In this article, we solve the strong openness conjecture on the multiplier ideal sheaf associated to any plurisubharmonic function, which was posed by Demailly.
The association between hydrogen sulfide (H2S) and cell wall composition with regard to the mitigation of cadmium (Cd) toxicity in Brassica napus L. was investigated. Cd caused growth retardation, ...leaf chlorosis, and decreased endogenous H2S content in Brassica napus roots. Stimulating l-cysteine desulfhydrase (LCD)-mediated H2S production with H2S releaser (NaHS) markedly improved plant growth, reduced Cd content in stems and leaves, and rescued Cd-induced chlorosis. Furthermore, increased Cd retention was observed in root cell walls, indicating that NaHS reduced Cd movement from the roots to upper-plant parts. Exogenous NaHS also significantly increased the content of pectin and the activity of pectin methylesterase in cell walls of roots, thereby increasing Cd retention in pectin fractions. However, intensification of H2S barely affected hemicellulose content under Cd stress. Intensified H2S signal, therefore, alleviates Cd toxicity in Brassica napus by increasing pectin content and its demethylation, increasing Cd fixation in cell walls, and reducing root-to-shoot Cd translocation.
Cardiac hypertrophy associated with various cardiovascular diseases results in heart failure and sudden death. A clear understanding of the mechanisms of hypertrophy will benefit the development of ...novel therapies. Long non-coding RNAs (lncRNAs) have been shown to play essential roles in many biological process, however, whether lncRNA-ROR plays functional roles in the reprogramming of cardiomyocyte remains unclear.
Here we show that lncRNA-ROR plays important roles in the pathogenesis of cardiac hypertrophy. In hypertrophic heart and cardiomyocytes, the expression of lncRNA-ROR is dramatically increased, downregulation of which attenuates the hypertrophic responses. Furthermore, the expression of lncRNA-ROR negatively correlates with miR-133, whose expression is increased when lncRNA-ROR is knocked down. In line with this, overexpression of miR-133 prevents the elevation of lncRNA-ROR and re-expression of ANP and BNP in cardiomyocytes subject to phenylephrine treatment.
Taken together, our study demonstrates that lncRNA-ROR promotes cardiac hypertrophy via interacting with miR-133, indicating that lncRNA-ROR could be targeted for developing novel antihypertrophic therapeutics.
The study mainly investigated the synergetic adsorption of hydrogen bonding and hydrophobic interaction. To simplify the adsorption driving forces and binding sites, the hydrophilic and hydrophobic ...microdomain was introduced onto polypropylene (PP) nonwoven. The amphiphilic structure was constructed for the adsorption of bisphenol A (BPA). A solvent shielding experiment was conducted to calculate the contributions of diverse interactions. Also, a specific structure without hydrophilic microdomain was constructed as comparison to determine the adsorption rate and quantify the diffusion behaviors. On the basis of double-exponential model, the adsorption process can be distinctly divided into three stages, namely film diffusion stage, intralayer diffusion stage, and dynamic equilibrium stage. The adsorption rate was dramatically improved due to the influence of hydrophilic microdomain and participation of hydrogen bonding adsorption. Discussions on adsorption priority were also proposed. The results of surface energy heterogeneity revealed that the hydrophilic microdomain or the hydrogen bonding site was occupied preferentially.
Osmotic stress arises from the difference between intracellular and extracellular osmolality. It induces cell swelling or shrinkage as a consequence of water influx or efflux, which threatens ...cellular activities. Mitogen-activated protein kinases (MAPKs) play central roles in signaling pathways in osmotic stress responses, including the regulation of intracellular levels of inorganic ions and organic osmolytes.
The present review summarizes the cellular osmotic stress response and the function and regulation of the vertebrate MAPK signaling pathways involved. We also describe recent findings regarding apoptosis signal-regulating kinase 3 (ASK3), a MAP3K member, to demonstrate its regulatory effects on signaling molecules beyond MAPKs.
MAPKs are rapidly activated by osmotic stress and have diverse roles, such as cell volume regulation, gene expression, and cell survival/death. There is significant cell type specificity in the function and regulation of MAPKs. Based on its activity change during osmotic stress and its regulation of the WNK1-SPAK/OSR1 pathway, ASK3 is expected to play important roles in osmosensing mechanisms and cellular functions related to osmoregulation.
MAPKs are essential for various cellular responses to osmotic stress; thus, the identification of the upstream regulators of MAPK pathways will provide valuable clues regarding the cellular osmosensing mechanism, which remains elusive in mammals. The elucidation of in vivo MAPK functions is also important because osmotic stress in physiological and pathophysiological conditions often results from changes in the intracellular osmolality. These studies potentially contribute to the establishment of therapeutic strategies against diseases that accompany osmotic perturbation.
•Osmotic stress causes cell swelling or shrinkage and has deleterious effects on cellular activities.•Cells can adapt to anisosmotic conditions by regulating the intracellular content of inorganic ions and organic osmolytes.•Mitogen-activated protein kinases (MAPKs) play central roles in osmotic stress signaling.•Apoptosis signal-regulating kinase 3 exhibits a unique responsiveness to osmotic stress and has potential importance in osmoregulation.•Studies regarding the upstream factors of MAPK pathways will contribute to reveal the mechanism by which mammalian cells sense osmotic stress.
As the resident immune cells in the central nervous system (CNS), microglia orchestrate immune responses and dynamically sculpt neural circuits in the CNS. Microglial dysfunction and mutations of ...microglia-specific genes have been implicated in many diseases of the CNS. Developing effective and safe vehicles for transgene delivery into microglia will facilitate the studies of microglia biology and microglia-associated disease mechanisms. Here, we report the discovery of adeno-associated virus (AAV) variants that mediate efficient in vitro and in vivo microglial transduction via directed evolution of the AAV capsid protein. These AAV-cMG and AAV-MG variants are capable of delivering various genetic payloads into microglia with high efficiency, and enable sufficient transgene expression to support fluorescent labeling, Ca2+ and neurotransmitter imaging and genome editing in microglia in vivo. Furthermore, single-cell RNA sequencing shows that the AAV-MG variants mediate in vivo transgene delivery without inducing microglia immune activation. These AAV variants should facilitate the use of various genetically encoded sensors and effectors in the study of microglia-related biology.Recombinant adeno-associated virus tools for enhanced microglial transduction in mice are reported. These viruses can be used to express functional reporters or genome editing tools with high microglial specificity, with the help of microglia-specific Cre lines.
Acquired resistance to tamoxifen remains a major obstacle in breast cancer (BC) treatment, since the underlying mechanism has not been fully elucidated. The long non-coding RNA (lncRNA) urothelial ...carcinoma-associated 1 (UCA1) has been recently shown to be dysregulated and plays important roles in progression of breast cancer. In the present study, we aimed to investigate the biological role and clinical significance of UCA1 in BC drug resistance. Hence, we used quantitative PCR assay to evaluate the UCA1 expression in tissues from patients with BC as well as established tamoxifen-resistant BC cell lines in vitro. We tested the viability, invasive ability and apoptosis rate in MCF-7 and T47D cells using MTT assay, transwell assay and flow cytometry assay, respectively. The influence of UCA1 on tumorigenesis was monitored by in vivo mice xenograft model. The activation of Wnt/β-catenin signaling pathway was evaluated by immunofluorescence assay, western blot assay and luciferase reporter assay, respectively. We found that the expression of UCA1 positively correlated with the pathological grade and mortality of breast cancer patients, moreover, expressions of UCA1 was increased significantly in the tamoxifen-resistant cell lines compared with the wild type parental cells. Ectopic expression of UCA1 promoted cell survival and resistance to tamoxifen treatment, whereas inhibition of UCA1 enhanced tamoxifen sensitivity of BC cells and induced more apoptotic cells. In addition, tamoxifen-resistant cells exhibited increased Wnt signaling activation as measured by the TOP/FOP Wnt luciferase reporter assay and β-catenin protein level compared with parental MCF-7 and T47D cells, respectively. In line with these data, UCA1 depletion attenuated the activity of Wnt/β-catenin pathway activation and the tumorigenicity of the tamoxifen-resistant BC cells. Taken together, our data highlights the pivotal role of UCA1-Wnt/β-catenin signaling pathway in the tamoxifen resistance in breast cancer, which could be targeted to improve the effectiveness and efficacy of tamoxifen treatment in breast cancer.
Traditional deep learning methods such as convolutional neural networks (CNN) have a high requirement for the number of labeled samples. In some cases, the cost of obtaining labeled samples is too ...high to obtain enough samples. To solve this problem, few-shot learning (FSL) is used. Currently, typical FSL methods work well on coarse-grained image data, but not as well on fine-grained image classification work, as they cannot properly assess the in-class similarity and inter-class difference of fine-grained images. In this work, an FSL framework based on graph neural network (GNN) is proposed for fine-grained image classification. Particularly, we use the information transmission of GNN to represent subtle differences between different images. Moreover, feature extraction is optimized by the method of meta-learning to improve the classification. The experiments on three datasets (CIFAR-100, CUB, and DOGS) have shown that the proposed method yields better performances. This indicates that the proposed method is a feasible solution for fine-grained image classification with FSL.
To assess the ameliorative effect of ursodeoxycholic acid (UDCA) on hydrogen peroxide (H
O
)-induced hepatocyte injury. In our in vivo experiments, we modelled hyperlipidemia in ApoE
mice subjected ...to a 3-month high-fat diet and found that HE staining of the liver showed severe liver injury and excessive H
O
was detected in the serum. We modelled oxidative stress injury in L02 cells by H
O
in vitro and analyzed the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and related genes. UDCA significantly improved the level of oxidative stress in H
O
-injured L02 cells (P < 0.05). In addition, UDCA improved the transcription levels of inflammation and oxidative stress-related genes (P < 0.05), showing anti-inflammatory and anti-oxidative stress effects. UDCA has a protective effect on H
O
-damaged L02 cells, which lays a theoretical foundation for its application development.
The development of deep learning provides a new research method for fault diagnosis. However, in the industrial field, the labeled samples are insufficient and the noise interference is strong so ...that raw data obtained by the sensor are occupied with noise signal. It is difficult to recognize time-domain fault signals under the severe noise environment. In order to solve these problems, the convolutional neural network (CNN) fusing frequency domain feature matching algorithm (FDFM), called CNN-FDFM, is proposed in this paper. FDFM extracts key frequency features from signals in the frequency domain, which can maintain high accuracy in the case of strong noise and limited samples. CNN automatically extracts features from time-domain signals, and by using dropout to simulate noise input and increasing the size of the first-layer convolutional kernel, the anti-noise ability of the network is improved. Softmax with temperature parameter T and D-S evidence theory are used to fuse the two models. As FDFM and CNN can provide different diagnostic information in frequency domain, and time domain, respectively, the fused model CNN-FDFM achieves higher accuracy under severe noise environment. In the experiment, when a signal-to-noise ratio (SNR) drops to -10 dB, the diagnosis accuracy of CNN-FDFM still reaches 93.33%, higher than CNN’s accuracy of 45.43%. Besides, when SNR is greater than -6 dB, the accuracy of CNN-FDFM is higher than 99%.
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