Fish bones (FBs) are aquatic by-products that are sources of antioxidant-active peptides, calcium dietary supplements, and biomedical materials. Usually, fermentation of these by-products via ...microorganisms brings desirable changes, enhancing their value. This study investigates the value addition of FB when fermented with
(MP) for different time intervals, such as 3 days (F3) and 6 days (F6). The results indicate that the soluble protein, peptide, amino acid and total phenol content, as well as the antioxidant capacity (DPPH, ABTS
radical scavenging activity, and relative reducing power), of F3 and F6 were significantly increased after fermentation. Furthermore, the ROS contents of F3 and F6 were reduced to a greater extent than that of hydrogen peroxide (H
O
) in Clone-9 cells. The MMP integrity, as well as the SOD, CAT, and GPx activity, of F3 and F6 were also increased significantly compared to the H
O
in Clone-9 cells. Notably, F3 and F6 displayed significant reductions in ROS content, as well as elevate, SOD activity and MMP integrity in Clone-9 cells, when compared with the native FB. These results indicate that the FBs fermented with MP for 3 days (F3), and 6 days (F6) have antioxidant capacity, with possible applications as natural food supplements.
TRIM28/KAP1/TIF1β is a crucial epigenetic modifier. Genetic ablation of
is embryonic lethal, although RNAi-mediated knockdown in somatic cells yields viable cells. Reduction in TRIM28 abundance at ...the cellular or organismal level results in polyphenism. Posttranslational modifications such as phosphorylation and sumoylation have been shown to regulate TRIM28 activity. Moreover, several lysine residues of TRIM28 are subject to acetylation, but how acetylation of TRIM28 affects its functions remains poorly understood. Here, we report that, compared with wild-type TRIM28, the acetylation-mimic mutant TRIM28-K304Q has an altered interaction with Krüppel-associated box zinc-finger proteins (KRAB-ZNFs). The
-K304Q knock-in cells were created in K562 erythroleukemia cells by CRISPR-Cas9 (Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein nuclease 9) gene editing method. Transcriptome analysis revealed that
-K304Q and
knockout K562 cells had similar global gene expression profiles, yet the profiles differed considerably from wild-type K562 cells. The expression levels of embryonic-related globin gene and a platelet cell marker integrin-beta 3 were increased in
-K304Q mutant cells, indicating the induction of differentiation. In addition to the differentiation-related genes, many zinc-finger-proteins genes and imprinting genes were activated in
-K304Q cells; they were inhibited by wild-type TRIM28 via binding with KRAB-ZNFs. These results suggest that acetylation/deacetylation of K304 in TRIM28 constitutes a switch for regulating its interaction with KRAB-ZNFs and alters the gene regulation as demonstrated by the acetylation mimic TRIM28-K304Q.
Approximately 45% of metastatic colorectal cancer (mCRC) patients with wild-type KRAS exon 2 are resistant to cetuximab treatment. We set out to identify additional genetic markers that might predict ...the response to cetuximab treatment. Fifty-three wild-type KRAS exon 2 mCRC patients were treated with cetuximab/irinotecan-based chemotherapy as a first- or third-line therapy. The mutational statuses of 10 EGFR pathway genes were analyzed in primary tumors using next-generation sequencing. BRAF, PIK3CA, KRAS (exons 3 and 4), NRAS, PTEN, and AKT1 mutations were detected in 6, 6, 5, 4, 1, and 1 patient, respectively. Four of the BRAF mutations were non-V600 variants. Four tumors harbored multiple co-existing (complex) mutations. All patients with BRAF mutations or complex mutation patterns were cetuximab non-responders. All patients but one harboring KRAS, NRAS, or BRAF mutations were non-responders. Mutations in any one of these three genes were associated with a poor response rate (7.1%) and reduced survival (PFS = 8.0 months) compared to wild-type patients (74.4% and 11.6 months). Our data suggest that KRAS, NRAS, and BRAF mutations predict response to cetuximab treatment in mCRC patients.
This work studied the potential of using eggshell (ES) (200–300 μm) waste as adsorbent for sequential removal of heavy metals, soluble microbial products, and dye wastes. In this study, among soluble ...microbial products, chicken egg white (CEW) proteins were selected as simulated contaminants. ES was applied to capture heavy metal ions (e.g., Cu2+ and Zn2+) and the formed eggshell metal (ES-M) complex was use to absorb soluble microbial products (e.g., soluble proteins), followed by subsequent removal of dyes from aqueous solutions using ES-M-CEW adsorbent. The experimental conditions for the adsorption of CEW proteins by ES-M include shaking rate, adsorption pH, isothermal and kinetic studies. The maximum protein adsorption by ES-Zn and ES-Cu were 175.67 and 153.65 mg/g, respectively. Optimal removal efficiencies of the ES-M-CEW particles for Acid Orange (AO7) and Toluidine blue (TBO) dyes were at pH 2 and 12, respectively, achieving performance of 75.38 and 114.18 mg/g, respectively. The removal of TBO dye by ES-M-CEW adsorbent was equilibrated at 5 min. The results showed that low cost and simple preparation of the modified ES particles are feasible for treating various wastewaters.
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•Modified eggshell (ES) particles shown to be feasible to treat various wastewaters.•Removal of heavy metal ions, CEW proteins and dyes studied using ES waste.•Maximum protein adsorption was 175.67 and 153.65 mg/g for ES-Zn and ES-Cu.•Optimal dye removal efficiency with ES-M-CEW was 75.38 mg/g (A07) and 114.18 mg/g (TBO).
Background Intrauterine exposure to tobacco smoke has been discerned as an important risk factor for low birth weight (LBW), small for gestational age (SGA), and preterm birth infants. In this cohort ...study, we investigated the association of the amount of parental smoking during the different pregnancy stages with birth weight and the incidence of preterm delivery. Methods Our study population was acquired from the Taiwan Birth Cohort Study. Between June 2005 and July 2006, 21,248 postpartum women were interviewed 6 months after their deliveries by a structured questionnaire. The parents were divided into four groups according to the amount of smoking during preconception, the first trimester, and the second and third trimesters. The relationships of parental smoking with gestational age and birth weight during the different pregnancy stages were assessed using multivariate linear regression. Multiple logistic regression analyses were performed to estimate the odds ratios and 95% confidence intervals of preterm delivery, LBW, and SGA infants during the different parental smoking status and the different pregnancy stages. Results After adjusting for the physical and socioeconomic status of the parents and for paternal smoking during the same period, we found that maternal smoking decreased birth weight. Compared with the nonsmoking groups, all the maternal smoking groups had higher incidences of LBW, SGA, and preterm birth infants, especially when the mothers smoked >20 cigarettes/day. The association of paternal smoking with LBW, SGA, and preterm birth infants was insignificant. Conclusion Maternal smoking is responsible for increased incidences of LBW and preterm delivery of babies, and therefore, smoking cessation/reduction should be advised to pregnant women to reduce morbidities in their neonates. Further studies are needed to clarify the correlation of fetal health with passive smoking, including exposure to environmental tobacco smoke and to other smokers in the family.
SARS-CoV-2 variants have emerged with enhanced pathogenicity and transmissibility, and escape from pre-existing immunity, suggesting first-generation vaccines and monoclonal antibodies may now be ...less effective. Here we present an approach for preventing clinical sequelae and the spread of SARS-CoV-2 variants. First, we affinity matured an angiotensin-converting enzyme 2 (ACE2) decoy protein, achieving 1000-fold binding improvements that extend across a wide range of SARS-CoV-2 variants and distantly related, ACE2-dependent coronaviruses. Next, we demonstrated the expression of this decoy in proximal airway when delivered via intranasal administration of an AAV vector. This intervention significantly diminished clinical and pathologic consequences of SARS-CoV-2 challenge in a mouse model and achieved therapeutic levels of decoy expression at the surface of proximal airways when delivered intranasally to nonhuman primates. Importantly, this long-lasting, passive protection approach is applicable in vulnerable populations such as the elderly and immune-compromised that do not respond well to traditional vaccination. This approach could be useful in combating COVID-19 surges caused by SARS-CoV-2 variants and should be considered as a countermeasure to future pandemics caused by one of the many pre-emergent, ACE2-dependent CoVs that are poised for zoonosis.
MicroRNAs (miRNA) mediate distinct gene regulatory pathways triggered by epidermal growth factor receptor (EGFR) activation, which occurs commonly in lung cancers with poor prognosis. In this study, ...we report the discovery and mechanistic characterization of the miRNA miR-7 as an oncogenic "oncomiR" and its role as a key mediator of EGFR signaling in lung cancer cells. EGFR activation or ectopic expression of Ras as well as c-Myc stimulated miR-7 expression in an extracellular signal-regulated kinase (ERK)-dependent manner, suggesting that EGFR induces miR-7 expression through a Ras/ERK/Myc pathway. In support of this likelihood, c-Myc bound to the miR-7 promoter and enhanced its activity. Ectopic miR-7 promoted cell growth and tumor formation in lung cancer cells, significantly increasing the mortality of nude mice hosts, which were orthotopically implanted with lung cancers. Quantitative proteomic analysis revealed that miR-7 decreased levels of the Ets2 transcriptional repression factor ERF, the coding sequence of which was found to contain a miR-7 complementary sequence. Indeed, ectopic miR-7 inhibited production of ERF messages with a wild-type but not a silently mutated coding sequence, and ectopic miR-7 rescued growth arrest produced by wild-type but not mutated ERF. Together, these results identified that ERF is a direct target of miR-7 in lung cancer. Our findings suggest that miR-7 may act as an important modulator of EGFR-mediated oncogenesis, with potential applications as a novel prognostic biomarker and therapeutic target in lung cancer.
Piriformospora indica (P. indica) is a mutualistic endophyte that colonizes plant roots. In this study, effects of P. indica on rice resistance against rice leaffolder (Cnaphalocrocis medinalis ...Guenée) were investigated. Growth inhibition and leaf injury caused by leaffolder larvae infestation in P. indica-colonized rice was significantly alleviated. Moreover, growth retardation was observed in larvae which fed on P. indica-colonized plants. JA-Ile levels and trypsin inhibitor activities in leaf tissues of P. indica-colonized plants were higher than those in noncolonized plants under leaffolder-infested conditions. P. indica effects on increasing trypsin inhibitor expression and reducing larval growth were repressed by aspirin. JA signaling drives P. indica-enhanced insect resistance in rice, and trypsin inhibitors might be candidates involved in this mechanism. Changes in antioxidant enzyme activities and malondialdehyde levels in P. indica-inoculated plants were observed, and it was demonstrated that oxidative stress induced by insect infestation could be reduced in P. indica-colonized plants.
The large amount of hysteresis and threshold voltage variation in carbon nanotube transistors impedes their use in highly integrated digital applications. The origin of this variability is elucidated ...by employing a top-coated, hydrophobic monolayer to passivate bottom-gated devices. Compared to passivating only the supporting substrate, it is found that covering the nanotube channel proves highly effective and robust at improving device-to-device consistencyhysteresis and threshold voltage variation are reduced by an average of 84 and 53%, respectively. The effect of gate and drain–source bias on hysteresis is considered, showing strong dependence that must be accounted for when analyzing the effectiveness of a passivation layer. These results provide both key insight into the origin of variability in carbon nanotube transistors and a promising path for resolving this significant obstacle.
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