Immune system evasion, distance tumor metastases, and increased cell proliferation are the main reasons for the progression of non-small cell lung cancer (NSCLC) and the death of NSCLC patients. ...Dysregulation of circular RNAs plays a critical role in the progression of NSCLC; therefore, further understanding the biological mechanisms of abnormally expressed circRNAs is critical to discovering novel, promising therapeutic targets for NSCLC treatment.
The expression of circular RNA fibroblast growth factor receptor 1 (circFGFR1) in NSCLC tissues, paired nontumor tissues, and cell lines was detected by RT-qPCR. The role of circFGFR1 in NSCLC progression was assessed both in vitro by CCK-8, clonal formation, wound healing, and Matrigel Transwell assays and in vivo by a subcutaneous tumor mouse assay. In vivo circRNA precipitation, RNA immunoprecipitation, and luciferase reporter assays were performed to explore the interaction between circFGFR1 and miR-381-3p.
Here, we report that circFGFR1 is upregulated in NSCLC tissues, and circFGFR1 expression is associated with deleterious clinicopathological characteristics and poor prognoses for NSCLC patients. Forced circFGFR1 expression promoted the migration, invasion, proliferation, and immune evasion of NSCLC cells. Mechanistically, circFGFR1 could directly interact with miR-381-3p and subsequently act as a miRNA sponge to upregulate the expression of the miR-381-3p target gene C-X-C motif chemokine receptor 4 (CXCR4), which promoted NSCLC progression and resistance to anti-programmed cell death 1 (PD-1)- based therapy.
Taken together, our results suggest the critical role of circFGFR1 in the proliferation, migration, invasion, and immune evasion abilities of NSCLC cells and provide a new perspective on circRNAs during NSCLC progression.
Bioactive species, including reactive oxygen species (ROS, including O
2
&z.rad;
−
, H
2
O
2
, HOCl,
1
O
2
, &z.rad;OH, HOBr,
etc.
), reactive nitrogen species (RNS, including ONOO
−
, NO, NO
2
, ...HNO,
etc.
), reactive sulfur species (RSS, including GSH, Hcy, Cys, H
2
S, H
2
S
n
, SO
2
derivatives,
etc.
), ATP, HCHO, CO and so on, are a highly important category of molecules in living cells. The dynamic fluctuations of these molecules in subcellular microenvironments determine cellular homeostasis, signal conduction, immunity and metabolism. However, their abnormal expressions can cause disorders which are associated with diverse major diseases. Monitoring bioactive molecules in subcellular structures is therefore critical for bioanalysis and related drug discovery. With the emergence of organelle-targeted fluorescent probes, significant progress has been made in subcellular imaging. Among the developed subcellular localization fluorescent tools, ROS, RNS and RSS (RONSS) probes are highly attractive, owing to their potential for revealing the physiological and pathological functions of these highly reactive, interactive and interconvertible molecules during diverse biological events, which are rather significant for advancing our understanding of different life phenomena and exploring new technologies for life regulation. This review mainly illustrates the design principles, detection mechanisms, current challenges, and potential future directions of organelle-targeted fluorescent probes toward RONSS.
The dynamic fluctuations of bioactive species in living cells are associated with numerous physiological and pathological phenomena. The emergence of organelle-targeted fluorescent probes has significantly facilitated our understanding on the biological functions of these species. This review describes the design, applications, challenges and potential directions of organelle-targeted bioactive species probes.
Calcium supplementation has been shown to be efficacious in mitigating the progression of senile osteoporosis (SOP) and reducing the incidence of osteoporotic fractures resulting from prolonged ...calcium shortage. In this study, Grifola frondosa (GF) peptides‐calcium chelate were synthesized through the interaction between peptide from GF and CaCl2. The chelation reaction was shown to involve the participation of the amino and carboxyl groups in the peptide, as revealed by scanning electron microscope, Fourier‐transform infrared, and ultraviolet spectrophotometry. Furthermore, a mouse model of (SOP) induced by d‐galactose was established (SCXK‐2018‐0004). Results demonstrated that low dosage of low‐molecular weight GF peptides‐calcium chelates (LLgps‐Ca) could significantly improve serum index and pathological features of bone tissue and reduce bone injury. Further research suggested that LLgps‐Ca could ameliorate SOP by modulating the disrupted metabolic pathway, which includes focal adhesion, extracellular matrix receptor interaction, and PI3K‐Akt signaling pathway. Using Western blot, the differentially expressed proteins were further confirmed. Thus, calciumchelating peptides from GF could serve as functional calcium agents to alleviate SOP.
NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER (NRT1/PTR) family (NPF) members are essential transporters for many substrates in plants, including nitrate, hormones, peptides, and secondary metabolites. ...Here, we report the global characterization of NPF in the important oil crop Brassica napus, including that for phylogeny, gene/protein structures, duplications, and expression patterns.
A total of 199 B. napus (BnaNPFs) NPF-coding genes were identified. Phylogenetic analyses categorized these genes into 11 subfamilies, including three new ones. Sequence feature analysis revealed that members of each subfamily contain conserved gene and protein structures. Many hormone-/abiotic stress-responsive cis-acting elements and transcription factor binding sites were identified in BnaNPF promoter regions. Chromosome distribution analysis indicated that BnaNPFs within a subfamily tend to cluster on one chromosome. Syntenic relationship analysis showed that allotetraploid creation by its ancestors (Brassica rapa and Brassica oleracea) (57.89%) and small-scale duplication events (39.85%) contributed to rapid BnaNPF expansion in B. napus. A genome-wide spatiotemporal expression survey showed that NPF genes of each Arabidopsis and B. napus subfamily have preferential expression patterns across developmental stages, most of them are expressed in a few organs. RNA-seq analysis showed that many BnaNPFs (32.66%) have wide exogenous hormone-inductive profiles, suggesting important hormone-mediated patterns in diverse bioprocesses. Homologs in a clade or branch within a given subfamily have conserved organ/spatiotemporal and hormone-inductive profiles, indicating functional conservation during evolution. qRT-PCR-based comparative expression analysis of the 12 BnaNPFs in the NPF2-1 subfamily between high- and low-glucosinolate (GLS) content B. napus varieties revealed that homologs of AtNPF2.9 (BnaNPF2.12, BnaNPF2.13, and BnaNPF2.14), AtNPF2.10 (BnaNPF2.19 and BnaNPF2.20), and AtNPF2.11 (BnaNPF2.26 and BnaNPF2.28) might be involved in GLS transport. qRT-PCR further confirmed the hormone-responsive expression profiles of these putative GLS transporter genes.
We identified 199 B. napus BnaNPFs; these were divided into 11 subfamilies. Allopolyploidy and small-scale duplication events contributed to the immense expansion of BnaNPFs in B. napus. The BnaNPFs had preferential expression patterns in different tissues/organs and wide hormone-induced expression profiles. Four BnaNPFs in the NPF2-1 subfamily may be involved in GLS transport. Our results provide an abundant gene resource for further functional analysis of BnaNPFs.
Abnormal findings include (1) hyperdynamic cardiac function, presented as the increase of cardiac output (CO) and ejection faction (EF) of the left ventricular (LV), with/without the decrease of ...peripheral vascular resistance, which is often seen in the early stage following the systemic inflammatory response; (2) acute stress-induced (takotsubo) cardiomyopathy, characterized as LV segmental contraction abnormalities and apical ballooning 1; (3) right ventricular (RV) enlargement and acute pulmonary hypertension, which are mainly caused by “internal factors” (including alveolar and pulmonary capillary damage caused by inflammation, hypoxia, and hypercapnia, leading to the increase of RV afterload) and “external factors” (including fluid overload, which causes the increase of RV preload, and unsuitable mechanical ventilation parameter setting, which affects the cardiac function by cardiopulmonary interaction); further, LV function will be affected because the right and left hearts are in the same pericardium; and (4) diffuse myocardial inhibition in the late stage, which is often caused by severe hypoxia, and long term of anoxia and inflammation. Critical ultrasonography is of great significance in fast identifying the types of shock and guide hemodynamic management. Since the focused cardiac ultrasound (FOCUS) was proposed in 2010 2, many different types of FOCUS exams for rapid evaluation of emergency or ICU patients have been introduced, including the focus-assessed transthoracic echocardiography (FATE) advanced FATE protocol 3, fluid administration limited by lung sonography (FALLS) protocol 4, and critical care chest ultrasonic examination (CCUE) protocol 5. In COVID-19 patients, the most common types of shock are septic shock and cardiogenic shock; however, we still need to exclude obstructive shock (massive pericardial effusion, right heart collapse, heart swing, RV enlargement and “D sign,” tricuspid valve regurgitation, pulmonary artery or deep vein thrombosis, etc.) and hypovolemic shock (decrease of CO, “papillary muscle kissing sign,” IVC collapse and high respiratory variability, etc.) first.
The plant-specific Teosinte-branched 1/Cycloidea/Proliferating (TCP) transcription factor genes are involved in plants' development, hormonal pathways, and stress response but their evolutionary ...history is uncertain. The genome-wide analysis performed here for 47 plant species revealed 535 TCP candidates in terrestrial plants and none in aquatic plants, and that TCP family genes originated early in the history of land plants. Phylogenetic analysis divided the candidate genes into Classes I and II, and Class II was further divided into CYCLOIDEA (CYC) and CINCINNATA (CIN) clades; CYC is more recent and originated from CIN in angiosperms. Protein architecture, intron pattern, and sequence characteristics were conserved in each class or clade supporting this classification. The two classes significantly expanded through whole-genome duplication during evolution. Expression analysis revealed the conserved expression of TCP genes from lower to higher plants. The expression patterns of Class I and CIN genes in different stages of the same tissue revealed their function in plant development and their opposite effects in the same biological process. Interaction network analysis showed that TCP proteins tend to form protein complexes, and their interaction networks were conserved during evolution. These results contribute to further functional studies on TCP family genes.
The current outbreak of coronavirus disease-2019 (COVID-19) poses unprecedented challenges to global health
. The new coronavirus responsible for this outbreak-severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2)-shares high sequence identity to SARS-CoV and a bat coronavirus, RaTG13
. Although bats may be the reservoir host for a variety of coronaviruses
, it remains unknown whether SARS-CoV-2 has additional host species. Here we show that a coronavirus, which we name pangolin-CoV, isolated from a Malayan pangolin has 100%, 98.6%, 97.8% and 90.7% amino acid identity with SARS-CoV-2 in the E, M, N and S proteins, respectively. In particular, the receptor-binding domain of the S protein of pangolin-CoV is almost identical to that of SARS-CoV-2, with one difference in a noncritical amino acid. Our comparative genomic analysis suggests that SARS-CoV-2 may have originated in the recombination of a virus similar to pangolin-CoV with one similar to RaTG13. Pangolin-CoV was detected in 17 out of the 25 Malayan pangolins that we analysed. Infected pangolins showed clinical signs and histological changes, and circulating antibodies against pangolin-CoV reacted with the S protein of SARS-CoV-2. The isolation of a coronavirus from pangolins that is closely related to SARS-CoV-2 suggests that these animals have the potential to act as an intermediate host of SARS-CoV-2. This newly identified coronavirus from pangolins-the most-trafficked mammal in the illegal wildlife trade-could represent a future threat to public health if wildlife trade is not effectively controlled.
Thermal barrier coatings (TBCs) can effectively protect the alloy substrate of hot components in aeroengines or land-based gas turbines by the thermal insulation and corrosion/erosion resistance of ...the ceramic top coat. However, the continuous pursuit of a higher operating temperature leads to degradation, delamination, and premature failure of the top coat. Both new ceramic materials and new coating structures must be developed to meet the demand for future advanced TBC systems. In this paper, the latest progress of some new ceramic materials is first reviewed. Then, a comprehensive spalling mechanism of the ceramic top coat is summarized to understand the dependence of lifetime on various factors such as oxidation scale growth, ceramic sintering, erosion, and calcium-magnesium-aluminium-silicate (CMAS) molten salt corrosion. Finally, new structural design methods for high-performance TBCs are discussed from the perspectives of lamellar, columnar, and nanostructure inclusions. The latest developments of ceramic top coat will be presented in terms of material selection, structural design, and failure mechanism, and the comprehensive guidance will be provided for the development of next-generation advanced TBCs with higher temperature resistance, better thermal insulation, and longer lifetime.
Nonalcoholic fatty liver disease(NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid ...economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines(including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future.
PDF
