Nonglycosylated Recombinant B-Chain of Type-2 Ribosome-Inactivating Protein from Viscum articulatum and Its Biological Effects on Peripheral Blood Mononuclear Cells.

Type-2 ribosome-inactivating proteins, composed of a toxic A-chain and lectin-like B-chain, display various biological functions, including cytotoxicity and immunomodulation. We here cloned the lectin-like B-chain encoding fragment of a newly identified type-2 RIP gene, articulatin gene, from Viscum articulatum, into a bacterial expression vector to obtain nonglycosylated recombinant protein expressed in inclusion bodies. After purification and protein refolding, soluble refolded recombinant articulatin B-chain (rATB) showed lectin activity specific toward galactoside moiety and was stably maintained while stored in low ionic strength solution. Despite lacking glycosylation, rATB actively bound leukocytes with preferential binding to monocytes and in vitro stimulated PBMCs to release cytokines without obvious cytotoxicity. These results implicated such a B-chain fragment as a potential immunomodulator.

Inhibition of mite-induced immunoglobulin E synthesis, airway inflammation, and hyperreactivity by herbal medicine STA-1.

The availability of STA-1 in suppressing allergen-induced immunoglobulin E (IgE) synthesis, airway inflammation and hyperreactivity in a murine model was investigated. The mice were intraperitoneally sensitized with Dermatophagoides pteronyssinus group 5 allergen (Der p 5) and orally treated with 300 mg/kg of STA-1 every other day for 14 days. The Der p 5-specific immunologic responses including changes of specific immunoglobulin G and E, cells in the broncholarvage fluid, and airway hyperreactivity were measured when mice received inhalation challenge with Der p 5 after sensitization for 21 days. By comparing with sham-treated groups, the synthesis of Der p 5-specific IgE was downregulated while the influx of eosinophils and neutrophils in the airway were remarkably reduced. In addition, Der p 5-induced airway hyperreactivity also was significantly eliminated by STA-1 treatment. These results showed that STA-1 could effectively suppress the Der p 5-induced allergic reactions, and the availability of STA-1 for the treatment of allergic asthma was demonstrated in this study.

Clinical evaluation of the Chinese herbal medicine formula STA-1 in the treatment of allergic asthma.

Although some formulae of traditional Chinese medicines (TCM) have been used for antiasthma treatment, few of them have had sufficient discussion on their efficacy, safety and mechanisms. In this study, the availability of the TCM formula STA-1 for the treatment of allergic asthma was investigated by conducting a double-blind, placebo-controlled and randomized trial. One hundred and twenty patients between the ages of 5 to 20 years with mild-to-moderate asthma were included. These patients were treated with either STA-1 or placebo in a dose of 80 g/kg/day and were administered twice daily for 6 months. The main outcome measures were a daily diary record of symptoms, supplementary bronchodilator and glucocorticoid treatment, changes of pulmonary function (forced expiratory volume in 1 s), changes of total and Dermatophagoides pteronyssinus (DP)-specific IgE and side effects. The results showed a statistically significant reduction of symptom scores, systemic steroid dose, total IgE and specific IgE in the STA-1 group. Furthermore, STA-1 also improved the pulmonary lung function FEV(1) compared with the placebo group and only minimal side effects were shown. These results suggested that STA-1 is available for the treatment of mild-to-moderate chronic asthma.

The efficacy and safety of heat-killed Lactobacillus paracasei for treatment of perennial allergic rhinitis induced by house-dust mite.

Live Lactobacillus paracasi 33 (LP33) may effectively improve the quality of life for patients with perennial allergic rhinitis. It has been demonstrated that heat-killed lactic acid bacteria (LAB) suppress specific immunoglobulin E synthesis and stimulate interleukin-12 production in animals. The aim of this study was, therefore, to evaluate the efficacy of heat-killed LP33 in the treatment of allergic rhinitis induced by house-dust-mite in human subjects. A total of 90 patients were enrolled in a randomized, double blind, placebo-controlled trial and assigned to three treatment groups. Patients in groups A and B received two capsules per day of live or heat-killed LAB (5 x 10(9) colony-forming units/capsule), respectively, over a period of 30 days while those in Group C received placebo capsules. A modified questionnaire on pediatric rhinoconjunctivitis-related quality of life was administered to all subjects or their parents during each clinical visit. The overall quality of life score decreased for groups A and B, as compared with the placebo group, in terms of both frequency (9.47 +/- 2.89, 6.30 +/- 2.19, vs. -3.47 +/- 1.53, respectively; p < 0.0001) and level of bother (5.91 +/- 3.21, 6.04 +/- 2.44, vs. -2.80 +/- 1.64, respectively; p = 0.004) after the 30-day treatment. The efficacy of the heat-killed LP33 was not inferior to the live variant. No obvious side effects were reported for either active treatment group during the study period. Our results suggest that heat-killed LP33 can effectively improve the overall quality of life for patients with allergic rhinitis, and that it may be efficacious as an alternative treatment.

Transient hypogammaglobulinemia of infancy presenting as Staphylococcus aureus sepsis with deep neck infection.

Transient hypogammaglobulinemia of infancy (THI) is characterized by a prolongation and accentuation of the physiologic hypogammaglobulinemia normally occurring during the first 3 to 6 months of life and recovers spontaneously between 18 and 36 months of age. Infants with THI may remain asymptomatic or develop recurrent sinopulmonary infections, but severe or life-threatening infections are rare. We report a case of THI in a previously healthy 1-year-old girl with Staphylococcus aureus sepsis who subsequently developed deep neck infection confirmed by magnetic resonance imaging. Intravenous oxacillin was administered for 21 days and she recovered completely. Immunologic studies were normal except for decreased immunoglobulin G levels. Under the impression of hypogammaglobulinemia with severe infection she received regular intravenous immunoglobulins (IVIG) replacement therapy every 4 weeks. One year later, the immunoglobulin concentrations had returned to the normal range even though IVIG had been discontinued for 4 months. This case report highlights the possibility of severe infection in THI, a disease which usually has a benign clinical course. As the diagnosis of THI can only be made with certainty in retrospect, long-term follow-up of clinical and immune system status is necessary.

Miller Fisher syndrome possibly related to mycoplasma pneumoniae infection: report of one case.

Ophthalmoplegia, ataxia, and areflexia were first described in 1956 by Miller Fisher and later were referred to as symptoms of Miller Fisher syndrome (MFS). This syndrome shares certain features with the Guillain-Barré syndrome (GBS), including areflexia, cerebrospinal fluid findings and often a postinfectious presentation. It was believed to be a variant of GBS, but Miller Fisher syndrome has several key clinical features which differ from GBS. The anatomic location and pathogenesis of MFS continue to be a matter of debate. Our report focuses on a 6-year-old female patient who developed MFS following a respiratory tract infection with a serologically proven Mycoplasma pneumoniae infection. Although several neurological complications after Mycoplasma pneumoniae infection have been reported, subsequent MFS development has rarely been reported previously.

Oral administration of a mite allergen expressed by zucchini yellow mosaic virus in cucurbit species downregulates allergen-induced airway inflammation and IgE synthesis.

BACKGROUND: Sublingual-swallow immunotherapy in house dust mite-related asthma has a good safety profile and improves respiratory function and bronchial hyperreactivity. Zucchini yellow mosaic virus (ZYMV) is envisaged as a promising viral vector for expressing large quantity of foreign proteins in cucurbit species. OBJECTIVE: We sought to investigate whether oral feeding of dust mite allergen expressed by ZYMV in a cucurbit species can suppress allergen-induced inflammation and IgE synthesis. METHODS: An infectious plant virus clone, p35SZYMV2-26, that contains the full-length cDNA to the genomic RNA of a Taiwan isolate of ZYMV, driven by the cauliflower mosaic virus 35S promoter, was engineered as an in vivo viral vector to express Dermatophagoides pteronyssinus group 5 allergen (Der p 5) in cucurbit species. Female BALB/c mice were intraperitoneally sensitized with Escherichia coli bacteria-expressed Der p 5 and orally treated with the virus-expressed Der p 5 (vDer p 5) extracted from the recombinant virus-infected squash plants. Der p 5-specific immunoglobulins were measured by ELISA, and bronchoalveolar lavage assays were used to measure airway inflammation. RESULTS: Infectivity assays and immunoblotting revealed that large quantities of free-form vDer p 5 are produced in the recombinant virus-infected squash plants. The recombinant virus carried and expressed the Der p 5 allergen in squash plants for at least 1 year after numerous passages. In animal tests, squash extract containing vDer p 5 inhibited Der p 5-specific IgE synthesis and airway inflammation. CONCLUSION: Our results suggest that oral feeding with allergen produced by the plant viral vector provides a novel approach for the therapy of allergic asthma.

Treatment of perennial allergic rhinitis with lactic acid bacteria.

Probiotics are perceived to exert beneficial effects in the prevention and treatment of allergic diseases via modifying the gut ecosystem. The aim of this study was to assess whether ingestion of fermented milk containing Lactobacillus paracasei-33 (LP-33), a strain newly isolated from the human intestinal tract, can improve the quality of life of patients with perennial allergic rhinitis. In a randomized, double-blind, placebo-controlled trial, we gave patients fermented milk with (n = 60) or without (n = 20) the addition of LP-33 (2 x 10(9) colony-forming units per bottle) for 30 days. A modified questionnaire concerning pediatric rhinoconjunctivitis quality of life was administered to all subjects or their parents at each clinical visit. Scores for the overall quality of life significantly decreased in the LP-33 group as compared with the placebo group, in both frequency (-16.02 +/- 2.14 vs. -7.27 +/- 3.55, respectively; p = 0.037) and level of bother (-16.35 +/- 2.33 vs. -6.20 +/- 3.13, respectively; p = 0.022) after the 30-day treatment. Subjects reported no severe adverse effects such as fever, abdominal pain, or diarrhea. The results suggest that ingestion of LP-33-fortified fermented milk for 30 days can effectively and safely improve the quality of life of patients with allergic rhinitis, and may serve as an alternative treatment for allergic rhinitis.

Facile synthesis of metal-chelating peptides on chip for protein array.

A unique peptide sequence of HGGHHG screening from a combinatorial synthetic peptide library showed a good chelating ability to bind a transition metal on a chip better than hexa-His peptide. It was directly conjugated with a His-Tagged proteins onto a chip in a mild aqueous solution and can be used this chip as a high throughput technique for protein array in order to detect and purify the His-Tagged proteins.