The Zoige pioneer plant Leymus secalinus has different endophytic bacterial community structures to adapt to environmental conditions.

Background: Leymus secalinus is a pioneer plant grown in the Zoige desertified alpine grassland and it is also one of the dominant plant species used for environmental remediation. L. secalinus plays a large role in vegetation reconstruction in sandy land, but the abundance and diversity of its endophytes have not yet been investigated. Objectives: This study was performed to investigate the changes in the endophytic bacterial community structure of L. secalinus under different ecological environments and to analyze the effects of environmental changes and different plant tissues on the L. secalinus endophytic bacteria. Methods: Leaf, stem, and root tissue samples of L. secalinus were collected from Zoige Glassland (Alpine sandy land) and an open field nursery (Control). DNA was extracted and the 16S ribosomal DNA was amplified. The sequence library was sequenced on an Illumina MiSeq platform and clustered by operational taxonomic units (OTUs). α-diversity and ß-diversity analyses, species diversity analyses, functional prediction, and redundancy (RDA) analyses for the soil physicochemical properties were conducted. Results: α-diversity and ß-diversity analyses showed that the endophytic bacteria in L. secalinus varied in different areas and tissues. The abundance of Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, which is related to nitrogen fixation, increased significantly in the L. secalinus found in the Zoige Grassland.Moreover, the abundance of nutrition metabolism and anti-stress abilities increased in functional prediction in the desert samples. The soil physicochemical properties had an insignificant influence on bacterial diversity. Conclusion: The changes in the endophytic bacterial community structure in L. secalinus were significant and were caused by environmental alterations and plant choice. The endophytic bacteria in L. secalinus grown in alpine sandy land may have greater anti-stress properties and the ability to fix nitrogen, which has potential value in environmental remediation and agricultural production.

CircTmeff1 Promotes Muscle Atrophy by Interacting with TDP-43 and Encoding A Novel TMEFF1-339aa Protein.

Skeletal muscle atrophy is a common clinical feature of many acute and chronic conditions. Circular RNAs (circRNAs) are covalently closed RNA transcripts that are involved in various physiological and pathological processes, but their role in muscle atrophy remains unknown. Global circRNA expression profiling indicated that circRNAs are involved in the pathophysiological processes of muscle atrophy. circTmeff1 is identified as a potential circRNA candidate that influences muscle atrophy. It is further identified that circTmeff1 is highly expressed in multiple types of muscle atrophy in vivo and in vitro. Moreover, the overexpression of circTmeff1 triggers muscle atrophy in vitro and in vivo, while the knockdown of circTmeff1 expression rescues muscle atrophy in vitro and in vivo. In particular, the knockdown of circTmeff1 expression partially rescues muscle mass in mice during established atrophic settings. Mechanistically, circTmeff1 directly interacts with TAR DNA-binding protein 43 (TDP-43) and promotes aggregation of TDP-43 in mitochondria, which triggers the release of mitochondrial DNA (mtDNA) into cytosol and activation of the cyclic GMP-AMP synthase (cGAS)/ stimulator of interferon genes (STING) pathway. Unexpectedly, TMEFF1-339aa is identified as a novel protein encoded by circTmeff1 that mediates its pro-atrophic effects. Collectively, the inhibition of circTmeff1 represents a novel therapeutic approach for multiple types of skeletal muscle atrophy.

[Medication law and mechanism of traditional Chinese medicine in prevention and treatment of epidemic diseases: based on traditional Chinese medicine theory of cold pestilence].

Epidemic diseases have caused huge harm to the society. Traditional Chinese medicine(TCM) has made great contributions to the prevention and treatment of them. It is of great reference value for fighting diseases and developing drugs to explore the medication law and mechanism of TCM under TCM theory. In this study, the relationship between the TCM theory of cold pestilence and modern epidemic diseases was investigated. Particularly, the the relationship of coronavirus disease 2019(COVID-19), severe acute respiratory syndrome(SARS), and influenza A(H1 N1) with the cold pestilence was identified and analyzed. The roles of TCM theory of cold pestilence in preventing and treating modern epidemic diseases were discussed. Then, through data mining and textual research, prescriptions for the treatment of cold pestilence were collected from major databases and relevant ancient books, and their medication laws were examined through analysis of high-frequency medicinals and medicinal pairs, association rules analysis, and cluster analysis. For example, the prescriptions with high confidence levels were identified: "Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Paeoniae Radix Alba" "Glycyrrhizae Radix et Rhizoma-Pinelliae Rhizoma-Bupleuri Radix", and TCM treatment methods with them were analyzed by clustering analysis to yield the medicinal combinations: "Zingiberis Rhizoma-Aconiti Lateralis Radix Praeparata-Ginseng Radix et Rhizoma" "Poria-Atractylodis Macrocephalae Rhizoma" "Cinnamomi Ramulus-Asari Radix et Rhizoma" "Citri Reticulatae Pericarpium-Perillae Folium" "Pinelliae Rhizoma-Magnoliae Officinalis Cortex-Atractylodis Rhizoma" "Paeoniae Radix Alba-Angelicae Sinensis Radix-Glycyrrhizae Radix et Rhizoma-Bupleuri Radix-Scutellariae Radix-Rhizoma Zingiberis Recens" "Ephedrae Herba-Armeniacae Semen Amarum-Gypsum Fibrosum" "Chuanxiong Rhizoma-Notopterygii Rhizoma et Radix-Angelicae Dahuricae Radix-Platycodonis Radix-Saposhnikoviae Radix". Then, according to the medication law for cold pestilence, the antiviral active components of medium-frequency and high-frequency medicinals were retrieved. It was found that these components exerted the antiviral effect by inhibiting virus replication, regulating virus proteins and antiviral signals, and suppressing protease activity. Based on network pharmacology, the mechanisms of the medicinals against severe acute respiratory syndrome coronavirus(SARS-CoV), 2019 novel coronavirus(2019-nCoV), and H1 N1 virus were explored. It was determined that the key targets were tumor necrosis factor(TNF), endothelial growth factor A(VEGFA), serum creatinine(SRC), epidermal growth factor receptor(EGFR), matrix metalloproteinase 9(MMP9), mitogen-activated protein kinase 14(MAPK14), and prostaglandin-endoperoxide synthase 2(PTGS2), which were involved the mitogen-activated protein kinase(MAPK) pathway, advanced glycation end-products(AGE)-receptor for AGE(RAGE) pathway, COVID-19 pathway, and mTOR pathway. This paper elucidated the medication law and mechanism of TCM for the prevention and treatment of epidemic diseases under the guidance of TCM theory of cold pestilence, in order to build a bridge between the theory and modern epidemic diseases and provide reference TCM methods for the prevention and treatment of modern epidemic diseases and ideas for the application of data mining to TCM treatment of modern diseases.

Differential Refinement Network for Zero-Shot Learning.

Zero-shot learning (ZSL) aims to recognize novel categories by merely utilizing disjoint seen samples. It is a challenging task as the knowledge of unseen objects is forbidden in the training stage, which easily leads to unseen samples degrading to mismatched categories. In order to alleviate the biased recognition problem, in this article, we propose a differential refinement network (DRNet) for ZSL, which aims to explore robust semantic-to-visual embedding. Our DRNet model consists of two subnetworks: basic network and differential network. The basic network targets to generate initial class-specific visual centers conditioned on corresponding semantic prototypes. The differential network is designed to predict class-unrelated differences between visual centers of arbitrary semantic prototype pairs, which are applied to further polish the initial visual centers. The motivation is that, by comparing different prototypes, interactions between various categories will be characterized, benefiting the generation of authentic and discriminative visual centers. Moreover, a modified episode-based training paradigm is explored to optimize the two subnetworks actively. In the training stage, we form a collection of episodes, each of which is an imitated ZSL task. Our DRNet is optimized by those sampled tasks rather than individual samples, which progressively learns skills to adapt and generalize to novel classes. Experiments on four challenging datasets demonstrate the effectiveness of our method.

Delivery of engineered extracellular vesicles with miR-29b editing system for muscle atrophy therapy.

Muscle atrophy is a frequently observed complication, characterized by the loss of muscle mass and strength, which diminishes the quality of life and survival. No effective therapy except exercise is currently available. In our previous study, repressing miR-29b has been shown to reduce muscle atrophy. In our current study, we have constructed artificially engineered extracellular vesicles for the delivery of CRISPR/Cas9 to target miR-29b (EVs-Cas9-29b). EVs-Cas9-29b has shown a favorable functional effect with respect to miR-29b repression in a specific and rapid manner by gene editing. In in vitro conditions, EVs-Cas9-29b could protect against muscle atrophy induced by dexamethasone (Dex), angiotensin II (AngII), and tumor necrosis factor-alpha (TNF-α). And EVs-Cas9-29b introduced in vivo preserved muscle function in the well-established immobilization and denervation-induced muscle atrophy mice model. Our work demonstrates an engineered extracellular vesicles delivery of the miR-29b editing system, which could be potentially used for muscle atrophy therapy.

Targeting miR-30d reverses pathological cardiac hypertrophy.

BACKGROUND: Pathological cardiac hypertrophy occurs in response to numerous stimuli and precedes heart failure (HF). Therapies that ameliorate pathological cardiac hypertrophy are highly needed. METHODS: The expression level of miR-30d was analyzed in hypertrophy models and serum of patients with chronic heart failure by qRT-PCR. Gain and loss-of-function experiments of miR-30d were performed in vitro. miR-30d gain of function were performed in vivo. Bioinformatics, western blot, luciferase assay, qRT-PCR, and immunofluorescence were performed to examine the molecular mechanisms of miR-30d. FINDINGS: miR-30d was decreased in both murine and neonatal rat cardiomyocytes (NRCMs) models of hypertrophy. miR-30d overexpression ameliorated phenylephrine (PE) and angiotensin II (Ang II) induced hypertrophy in NRCMs, whereas the opposite phenotype was observed when miR-30d was downregulated. Consistently, the miR-30d transgenic rat was found to protect against isoproterenol (ISO)-induced pathological hypertrophy. Mechanistically, methyltransferase EZH2 could promote H3K27me3 methylation in the promotor region of miR-30d and suppress its expression during the pathological cardiac hypertrophy. miR-30d prevented pathological cardiac hypertrophy via negatively regulating its target genes MAP4K4 and GRP78 and inhibiting pro-hypertrophic nuclear factor of activated T cells (NFAT). Adeno-associated virus (AAV) serotype 9 mediated-miR-30d overexpression exhibited beneficial effects in murine hypertrophic model. Notably, miR-30d was reduced in serum of patients with chronic heart failure and miR-30d overexpression could significantly ameliorate pathological hypertrophy in human embryonic stem cell-derived cardiomyocytes. INTERPRETATION: Overexpression of miR-30d may be a potential approach to treat pathological cardiac hypertrophy. FUNDING: This work was supported by the grants from National Key Research and Development Project (2018YFE0113500 to J Xiao), National Natural Science Foundation of China (82020108002 to J Xiao, 81900359 to J Li), the grant from Science and Technology Commission of Shanghai Municipality (20DZ2255400 and 21XD1421300 to J Xiao, 22010500200 to J Li), Shanghai Sailing Program (19YF1416400 to J Li), the "Dawn" Program of Shanghai Education Commission (19SG34 to J Xiao), the "Chen Guang" project supported by the Shanghai Municipal Education Commission and Shanghai Education Development Foundation (19CG45 to J Li).

The first complete mitochondrial genome of the genus Dendronereis, represented by D. chipolini Hsueh, 2019 (Annelida, Nereididae) from Beibu Gluf, China.

The genus Dendronereis Peters, 1854 is characterized in the polychaete family Nereididae by its feather-shaped branchiae on the anterior segments. In this study, we present the first complete mitogenome of Dendronereis, represented by D. chipolini Hsueh, 2019, collected from Beibu Gulf, China. The nucleotide composition is biased toward A + T nucleotides, accounting 31.5% for A, 22.3% for C, 14.7% for G and 31.5% for T. The assembled mitogenome is 15,763 bp in length, with a typical set of 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA), 2 ribosomal RNA (rRNA), and 1 non-coding control region. All genes are encoded on H-strand. The control region is 1260 bp in length and located between tRNA-Gly and tRNA-Met. Phylogenetic study showed that D. chipolini is arranged with high support into the clade of Namanereidinae. The complete mitogenome provides important molecular data for investigating the phylogeny and evolution of the nereid animals.

Knockdown of long non-coding RNA SOX21-AS1 attenuates amyloid-ß-induced neuronal damage by sponging miR-107.

BACKGROUND: Alzheimer's disease (AD), which has no effective drugs to delay or prevent its progression, is a multifactorial complex neurodegenerative disease. Long non-coding RNA SOX21 antisense RNA1 (SOX21-AS1) is associated with the development of AD, but the underlying molecular mechanism of SOX21-AS1 in AD is still largely unclear. METHODS: To construct the AD model, SH-SY5Y and SK-N-SH cells were treated with amyloid-ß1-42 (Aß1-42). Quantitative real-time polymerase chain reaction (qRT-PCR) was executed to detect the expression of SOX21-AS1 and miRNA-107. Western blot analysis was utilized to assess the levels of phosphorylated Tau (p-Tau). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) or flow cytometry assay was employed to determine the viability and apoptosis of SH-SY5Y and SK-N-SH cells. The relationship between SOX21-AS1 and miRNA-107 was verified with the dual-luciferase reporter assay. RESULTS: SOX21-AS1 expression was augmented while miR-107 expression was decreased in Aß1-42-treated SH-SY5Y and SK-N-SH cells. Moreover, Aß1-42 elevated the levels of p-Tau and impeded viability and induced apoptosis of SH-SY5Y and SK-N-SH cells. Also, SOX21-AS1 silencing attenuated Aß1-42 mediated the levels of p-Tau, viability, and apoptosis of SH-SY5Y and SK-N-SH cells. Importantly, SOX21-AS1 acted as a sponge for miR-107 in SH-SY5Y and SK-N-SH cells. Furthermore, the increase in p-Tau levels and apoptosis and the repression of viability of Aß1-42-treated SH-SY5Y and SK-N-SH cells mediated by miR-107 inhibition were partly recovered by SOX21-AS1 depletion. CONCLUSION: SOX21-AS1 silencing could attenuate Aß1-42-induced neuronal damage by sponging miR-107, which provided a possible strategy for the treatment of AD.

Deep reinforcement learning for weak human activity localization.

Human activity localization aims at recognizing contents and detecting locations of activities in video sequences. With an increasing number of untrimmed video data, traditional activity localization methods always suffer from two major limitations. First, detailed annotations are needed in most existing methods, i.e., bounding-box annotations in every frame, which are both expensive and time consuming. Second, the search space is too large for 3D activity localization, which requires generating a large number of proposals. In this paper, we propose a unified deep Q-network with weak reward and weak loss (DWRLQN) to address the two problems. Certain weak knowledge and weak constraints involving the temporal dynamics of human activity are incorporated into a deep reinforcement learning framework under sparse spatial supervision, where we assume that only a portion of frames are annotated in each video sequence. Experiments on UCF-Sports, UCF-101 and sub-JHMDB demonstrate that our proposed model achieves promising performance by only utilizing a very small number of proposals. More importantly, our DWRLQN trained with partial annotations and weak information even outperforms fully supervised methods.

[The exploration of the academic thought of external treatment master-Wu ShiJi].

To explore Wu Shiji's academic thought, his external treatment method were arranged and summarized, such as treatment based on triple energizer differentiation, the theory of plaster heals various disease and the combination of the application of acupuncture, moxibustion and plaster etc. It has been proved that Wu's external treatment had compiled all the advantages of each school of Chinese medicine before his era, rich in content and convenient to use. So it values highly in clinical practice and has provided great convenience for the modern clinical research of external treatment.