ABSTRACT
OBJECTIVES: Lung cancer is one of the malignant tumors that threaten human health seriously. Long non-coding RNA (lncRNA) is an important factor affecting tumorigenesis and development. However, the mechanism of lncRNA in lung cancer progression remains to be further explored. METHODS: In this study, the TCGA database was analyzed, and LINC01572 was found to be increased in lung adenocarcinoma (LUAD) tissues. Thereafter, with the help of databases including lncBase, TargetScan, and mirDIP, as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, LINC01572/miRNA-338-5p/TTK regulatory axis and downstream p53 signaling pathway were excavated. qRT-PCR was adopted to detect levels of LINC01572, miRNA-338-5p, and TTK in LUAD cells. The role that LINC01572 played in LUAD cells was validated by CCK-8 assay, flow cytometry, colony formation, Transwell, and scratch healing assays. The binding ability between LINC01572/TTK and miRNA-338-5p was then verified by dual-luciferase and RIP analysis. KEY FINDINGS: The results of this study demonstrated that LINC01572 was elevated in LUAD cells compared with normal cells. The overexpression of LINC01572 promoted the proliferative and migratory properties of LUAD cells but inhibited cell apoptosis. The inhibition of LINC01572 resulted in the opposite result. In addition, rescue experiments revealed that LINC01572, as a molecular sponge of miRNA-338-5p, targeted TTK to manipulate p53 for facilitating LUAD cell malignant progression. Apart from this, we constructed a mouse xenograft model and confirmed that the knockdown of LINC01572 hindered the growth of LUAD solid tumors in vivo. CONCLUSIONS: Our findings illuminated the molecular mechanism of LINC01572 influencing LUAD and provided new insights for targeted therapy of LUAD cells.
Subject(s)
Adenocarcinoma of Lung , Disease Progression , Gene Expression Regulation, Neoplastic , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Tumor Suppressor Protein p53 , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Tumor Suppressor Protein p53/metabolism , Tumor Suppressor Protein p53/genetics , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/metabolism , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/metabolism , Animals , Cell Line, Tumor , Mice , Cell Proliferation/genetics , Mice, Nude , Protein-Tyrosine Kinases/genetics , Protein-Tyrosine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Mice, Inbred BALB C , Signal Transduction , Cell Movement/genetics , Apoptosis/genetics , A549 CellsABSTRACT
Nisin (Ni) is a polypeptide bacteriocin produced by lactic streptococci (probiotics) that can inhibit the majority of gram-positive bacteria, and improve the growth performance of broilers, and exert antioxidative and anti-inflammatory properties. The present study investigated the potential preventive effect of Nisin on necrotic enteritis induced by Clostridium perfringens (Cp) challenge. A total of 288 Arbor Acres broiler chickens of 1-d-olds were allocated using 2â ×â 2 factorial arrangement into four groups with six replicates (12 chickens per replicate), including: (1) control group (Con, basal diet), (2) Cp challenge group (Cp, basal dietâ +â 1.0â ×â 108 CFU/mL Cp), (3) Ni group (Ni, basal dietâ +â 100 mg/kg Ni), and (4) Niâ +â Cp group (Niâ +â Cp, basal dietâ +â 100 mg/kg Niâ +â 1.0â ×â 108 CFU/mL Cp). The results showed that Cp challenge decreased the average daily gain (ADG) of days 15 to 21 (P<0.05) and increased interleukin-6 (IL-6) content in the serum (Pâ <â 0.05), as well as a significant reduction in villus height (VH) and the ratio of VH to crypt depth (VCR) (P<0.05) and a significant increase in crypt depth (CD) of jejunum (P<0.05). Furthermore, the mRNA expressions of Occludin and Claudin-1 were downregulated (P<0.05), while the mRNA expressions of Caspase3, Caspase9, Bax, and Bax/Bcl-2 were upregulated (P<0.05) in the jejunum. However, the inclusion of dietary Ni supplementation significantly improved body weight (BW) on days 21 and 28, ADG of days 15 to 21 (P<0.05), decreased CD in the jejunum, and reduced tumor necrosis factor-α (TNF-α) content in the serum (P<0.05). Ni addition upregulated the mRNA levels of Claudin-1 expression and downregulated the mRNA expression levels of Caspase9 in the jejunum (P<0.05). Moreover, Cp challenge and Ni altered the cecal microbiota composition, which manifested that Cp challenge decreased the relative abundance of phylum Fusobacteriota and increased Shannon index (P<0.05) and the trend of phylum Proteobacteria (0.05
Necrotic enteritis (NE), a severe digestive disorder in broiler chickens caused by Clostridium perfringens (Cp), a gram-positive bacterium, is a widespread issue in the global poultry industry, leading to significant economic losses. Nisin (Ni), a polypeptide bacteriocin produced by probiotic lactic streptococci, has been found to enhance daily weight gain and feed intake, while also exhibiting inhibitory effects on gram-positive bacteria and anti-inflammatory properties. In this study, a NE infection model in broilers was established to examine the potential preventive effects of Ni. These results demonstrated that Cp challenge reduced growth performance, caused inflammatory responses and intestinal apoptosis, damaged intestinal morphology and barrier function, and was accompanied by changes in the composition of the gut microbiota. Dietary supplementation with Ni improved growth performance and protected intestine against Cp challenge-induced damage in broilers. As a result, Ni may be a potential safe and effective additive for NE prevention in broiler production.
Subject(s)
Clostridium Infections , Nisin , Poultry Diseases , Animals , Clostridium perfringens , Chickens , Intestines , Clostridium Infections/prevention & control , Clostridium Infections/veterinary , Clostridium Infections/microbiology , Nisin/pharmacology , Claudin-1 , bcl-2-Associated X Protein/pharmacology , Diet/veterinary , RNA, Messenger/genetics , Immunity , Poultry Diseases/microbiology , Dietary Supplements , Animal Feed/analysisABSTRACT
INTRODUCTION: To study the prognostic factors of patients with chest pain and without obstructive coronary artery disease is of great significance for the management of such patients. We assessed whether a high-sensitivity troponin I (hs-TnI) is associated with prognosis in patients with chest pain and without obstructive coronary artery disease. METHODS: From 2011 to 2017, 489 consecutively hospitalized patients with chest pain and without significant coronary artery stenosis (<50%) were tested for hs-TnI and underwent stress myocardial contrast echocardiography (MCE). Myocardial blood flow reserve (MBFR) was measured by stress MCE. Patients were followed (median, 41 months) for composite endpoints, including cardiovascular death and non-fatal myocardial infarction. Cox proportional hazards models were performed to determine associations between hs-TnI and the composite endpoints. RESULTS: Among 489 patients with chest pain and without significant coronary artery stenosis, 257 patients (52.6%) had elevated hs-TnI. Compared to patients with normal hs-TnI, patients with elevated hs-TnI were older (p = 0.013) and had a higher prevalence of atrial fibrillation (p = 0.003), higher left ventricular mass index (p = 0.002) and E/e' septal (p < 0.001), and a lower MBFR (p < 0.001). After adjustment, there was still a significant association between hs-TnI and MBFR (odds ratio = 1.145; 95% confidence interval [CI], 1.079-1.214; p < 0.001). Compared with patients with normal hs-TnI, patients with elevated hs-TnI had a greater cumulative event rate (log-rank p = 0.002). Males (hazard ratio [HR], 4.770; 95% CI, 1.175-19.363; p = 0.029) and reduced MBFR (HR, 2.496; 95% CI, 1.446-4.311; p = 0.001) were risk factors associated with composite endpoints in patients with elevated hs-TnI. CONCLUSIONS: In patients with chest pain and without obstructive coronary artery disease, elevated hs-TnI is associated with decreased myocardial perfusion by contrast echocardiography as well as a higher incidence of cardiovascular events.
Subject(s)
Coronary Artery Disease , Coronary Stenosis , Myocardial Infarction , Male , Humans , Coronary Artery Disease/diagnostic imaging , Myocardial Infarction/epidemiology , Prognosis , Troponin I , Coronary Stenosis/diagnostic imaging , Chest Pain/etiology , BiomarkersABSTRACT
Pollen development and its fertility are obligatory conditions for the reproductive success of flowing plants. Sucrose transporter 3 (OsSUT3) is known to be preferentially expressed and may play critical role in developing pollen. A 31-bp InDel was identified as a unique variation and was shown to be responsible for the expression of downstream gene in our previous study. In this study, to analyze the changes of gene expression triggered by 31-bp InDel during pollen development, two vectors (p385-In/Del::OsSUT3-GUS) were constructed and then stably introduced into rice. Histochemical and quantitative real-time PCR (qRT-PCR) analysis of transgenic plants showed that 31-bp deletion drastically reduced the expressions of downstream genes, including both OsSUT3 and GUS in rice panicle at booting stage, especially that of OsSUT3. The transcriptome profile of two types of panicles at booting stage revealed a total of 1028 differentially expressed genes (DEGs) between 31-bp In and 31-bp Del transgenic plants. Further analyses showed that 397 of these genes were significantly enriched for the 'metabolic process' and 'binding'. Among them, nineteen genes had a strong relationship with starch and sucrose metabolism and were identified as candidate genes potentially associated with the starch accumulation in rice pollen, which that was also verified via qRT-PCR. In summary, 31-bp InDel plays a crucial role not only in the regulation of downstream genes but in the expression of sucrose-starch metabolizing genes in multiple biological pathways, and provides a different regulation mechanism for sucrose metabolism in pollen.
Subject(s)
Oryza , Oryza/metabolism , 5' Untranslated Regions , Gene Expression Profiling , Transcriptome , Starch/metabolism , Gene Expression Regulation, PlantABSTRACT
In recent years, the accelerated development of G-quadruplexes and hydrogels has driven the development of intelligent biomaterials. Based on the excellent biocompatibility and special biological functions of G-quadruplexes, and the hydrophilicity, high-water retention, high water content, flexibility and excellent biodegradability of hydrogels, G-quadruplex hydrogels are widely used in various fields by combining the dual advantages of G-quadruplexes and hydrogels. Here, we provide a systematic and comprehensive classification of G-quadruplex hydrogels in terms of preparation strategies and applications. This paper reveals how G-quadruplex hydrogels skillfully utilize the special biological functions of G-quadruplexes and the skeleton structure of hydrogels, and expounds its applications in the fields of biomedicine, biocatalysis, biosensing and biomaterials. In addition, we deeply analyze the challenges in preparation, applications, stability and safety of G-quadruplex hydrogels, as well as potential future development directions.
Subject(s)
Biocompatible Materials , G-Quadruplexes , Hydrogels , Hydrogels/chemistry , Hydrogels/therapeutic use , Biocompatible Materials/chemistry , Biocompatible Materials/therapeutic use , Humans , Biosensing Techniques , Wound Healing , Infections/drug therapy , Neoplasms/drug therapy , AnimalsABSTRACT
Synthetic red fluorescent protein (RFP) chromophores have emerged as valuable tools for biological imaging and therapeutic applications, but their application in the visualization of endogenous RNA G-quadruplexes (G4s) in living cells has been rarely reported so far. Here, by integrating the group of the excellent G4 dye ThT, we modulate RFP chromophores to create a novel fluorescent probe DEBIT with red emission. DEBIT selectively recognizes the G4 structure with the advantage of strong binding affinity, high selectivity, and excellent photostability. Using DEBIT as a fluorescent indicator, the real-time monitoring of RNA G4 in biological systems can be achieved. In summary, our work expands the application of synthetic RFP chromophores and provides an essential dye category to the classical G4 probes.
Subject(s)
G-Quadruplexes , Fluorescent Dyes/chemistry , Luminescent Proteins/genetics , RNA/chemistry , Red Fluorescent ProteinABSTRACT
Ultra-thin rare earth iron garnet (RIG) films with a narrow ferromagnetic resonance (FMR) line width and a low damping factor have attracted a great deal of attention for microwave and spintronic applications. In this work, 200â nm Y3(GaAlFe)5O12 garnet (GaAl-YIG) films were prepared on gadolinium gallium garnet (GGG) substrates by liquid-phase epitaxy (LPE) with low saturation magnetization. The microstructural properties, chemical composition, and magnetostatic and dynamic magnetization characteristics of the films are discussed in detail. According to the structural analysis, these films exhibit a low surface roughness of less than 0.5â nm. The GaAl-YIG films show an obvious temperature dependence of lattice parameter and strain state, and the film's parameter is perfectly matched with that of the GGG substrate at 810°C. There is a clear variation in the Pb level, which brings about a gradual enhancement of the coercivity and a diminution of the squareness ratio of magnetic hysteresis loops as the growth temperature is reduced. Slight changes in surface roughness, strain condition and content of Pb induce the FMR line width and damping factor to vary on a small scale. The line width is less than 10.17â Oe at 12â GHz and the damping factor is of the order of 10-4. All these properties demonstrate that these ultra-thin GaAl-YIG films are of benefit for the development of devices operated at lower frequencies and in lower fields.
ABSTRACT
Mixed brushes consisting of flexible and semiflexible polymers of the same chain length exhibit a height-switching phenomenon because of rigidity-dependent critical adsorption [Yang et al. Macromolecules 2020, 53, 7369]. Semiflexible polymers stand higher at weak surface attraction (high temperature), but they close to the attractive surface at strong attraction (low temperature). In this work, the height-switching dynamics of the mixed polymer brushes is studied by Metropolis Monte Carlo simulation. The height-switching time is calculated by a sudden change in the surface attraction. Two surface attraction change modes, i.e., the weak-to-strong mode where the attraction is changed from weak to strong and the strong-to-weak mode where it is changed from strong to weak, are investigated. Simulation results show that the height-switching time is related to the grafting density, the polymer stiffness, and surface attraction change mode. We find that the height-switching time is significantly decreased for the strong-to-weak mode. And our results also show that the height switching in the mixed polymer brushes is reversible.
ABSTRACT
Coronary artery spasm (CAS) may induce lethal ventricular arrhythmia due to severe and prolonged vessel constriction. Tyrosine kinase inhibitors are associated with the occurrence of CAS. Optimal medical treatment is the first-line therapeutic option for the management of CAS, whereas patients who experienced aborted sudden cardiac death (SCD) may benefit from implantable cardioverter-defibrillator (ICD) implantation. We report a case of a 63-year-old Chinese man receiving tyrosine kinase inhibitor treatment for liver cancer who presented with recurrent chest discomfort and syncope with an elevation of high-sensitivity troponin T. Emergent coronary angiography showed sub-total occlusion of the left anterior descending artery without other signs of CAS. Percutaneous transluminal coronary angioplasty with a drug-coated balloon was performed successfully with the guidance of intravascular ultrasound. After 5 months, the patient returned to the emergency room for chest discomfort and another episode of syncope. The electrocardiogram showed ST-segment elevation in the inferior and V5-V6 leads compared to the previous event. Coronary angiography was repeated immediately and showed significant luminal stenosis at the midportion of the right coronary artery (RCA), whereas, after administration of intracoronary nitroglycerine, a remarkable recovery of RCA patency was noticed. A diagnosis of CAS was made, and soon after that, the patient rapidly developed ventricular arrhythmia in the coronary care unit. After successful resuscitation, the patient recovered completely and received long-acting calcium channel blockers as well as nitrates therapy. ICD implantation was performed considering the high risk of recurrence of life-threatening ventricular arrhythmia. During the follow-up period, the patient has been free of angina, syncope, or ventricular arrhythmia, and ICD interrogation showed no ventricular tachycardia or ventricular fibrillation. We first reported the case of a patient with CAS induced by regorafenib treatment complicated with severe atherosclerotic coronary disease who survived from sudden cardiac arrest. ICD implantation is indicated in patients who experienced aborted SCD for the prevention of the next lethal ventricular arrhythmia.
ABSTRACT
Acetylcholinesterase (AChE), a crucial enzyme related to liver function, is involved in numerous physiological processes such as neurotransmission and muscular contraction. The currently reported techniques for detecting AChE mainly rely on a single signal output, limiting their high-accuracy quantification. The few reported dual-signal assays are challenging to implement in dual-signal point-of-care testing (POCT) because of the need for large instruments, costly modifications, and trained operators. Herein, we report a colorimetric and photothermal dual-signal POCT sensing platform based on CeO2-TMB (3,3',5,5'-tetramethylbenzidine) for the visualization of AChE activity in liver-injured mice. The method compensates for the false positives of a single signal and realizes the rapid, low-cost portable detection of AChE. More importantly, the CeO2-TMB sensing platform enables the diagnosis of liver injury and provides an effective tool for studying liver disease in basic medicine and clinical applications. Rapid colorimetric and photothermal biosensor for sensitive detection of acetylcholinesterase (I) and acetylcholinesterase levels in mouse serum (II).
Subject(s)
Acetylcholinesterase , Biosensing Techniques , Mice , Animals , Colorimetry/methods , Liver , Benzidines , Biosensing Techniques/methodsABSTRACT
Erianthus produces substantial biomass, exhibits a good Brix value, and shows wide environmental adaptability, making it a potential biofuel plant. In contrast to closely related sorghum and sugarcane, Erianthus can grow in degraded soils, thus releasing pressure on agricultural lands used for biofuel production. However, the lack of genomic resources for Erianthus hinders its genetic improvement, thus limiting its potential for biofuel production. In the present study, we generated a chromosome-scale reference genome for Erianthus fulvus Nees. The genome size estimated by flow cytometry was 937 Mb, and the assembled genome size was 902 Mb, covering 96.26% of the estimated genome size. A total of 35 065 protein-coding genes were predicted, and 67.89% of the genome was found to be repetitive. A recent whole-genome duplication occurred approximately 74.10 million years ago in the E. fulvus genome. Phylogenetic analysis showed that E. fulvus is evolutionarily closer to S. spontaneum and diverged after S. bicolor. Three of the 10 chromosomes of E. fulvus formed through rearrangements of ancestral chromosomes. Phylogenetic reconstruction of the Saccharum complex revealed a polyphyletic origin of the complex and a sister relationship of E. fulvus with Saccharum sp., excluding S. arundinaceum. On the basis of the four amino acid residues that provide substrate specificity, the E. fulvus SWEET proteins were classified as mono- and disaccharide sugar transporters. Ortho-QTL genes identified for 10 biofuel-related traits may aid in the rapid screening of E. fulvus populations to enhance breeding programs for improved biofuel production. The results of this study provide valuable insights for breeding programs aimed at improving biofuel production in E. fulvus and enhancing sugarcane introgression programs.
Subject(s)
Saccharum , Saccharum/genetics , Biofuels , Phylogeny , Chromosomes, Plant/genetics , Plant BreedingABSTRACT
With the development of miniaturization of high-energy laser systems, a new Faraday rotator material must be studied to realize the miniaturization and integration of optical isolators. In this paper, high-quality (TbBi)3Fe5O12 (TbBiIG) and Ca-doped (TbBi)3Fe5O12 (Ca: TbBiIG) single crystal films with hundreds of microns thickness were grown by liquid phase epitaxy method on (111) oriented garnet substrate. The crystal structure, magneto-optical (MO), optical and laser induced damage properties were investigated in detail. We found that the (TbBi)3Fe5O12 film has outstanding magneto-optical and laser-induced damage properties. Optical and MO properties indicate that TbBiIG films have a high specific faraday rotation angle of 1452 deg/cm at 1310 nm, and 2812 deg/cm at 1064 nm, absorption coefficient (α) is 5.63 cm-1 and 15.7 cm-1 at 1310 nm and 1064 nm, respectively. The laser-induced damage threshold (LIDT) of TbBiIG irradiated by a multi-frequency laser is 8.91 J/cm2. The light absorption has a significant impact on LIDT value. Rare-earth ion doped iron garnet (RIG) material is a very potential MO material, which can greatly reduce the size and weight of optical isolators in the 1064 nm band.
ABSTRACT
OBJECTIVE: To assess the cognitive effectiveness and safety of tau-targeting drugs for Alzheimer's disease (AD) METHODS: The MEDLINE, Embase, Cochrane Library, PsycINFO, ClinicalTrials.gov, and WHO International Clinical Trials Registry Platform databases were searched from inception to 22 November 2021. A systematic review and meta-analysis of randomized controlled trials were performed RESULTS: Thirty-four randomized controlled trials comprising 5549 participants, of which fifteen (51.7%) had a low risk of bias, were included. The meta-analysis showed no differences in the cognitive subscale of the AD: Assessment Scale (ADAS-Cog) between anti-tau drugs and placebo (mean difference [MD]: -0.77, 95% CI: -1.64 to 0.10; minimal important difference 3.1-3.8 points, moderate certainty evidence). For ADAS-Cog, the results subgroup analysis suggested a statistical effect of tau posttranslational modifications on drug inhibition (MD: -0.80, 95% CI: -1.43 to -0.17), which was not seen with tau aggregation inhibitors or immunotherapy (interaction p = 0.24). A total of 11.0%, 5.2%, and 4.8% of drugs inhibiting tau aggregation, immunotherapy, and drugs targeting posttranslational modifications, respectively, had a reduced risk of dropouts due to adverse events (AEs). DISCUSSION: Current evidence suggests that anti-tau drugs are unlikely to have an important impact on slowing cognitive impairment. Although the subgroup analysis suggested that inhibition of tau posttranslational modifications is statistically effective and generally safer because of reduced dropouts due to AEs, the analysis has limited credibility. Additional large-scale and well-designed randomized and placebo-controlled trials will be necessary to explore the benefit of a certain type of anti-tau drug for AD.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/drug therapy , Cognitive Dysfunction/drug therapyABSTRACT
Adsorption of polymer chains on a solid surface is a universal interfacial behavior. Loops in the adsorbed chains are considered to exert a significant effect on the overall properties of a substrate-supported polymer film via entanglement with non-adsorbed chains in the film. In this work, the size and stability of loops formed by adsorbed homopolymer chains on an attractive substrate were studied by Langevin dynamics simulations. The size of loops decreases while the stability increases with increasing attraction strength of the substrate. In contrast, with an increase in the polymer concentration, the size of loops increases but the stability decreases. However, both the size and stability of loops increase with increasing chain length. Simulation results show that the optimal conditions for forming large and stable loops are long homopolymer chains, substrates with moderate attraction strength, and moderate polymer concentration.
ABSTRACT
Saccharum spontaneum is a founding Saccharum species and exhibits wide variation in ploidy levels. We have assembled a high-quality autopolyploid genome of S. spontaneum Np-X (2n = 4x = 40) into 40 pseudochromosomes across 10 homologous groups, that better elucidates recent chromosome reduction and polyploidization that occurred circa 1.5 million years ago (Mya). One paleo-duplicated chromosomal pair in Saccharum, NpChr5 and NpChr8, underwent fission followed by fusion accompanied by centromeric split around 0.80 Mya. We inferred that Np-X, with x = 10, most likely represents the ancestral karyotype, from which x = 9 and x = 8 evolved. Resequencing of 102 S. spontaneum accessions revealed that S. spontaneum originated in northern India from an x = 10 ancestor, which then radiated into four major groups across the Indian subcontinent, China, and Southeast Asia. Our study suggests new directions for accelerating sugarcane improvement and expands our knowledge of the evolution of autopolyploids.
Subject(s)
Saccharum , Chromosomes , Genome, Plant/genetics , Genomics , Ploidies , Saccharum/geneticsABSTRACT
The ferrimagnetic insulator iron garnets, tailored artificially with specific compositions, have been widely utilized in magneto-optical (MO) devices. The adjustment on synthesis always induces structural variation, which is underestimated due to the limited knowledge of the local structures. Here, by analyzing the structure and magnetic properties, two different antiphase boundaries (APBs) with individual interfacial structure are investigated in substituted iron garnet film. We reveal that magnetic signals decrease in the regions close to APBs, which implies degraded MO performance. In particular, the segregation of oxygen deficiencies across the APBs directly leads to reduced magnetic elements, further decreases the magnetic moment of Fe and results in a higher absorption coefficient close to the APBs. Furthermore, the formation of APBs can be eliminated by optimizing the growth rate, thus contributing to the enhanced MO performance. These analyses at the atomic scale provide important guidance for optimizing MO functional materials.
ABSTRACT
Choroidal metastasis as an initial presenting feature of lung cancer with EML4-ALK translocation is exceedingly rare and greatly impacts patient quality of life (QOL). There are no recommended treatments for such patients, and palliative care remains limited. It is unclear whether surgical resection of primary pulmonary lesions, systemic antitumor therapy, targeted therapy, or localized ocular therapy are effective in treating choroidal metastases in EML4-ALK rearranged oligometastatic non-small cell lung cancer (NSCLC). Here, we present the case of choroidal metastases secondary to lung cancer and EML4-ALK translocation in a 57-year-old woman who firstly underwent resection of lung lesions followed by oral administration of crizotinib without local treatment or systemic chemotherapy. Since then she had a rapid and complete response to crizotinib with 27 months of progression-free survival.
ABSTRACT
Karyotypes provide key cytogenetic information on the phylogenetic relationships and evolutionary origins in related eukaryotic species. Despite our knowledge of the chromosome numbers of sugarcane and its wild relatives, the chromosome composition and evolution among the species in the Saccharum complex have been elusive owing to the complex polyploidy and the large numbers of chromosomes of these species. Oligonucleotide-based chromosome painting has become a powerful tool of cytogenetic studies especially for plant species with large numbers of chromosomes. We developed oligo-based chromosome painting probes for all 10 chromosomes in Saccharum officinarum (2n = 8x = 80). The 10 painting probes generated robust fluorescence in situ hybridization signals in all plant species within the Saccharum complex, including species in the genera Saccharum, Miscanthus, Narenga and Erianthus. We conducted comparative chromosome analysis using the same set of probes among species from four different genera within the Saccharum complex. Excitingly, we discovered several novel cytotypes and chromosome rearrangements in these species. We discovered that fusion from two different chromosomes is a common type of chromosome rearrangement associated with the species in the Saccharum complex. Such fusion events changed the basic chromosome number and resulted in distinct allopolyploids in the Saccharum complex.
Subject(s)
Chromosome Painting , Saccharum , Chromosome Painting/methods , Chromosomes, Plant/genetics , In Situ Hybridization, Fluorescence/methods , Phylogeny , Saccharum/geneticsABSTRACT
We report the magneto-optical Faraday response of bismuth-gadolinium-substituted rare-earth iron garnet at terahertz frequencies ranging from 100â GHz to 1.2 THz. The maximum transmittance of ±45° component is about 60% near the frequency point of 0.63 THz. When the external magnetic field change from -100 mT to +100 mT, the Faraday rotation angle is between -6° and +7.5°. The overall change of ellipticity is relatively small. The maximum value of the Verdet constant is about 260 °/mm/T at 0.1 THz and then gradually decreases to 80 °/mm/T at 1.2 THz. Within the considered frequency range, the thick film exhibits magnetically tunable, non-reciprocal characters and a strong magneto-optical effect within a small external magnetic field at room temperature, which will be widely used for the terahertz isolators, circulators, nonreciprocal phase shifters, and magneto-optical modulators.
ABSTRACT
Tumor necrosis factor α-induced protein 1 (TNFAIP1) has been documented as a vital regulator of apoptosis and oxidative stress under various pathological conditions. However, whether TNFAIP1 plays a role in myocardial ischemia/reperfusion (I/R) injury has not been well investigated. This work aimed to evaluate the possible role of TNFAIP1 in mediating myocardial I/R injury. Firstly, we demonstrated that TNFAIP1 expression was dramatically increased in rat cardiomyocytes following hypoxia/reoxygenation (H/R) in vitro, and in rat myocardial tissues following I/R treatment in vivo. Silencing of TNFAIP1 alleviated H/R-induced apoptosis, oxidative stress and inflammatory response in rat cardiomyocytes in vitro. Moreover, knockdown of TNFAIP1 ameliorated I/R-induced myocardial injury, infarction size, cardiac apoptosis, oxidative stress and inflammatory response in vivo. Further investigation elucidated that knockdown of TNFAIP1 enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling associated with modulation of the Akt/glycogen synthase kinase-3ß (GSK-3ß) pathway in vitro and in vivo. Inhibition of Akt markedly abrogated TNFAIP1-knockdown-mediated Nrf2 activation in cardiomyocytes following H/R injury. In addition, suppression of Nrf2 significantly diminished TNFAIP1-knockdown-induced cardioprotective effects in H/R-exposed cardiomyocytes. In summary, this work elucidates that inhibition of TNFAIP1 ameliorates myocardial I/R injury by potentiating Nrf2 signaling via the modulation of the Akt/GSK-3ß pathway. Our study highlights a vital role of the TNFAIP1/Akt/GSK-3ß/Nrf2 pathway in mediating myocardial I/R injury and suggests TNFAIP1 as an attractive target for treatment of this disease.