Long noncoding RNAs (lncRNA) play important roles in the tumorigenesis and progression of cancers. However, the clinical significance of lncRNAs and their regulatory mechanisms in nasopharyngeal ...carcinogenesis (NPC) are largely unknown. Here, based on a microarray analysis, we identified 384 dysregulated lncRNAs, of which,
was one of the most upregulated lncRNAs in NPC.
significantly associated with poor survival in NPC. N(6)-Methyladenosine (m6A) was highly enriched within
and enhanced its RNA stability.
functioned as an oncogenic lncRNA that promoted NPC cell proliferation, migration, invasion, tumor growth, and metastasis. Mechanistically,
functioned as a competing endogenous RNA (ceRNA) for sponging miR-590-3p and miR-1275, leading to the upregulation of their target
(
), and the activation of FAK/PI3K/Akt signaling to promote NPC cell proliferation and invasion. In summary, our study reveals a potential ceRNA regulatory pathway in which
modulates
expression by binding to miR-590-3p and miR-1275, ultimately promoting tumorigenesis and metastasis in NPC. SIGNIFICANCE: These findings demonstrate the clinical significance of the lncRNA
in nasopharyngeal carcinoma (NPC) and the regulatory mechanism involved in NPC development and progression, providing a novel prognostic indicator and promising therapeutic target.
Grain size is an important component trait of grain yield, which is frequently threatened by abiotic stress. However, little is known about how grain yield and abiotic stress tolerance are regulated. ...Here, we characterize GSA1, a quantitative trait locus (QTL) regulating grain size and abiotic stress tolerance associated with metabolic flux redirection. GSA1 encodes a UDP-glucosyltransferase, which exhibits glucosyltransferase activity toward flavonoids and monolignols. GSA1 regulates grain size by modulating cell proliferation and expansion, which are regulated by flavonoid-mediated auxin levels and related gene expression. GSA1 is required for the redirection of metabolic flux from lignin biosynthesis to flavonoid biosynthesis under abiotic stress and the accumulation of flavonoid glycosides, which protect rice against abiotic stress. GSA1 overexpression results in larger grains and enhanced abiotic stress tolerance. Our findings provide insights into the regulation of grain size and abiotic stress tolerance associated with metabolic flux redirection and a potential means to improve crops.
Abstract This study analyzes the variations in the thermodynamic cycle and energy of a tropical cyclone (TC) under the influence of vertical wind shear (VWS), exploring the possible thermodynamic ...pathways through which VWS affects TC intensity. The maximum energy harnessed by the TC diminishes alongside a decrease in storm intensity in the presence of VWS. In the sheared TC, the ascending branch of the thermodynamic cycles of TC shifts toward lower entropy, which is related to the reduction in entropy in the eyewall and/or the increase in entropy and enhanced upward motion outside the eyewall. Moreover, the descending leg shifts toward higher entropy due to the increase in entropy and weakening of downward motion in both the ambient environment and the upper troposphere. These changes in the ascending and descending branches could reduce the work done by the heat engine cycle, with the former playing a primary role in the presence of VWS. Given that the ascending branch is influenced by the eyewall and the rainbands outside the eyewall under VWS, the thermodynamic pathways could be categorized into inner ventilation and outer ventilation based on the location of their roles. The pathways associated with inner ventilation primarily reduce the entropy in the eyewall. In addition to the conventional low- and midlevel ventilation, the inner ventilation also encompasses new pathways entering the midlevel eyewall after descending from the upper level and ascending from the boundary layer. Conversely, the pathways of outer ventilation are related to the increase in the entropy outside the eyewall. These include the ascent of high-entropy air to the middle and upper troposphere related to the inner and outer rainbands, the outward advection of high-entropy air from the eyewall in the midlevel and upper level, and air warming by the descending draft from the upper- to midlevel troposphere. These insights contribute to a nuanced understanding of the sophisticated interactions within TCs and their response to VWS. Significance Statement Vertical wind shear (VWS) is known to modify the thermodynamic structure of tropical cyclones (TCs), thereby affecting their development. The incorporation of multiple thermodynamic mechanisms amplifies the complexity of related studies and predictions. Within the context of a unified heat engine framework, this study aims to paint a relatively comprehensive picture of the key thermodynamic pathways through which VWS impacts the intensity of TCs. Contrary to previous studies, we emphasize the increase in entropy and the intensified upward motion outside the eyewall, which play pivotal roles in diminishing the intensity of TCs in the presence of VWS. Gaining an understanding of these critical mechanisms and structural changes offers insights and guidance that can enhance the prediction of sheared TCs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The output of an RLK-MAPK signaling pathway maintains cytokinin homeostasis, thereby determining spikelet number per panicle in rice.
Abstract
Grain number is a flexible trait that strongly ...contributes to grain yield. In rice (Oryza sativa), the OsMKKK10-OsMKK4-OsMPK6 cascade, which is negatively regulated by the dual-specificity phosphatase GSN1, coordinates the trade-off between grain number and grain size. However, the specific components upstream and downstream of the GSN1-MAPK module that regulate spikelet number per panicle remain obscure. Here, we report that ERECTA1 (OsER1), a negative regulator of spikelet number per panicle, acts upstream of the OsMKKK10-OsMKK4-OsMPK6 cascade and that the OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway is required to maintain cytokinin homeostasis. OsMPK6 directly interacts with and phosphorylates the zinc finger transcription factor DST to enhance its transcriptional activation of CYTOKININ OXIDASE2 (OsCKX2), indicating that the OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway shapes panicle morphology by regulating cytokinin metabolism. Furthermore, overexpression of either DST or OsCKX2 rescued the spikelet number phenotype of the oser1, osmkkk10, osmkk4, and osmpk6 mutants, suggesting that the DST-OsCKX2 module genetically functions downstream of the OsER1-OsMKKK10-OsMKK4-OsMPK6 pathway. These findings reveal specific crosstalk between a MAPK signaling pathway and cytokinin metabolism, shedding light on how developmental signals modulate phytohormone homeostasis to shape the inflorescence.
How the plasma membrane senses external heat-stress signals to communicate with chloroplasts to orchestrate thermotolerance remains elusive. We identified a quantitative trait locus,
Thermo-tolerance ...3
(
TT3
), consisting of two genes,
TT3.1
and
TT3.2
, that interact together to enhance rice thermotolerance and reduce grain-yield losses caused by heat stress. Upon heat stress, plasma membrane–localized E3 ligase TT3.1 translocates to the endosomes, on which TT3.1 ubiquitinates chloroplast precursor protein TT3.2 for vacuolar degradation, implying that TT3.1 might serve as a potential thermosensor. Lesser accumulated, mature TT3.2 proteins in chloroplasts are essential for protecting thylakoids from heat stress. Our findings not only reveal a
TT3.1-TT3.2
genetic module at one locus that transduces heat signals from plasma membrane to chloroplasts but also provide the strategy for breeding highly thermotolerant crops.
Heat tolerance in rice
Too much heat can damage a plant’s chloroplasts, driving yield down when temperatures exceed a crop’s normal tolerance. Zhang
et al
. identified a locus with two genes that together enhance rice thermotolerance. The ubiquitin ligase activity of Thermo-tolerance 3.1 (TT3.1) drove degradation of TT3.2, a chloroplast precursor protein that can trigger chloroplast damage in the context of heat stress. Together, these protein products respond to heat and control the damage. —PJH
A tag team of protein degradation protects rice plants from excess heat.
Phanerozoic growth of continental crust has widely been considered as an important geological phenomenon and mainly occurs in an arc setting. However, the crustal growth models (mantle-derived basalt ...underplating or accretion of island or intra-oceanic arc complexes or oceanic plateau) have been disputed. Here we present new zircon LA–ICPMS U–Pb age, whole-rock major and trace element, Sr–Nd and zircon Hf isotopic data for Late Mesozoic intermediate–felsic intrusive rocks in the Rena Co area in southern Qiangtang, central Tibet. LA–ICP–MS zircon U–Pb dating for two granodiorite and three diorite samples and one granodiorite porphyry sample gives ages of ca. 150Ma, ca. 112Ma, respectively, indicating they were generated in the Late Jurassic–Early Cretaceous. All rocks are sub-alkaline in composition and belong to the high-Kcal-alkaline series. The ~150Ma diorites (SiO2=57.9–61.2wt.%) exhibit relatively high MgO (3.13–3.88wt.%) and Cr (52.4–282ppm) contents and Mg# (47–51) values, similar to magnesian diorites. They are geochemically characterized by uniformly low εNd(t) (−5.5 to −5.2), high (87Sr/86Sr)i (0.7071 to 0.7078) and Th/La (0.22–0.32), and variable zircon εHf(t) (−8.7 to +4.8) values. They were probably generated by melting of oceanic sediment diapirs, followed by interaction with the surrounding mantle during the northward subduction of Bangong–Nujiang Oceanic lithosphere. The ~150Ma granodiorites and ~112Ma granodiorite porphyries are characterized by low MgO (<3wt.%) contents and Mg# (<45) values, high Al2O3 (>15%wt.%) and Sr (>400ppm) and low Y (<18ppm) and Yb (<1.9ppm) contents, and high Sr/Y and La/Yb ratios, which are similar to those of typical adakites. The granodiorites have low εNd(t) (−7.6 to −3.7) and zircon εHf(t) (−9.8 to +0.2) and high (87Sr/86Sr)i (0.7069 to 0.7086) values, and were likely produced by partial melting of a thickened and heterogeneous ancient lower continental crust. The relatively depleted isotope compositions (87Sr/86Sr)i=0.7054–0.7065; εNd(t)=−0.61 to +0.25; zircon εHf(t)=+4.7 to +9.7 of the granodiorite porphyries indicate that they were most probably generated by partial melting of newly underplated and thickened basaltic lower crust. Taking into account ophiolites in the Bangong–Nujiang Suture and Late Mesozoic magmatic rocks in the southern Qiangtang sub-block, we suggest that this area was located in a continental arc setting. Moreover, from the Late Jurassic to Early Cretaceous, the ancient lower crust in the southern Qiangtang sub-block was gradually replaced by mantle-derived juvenile materials. The crustal evolution indicates that, in a continental arc, basaltic magma underplating plays a key role in vertical crustal growth.
•Late Mesozoic intermediate–felsic intrusive rocks in southern Qiangtang, Tibet•~150Ma diorites generated by melting of oceanic sediment diapirs•~150Ma granodiorites mainly derived from thickened ancient lower continental crust•112Ma granodiorite porphyries mainly originating from newly underplated basaltic lower crust•Underplating of juvenile arc basaltic magmas plays an important role in crustal growth.
Alternative splicing (AS) has emerged as a key event in tumor development and microenvironment formation. However, comprehensive analysis of AS and its clinical significance in head and neck squamous ...cell carcinoma (HNSC) is urgently required.
Genome-wide profiling of AS events using RNA-Seq data from The Cancer Genome Atlas (TCGA) program was performed in a cohort of 464 patients with HNSC. Cancer-associated AS events (CASEs) were identified between paired HNSC and adjacent normal tissues and evaluated in functional enrichment analysis. Splicing networks and prognostic models were constructed using bioinformatics tools. Unsupervised clustering of the CASEs identified was conducted and associations with clinical, molecular and immune features were analyzed.
We detected a total of 32,309 AS events and identified 473 CASEs in HNSC; among these, 91 were validated in an independent cohort (n = 15). Functional protein domains were frequently altered, especially by CASEs affecting cancer drivers, such as PCSK5. CASE parent genes were significantly enriched in pathways related to HNSC and the tumor immune microenvironment, such as the viral carcinogenesis (FDR < 0.001), Human Papillomavirus infection (FDR < 0.001), chemokine (FDR < 0.001) and T cell receptor (FDR < 0.001) signaling pathways. CASEs enriched in immune-related pathways were closely associated with immune cell infiltration and cytolytic activity. AS regulatory networks suggested a significant association between splicing factor (SF) expression and CASEs and might be regulated by SF methylation. Eighteen CASEs were identified as independent prognostic factors for overall and disease-free survival. Unsupervised clustering analysis revealed distinct correlations between AS-based clusters and prognosis, molecular characteristics and immune features. Immunogenic features and immune subgroups cooperatively depict the immune features of AS-based clusters.
This comprehensive genome-wide analysis of the AS landscape in HNSC revealed novel AS events related to carcinogenesis and immune microenvironment, with implications for prognosis and therapeutic responses.
•Two igneous pulses (ca. 290 Ma and 285 Ma) recognized for the Qiangtang-Panjal LIP.•The LIP was generated by a mantle plume and emplacement guided by slab pull forces.•The Neo-Tethys Ocean was ...initially opened at ∼285 Ma phase.
Northward drift of the Cimmerian microcontinents and opening of the Neo-Tethys Ocean in Early Permian are prominent events in northern Gondwana's protracted breakup history. However, the geodynamic setting responsible for these events is controversial. The dispersal of the eastern Cimmerian microcontinents was accompanied by the emplacement of Qiangtang-Panjal large igneous province (QP-LIP). Previously published zircon U-Pb data imply the QP-LIP was emplaced over a long interval (320-280 Ma) but are inconsistent with the short eruption interval constrained by biostratigraphic studies. New secondary ion mass spectrometry (SIMS) zircon U-Pb ages from 15 mafic dikes and gabbroic intrusions from the Southern Qiangtang terrane as well as age data from other parts of the QP-LIP show a much shorter duration (∼290−285 Ma) for this LIP. The QP-LIP was characterized by an initial ∼290 Ma alkalic and tholeiitic phases and a subsequent ∼285 Ma tholeiitic phase, in agreement with regional biostratigraphic data constraining the timing of departure of the eastern Cimmerian microcontinents from Gondwana at ∼285 Ma and the opening of the Neo-Tethys Ocean. The QP-LIP was most likely the consequence of the arrival in the upper mantle of a mantle plume beneath the northern Gondwanan margin. This event, in combination with slab pull associated with subduction beneath Laurasia, may have caused extension and rifting of east Cimmerian continental fragments from the northern margin of Gondwana. This study may elucidate the mechanism responsible for repeated episodes of one-way northward drifting terranes from northern Gondwana that commenced in Paleozoic.
Frontier evidence suggests that dysregulation of long noncoding RNAs (lncRNA) is ubiquitous in all human tumors, indicating that lncRNAs might have essential roles in tumorigenesis. Therefore, an ...in-depth study of the roles of lncRNA in nasopharyngeal carcinoma (NPC) carcinogenesis might be helpful to provide novel therapeutic targets. Here we report that lncRNA TINCR was significantly upregulated in NPC and was associated positively with poor survival. Silencing TINCR inhibited NPC progression and cisplatin resistance. Mechanistically, TINCR bound ACLY and protected it from ubiquitin degradation to maintain total cellular acetyl-CoA levels. Accumulation of cellular acetyl-CoA promoted
lipid biosynthesis and histone H3K27 acetylation, which ultimately regulated the peptidyl arginine deiminase 1 (PADI1)-MAPK-MMP2/9 pathway. In addition, insulin-like growth factor 2 mRNA-binding protein 3 interacted with TINCR and slowed its decay, which partially accounted for TINCR upregulation in NPC. These findings demonstrate that TINCR acts as a crucial driver of NPC progression and chemoresistance and highlights the newly identified TINCR-ACLY-PADI1-MAPK-MMP2/9 axis as a potential therapeutic target in NPC. SIGNIFICANCE: TINCR-mediated regulation of a PADI1-MAPK-MMP2/9 signaling pathway plays a critical role in NPC progression and chemoresistance, marking TINCR as a viable therapeutic target in this disease.
Synergistic therapy has shown greater advantages compared with monotherapy. However, the complex multiple‐administration plan and potential side effects limit its clinical application. A ...transformable specific‐responsive peptide (TSRP) is utilized to one‐step achieve synergistic therapy integrating anti‐tumor, anti‐angiogenesis and immune response. The TSRP is composed of: i) Recognition unit could specifically target and inhibit the biological function of FGFR‐1; ii) Transformable unit could self‐assembly and trigger nanofibers formation; iii) Reactive unit could specifically cleaved by MMP‐2/9 in tumor micro‐environment; iv) Immune unit, stimulate the release of immune cells when LTX‐315 (Immune‐associated oncolytic peptide) exposed. Once its binding to FGFR‐1, the TSRP could cleaved by MMP‐2/9 to form the nanofibers on the cell membrane, with a retention time of up to 12 h. Through suppressing the phosphorylation levels of ERK 1/2 and PI3K/AKT signaling pathways downstream of FGFR‐1, the TSRP significant inhibit the growth of tumor cells and the formation of angioginesis. Furthermore, LTX‐315 is exposed after TSRP cleavage, resulting in Calreticulin activation and CD8+ T cells infiltration. All above processes together contribute to the increasing survival rate of tumor‐bearing mice by nearly 4‐folds. This work presented a unique design for the biological application of one‐step synergistic therapy of bladder cancer.
A transformable specific‐responsive peptide (TSRP) can one step simultaneously combine antitumor, antiangiogenesis, and immune therapy, ultimately suppressing the progression of bladder cancer.
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