Tea plant (Camellia sinensis) is an economically important beverage crop. Drought stress (DS) seriously limits the growth and development of tea plant, thus affecting crop yield and quality. To ...elucidate the molecular mechanisms of tea plant responding to DS, we performed transcriptomic analysis of tea plant during the three stages control (CK) and during DS, and recovery (RC) after DS using RNA sequencing (RNA-Seq). Totally 378.08 million high-quality trimmed reads were obtained and assembled into 59,674 unigenes, which were extensively annotated. There were 5,955 differentially expressed genes (DEGs) among the three stages. Among them, 3,948 and 1,673 DEGs were up-regulated under DS and RC, respectively. RNA-Seq data were further confirmed by qRT-PCR analysis. Genes involved in abscisic acid (ABA), ethylene, and jasmonic acid biosynthesis and signaling were generally up-regulated under DS and down-regulated during RC. Tea plant potentially used an exchange pathway for biosynthesis of indole-3-acetic acid (IAA) and salicylic acid under DS. IAA signaling was possibly decreased under DS but increased after RC. Genes encoding enzymes involved in cytokinin synthesis were up-regulated under DS, but down-regulated during RC. It seemed probable that cytokinin signaling was slightly enhanced under DS. In total, 762 and 950 protein kinases belonging to 26 families were differentially expressed during DS and RC, respectively. Overall, 547 and 604 transcription factor (TF) genes belonging to 58 families were induced in the DS vs. CK and RC vs. DS libraries, respectively. Most members of the 12 TF families were up-regulated under DS. Under DS, genes related to starch synthesis were down-regulated, while those related to starch decomposition were up-regulated. Mannitol, trehalose and sucrose synthesis-related genes were up-regulated under DS. Proline was probably mainly biosynthesized from glutamate under DS and RC. The mechanism by which ABA regulated stomatal movement under DS and RC was partly clarified. These results document the global and novel responses of tea plant during DS and RC. These data will serve as a valuable resource for drought-tolerance research and will be useful for breeding drought-resistant tea cultivars.
Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to ...increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.
Abstract
The two-dimensional topological insulators host a full gap in the bulk band, induced by spin–orbit coupling (SOC) effect, together with the topologically protected gapless edge states. ...However, it is usually challenging to suppress the bulk conductance and thus to realize the quantum spin Hall (QSH) effect. In this study, we find a mechanism to effectively suppress the bulk conductance. By using the quasiparticle interference technique with scanning tunneling spectroscopy, we demonstrate that the QSH candidate single-layer 1
T
’-WTe
2
has a semimetal bulk band structure with no full SOC-induced gap. Surprisingly, in this two-dimensional system, we find the electron–electron interactions open a Coulomb gap which is always pinned at the Fermi energy (
E
F
). The opening of the Coulomb gap can efficiently diminish the bulk state at the
E
F
and supports the observation of the quantized conduction of topological edge states.
Squamous cell carcinomas (SCCs) are aggressive malignancies. Previous report demonstrated that master transcription factors (TFs) TP63 and SOX2 exhibited overlapping genomic occupancy in SCCs. ...However, functional consequence of their frequent co-localization at super-enhancers remains incompletely understood. Here, epigenomic profilings of different types of SCCs reveal that TP63 and SOX2 cooperatively and lineage-specifically regulate long non-coding RNA (lncRNA) CCAT1 expression, through activation of its super-enhancers and promoter. Silencing of CCAT1 substantially reduces cellular growth both in vitro and in vivo, phenotyping the effect of inhibiting either TP63 or SOX2. ChIRP analysis shows that CCAT1 forms a complex with TP63 and SOX2, which regulates EGFR expression by binding to the super-enhancers of EGFR, thereby activating both MEK/ERK1/2 and PI3K/AKT signaling pathways. These results together identify a SCC-specific DNA/RNA/protein complex which activates TP63/SOX2-CCAT1-EGFR cascade and promotes SCC tumorigenesis, advancing our understanding of transcription dysregulation in cancer biology mediated by master TFs and super-enhancers.
Long non-coding RNAs (lncRNAs) are expressed in tissue-specific pattern, but it is not clear how these are regulated. We aimed to identify squamous cell carcinoma (SCC)-specific lncRNAs and ...investigate mechanisms that control their expression and function.
We studied expression patterns and functions of 4 SCC-specific lncRNAs. We obtained 113 esophageal SCC (ESCC) and matched non-tumor esophageal tissues from a hospital in Shantou City, China, and performed quantitative reverse transcription polymerase chain reaction assays to measure expression levels of LINC01503. We collected clinical data from patients and compared expression levels with survival times. LINC01503 was knocked down using small interfering RNAs and oligonucleotides in TE7, TE5, and KYSE510 cell lines and overexpressed in KYSE30 cells. Cells were analyzed by chromatin immunoprecipitation sequencing, luciferase reporter assays, colony formation, migration and invasion, and mass spectrometry analyses. Cells were injected into nude mice and growth of xenograft tumors was measured. LINC01503 interaction with proteins was studied using fluorescence in situ hybridization, RNA pulldown, and RNA immunoprecipitation analyses.
We identified a lncRNA, LINC01503, which is regulated by a super enhancer and is expressed at significantly higher levels in esophageal and head and neck SCCs than in non-tumor tissues. High levels in SCCs correlated with shorter survival times of patients. The transcription factor TP63 bound to the super enhancer at the LINC01503 locus and activated its transcription. Expression of LINC01503 in ESCC cell lines increased their proliferation, colony formation, migration, and invasion. Knockdown of LINC01503 in SCC cells reduced their proliferation, colony formation, migration, and invasion, and the growth of xenograft tumors in nude mice. Expression of LINC01503 in ESCC cell lines reduced ERK2 dephosphorylation by DUSP6, leading to activation of ERK signaling via MAPK. LINC01503 disrupted the interaction between EBP1 and the p85 subunit of PI3K, increasing AKT signaling.
We identified an lncRNA, LINC01503, which is increased in SCC cells compared with non-tumor cells. Increased expression of LINC01503 promotes ESCC cell proliferation, migration, invasion, and growth of xenograft tumors. It might be developed as a biomarker of aggressive SCCs in patients.
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The collagenases of Vibrio species, many of which are pathogens, have been regarded as an important virulence factor. However, there is little information on the structure and collagenolytic ...mechanism of Vibrio collagenase. Here, we report the crystal structure of the collagenase module (CM) of Vibrio collagenase VhaC and the conformation of VhaC in solution. Structural and biochemical analyses and molecular dynamics studies reveal that triple-helical collagen is initially recognized by the activator domain, followed by subsequent cleavage by the peptidase domain along with the closing movement of CM. This is different from the peptidolytic mode or the proposed collagenolysis of Clostridium collagenase. We propose a model for the integrated collagenolytic mechanism of VhaC, integrating the functions of VhaC accessory domains and its collagen degradation pattern. This study provides insight into the mechanism of bacterial collagenolysis and helps in structure-based drug design targeting of the Vibrio collagenase.
This paper presents a new damping control scheme for piezo-actuated nanopositioning stages with recursive delayed position feedback (RDPF). The RDPF is proposed to attenuate the resonant mode of the ...nanopositioning stage in the inner feedback loop, which results in a neutral-type time-delay system. To realize the pole placement of this system, a new numerical integration method is proposed to determine the rightmost pole and select the parameters of the RDPF. Then, a high-gain proportional-integral (PI) controller is designed in the outer loop to minimize the tracking errors caused by the hysteresis nonlinearity and modeling uncertainties. To validate the effectiveness of the proposed approach, comparative experiments are conducted on a piezo-actuated nanopositioning stage. Experimental results demonstrate that the proposed approach improves the control bandwidth of the system from 32.5 Hz (with the PI controller) and 687 Hz (with the conventional delayed position feedback based controller) to 793 Hz.
AXL is expressed in many types of cancer and promotes cancer cell survival, metastasis and drug resistance. Here, we focus on identifying modulators that regulate AXL at the mRNA level. We have ...previously observed that the AXL promoter activity is inversely correlated with the AXL expression levels, suggesting that post-transcriptional mechanisms exist that down-regulate the expression of AXL mRNA. Here we show that the RNA binding protein PTBP1 (polypyrimidine tract-binding protein) directly targets the 5'-UTR of AXL mRNA in vitro and in vivo. Moreover, we also demonstrate that PTBP1, but not PTBP2, inhibits the expression of AXL mRNA and the RNA recognition motif 1 (RRM1) of PTBP1 is crucial for this interaction. To clarify how PTBP1 regulates AXL expression at the mRNA level, we found that, while the transcription rate of AXL was not significantly different, PTBP1 decreased the stability of AXL mRNA. In addition, over-expression of AXL may counteract the PTBP1-mediated apoptosis. Knock-down of PTBP1 expression could enhance tumor growth in animal models. Finally, PTBP1 was found to be negatively correlated with AXL expression in lung tumor tissues in Oncomine datasets and in tissue micro-array (TMA) analysis. In conclusion, we have identified a molecular mechanism of AXL expression regulation by PTBP1 through controlling the AXL mRNA stability. These findings may represent new thoughts alternative to current approaches that directly inhibit AXL signaling and may eventually help to develop novel therapeutics to avoid cancer metastasis and drug resistance.
Combined analyses of deep tow magnetic anomalies and International Ocean Discovery Program Expedition 349 cores show that initial seafloor spreading started around 33 Ma in the northeastern South ...China Sea (SCS), but varied slightly by 1–2 Myr along the northern continent‐ocean boundary (COB). A southward ridge jump of ∼20 km occurred around 23.6 Ma in the East Subbasin; this timing also slightly varied along the ridge and was coeval to the onset of seafloor spreading in the Southwest Subbasin, which propagated for about 400 km southwestward from ∼23.6 to ∼21.5 Ma. The terminal age of seafloor spreading is ∼15 Ma in the East Subbasin and ∼16 Ma in the Southwest Subbasin. The full spreading rate in the East Subbasin varied largely from ∼20 to ∼80 km/Myr, but mostly decreased with time except for the period between ∼26.0 Ma and the ridge jump (∼23.6 Ma), within which the rate was the fastest at ∼70 km/Myr on average. The spreading rates are not correlated, in most cases, to magnetic anomaly amplitudes that reflect basement magnetization contrasts. Shipboard magnetic measurements reveal at least one magnetic reversal in the top 100 m of basaltic layers, in addition to large vertical intensity variations. These complexities are caused by late‐stage lava flows that are magnetized in a different polarity from the primary basaltic layer emplaced during the main phase of crustal accretion. Deep tow magnetic modeling also reveals this smearing in basement magnetizations by incorporating a contamination coefficient of 0.5, which partly alleviates the problem of assuming a magnetic blocking model of constant thickness and uniform magnetization. The primary contribution to magnetic anomalies of the SCS is not in the top 100 m of the igneous basement.
Key Points:
Deep tow magnetics and IODP Expedition 349 constrained opening history
Variations are observed in spreading rate and onset of drifting and ridge jump
Magnetic anomalies are not primarily sourced from the top 100 m of the basement
Purpose
To evaluate the potential preventive effect of probiotics on ventilator-associated pneumonia (VAP).
Methods
This was an open-label, randomized, controlled multicenter trial involving 235 ...critically ill adult patients who were expected to receive mechanical ventilation for ≥48 h. The patients were randomized to receive (1) a probiotics capsule containing live
Bacillus subtilis
and
Enterococcus faecalis
(Medilac-S) 0.5 g three times daily through a nasogastric feeding tube plus standard preventive strategies or (2) standard preventive strategies alone, for a maximum of 14 days. The development of VAP was evaluated daily, and throat swabs and gastric aspirate were cultured at baseline and once or twice weekly thereafter.
Results
The incidence of microbiologically confirmed VAP in the probiotics group was significantly lower than that in the control patients (36.4 vs. 50.4 %, respectively;
P
= 0.031). The mean time to develop VAP was significantly longer in the probiotics group than in the control group (10.4 vs. 7.5 days, respectively;
P
= 0.022). The proportion of patients with acquisition of gastric colonization of potentially pathogenic microorganisms (PPMOs) was lower in the probiotics group (24 %) than the control group (44 %) (
P
= 0.004). However, the proportion of patients with eradication PPMO colonization on both sites of the oropharynx and stomach were not significantly different between the two groups. The administration of probiotics did not result in any improvement in the incidence of clinically suspected VAP, antimicrobial consumption, duration of mechanical ventilation, mortality and length of hospital stay.
Conclusion
Therapy with the probiotic bacteria
B. Subtilis
and
E. faecalis
are an effective and safe means for preventing VAP and the acquisition of PPMO colonization in the stomach.
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