AoBck1 and AoMkk1 Are Necessary to Maintain Cell Wall Integrity, Vegetative Growth, Conidiation, Stress Resistance, and Pathogenicity in the Nematode-Trapping Fungus Arthrobotrys oligospora

The cell wall integrity (CWI) pathway is composed of three mitogen-activated protein kinases (MAPKs), Bck1, Mkk1/2, and Slt2, and is one of the main signaling pathways for fungal pathogenesis, cell wall synthesis, and integrity maintenance. In this study, we characterized orthologs of Saccharomyces cerevisiae Bck1 and Mkk1 in the nematode-trapping (NT) fungus Arthrobotrys oligospora by multiple phenotypic comparison, and the regulation of conidiation and cell wall synthesis was analyzed using real-time PCR (RT-PCR). Both ΔAoBck1 and ΔAoMkk1 mutants showed severe defects in vegetative growth, cell nucleus number, and stress resistance. Both the mutants were unable to produce spores, and the transcription of several genes associated with sporulation and cell wall biosynthesis was markedly downregulated during the conidiation stage. Further, cell walls of the ΔAoBck1 and ΔAoMkk1 mutants were severely damaged, and the Woronin body failed to respond to cellular damage. In particular, the mutants lost the ability to produce mycelial traps for nematode predation. Taken together, AoBck1 and AoMkk1 play a conserved role in mycelial growth and development, CWI, conidiation, multi-stress tolerance, trap formation, and pathogenicity. We highlighted the role of AoBck1 and AoMkk1 in regulating the Woronin body response to cellular damage and cell nucleus development in A. oligospora

Protective Effect and Mechanism of Chinese Yam Total Protein on High D-Glucose Induced Oxidative Stress in Human Umbilical Vein Endothelial Cells

To explored the protective effect and mechanism of Chinese yam total protein in human umbilical vein endothelial cells (HUVECs) with high-concentration D-glucose (HG)-induced oxidative stress injury. The HUVECs injury model was established by 50 mmol/L HG. HUVECs were randomly divided into control, model, low-dose Chinese yam total protein (0.5 mg/mL), and high-dose Chinese yam total protein (1 mg/mL) groups. The effects of Chinese yam total protein on the viability, morphology, and angiogenetic ability of HUVECs treated with HG were evaluated. The reactive oxygen species (ROS) level, superoxide dismutase (SOD) and catalase (CAT) activities in cells were determined. The nitric oxide (NO), 8-hydroxy deoxyguanosine (8-OHdG), malondialdehyde (MDA), interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels in culture medium supernatant were measured. Protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X (Bax), thioredoxin-interacting protein (Txnip), NOD-like receptor protein 3 (NLRP3), cleaved Caspase-1, and IL-1β were determined. The results showed that Chinese yam total protein could significantly increased the cell viability of HUVECs treated with HG (P<0.01), improved cell apoptotic morphology, and significantly increased the activities of SOD and CAT (P<0.05, P<0.01) and ratio of apoptosis-related proteins (Bcl-2/Bax), angiogenetic ability and nitric oxide (NO) secretion. Moreover, Chinese yam total protein significantly decreased the levels of ROS, MDA, 8-OHdG, IL-1β, and IL-6 (P<0.05, P<0.01) and the expression levels of inflammation-related proteins (Txnip, NLRP3, cleaved Caspase-1, and IL-1β) (P<0.05, P<0.01). Changes in these indicators showed a significant concentration-dependent manner. The results indicate that Chinese yam total protein may protect against HG-induced oxidative stress by inhibiting the Txnip/NLRP3 signaling pathway, restoring the oxidative balance, and reducing the inflammatory response of HUVECs

Word Embeddings via Causal Inference: Gender Bias Reducing and Semantic Information Preserving

With widening deployments of natural language processing (NLP) in daily life, inherited social biases from NLP models have become more severe and problematic. Previous studies have shown that word embeddings trained on human-generated corpora have strong gender biases that can produce discriminative results in downstream tasks. Previous debiasing methods focus mainly on modeling bias and only implicitly consider semantic information while completely overlooking the complex underlying causal structure among bias and semantic components. To address these issues, we propose a novel methodology that leverages a causal inference framework to effectively remove gender bias. The proposed method allows us to construct and analyze the complex causal mechanisms facilitating gender information flow while retaining oracle semantic information within word embeddings. Our comprehensive experiments show that the proposed method achieves state-of-the-art results in gender-debiasing tasks. In addition, our methods yield better performance in word similarity evaluation and various extrinsic downstream NLP tasks

Expression of the Inhibitory Receptor TIGIT Is Up-Regulated Specifically on NK Cells With CD226 Activating Receptor From HIV-Infected Individuals

Natural killer (NK) cells are important for maintenance of innate immune system stability and serve as a first line of defense against tumors and virus infections; they can act either directly or indirectly and are regulated via co-operation between inhibitory and stimulatory surface receptors. The recently reported inhibitory receptor, TIGIT, can be expressed on the NK cell surface; however, the expression level and function of TIGIT on NK cells during HIV infection is unknown. In this study, for the first time, we investigated the expression and function of TIGIT in NK cells from HIV-infected individuals. Our data demonstrate that the level of TIGIT is higher on NK cells from patients infected with human immunodeficiency virus (HIV) compared with HIV-negative healthy controls. TIGIT expression is inversely correlated with CD4+ T cell counts and positively correlated with plasma viral loads. Additionally, levels of the TIGIT ligand, CD155, were higher on CD4+ T cells from HIV-infected individuals compared with those from healthy controls; however, there was no difference in the level of the activating receptor, CD226, which recognizes the same ligands as TIGIT. Furthermore, TIGIT was found to specifically up-regulated on CD226+ NK cells in HIV-infected individuals, and either rIL-10, or rIL-12 + rIL-15, could induce TIGIT expression on these cells. In addition, high TIGIT expression inhibited the production of interferon-gamma (IFN-γ) by NK cells, while TIGIT inhibition restored IFN-γ production. Overall, these results highlight the important role of TIGIT in NK cell function and suggest a potential new avenue for the development of therapeutic strategies toward a functional cure for HIV

Ginsenosides on stem cells fate specification—a novel perspective

Recent studies have demonstrated that stem cells have attracted much attention due to their special abilities of proliferation, differentiation and self-renewal, and are of great significance in regenerative medicine and anti-aging research. Hence, finding natural medicines that intervene the fate specification of stem cells has become a priority. Ginsenosides, the key components of natural botanical ginseng, have been extensively studied for versatile effects, such as regulating stem cells function and resisting aging. This review aims to summarize recent progression regarding the impact of ginsenosides on the behavior of adult stem cells, particularly from the perspective of proliferation, differentiation and self-renewal

NKG2C+NKG2A− Natural Killer Cells are Associated with a Lower Viral Set Point and may Predict Disease Progression in Individuals with Primary HIV Infection

Natural killer (NK) cells are the first line of defense against pathogens of the immune system and also play an important role in resistance against HIV. The activating receptor NKG2C and the inhibitory receptor NKG2A co-modulate the function of NK cells by recognizing the same ligand, HLA-E. However, the role of NKG2A and NKG2C on viral set point and the prediction of HIV disease progression have been rarely reported. In this study, we determined the expression of NKG2C or NKG2A on the surface of NK cells from 22 individuals with primary HIV infection (PHI) stage and 23 HIV-negative normal control (NC) subjects. The CD4+ T cell count and plasma level of HIV RNA in the infected individuals were longitudinally followed-up for about 720 days. The proportion of NKG2C+NKG2A− NK cells was higher in subjects from the low set point group and was negatively correlated with the viral load. In addition, strong anti-HIV activities were observed in NKG2C+ NK cells from the HIV-positive donors. Furthermore, a proportion of NKG2C+NKG2A− NK cells &gt;35.45%, and a ratio of NKG2C/NKG2A &gt;1.7 were predictive for higher CD4+ T cell counts 720 days after infection. Collectively, the experimental results allow us to draw the conclusion that NKG2C+ NK cells might exert an antiviral effect and that the proportion of NKG2C+NKG2A− NK cells, and the ratio of NKG2C/NKG2A, are potential biomarkers for predicting HIV disease progression

Stem Cells in the Treatment of Neuropathic Pain: Research Progress of Mechanism

Neuropathic pain (NP) is pain caused by somatosensory nervous system injury or disease. Its prominent symptoms are spontaneous pain, hyperalgesia, and allodynia, and the sense of pain is extremely strong. Owing to the complex mechanism, conventional painkillers lack effectiveness. Recently, research on the treatment of NP by stem cells is increasing and promising results have been achieved in preclinical research. In this review, we briefly introduce the neuropathic pain, the current treatment strategy, and the development of stem cell therapy, and we collected the experimental and clinical trial articles of many kinds of stem cells in the treatment of neuropathic pain from the past ten years. We analyzed and summarized the general efficacy and mechanism of stem cells in the treatment of neuropathic pain. We found that the multiple-mechanism approach was different from the single mechanism of routine clinical drugs; stem cells play a role in peripheral mechanism, central mechanism, and disinhibition of spinal cord level that lead to neuropathic pain, so they are more effective in analgesia and treatment of neuropathic pain

Evolutionary causes of global patterns of species richness in regional fern floras across the world

Aim: Globally, biodiversity is unevenly distributed, as a result of varying environmental conditions and regionally different historical processes. The influence of the latter on current diversity patterns is poorly understood. We explore geographic patterns of matches and mismatches between phylogenetic relatedness metrics measuring different depths of evolutionary history and investigate the effects of evolutionary legacy at different evolutionary depths on species density of ferns. Methods: We divided the globe into 392 geographic regions on land, and collated species lists of ferns for each geographic region. We related species richness to phylogenetic metrics reflecting different depths of evolutionary history (standardized effect sizes of mean nearest taxon distance and mean pairwise distance, MNTD$_{ses}$ and MPD$_{ses}$, respectively) for ferns in regional floras across the world. Location: Global. Time Period: Current. Taxon: Ferns. Results: We show that different centers of fern diversity have strikingly different phylogenetic composition. We find that overall fern species diversity is negatively correlated with both MNTD$_{ses}$ and MPD$_{ses}$, so that regions with high species diversity tend to have clustered species assemblages, whereas species‐poor regions tend to have overdispersed species assemblages. At the global extent, MNTD$_{ses}$ and MPD$_{ses}$ together explained 62.2%, 19.3%, and 65.7% of the variation in species diversity for all ferns as a whole, non‐polypod ferns, and polypods, respectively. Main Conclusions: Our study suggests that current geographic patterns of fern species richness are driven, at least in part, by evolutionary history of ferns, which varies among biogeographic regions

Human Activity Influences on Vegetation Cover Changes in Beijing, China, from 2000 to 2015

For centuries, the rapid development of human society has already made human activity the dominant factor in the terrestrial ecosystem. As the city of greatest importance in China, the capital Beijing has experienced eco-environmental changes with unprecedented economic and population growth during the past few decades. To better understand the ecological transition and its correlations in Beijing, Landsat Thematic Mapper (TM) and Operational Land Imager (OLI) images were used to investigate vegetation coverage changes using a dimidiate pixel model. Piecewise linear regression, bivariate-partial correlation analysis, and factor analysis were applied to the probing of the relationship between vegetation coverage changes and climatic/human-induced factors. The results showed that from 2000 to 2005, 2005 to 2010, and 2010 to 2015, Beijing experienced both restoration (6.33%, 10.08%, and 12.81%, respectively) and degradation (13.62%, 9.35%, and 9.49%, respectively). The correlation analysis results between climate and vegetation changes demonstrated that from 2000 to 2015, both the multi-year annual mean temperature (r = −0.819, p &lt; 0.01) and the multi-year annual mean precipitation (r = 0.653, p &lt; 0.05) had a significantly correlated relationship with vegetation change. The Beijing-Tianjin Sandstorm Source Control Project (BTSSCP) has shown beneficial spatial effects on vegetation restoration; the total effectiveness in conservation areas (84.94 in 2000–2010) was much better than non-BTSSCP areas (34.34 in 2000–2010). The most contributory socioeconomic factors were the population (contribution = 54.356%) and gross domestic product (GDP) (contribution = 30.677%). The population showed a significantly negative correlation with the overall vegetation coverage (r = −0.684, p &lt; 0.05). The GDP was significantly negatively correlated with vegetation in Tongzhou, Daxing, Central city, Fangshan, Shunyi, and Changping (r = −0.601, p &lt; 0.01), while positively related in Huairou, Miyun, Pinggu, Mentougou and Yanqing (r = 0.614, p &lt; 0.01). These findings confirm that human activity is a very significant factor in impacting and explaining vegetation changes, and that some socioeconomic influences on vegetation coverage are highly spatially heterogeneous, based on the context of different areas

Global patterns and climatic determinants of phylogenetic structure of regional fern floras

Knowledge of relationships between phylogenetic structure of a biological assemblage and ecological factors that drive the variation of phylogenetic structure among regions is crucial for understanding the causes of variation in taxonomic composition and richness among regions, but this knowledge is lacking for the global flora of ferns. Here, we fill this critical knowledge gap. We divided the globe into 392 geographic units on land, collated species lists of ferns for each geographic unit, and used different phylogenetic metrics (tip- vs basal-weighted) reflecting different evolutionary depths to quantify phylogenetic structure. We then related taxonomic and phylogenetic structure metrics to six climatic variables for ferns as a whole and for two groups of ferns (old clades vs polypods) reflecting different evolutionary histories across the globe and within each continental region. We found that when old clades and polypods were considered separately, temperature-related variables explained more variation in these metrics than did precipitation-related variables in both groups. When analyses were conducted for continental regions separately, this pattern holds in most cases. Climate extremes have a stronger relationship with phylogenetic structure of ferns than does climate seasonality. Climatic variables explained more variation in phylogenetic structure at deeper evolutionary depths