Long noncoding RNAs (lncRNAs) are essential regulators of gene expression in eukaryotes. Despite increasing knowledge on the function of lncRNAs, little is known about their effects on crop yield. ...Here, we identify a lncRNA transcribed from the antisense strand of neighbouring gene LRK (leucine-rich repeat receptor kinase) cluster named LAIR (LRK Antisense Intergenic RNA). LAIR overexpression increases rice grain yield and upregulates the expression of several LRK genes. Additionally, chromatin immunoprecipitation assay results indicate H3K4me3 and H4K16ac are significantly enriched at the activated LRK1 genomic region. LAIR binds histone modification proteins OsMOF and OsWDR5 in rice cells, which are enriched in LRK1 gene region. Moreover, LAIR is demonstrated to bind 5' and 3' untranslated regions of LRK1 gene. Overall, this study reveals the role of lncRNA LAIR in regulating rice grain yield and lncRNAs may be useful targets for crop breeding.
Abstract
Study of human disease remains challenging due to convoluted disease etiologies and complex molecular mechanisms at genetic, genomic, and proteomic levels. Many machine learning-based ...methods have been developed and widely used to alleviate some analytic challenges in complex human disease studies. While enjoying the modeling flexibility and robustness, these model frameworks suffer from non-transparency and difficulty in interpreting each individual feature due to their sophisticated algorithms. However, identifying important biomarkers is a critical pursuit towards assisting researchers to establish novel hypotheses regarding prevention, diagnosis and treatment of complex human diseases. Herein, we propose a Permutation-based Feature Importance Test (PermFIT) for estimating and testing the feature importance, and for assisting interpretation of individual feature in complex frameworks, including deep neural networks, random forests, and support vector machines. PermFIT (available at
https://github.com/SkadiEye/deepTL
) is implemented in a computationally efficient manner, without model refitting. We conduct extensive numerical studies under various scenarios, and show that PermFIT not only yields valid statistical inference, but also improves the prediction accuracy of machine learning models. With the application to the Cancer Genome Atlas kidney tumor data and the HITChip atlas data, PermFIT demonstrates its practical usage in identifying important biomarkers and boosting model prediction performance.
Shift metabolism profile from mitochondrial oxidative phosphorylation to aerobic glycolysis (Warburg effect) is a key for tumor cell growth and metastasis. Therefore, suppressing the tumor aerobic ...glycolysis shows a great promise in anti-tumor therapy. In the present study, we study the role of shikonin, a naphthoquinone isolated from the traditional Chinese medicine Lithospermum, in inhibiting tumor aerobic glycolysis and thus tumor growth. We found that shikonin dose-dependently inhibited glucose uptake and lactate production in Lewis lung carcinoma (LLC) and B16 melanoma cells, confirming the inhibitory effect of shikonin on tumor aerobic glycolysis. Treatment of shikonin also decreased tumor cell ATP production. Furthermore, pyruvate kinase M2 (PKM2) inhibitor or activator respectively altered the effect of shikonin on tumor cell aerobic glycolysis, suggesting that suppression of cell aerobic glycolysis by shikonin is through decreasing PKM2 activity. Western blot analysis confirmed that shikonin treatment reduced tumor cell PKM2 phosphorylation though did not reduce total cellular PKM2 level. In vitro assay also showed that shikonin treatment significantly promoted tumor cell apoptosis compared to untreated control cells. Finally, when mice implanted with B16 cells were administered with shikonin or control vehicle, only shikonin treatment significantly decreased B16 tumor cell growth. In conclusion, this study demonstrates that shikonin inhibits tumor growth in mice by suppressing PKM2-mediated aerobic glycolysis.
• COVID-19 has a great threat to world health.• We investigated clinical features of patients with abnormal imaging findings.• Those with abnormal images have more obvious clinical and laboratory ...features.• Combing clinical data with imaging scores can predict severe/critical type.
To investigate the epidemiological and clinical characteristics of COVID-19 patients with abnormal imaging findings.
Patients confirmed with SARS-CoV-2 infection in Zhejiang province from January 17 to February 8 who had undergone CT or X-ray were enrolled. Epidemiological and clinical data were analyzed among those with abnormal or normal imaging findings.
Excluding 72 patients with normal images, 230 of 573 patients showed abnormalities affecting more than two lung lobes. The median radiographic score was 2.0, and there was a negative correlation between that score and the oxygenation index (ρ = −0.657, P < 0.001). Patients with abnormal images were older (46.65 ± 13.82), with a higher rate of coexisting condition (28.8%), a lower rate of exposure history, and longer time between onset and confirmation (5 days) than non-pneumonia patients (all P < 0.05). A higher rate of fever, cough, expectoration and headache, a lower level of lymphocytes, albumin, and serum sodium levels and a higher total bilirubin, creatine kinase, lactate dehydrogenase, and C-reactive protein levels and a lower oxygenation index were observed in pneumonia patients (all P < 0.05). Muscle ache, shortness of breath, nausea and vomiting, lower lymphocytes levels, and higher serum creatinine and radiographic score at admission were predictive factors for the severe/critical subtype.
Patients with abnormal images have more obvious clinical manifestations and laboratory changes. Combing clinical features and radiographic scores can effectively predict severe/critical types.
•Different high confining pressures and constant upper and lower limit loads is carried out.•The dynamic crack propagation evolution of predamaged granite in the whole of uniaxial recompression is ...analyzed.•Using acoustic emission b value and R value to judge rock dynamic evolution.
As the mining industry continues to mine deep, the safety and stability of deep rock masses (such as pillars) in a complex geostress environment become increasingly important. By selecting granite as the object, a uniaxial compression experiment was designed for predamaged specimens prepared under high confining pressure cyclic loading. The porosity, secondary uniaxial peak strength, and the dynamic fracture characteristics of saturated granite before and after predamage test in the whole process were obtained by nuclear magnetic resonance (NMR) and acoustic emission (AE) analyses. The porosity increment of granite before and after high confining pressure cyclic loading test indicates that the granite has different degrees of mesoscopic damage. The high confining pressure cyclic loading in predamage experiment makes the granite release a stronger energy signal when it ruptures, but the higher the number of cycles, the weaker this energy signal. The stress-strain curve can be divided into four stages: I, II, III, and IV, the fracture mode of natural saturated granite is tensile crack-tensile crack-tensile crack-mixed crack, and the fracture mode of saturated granite after predamage changes into tensile crack-shear crack-shear crack-mixed crack. The distribution range and rise and fall of CV(r) have a certain symmetry with the b-value. The reference value of predamaged saturated granite is CV(r) = 1.2.
Gut bacteria modulate the response to immune checkpoint blockade (ICB) treatment in cancer, but the effect of diet and supplements on this interaction is not well studied. We assessed fecal ...microbiota profiles, dietary habits, and commercially available probiotic supplement use in melanoma patients and performed parallel preclinical studies. Higher dietary fiber was associated with significantly improved progression-free survival in 128 patients on ICB, with the most pronounced benefit observed in patients with sufficient dietary fiber intake and no probiotic use. Findings were recapitulated in preclinical models, which demonstrated impaired treatment response to anti–programmed cell death 1 (anti–PD-1)–based therapy in mice receiving a low-fiber diet or probiotics, with a lower frequency of interferon-γ–positive cytotoxic T cells in the tumor microenvironment. Together, these data have clinical implications for patients receiving ICB for cancer.
Magnetite−silica nanocomposites were controllably synthesized by a sol−gel approach, using electrostatically stabilized magnetite nanoparticles as seeds. By virtue of the complexation occurring ...between the iron ions on the magnetic nanoparticles and the citrate groups, highly stable magnetic fluid (MF) containing well-dispersed magnetite nanoparticles can be obtained. Controlling the surface modification degree, magnetite nanoparticles charged with different amount of citrate groups can be obtained for coating process with silica through the seeded sol−gel approach, and magnetite−silica nanocomposites with morphologies including irregular clusters, core−shell particles can be synthesized. Moreover, silica−magnetite particles with well-defined core−shell structure and controllable silica thickness can be synthesized.
Steel slag is an industrial solid waste, which can provide a new calcium source for microbial mineralization as it contains abundant calcium elements. This study treated cemented backfill material ...with microorganisms and steel slag to enhance its performance. The influence of microbial treatment on the strength, microstructure, and pore characteristics of the backfill was assessed using a strength test, nuclear magnetic resonance, scanning electron microscopy, and X-ray diffraction. The results indicate that (1) the microbial mineralization and the hydration reaction take place at the same time; (2) when the proportion of bacterial solution exceeded 50%, microorganisms excessively consumed Ca2+, which hindered the following hydration reaction; (3) the additional amount of bacterial solution added into the steel-slag-based cemented backfill material should be less than 50%, which increases the strength by up to 22.10%; (4) the excessive bacterial solution sharply reduces the strength of the backfill even by 21.41%; and (5) the addition of bacterial solution affects the pore characteristics. A 50% bacterial solution can make backfill reach its lowest porosity. The strength has an inversely proportional relationship with porosity, diameter, and roundness (σ = ax + b, a < 0).
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