Targeted therapy with tyrosine kinase inhibitors (TKI) provides survival benefits to a majority of patients with non-small cell lung cancer (NSCLC). However, resistance to TKI almost always develops ...after treatment. Although genetic and epigenetic alterations have each been shown to drive resistance to TKI in cell line models, clinical evidence for their contribution in the acquisition of resistance remains limited. Here, we employed liquid biopsy for simultaneous analysis of genetic and epigenetic changes in 122 Vietnamese NSCLC patients undergoing TKI therapy and displaying acquired resistance. We detected multiple profiles of resistance mutations in 51 patients (41.8%). Of those, genetic alterations in EGFR, particularly EGFR amplification (n = 6), showed pronounced genome instability and genome-wide hypomethylation. Interestingly, the level of hypomethylation was associated with the duration of response to TKI treatment. We also detected hypermethylation in regulatory regions of Homeobox genes which are known to be involved in tumor differentiation. In contrast, such changes were not observed in cases with MET (n = 4) and HER2 (n = 4) amplification. Thus, our study showed that liquid biopsy could provide important insights into the heterogeneity of TKI resistance mechanisms in NSCLC patients, providing essential information for prediction of resistance and selection of subsequent treatment.
This paper reviewed the Se in the environment (including total Se in soil, water, plants, and food), the daily Se intake and Se content in human hair were also examined to elucidate Se distribution ...in the environment and its effects on human health in China. Approximately 51% of China is Se deficiency in soil, compared with 72% in the survey conducted in 1989. Low Se concentrations in soil, water, plants, human diet and thus human hair were found in most areas of China. The only significant difference was observed between Se-rich and Se-excessive areas for Se contents in water, staple cereal, vegetables, fruits, and animal-based food, no remarkable contrast was found among other areas (p>0.05). This study also demonstrated that 39–61% of Chinese residents have lower daily Se intakes according to WHO/FAO recommended value (26–34μg/day). Further studies should focus on thoroughly understanding the concentration, speciation, and distribution of Se in the environment and food chain to successfully utilize Se resources, remediate Se deficiency, and assess the Se states and eco-effects on human health.
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•In China, the Se deficient area decreased from 72% in 1989 to 51% nowadays.•Soil Se content descended as Northwest>South>Central>East>Southwest>Northeast>North China.•Some new Se-rich areas were found in low Se parts of China area as belt or spot.•Se in cereals and meat was significantly correlated with the corresponding soil Se content.
The present study aimed to evaluate the effectiveness of using platelet-rich fibrin (PRF) as the apical matrix for the placement of MTA in nonsurgical endodontic therapy for teeth with periapical ...lesions and open apices.
Twelve teeth from eleven patients with periapical periodontitis and open apices were enrolled in the study. Nonsurgical endodontic therapy was performed with the PRF used as an apical barrier and the MTA manipulated as an apical plug for further thermoplasticized gutta percha in the remaining part of the root canal. Clinical signs and periapical digital radiographs were recorded and analyzed to evaluate the curing progress after periodical follow-ups of 1, 3, and 6 months. The horizontal dimension of the periapical lesion was determined, and the changes in the dimensions were recorded each time. The Friedman test was used for statistical analysis, with P < .05 serving as the threshold for determining statistical significance.
All patients had no clinical symptoms after the first month of treatment, with a significant reduction in the periapical lesion after periodical appointments.
PRF is an effective barrier when combined with MTA for the treatment of teeth with periapical periodontitis and open apices.
In agricultural production, abiotic stresses are known as the main disturbance leading to
negative impacts on crop performance. Research on elucidating plant defense mechanisms against the
stresses ...at molecular level has been addressed for years in order to identify the major contributors in
boosting the plant tolerance ability. From literature, numerous genes from different species, and from
both functional and regulatory gene categories, have been suggested to be on the list of potential candidates
for genetic engineering. Noticeably, enhancement of plant stress tolerance by manipulating
expression of Transcription Factors (TFs) encoding genes has emerged as a popular approach since
most of them are early stress-responsive genes and control the expression of a set of downstream target
genes. Consequently, there is a higher chance to generate novel cultivars with better tolerance to
either single or multiple stresses. Perhaps, the difficult task when deploying this approach is selecting
appropriate gene(s) for manipulation. In this review, on the basis of the current findings from molecular
and post-genomic studies, our interest is to highlight the current understanding of the roles of TFs
in signal transduction and mediating plant responses towards abiotic stressors. Furthermore, interactions
among TFs within the stress-responsive network will be discussed. The last section will be reserved
for discussing the potential applications of TFs for stress tolerance improvement in plants.
Organic Acids (OAs) are important components in the rhizosphere soil and influence Se bioavailability in soil. OAs have a bidirectional contrasting effect on Se bioavailability. Understanding the ...interaction of OAs with Se is essential to assessing Se bioavailability in soil and clarifying the role of OAs in controlling the behavior and fate of Se in soil. This review examines the mechanisms for the (im)mobilization of Se by OAs and discusses the practical implications of these mechanisms in relation to sequestration and bioavailability of Se in soil.
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•Organic acids can interact with Se in soil by adsorption, complexation and reduction processes.•Organic acids result in Se immobilization and mobilization in soil, thus the bioavailability.•FA–Se may be a latent source of available Se in soil and HA–Se is a sink of Se under some conditions.•The direct association mechanism between Se, and FAs and HAs can be visualized.
•NiO/PPy hybrid films synthesized by simple vapour-phase polymerization.•NiO/PPy ratios obtained by regulating FeCl3 oxidant contents on NiO-nanoparticles.•NiO/PPy hybrid films having high sensing ...performance of response, selectivity, and reversibility to NH3 gas.•Experimental results verified the existence of NiO/PPy hybrid structure.
In this work, NiO/PPy hybrid nanostructured films were fabricated by chemical vapor-phase polymerization using NiO nanoparticles films drop-coated FeCl3 oxidant on Al2O3 substrates. The NiO nanoparticles with a size of about 20 nm were synthesized by a hydrothermal method. Different ratios between NiO and PPy in the NiO/PPy hybrid films were modified by regulating FeCl3 oxidant content when using FeCl3 solutions with concentrations of 0.15, 0.2, 0.4, 0.8, and 1.5 M. X-ray diffraction, scanning electron microscope, high-resolution transmission electron microscopy, Fourier-transform infrared spectroscopy, and Raman scattering spectroscopy were used to analyze specific material characteristics of these films. The gas-sensing performance of the films was examined by exploring their resistances responding to NH3, NO2, H2, CO, and relative humidity at an operating temperature range from 25 to 110 °C. The NiO/PPy hybrid films presented to have a very high sensitivity to NH3 gas in comparison to the non-hybrid films based on only NiO or PPy. The highest sensitivity to NH3 gas (the sensing response S = 246.6 % for 350 ppm at 25 °C) was found for the NiO/PPy film with the used 0.2 M FeCl3 oxidant solution. The gas-sensing performance of the NiO/PPy films was suggested by the main contribution of the hybrid nanostructure between NiO nanoparticles and PPy.
A better understanding of the benefits of selenium (Se) fertilization to alleviate the toxicity of mercury (Hg) on plants and of the underlying mechanisms involved in Hg stress is important for the ...remediation of soils contaminated by Hg. This study is aimed to explore the effects of the application of selenite to alleviate the toxicity of Hg in soils to plants and related mechanisms involved in this process. The chemical (Hg uptake of pak choi), biological (root and shoot length, root and shoot weight) and physiological effects (antioxidant enzyme activities, non-enzymatic antioxidant contents (proline) and lipid peroxidation products (malondialdehyde)) produced over plants by the application of different doses of Hg and Se to soil has been investigated through a pot experiment, which was conducted with exposure to different dosages of mercuric chloride (0, 1.0, 2.0, and 3.0 mg/kg soil) and sodium selenite (0, 0.5, 1.0, and 2.5 mg/kg soil). Results indicated that single high Hg treatment (3.0 mg/kg Hg) resulted in significantly increase in Hg uptake by plants (P < 0.01), thus the growth of pak choi was inhibited. However, the Se application at 1.0 and 2.5 mg/kg led to significantly alleviated Hg uptake by plants (P < 0.05). Meanwhile, the low Se (at 0.5 and 1.0 mg/kg) applied to soil induced significantly improvement the growth of pak choi (P < 0.05) by elevating the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), glutathione peroxidase (GSH-Px) enzymes and the content of chlorophyll (SPAD value) as well as suppressed the lipid peroxidation products contents (MDA) and proline. Results collectively indicated that applied Se played an important role in promoting the detoxification of Hg and growth of pak choi under oxidative stress. Notably, this role may only be significant when Se application at the appropriate concentration (≤ 1.0 mg/kg).
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•High level of Hg in soil produced significant deleterious effects on pak choi.•Se application alleviated Hg toxicity in soil by reducing Hg uptake of pak choi.•Se application resulted in antioxidant ability increase, lipid peroxidation decrease.•Applied low Se level to soil (1.0 mg/kg) significant reduce Hg toxicity to plants.
Comprehensive profiling of actionable mutations in non-small cell lung cancer (NSCLC) is vital to guide targeted therapy, thereby improving the survival rate of patients. Despite the high incidence ...and mortality rate of NSCLC in Vietnam, the actionable mutation profiles of Vietnamese patients have not been thoroughly examined. Here, we employed massively parallel sequencing to identify alterations in major driver genes (EGFR, KRAS, NRAS, BRAF, ALK and ROS1) in 350 Vietnamese NSCLC patients. We showed that the Vietnamese NSCLC patients exhibited mutations most frequently in EGFR (35.4%) and KRAS (22.6%), followed by ALK (6.6%), ROS1 (3.1%), BRAF (2.3%) and NRAS (0.6%). Interestingly, the cohort of Vietnamese patients with advanced adenocarcinoma had higher prevalence of EGFR mutations than the Caucasian MSK-IMPACT cohort. Compared to the East Asian cohort, it had lower EGFR but higher KRAS mutation prevalence. We found that KRAS mutations were more commonly detected in male patients while EGFR mutations was more frequently found in female. Moreover, younger patients (<61 years) had higher genetic rearrangements in ALK or ROS1. In conclusions, our study revealed mutation profiles of 6 driver genes in the largest cohort of NSCLC patients in Vietnam to date, highlighting significant differences in mutation prevalence to other cohorts.
This study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II (PIVKA-II), and combined biomarkers ...for non-B non-C hepatocellular carcinoma (NBNC-HCC). A total of 681 newly-diagnosed primary liver disease subjects (385 non-HCC, 296 HCC) who tested negativity for the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) enrolled in this study. At the cut-off point of 3.8 ng/mL, AFP helps to discriminate HCC from non-HCC with an area under the curve (AUC) value of 0.817 (95% confidence interval CI: 0.785-0.849). These values of AFP-L3 (cut-off 0.9%) and PIVKA-II (cut-off 57.7 mAU/mL) were 0.758 (95%CI: 0.725-0.791) and 0.866 (95%CI: 0.836-0.896), respectively. The Bayesian Model Averaging (BMA) statistic identified the optimal model, including patients' age, aspartate aminotransferase, AFP, and PIVKA-II combination, which helps to classify HCC with better performance (AUC = 0.896, 95%CI: 0.872-0.920, P < 0.001). The sensitivity and specificity of the optimal model reached 81.1% (95%CI: 76.1-85.4) and 83.2% (95%CI: 78.9-86.9), respectively. Further analyses indicated that AFP and PIVKA-II markers and combined models have good-to-excellent performance detecting curative resected HCC, separating HCC from chronic hepatitis, dysplastic, and hyperplasia nodules.
The aim of the present pilot study was to assess the effectiveness of the platelet-rich fibrin (PRF) apical barrier for the placement of MTA for the treatment of teeth with periapical lesions and ...open apices.
A total of thirty teeth on twenty-eight patients with open apices and periapical periodontitis were enrolled and divided into two groups in the present pilot study. In the PRF group (fourteen teeth in thirteen patients), nonsurgical endodontic treatment was performed using PRF as an apical matrix, after which the apical plug of the MTA was created. For the non-PRF group (fourteen teeth in fourteen patients), nonsurgical endodontic therapy was performed using only the MTA for an apical plug with no further periapical intervention. Clinical findings and periapical digital radiographs were used for evaluating the healing progress after periodic follow-ups of 1, 3, 6, and 9 months. The horizontal dimension of the periapical lesion was gauged, and the changes in the dimensions were recorded each time. The Friedman test, Dunn-Bonferroni post hoc correction, and Mann-Whitney U test were used for statistical analysis, with P < 0.05 serving as the threshold for determining statistical significance.
All patients in both groups in the present pilot study had no clinical symptoms after 1 month, with a significant reduction in the periapical lesion after periodic appointments. The lesion width of the PRF group was significantly smaller than that of the non-PRF group in the sixth and ninth month after treatment.
PRF is a promising apical barrier matrix when combined with MTA for the treatment of teeth with open apices and periapical periodontitis. Small number of study subjects and the short time of follow-up period limit the generalizability of these results.
TCTR, TCTR20221109006. Registered 09 November 2022 - Retrospectively registered, https://www.thaiclinicaltrials.org/show/TCTR20221109006 .
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