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1.
J Oncol ; 2022: 3477148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35069733

RESUMO

Background: Serine/arginine-rich splicing factor 9 (SRSF9) is one of the members of SRSF gene family and related to the tumorigenesis and the progression of tumor. However, whether SRSF9 has a crucial role across pan-cancer is still unknown. Methods: In this study, we used public databases, such as The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), and Genotype-Tissue Expression (GTEx), to analyze SRSF9 expression level among tumor and normal cells. Survival analysis, K-M plotter, and PrognoScan were used to analyze the prognosis value of SRSF9, regarding to overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI). Moreover, we performed the correlation between SRSF9 and clinical characteristics (including the outcome of prognosis), as well as molecular events of tumor mutation burden (TMB), microsatellite instability (MSI), immune checkpoint gene, tumor microenvironment (TME), immune infiltrating cells, mismatch repair (MMR) genes, m6A genes, DNA methyltransferases, and neoantigen with bioinformatics methods and TISIDB, TIMER, and Sangerbox websites. Results: In general, SRSF9 expression was upregulated in most cancers, such as BLCA, CHOL, and UCEC, which SRSF9 was associated with short survival and severe progression. In COAD, STAD, and UCEC, SRSF9 expression was positively related to both TMB and MSI. In BRCA, BLCA, ESCA, GBM, HNSC, LUSC, LUAD, OV, PRAD, TGCT, THCA, and UCEC, both immune score and stomal score showed a negative relationship with SRSF9 expression. Immune score showed a positive relationship with SRSF9 expression in LGG. SRSF9 expression had a significant and positive correlation with six types of immune infiltration cells in LGG, KIRC, LIHC, PCPG, PRAD, SKCM, THCA, and THYM, except in LUSC. In LIHC, SRSF9 was highly significant correlated with most immune checkpoint genes. For neoantigens, correlation between SRSF9 and the quantity of neoantigens was significantly positive in some cancer types. SRSF9 was also correlated with MMR genes, m6A genes, and DNA methyltransferases. In the 33 cancer types, gene set enrichment analysis (GSEA) demonstrated that SRSF9 was correlated with multiple functions and signaling pathways. Conclusion: These findings demonstrated that SRSF9 may be a new biomarker for the prognosis and immunotherapy in various cancers. As a result, it will be beneficial to provide new therapies for cancer patients, thereby improving the treatment and prognosis of cancer patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35050588

RESUMO

The low energy density and low cost performance of electrochemical capacitors (ECs) are the principal factors that limit the wide applications of ECs. In this work, we used enzymatic hydrolysis lignin as the carbon source and an ammonia activation methodology to prepare nitrogen-doped lignin-derived porous carbon (NLPC) electrode materials with high specific surface areas. We elucidated the free radical mechanism of ammonia activation and the relationship between nitrogen doping configurations, doping levels, and preparation temperatures. Furthermore, we assembled NLPC∥NLPC symmetric ECs and NLPC∥Zn asymmetric ECs using aqueous sulfate electrolytes. Compared with the ECs using KOH aqueous electrolyte, the energy densities of NLPC∥NLPC and NLPC∥Zn ECs were significantly improved. The divergence of charge storage characteristics in KOH, Na2SO4, and ZnSO4 electrolytes were compared by analyzing their area surface capacitance. This work provides a strategy for the sustainable preparation of lignin-derived porous carbons toward ECs with high energy densities.

3.
SLAS Discov ; 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35063690

RESUMO

Covalent inhibitors targeting the main protease (Mpro, or 3CLpro) of SARS-CoV-2 have shown promise in preclinical investigations. Herein, we report the discovery of two new series of molecules that irreversibly bind to SARS-CoV-2 Mpro. These acrylamide containing molecules were discovered using our DNA-encoded library (DEL) screening platform. Following selection against SARS-CoV-2 Mpro, off-DNA compounds were synthesized and investigated to determine their inhibitory effects, the nature of their binding, and generate preliminary structure-activity relationships. LC-MS analysis indicates a 1:1 (covalent) binding stoichiometry between our hit molecules and SARS-CoV-2 Mpro. Fluorescent staining assay for covalent binding in the presence of cell lysate suggests reasonable selectivity for SARS-CoV-2 Mpro. And lastly, inhibition of enzymatic activity was also observed against a panel of 3CLpro enzymes from different coronavirus strains, with IC50 values ranging from inactive to single digit micromolar. Our results indicate that DEL selection is a useful approach for identifying covalent inhibitors of cysteine proteases.

4.
J Colloid Interface Sci ; 607(Pt 2): 1953-1962, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34695744

RESUMO

HYPOTHESIS: Developing the supercritical carbon dioxide microemulsion with a broad water content (W0) window can provide more possibility for designing highly efficient chemical processes, which is challenging due to the lack of comprehension about its formation mechanism. Molecular dynamics simulation method is expected to reveal the microscopic stabilization mechanism of high-W0 microemulsions. SIMULATIONS: All-atom molecular dynamics simulations of the ternary systems with varied W0 stabilized by 4FG(EO)2 surfactant were designed according to phase behavior experiments. A systematic investigation was performed concerning the self-assembling, equilibrium morphology and detailed microstructure of the microemulsion droplet. An in-depth comparative study about the distribution of both H2O and CO2, the interfacial behaviors of 4FG(EO)2, as well as the microscopic interactions was conducted. FINDINGS: For the first time, direct evidence was provided for the formation of water-in-carbon dioxide microemulsion with extremely high W0 (80) under the effect of 4FG(EO)2. Furthermore, a unique interfacial phenomenon, i. e. CO2 accumulating at the interface, was revealed to be responsible for the formation and enhanced stability of the nanosized droplet with high W0. This should set a new guiding star for synthesizing and selecting effective interfacial modifiers to create high-W0 microemulsions.

5.
IEEE Trans Image Process ; 31: 949-961, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34965208

RESUMO

Hashing is a practical approach for the approximate nearest neighbor search. Deep hashing methods, which train deep networks to generate compact and similarity-preserving binary codes for entities (e.g. images), have received lots of attention in the information retrieval community. A representative stream of deep hashing methods is triplet-based hashing that learns hashing models from triplets of data. The existing triplet-based hashing methods only consider triplets that are in the form of (q,q+,q-) , where q and q+ are in the same class and q and q- are in different classes. However, the number of possible triplets is approximately the cube of training examples, triplets used in the existing methods are only a small fraction of all possible triplets. This motivates us to develop a new triplet-based hashing method that adopts many more triplets in training phase. We propose Deep Listwise Triplet Hashing (DLTH) that introduces more triplets into batch-based training and a novel listwise triplet loss to capture the relative similarity in new triplets. This method has a pipeline of two steps. In Step 1, we propose a novel way to generate triplets from the soft class labels obtained by knowledge distillation module, where the triplets in the form of (q,q+,q-) are a subset of the newly obtained triplets. In Step 2, we develop a novel listwise triplet loss to train the hashing network, which seeks to capture the relative similarity between images in triplets according to soft labels. We conduct comprehensive image retrieval experiments on four benchmark datasets. The experimental results show that the proposed method has superior performances over state-of-the-art baselines.

6.
Int J Mol Sci ; 22(23)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34884549

RESUMO

The O-antigen is the outermost component of the lipopolysaccharide layer in Gram-negative bacteria, and the variation of O-antigen structure provides the basis for bacterial serological diversity. Here, we determined the O-antigen structure of an Escherichia coli strain, LL004, which is totally different from all of the E. coli serogroups. The tetrasaccharide repeating unit was determined as →4)-ß-d-Galp-(1→3)-ß-d-GlcpNAc6OAc(~70%)-(1→3)-ß-d-GalpA-(1→3)-ß-d-GalpNAc-(1→ with monosaccharide analysis and NMR spectra. We also characterized the O-antigen gene cluster of LL004, and sequence analysis showed that it correlated well with the O-antigen structure. Deletion and complementation testing further confirmed its role in O-antigen biosynthesis, and indicated that the O-antigen of LL004 is assembled via the Wzx/Wzy dependent pathway. Our findings, in combination, suggest that LL004 should represent a novel serogroup of E. coli.

7.
Small Methods ; 5(11): e2100896, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34927974

RESUMO

Lignin, one of the renewable constituents in natural plant biomasses, holds great potential as a sustainable source of functional carbon materials. Tremendous research efforts have been made on lignin-derived carbon electrodes for rechargeable batteries. However, lignin is considered as one of the most promising carbon precursors for the development of high-performance, low-cost porous carbon electrode materials for supercapacitor applications. Yet, these efforts have not been reviewed in detail in the current literature. This review, therefore, offers a basis for the utilization of lignin as a pivotal precursor for the synthesis of porous carbons for use in supercapacitor electrode applications. Lignin chemistry, the synthesis process of lignin-derived porous carbons, and future directions for developing better porous carbon electrode materials from lignin are systematically reviewed. Technological hurdles and approaches that should be prioritized in future research are presented.

8.
Plant J ; 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34919775

RESUMO

Sphingolipids, a class of bioactive lipids, play a critical role in signal transduction. Ceramides, which are central components of sphingolipid metabolism, are involved in plant development and defense. However, the mechanistic link between ceramides and downstream signaling remains unclear. Here, the mutation of alkaline ceramidase in a ceramide kinase mutant acd5 resulted in spontaneous programmed cell death early in development and was accompanied by ceramide accumulation, while other types of sphingolipids, such as long chain base, glucosylceramide, and glycosyl inositol phosphorylceramide, remained at the same level as the wild-type plants. Analysis of the transcriptome indicated that genes related to the salicylic acid (SA) pathway and oxidative stress pathway were induced dramatically in acer acd5 plants. Comparison of the level of reactive oxygen species (ROS), SA, and ceramides in the wild-type and acer acd5 plants at different developmental stages indicated that the acer acd5 mutant exhibited constitutive activation of SA and ROS signaling, which occurred simultaneously with the alteration of ceramides. Overexpressing NahG in the acer acd5 mutant could completely suppress its cell death and ceramide accumulation, while benzo-(1,2,3)-thiadiazole-7-carbothioc acid S-methyl ester treatment restored its phenotype again. Moreover, we found that the plasma membrane of acer acd5 mutant was the main site of ROS production. Ceramides accumulated in the plasma membrane of acer acd5, directly binding and activating the NADPH oxidase RbohD and promoting hydrogen peroxide generation and SA- or defense-related gene activation. Our data illustrated that ceramides play an essential role in plant defense.

9.
Comput Intell Neurosci ; 2021: 2464648, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34961814

RESUMO

Aiming at the problem of insignificant target morphological features, inaccurate detection and unclear boundary of small-target regions, and multitarget boundary overlap in multitarget complex image segmentation, combining the image segmentation mechanism of generative adversarial network with the feature enhancement method of nonlocal attention, a generative adversarial network fused with attention mechanism (AM-GAN) is proposed. The generative network in the model is composed of residual network and nonlocal attention module, which use the feature extraction and multiscale fusion mechanism of residual network, as well as feature enhancement and global information fusion ability of nonlocal spatial-channel dual attention to enhance the target features in the detection area and improve the continuity and clarity of the segmentation boundary. The adversarial network is composed of fully convolutional networks, which penalizes the loss of information in small-target regions by judging the authenticity of prediction and label segmentation and improves the detection ability of the generative adversarial model for small targets and the accuracy of multitarget segmentation. AM-GAN can use the GAN's inherent mechanism that reconstruct and repair high-resolution image, as well as the ability of nonlocal attention global receptive field to strengthen detail features, automatically learn to focus on target structures of different shapes and sizes, highlight salient features useful for specific tasks, reduce the loss of image detail features, improve the accuracy of small-target detection, and optimize the segmentation boundary of multitargets. Taking medical MRI abdominal image segmentation as a verification experiment, multitargets such as liver, left/right kidney, and spleen are selected for segmentation and abnormal tissue detection. In the case of small and unbalanced sample datasets, the class pixels' accuracy reaches 87.37%, the intersection over union is 92.42%, and the average Dice coefficient is 93%. Compared with other methods in the experiment, the segmentation precision and accuracy are greatly improved. It shows that the proposed method has good applicability for solving typical multitarget image segmentation problems such as small-target feature detection, boundary overlap, and offset deformation.


Assuntos
Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Coleta de Dados
10.
World J Gastrointest Oncol ; 13(10): 1466-1474, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34721778

RESUMO

Ampullary adenomatous lesions of the gastrointestinal tract are rare and can be asymptomatic. Therefore, ampullary adenomas with malignant potential require prompt removal, regardless of whether they are adenomatous or carcinomatous lesions. Endoscopic papillectomy is a safe and effective alternative therapy to surgery to treat duodenal papillary lesions in selected patients. Accurate preoperative diagnosis and staging of ampullary adenomatous lesions are critical for predicting prognosis and determining the most appropriate therapeutic approach. Furthermore, the management and prevention of adverse events and endoscopic treatment for remnant or recurrent lesions and surveillance are essential for successful endoscopic management of ampullary adenomatous lesions. This literature review was based on PubMed and MEDLINE and focused on recent advancements in the endoscopic papillectomy technique to provide a comprehensive view of endoscopic papillectomy to treat ampullary adenomatous lesions.

11.
Adv Mater ; : e2106937, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34752665

RESUMO

Aqueous zinc-ion batteries are regarded as ideal candidates for stationary energy-storage systems due to their low cost and high safety. However, zinc can readily grow into dendrites, leading to limited cycling performance and quick failure of the batteries. Herein, a novel strategy is proposed to mitigate this dendrite problem, in which a selectively polarized ferroelectric polymer material (poly(vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE))) is employed as a surface protective layer on zinc anodes. Such a polarized ferroelectric polymer layer can enable a locally concentrated zinc-ion distribution along the coated surface and thus enable the horizontal growth of zinc plates. As a result, symmetrical zinc batteries using such anodes exhibit long cycling lifespan at 0.2 mA cm-2 , 0.2 mAh cm-2 for 2000 h, and a high rate performance up to 15 mA cm-2 . Also, the full cell (including a Zn-MnO2 battery and a zinc-ion capacitor) based on this anode is demonstrated. This work provides a novel strategy to protect the zinc anode and even other metal anodes exploiting polymer ferroelectricity.

12.
Cell Discov ; 7(1): 106, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34728622

RESUMO

Polyamines are important polycations that play critical roles in mammalian cells. ATP13A2 belongs to the orphan P5B adenosine triphosphatases (ATPase) family and has been established as a lysosomal polyamine exporter to maintain the normal function of lysosomes and mitochondria. Previous studies have reported that several human neurodegenerative disorders are related to mutations in the ATP13A2 gene. However, the transport mechanism of ATP13A2 in the lysosome remains unclear. Here, we report the cryo-electron microscopy (cryo-EM) structures of three distinct intermediates of the human ATP13A2, revealing key insights into the spermine (SPM) transport cycle in the lysosome. The transmembrane domain serves as a substrate binding site and the C-terminal domain is essential for protein stability and may play a regulatory role. These findings advance our understanding of the polyamine transport mechanism, the lipid-associated regulation, and the disease-associated mutants of ATP13A2.

13.
Chemistry ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34811828

RESUMO

Recently, we presented a strategy for packaging peptides as side-chains in high-density brush polymers. For this globular protein-like polymer (PLP) formulation, therapeutic peptides were shown to resist proteolytic degradation, enter cells efficiently and maintain biological function. In this paper, we establish the role charge plays in dictating the cellular uptake of these peptide formulations, finding that peptides with a net positive charge will enter cells when polymerized, while those formed from anionic or neutral peptides remain outside of cells. Given these findings, we explored whether cellular uptake could be selectively induced by a stimulus. In our design, a cationic peptide is appended to a sequence of charge-neutralizing anionic amino acids via stimuli-responsive cleavable linkers. As a proof-of-concept study, we tested this strategy with two different classes of stimuli, exogenous UV light and an enzyme (a matrix metalloproteinase) associated with the inflammatory response. The key finding is that these materials enter cells only when acted upon by the stimulus. This approach makes it possible to achieve delivery of the polymers, therapeutic peptides or an appended cargo into cells in response to an appropriate stimulus.

14.
J Neurooncol ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797524

RESUMO

PURPOSE: Autophagy-dependent tumorigenic growth is one of the most commonly reported molecular mechanisms in glioblastoma (GBM) progression. However, the mechanistic correlation between autophagy and GBM is still largely unexplored, especially the roles of autophagy-related genes involved in GBM oncogenesis. In this study, we aimed to explore the genetic alterations that interact with both autophagic activity and GBM tumorigenesis, and to investigate the molecular mechanisms of autophagy involved in GBM cell death and survival. METHOD: For this purpose, we systematically explored the alterations of autophagic molecules at the genome level in human GBM samples through deep RNA sequencing. The effect of genetic and pharmacologic inhibition of ERK on GBM growth in vitro and in vivo was researched. An image-based tracking analysis of LC3 using mCherry-eGFP-LC3 plasmid, and transmission electron microscopy were utilized to monitor autophagic flux. Immunoblot analysis was used to measure the related proteins. RESULTS: MAPK ERK expression was identified as one of the most probable autophagy-related transcriptional responses during GBM growth. The genetic and pharmacologic inhibition of ERK in vivo and in vitro led to cell death, demonstrating its critical role for GBM proliferation and survival. To our surprise, autophagic activities were excessively activated and resulted in cytodestructive effects on GBM cells upon ERK inhibitor treatment. Furthermore, based on the observation of downregulation of mTOR signaling, we speculated the ERK inhibitor-induced GBM cells death might depend on mTOR-mediated pathway, leading to autophagy dysregulation. Accordingly, the in vivo and in vitro experiments revealed that the mTOR inhibitor rapamycin further increased cell mortality and exhibited enhanced antitumor effect on GBM cells when co-treated with the ERK inhibitor. CONCLUSION: Our data creatively demonstrated that the autophagy-related regulator ERK maintains autophagic activity during GBM tumorigenesis via mTOR signaling pathway. The pharmacologic inhibition of both mTOR and ERK signaling exhibited synergistic therapeutic effect on GBM growth in vivo and in vitro, which has certain novelty and may provide a potential therapeutic approach for GBM treatment in the future.

15.
Cancer Biol Med ; 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34846109

RESUMO

OBJECTIVE: The number of immediate breast reconstruction (IBR) procedures has been increasing in China. This study aimed to investigate the oncological safety of IBR, and to compare the survival and surgical outcomes between implant-based and autologous reconstruction. METHODS: Data from patients diagnosed with invasive breast cancer who underwent immediate total breast reconstruction between 2001 and 2016 were retrospectively reviewed. Long-term breast cancer-specific survival (BCSS), disease-free survival (DFS), and locoregional recurrence-free survival (LRFS) were evaluated. Patient satisfaction with the breast was compared between the implant-based and autologous groups. BCSS, DFS, and LRFS were compared between groups after propensity score matching (PSM). RESULTS: A total of 784 IBR procedures were identified, of which 584 were performed on patients with invasive breast cancer (implant-based, n = 288; autologous, n = 296). With a median follow-up of 71.3 months, the 10-year estimates of BCSS, DFS, and LRFS were 88.9% [95% confidence interval (CI) (85.1%-93.0%)], 79.6% [95% CI (74.7%-84.8%)], and 94.0% [95% CI (90.3%-97.8%)], respectively. A total of 124 patients completed the Breast-Q questionnaire, and no statistically significant differences were noted between groups (P = 0.823). After PSM with 27 variables, no statistically significant differences in BCSS, DFS, and LRFS were found between the implant-based (n = 177) and autologous (n = 177) groups. Further stratification according to staging, histological grade, lymph node status, and lymph-venous invasion status revealed no significant survival differences between groups. CONCLUSIONS: Both immediate implant-based and autologous reconstruction were reasonable choices with similar long-term oncological outcomes and patient-reported satisfaction among patients with invasive breast cancer in China.

16.
Transl Androl Urol ; 10(10): 3815-3825, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34804824

RESUMO

Background: The diagnostic methods of prostate cancer (PCa) present major drawbacks in that serum prostate specific antigen (PSA) testing lacks specificity for PCa and prostate needle biopsy is a painful and highly invasive procedure for patients. Thus, new alternative screening methods which are specific and non-invasive both in the early detection and in the clinical definitive diagnosis of PCa are in urgent need. Long non-coding RNA MYU has been shown to promote PCa cell proliferation and migration, and is significantly upregulated both at the cellular and tumor tissue level. Therefore, long non-coding RNA MYU may be a new potential diagnostic biomarker for PCa. Methods: In the present study, we successfully developed a highly sensitive digital PCR assay to detect long non-coding RNA in clinical urine samples. dPCR was carried out using Qx200 ddPCR EvaGreen Supermix (Bio-Rad) according to the manufacturer's instructions. Results: Our results indicated that the digital PCR assay showed better linearity, repeatability, and reproducibility when compared with real-time quantitative PCR. In addition, we identified the normalized MYU level and used the digital PCR assay to measure it in 100 clinical urine samples. Our study showed that the normalized MYU level is a promising diagnostic biomarker for predicting and evaluating the malignancy of PCa. Conclusions: Our findings presented a non-invasive liquid biopsy method to detect an alternative diagnostic parameter which can assist the diagnosis of PCa in clinical practice.

17.
Chin Med J (Engl) ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34839316

RESUMO

BACKGROUND: Prospective analyses have yet to identify a consistent relationship between sleep duration and the incidence of gastrointestinal (GI) cancers. The effect of changes in sleep duration on GI cancer incidence has scarcely been studied. Therefore, we aimed to examine the association between baseline sleep duration and annual changes in sleep duration and GI cancer risk in a large population-based cohort study. METHODS: A total of 123,495 participants with baseline information and 83,511 participants with annual changes in sleep duration information were prospectively observed from 2006 to 2015 for cancer incidence. Cox proportional-hazards models were used to calculate hazard ratios (HRs) and their confidence intervals (CIs) for GI cancers according to sleep duration and annual changes in sleep duration. RESULTS: In baseline sleep duration analyses, short sleep duration (≤5 h) was significantly associated with a lower risk of GI cancer in females (HR: 0.31, 95% CI: 0.10-0.90), and a linear relationship between baseline sleep duration and GI cancer was observed (P = 0.010), especially in males and in the >50-year-old group. In the annual changes in sleep duration analyses, with stable category (0 to -15 min/year) as the control group, decreased sleep duration (≤-15 min/year) was significantly associated with the development of GI cancer (HR: 1.29; 95% CI: 1.04-1.61), especially in the >50-year-old group (HR: 1.32; 95% CI: 1.01-1.71), and increased sleep duration (>0 min/year) was significantly associated with GI cancer in females (HR: 2.89; 95% CI: 1.14-7.30). CONCLUSIONS: Both sleep duration and annual changes in sleep duration were associated with the incidence of GI cancer.

18.
J Spinal Cord Med ; : 1-8, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34698622

RESUMO

BACKGROUND: Spinal cord injury (SCI) refers to the interruption of the tracts inside the spinal cord caused by various factors. The repair of damaged axons has always been a difficult point in clinical treatment and neuroscience research. The treatment of SCI with Buyang huanwu decoction (BYHWD), a well-known recipe for invigorating Qi (a vital force forming part of any living entity in traditional Chinese culture) and promoting blood circulation, shows a good effect. METHODS: The rubrospinal tract (RST) transection model in rats was established in this study and rats were administrated with low (BL), medium (BM), or high (BH) doses of BYHWD. RESULTS: Compared with the SCI group, BL, BM moderately, and BH significantly improved the motor function of forelimbs and increased the number of red nucleus neurons in SCI rats. As for the possible molecular mechanism, BL, BM moderately, and BH significantly increased mTOR whereas decreased Beclin-1 and LC3 in the red nucleus. CONCLUSION: In conclusion, low, medium, and high doses of BYHWD could promote neural recovery in SCI rats through improving motor function and neuron survival in the red nucleus. The neuroprotective effects of BYHWD might be associated with affecting the mTOR signaling pathway and autophagy.

19.
Plant Physiol ; 187(3): 1713-1727, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34618068

RESUMO

Sphingolipids are structural components of the lipid bilayer that acts as signaling molecules in many cellular processes, including cell death. Ceramides, key intermediates in sphingolipid metabolism, are phosphorylated by the ceramide kinase ACCELERATED CELL DEATH5 (ACD5). The loss of ACD5 function leads to ceramide accumulation and spontaneous cell death. Here, we report that the jasmonate (JA) pathway is activated in the Arabidopsis (Arabidopsis thaliana) acd5 mutant and that methyl JA treatment accelerates ceramide accumulation and cell death in acd5. Moreover, the double mutants of acd5 with jasmonate resistant1-1 and coronatine insensitive1-2 exhibited delayed cell death, suggesting that the JA pathway is involved in acd5-mediated cell death. Quantitative sphingolipid profiling of plants treated with methyl JA indicated that JAs influence sphingolipid metabolism by increasing the levels of ceramides and hydroxyceramides, but this pathway is dramatically attenuated by mutations affecting JA pathway proteins. Furthermore, we showed that JAs regulate the expression of genes encoding enzymes in ceramide metabolism. Together, our findings show that JAs accelerate cell death in acd5 mutants, possibly by modulating sphingolipid metabolism and increasing ceramide levels.

20.
Artigo em Inglês | MEDLINE | ID: mdl-34695004

RESUMO

Aspect extraction is one of the key tasks in fine-grained sentiment analysis. This task aims to identify explicit opinion targets from user-generated documents. Currently, the mainstream methods for aspect extraction are built on recurrent neural networks (RNNs), which are difficult to parallelize. To accelerate the training/testing process, convolutional neural network (CNN)-based methods are introduced. However, such models usually utilize the same set of filters to convolve all input documents, and hence, the unique information inherent in each document may not be fully captured. To alleviate this issue, we propose a CNN-based model that employs a set of dynamic filters. Specifically, the proposed model extracts the aspects in a document using the filters generated from the aspect information intrinsic in the document. With the dynamically generated filters, our model is capable of learning more important features concerning aspects, thus promoting the effectiveness of aspect extraction. Furthermore, considering that aspects can be grouped into certain topics that conversely indicate the target words that need to be extracted, we naturally introduce a neural topic model (NTM) and integrate latent topics into the CNN-based module to help identify aspects. Experiments on two benchmark datasets demonstrate that the joint model is able to effectively identify aspects and produce interpretable topics.

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