The ADJUVANT study reported the comparative superiority of adjuvant gefitinib over chemotherapy in disease-free survival of resected EGFR-mutant stage II-IIIA non-small cell lung cancer (NSCLC). ...However, not all patients experienced favorable clinical outcomes with tyrosine kinase inhibitors (TKI), raising the necessity for further biomarker assessment. In this work, by comprehensive genomic profiling of 171 tumor tissues from the ADJUVANT trial, five predictive biomarkers are identified (TP53 exon4/5 mutations, RB1 alterations, and copy number gains of NKX2-1, CDK4, and MYC). Then we integrate them into the Multiple-gene INdex to Evaluate the Relative benefit of Various Adjuvant therapies (MINERVA) score, which categorizes patients into three subgroups with relative disease-free survival and overall survival benefits from either adjuvant gefitinib or chemotherapy (Highly TKI-Preferable, TKI-Preferable, and Chemotherapy-Preferable groups). This study demonstrates that predictive genomic signatures could potentially stratify resected EGFR-mutant NSCLC patients and provide precise guidance towards future personalized adjuvant therapy.
Hand, foot, and mouth disease (HFMD) is a common infectious disease occurring in children under 5 years of age worldwide, and Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CVA-16) are identified ...as the predominant pathogens. In recent years, Coxsackievirus A6 (CVA-6) and Coxsackievirus A10 (CVA-10) have played more and more important role in a series of HFMD outbreaks. This study aimed to understand the epidemic characteristics associated with HFMD outbreak in Guangzhou, 2018.
The clinical and laboratory data of 1220 enterovirus-associated HFMD patients in 2018 were analysed in this study. Molecular diagnostic methods were performed to identify its serotypes. Phylogenetic analyses were depicted based on the complete VP1 gene.
There were 21 enterovirus serotypes detected in Guangzhou in 2018. Three serotypes of enterovirus, CVA-6 (364/1220, 29.8%), CVA-10 (305/1220, 25.0%), and CVA-16 (397/1220, 32.5%), were identified as the causative pathogens and accounted for 87.3% among all 1220 HFMD patients. In different seasons, CVA-6 was the predominant pathogen of HFMD during autumn, and CVA-10 as well as CVA-16 were more prevalent in summer. Patients infected by CVA-6, CVA-10 or CVA-16 showed similar clinical features and laboratory characteristics, and the ratios of severe HFMD were 5.8, 5.9, and 1.5% in the three serotypes. Phylogenetic analyses of VP1 sequences showed that the CVA-6, CVA-10, and CVA-16 sequences belonged to the sub-genogroup E2, genogroup E, and genogroup B1, respectively.
CVA-6, CVA-10, and CVA-16 were the predominant and co-circulated serotypes in Guangzhou China, 2018, which should be the new target for prevention and control of HFMD. Our findings provide useful information for diagnosis, treatment, and prevention of HFMD.
Serine/threonine protein kinase 25 (STK25) is a critical regulator of ectopic lipid storage, glucose and insulin homeostasis, fibrosis, and meta-inflammation. More and more studies have revealed a ...strong correlation between STK25 and human diseases. On the one hand, STK25 can affect glucose and fatty acid metabolism in normal cells or tumors. On the other hand, STK25 participates in autophagy, cell polarity, cell apoptosis, and cell migration by activating various signaling pathways. This article reviews the composition and function of STK25, the energy metabolism and potential drugs that may target STK25, and the research progress of STK25 in the occurrence and development of tumors, to provide a reference for the clinical treatment of tumors.
As a cool-season grass species, tall fescue (Festuca arundinacea) is challenged by increasing temperatures. Heat acclimation or activation of leaf senescence, are two main strategies when tall fescue ...is exposed to heat stress (HS). However, lacking a genome sequence, the complexity of hexaploidy nature, and the short read of second-generation sequencing hinder a comprehensive understanding of the mechanism. This study aims to characterize the molecular mechanism of heat adaptation and heat-induced senescence at transcriptional and post-transcriptional levels.
Transcriptome of heat-treated (1 h and 72 h) and senescent leaves of tall fescue were generated by combining single-molecular real-time and Illumina sequencing. In total, 4076; 6917, and 11,918 differentially expressed genes (DEGs) were induced by short- and long-term heat stress (HS), and senescence, respectively. Venn and bioinformatics analyses of DEGs showed that short-term HS strongly activated heat shock proteins (Hsps) and heat shock factors (Hsfs), as well as specifically activated FK506-binding proteins (FKBPs), calcium signaling genes, glutathione S-transferase genes, photosynthesis-related genes, and phytohormone signaling genes. By contrast, long-term HS shared most of DEGs with senescence, including the up-regulated chlorophyll catabolic genes, phytohormone synthesis/degradation genes, stress-related genes, and NACs, and the down-regulated photosynthesis-related genes, FKBPs, and catalases. Subsequently, transient overexpression in tobacco showed that FaHsfA2a (up-regulated specifically by short-term HS) reduced cell membrane damages caused by HS, but FaNAC029 and FaNAM-B1 (up-regulated by long-term HS and senescence) increased the damages. Besides, alternative splicing was widely observed in HS and senescence responsive genes, including Hsps, Hsfs, and phytohormone signaling/synthesis genes.
The short-term HS can stimulate gene responses and improve thermotolerance, but long-term HS is a damage and may accelerate leaf senescence. These results contribute to our understanding of the molecular mechanism underlying heat adaptation and heat-induced senescence.
Although more attention has been paid to microplastics (MPs) pollution in environment, research on the synthetic influence of microplastic and heavy metals remains limited. To help fill this ...information gap, we investigated the adsorption behavior of virgin polyvinyl chloride microplastics (PVCMPs) (≤450 µm white spherical powder) on cadmium (II). The effects on seed germination, seedling growth, photosynthetic system, oxidative stress indicators of lettuce, and changes in Cd bioavailability were evaluated under Cd2+ (25 μmol/L), PVCMPs (200 mg/L), and PVCMP-Cd combined (200 mg/L + 25 μmol/L) exposures in hydroponic system. The results demonstrated that the PVCMPs effectively adsorbed Cd ions, which validated by the pseudo-second-order kinetic and the Langmuir isotherm models, indicating the sorption of Cd2+ on the PVCMPs was primary chemisorption and approximates monomolecular layer sorption. Compared to MPs, Cd significantly inhibits plant seed germination and seedling growth and development. However, Surprising improvement in seed germination under PVCMPs-Cd exposure was observed. Moreover, Cd2+ and MPs alone or combined stress caused oxidative stress with reactive oxygen species (ROS) including H2O2, O2- and Malondialdehyde (MDA) accumulation in plants, and substantially damaged to photosynthesis. With the addition of PVCMPs, the content of Cd in the leaves significantly (P<0.01) decreased by 1.76-fold, and the translocation factor and Cd2+removal rate in the water substantially (P<0.01) decreased by 6.73-fold and 1.67-fold, respectively in contrast to Cd2+ stress alone. Therefore, it is concluded the PVCMP was capable of reducing Cd contents in leaves, alleviating Cd toxicity in lettuce. Notably, this study provides a scientific foundation and reference for comprehending the toxicological interactions between microplastics and heavy metals in the environment.
•PVCMPs effectively adsorb Cd ions, validated by kinetic and isotherm models.•Causing oxidative stress with ROS accumulation, and substantial damage to photosynthesis under alone and combined stress.•Surprising improvement in seed germination under PVCMPs-Cd exposure.•PVCMPs reduce Cd concentrations in leaves, alleviating Cd toxicity in lettuce.
Background: To retrospectively assess the efficacy and safety of sevoflurane inhalation anesthesia for the treatment of ankyloglossia on uncooperative pediatric outpatients. Methods: Pediatric ...patients with ankyloglossia (Degree 3 to Degree 5, coarse or thick) were enrolled in this retrospective analysis. The treatment of ankyloglossia was conducted with sevoflurane induction (8%) and maintenance (2%−3%) continuously with nasal cannula. Heart rate, respiratory rate, electrocardiogram, blood pressure, and peripheral blood oxygen saturation were monitored continuously during operations. Onset time, recovery time, adverse complications were recorded until Aldrete score was ≥ 9. Patients were followed up 24 h, 1 and 2 weeks after operation. Results: One hundred and thirty-seven children completed surgeries with ideal anesthesia status. The operation duration were 10-20 minutes (15.15 ± 2.04), and the children woke up in 10-30 minutes (18.95 ± 3.91). The average intra-operative blood oxygen saturation were lower than preoperative ones (p = .005). Adverse effects were 13.1%, including 3 (2.2%) respiratory depression (SpO
2
< 90%), 11 (8.0%) dysphoria and crying during recovery, 2 (1.5%) transient fever symptom. Conclusions: Sevoflurane inhalation anesthesia in the treatment of ankyloglossia resulted in rapid onset and recovery, with few adverse reactions and significant clinical efficacy, and was suited to uncooperative pediatric outpatients.
Whole body vibration (WBV) has been suggested to improve athletes' neuromuscular strength and power. This study investigated the effect of single WBV stimulation on volleyball-specific performance. ...The participants were 20 elite male volleyball players who performed a 1-min warm-up exercise on a vibration platform at a frequency of 30 Hz and peak-to-peak displacement of 2 mm. After the warm-up exercise, the participants performed a blocking agility test (BAT), 10-m sprinting test, agility T-test, and counter movement jump test. We compared the participants' performance at four time points (Pretest, Post 0, Post 1, and Post 2). The results revealed that the participants' BAT performance and maximum rate of force development improved significantly 1 min after the vibration stimulation (p < 0.01). The WBV (frequency of 30-Hz, peak-to-peak displacement of 2 mm) intervention significantly improved the volleyball-specific defensive performance and speed strength of the participants. Accordingly, by undergoing WBV as a form of warm-up exercise, the technique and physical fitness of volleyball players can be improved.
Unlike the single grating Czerny-Turner configuration spectrometers, a super-high spectral resolution optical spectrometer with zero coma aberration is first experimentally demonstrated by using a ...compound integrated diffraction grating module consisting of 44 high dispersion sub-gratings and a two-dimensional backside-illuminated charge-coupled device array photodetector. The demonstrated super-high resolution spectrometer gives 0.005 nm (5 pm) spectral resolution in ultra-violet range and 0.01 nm spectral resolution in the visible range, as well as a uniform efficiency of diffraction in a broad 200 nm to 1000 nm wavelength region. Our new zero-off-axis spectrometer configuration has the unique merit that enables it to be used for a wide range of spectral sensing and measurement applications.
To reproduce hemodynamic stress microenvironments of endothelial cells
in vitro
is of vital significance, by which one could exploit the quantitative impact of hemodynamic stresses on endothelial ...function and seek innovative approaches to prevent circulatory system diseases. Although microfluidic technology has been regarded as an effective method to create physiological microenvironments, a microfluidic system to precisely reproduce physiological arterial hemodynamic stress microenvironments has not been reported yet. In this paper, a novel microfluidic chip consisting of a cell culture chamber with on-chip afterload components designed by the principle of input impedance to mimic the global hemodynamic behaviors is proposed. An external feedback control system is developed to accurately generate the input pressure waveform. A lumped parameter hemodynamic model (LPHM) is built to represent the input impedance to mimic the on-chip global hemodynamic behaviors. Sensitivity analysis of the model parameters is also elaborated. The performance of reproducing physiological blood pressure and wall shear stress is validated by both numerical characterization and flow experiment. Investigation of intracellular calcium ion dynamics in human umbilical vein endothelial cells is finally conducted to demonstrate the biological applicability of the proposed microfluidic system.
This paper reports a novel microfluidic system containing a microfluidic chip with a feedback control system to precisely and stably reproduce the physiologically relevant BP and WSS signals in the human common carotid artery.
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