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"Yang, Shun"
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Understanding the role of neutrophils in acute respiratory distress syndrome
Acute respiratory distress syndrome (ARDS) is difficult to treat and is associated with a high mortality rate. The most severe form of coronavirus disease 2019 (COVID-19) also leads to life-threatening ARDS. Neutrophil counts are positively correlated with disease severity in ARDS. Neutrophil activation not only plays a significant role in immune defense against infections, but also causes tissue damage and leads to inflammatory diseases. Activated neutrophils rapidly migrate to inflamed lung tissue, releasing toxic granular contents and generating neutrophil extracellular traps. In the last few decades, it has become apparent that neutrophils occupy a central role in ARDS pathology. In this review, we summarize the neutrophil inflammatory responses and their relationships to ARDS. According to the current literature, understanding the function of neutrophils may be helpful in the treatment of ARDS.
Journal Article
Self-organizing maps of typhoon tracks allow for flood forecasts up to two days in advance
Typhoons are among the greatest natural hazards along East Asian coasts. Typhoon-related precipitation can produce flooding that is often only predictable a few hours in advance. Here, we present a machine-learning method comparing projected typhoon tracks with past trajectories, then using the information to predict flood hydrographs for a watershed on Taiwan. The hydrographs provide early warning of possible flooding prior to typhoon landfall, and then real-time updates of expected flooding along the typhoon’s path. The method associates different types of typhoon tracks with landscape topography and runoff data to estimate the water inflow into a reservoir, allowing prediction of flood hydrographs up to two days in advance with continual updates. Modelling involves identifying typhoon track vectors, clustering vectors using a self-organizing map, extracting flow characteristic curves, and predicting flood hydrographs. This machine learning approach can significantly improve existing flood warning systems and provide early warnings to reservoir management.
Tropical cyclones can cause severe flooding when making landfall, but these water flows can often only be forecasted a few hours before. Here, the authors present a new approach using self-organizing maps and flow characteristic curves to predict tropical cyclone related runoff up to two days in advance.
Journal Article
Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis
There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed. Some of the arresting actions of melatonin on cancer are clearly membrane receptor-mediated while others are membrane receptor-independent and involve direct intracellular actions of this ubiquitously-distributed molecule. While the emphasis of melatonin/cancer research has been on the role of the indoleamine in restraining breast cancer, this is changing quickly with many cancer types having been shown to be susceptible to inhibition by melatonin. There are several facets of this research which could have immediate applications at the clinical level. Many studies have shown that melatonin’s co-administration improves the sensitivity of cancers to inhibition by conventional drugs. Even more important are the findings that melatonin renders cancers previously totally resistant to treatment sensitive to these same therapies. Melatonin also inhibits molecular processes associated with metastasis by limiting the entrance of cancer cells into the vascular system and preventing them from establishing secondary growths at distant sites. This is of particular importance since cancer metastasis often significantly contributes to death of the patient. Another area that deserves additional consideration is related to the capacity of melatonin in reducing the toxic consequences of anti-cancer drugs while increasing their efficacy. Although this information has been available for more than a decade, it has not been adequately exploited at the clinical level. Even if the only beneficial actions of melatonin in cancer patients are its ability to attenuate acute and long-term drug toxicity, melatonin should be used to improve the physical wellbeing of the patients. The experimental findings, however, suggest that the advantages of using melatonin as a co-treatment with conventional cancer therapies would far exceed improvements in the wellbeing of the patients.
Journal Article
Terpene Derivatives as a Potential Agent against Antimicrobial Resistance (AMR) Pathogens
The evolution of antimicrobial resistance (AMR) in pathogens has prompted extensive research to find alternative therapeutics. Plants rich with natural secondary metabolites are one of the go-to reservoirs for discovery of potential resources to alleviate this problem. Terpenes and their derivatives comprising of hydrocarbons, are usually found in essential oils (EOs). They have been reported to have potent antimicrobial activity, exhibiting bacteriostatic and bactericidal effects against tested pathogens. This brief review discusses the activity of terpenes and derivatives against pathogenic bacteria, describing the potential of the activity against AMR followed by the possible mechanism exerted by each terpene class. Finally, ongoing research and possible improvisation to the usage of terpenes and terpenoids in therapeutic practice against AMR are discussed.
Journal Article
Function and Regulation of Ammonium Transporters in Plants
Ammonium transporter (AMT)-mediated acquisition of ammonium nitrogen from soils is essential for the nitrogen demand of plants, especially for those plants growing in flooded or acidic soils where ammonium is dominant. Recent advances show that AMTs additionally participate in many other physiological processes such as transporting ammonium from symbiotic fungi to plants, transporting ammonium from roots to shoots, transferring ammonium in leaves and reproductive organs, or facilitating resistance to plant diseases via ammonium transport. Besides being a transporter, several AMTs are required for the root development upon ammonium exposure. To avoid the adverse effects of inadequate or excessive intake of ammonium nitrogen on plant growth and development, activities of AMTs are fine-tuned not only at the transcriptional level by the participation of at least four transcription factors, but also at protein level by phosphorylation, pH, endocytosis, and heterotrimerization. Despite these progresses, it is worth noting that stronger growth inhibition, not facilitation, unfortunately occurs when AMT overexpression lines are exposed to optimal or slightly excessive ammonium. This implies that a long road remains towards overcoming potential limiting factors and achieving AMT-facilitated yield increase to accomplish the goal of persistent yield increase under the present high nitrogen input mode in agriculture.
Journal Article
TIMP-3 as a therapeutic target for cancer
Tissue inhibitor of metalloproteinase-3 (TIMP-3), a secreted glycoprotein, plays an important role in carcinogenesis. It can bind to many proteinases to suppress their activity and thus protect the extracellular matrix from degradation. TIMP-3 may have many anticancer properties, including apoptosis induction and antiproliferative, antiangiogenic, and antimetastatic activities. This review summarizes the structure, proteinase inhibition ability, genetic and epigenetic regulation, cancer therapy potential, and contribution to cancer development of TIMP-3. Furthermore, in this review we discuss its potential as a biomarker for predicting cancer progression and the current state of drugs that target TIMP-3, either alone or in combination with clinical treatment. In conclusion, TIMP-3 can be a biomarker of cancer and a potential target for cancer therapy. This review article can serve as a basis to understand how to modulate TIMP-3 levels as a drug target of cancers.
Journal Article
Is Best Answer Really the Best Answer? The Politeness Bias
Popular knowledge management platforms such as community-based question answering sites (CQAs) and electronic networks of practice (ENPs) rely on accurate quality assessment of user-contributed content to ensure effective knowledge creation and exchange. However, quality assessment is subjective by nature. Based on the politeness theory, we hypothesize that answers written more politely are more likely to be perceived as high quality answers by the question asker due to the low face threat. We first test our hypotheses through a random coefficient logit model with data obtained from Stack Exchange, a popular CQA platform. We then conduct a randomized experiment where we exogenously manipulate the politeness level of otherwise similar answers. Our analyses, based on both the Stack Exchange dataset and the randomized experiment, lend strong support to the existence of a politeness bias, which affects question askers’ subjective evaluation of answer quality. This study contributes to the literature in knowledge management, cognitive bias, and behavioral issues in information systems.
Journal Article
Tris DBA ameliorates IgA nephropathy by blunting the activating signal of NLRP3 inflammasome through SIRT1‐ and SIRT3‐mediated autophagy induction
Tris (dibenzylideneacetone) dipalladium (Tris DBA), a small‐molecule palladium complex, can inhibit cell growth and proliferation in pancreatic cancer, lymphocytic leukaemia and multiple myeloma. Given that this compound is particularly active against B‐cell malignancies, we have been suggested that it can alleviate immune complexes (ICs)–mediated conditions, especially IgA nephropathy (IgAN). The therapeutic effects of Tris DBA on glomerular cell proliferation and renal inflammation and mechanism of action were examined in a mouse model of IgAN. Treatment of IgAN mice with Tris DBA resulted in markedly improved renal function, albuminuria and renal pathology, including glomerular cell proliferation, neutrophil infiltration, sclerosis and periglomerular inflammation in the renal interstitium, together with (Clin J Am Soc Nephrol. 2011, 6, 1301‐1307) reduced mitochondrial ROS generation; (Am J Physiol‐Renal Physiol. 2011. 301, F1218‐F1230) differentially regulated autophagy and NLRP3 inflammasome; (Clin J Am Soc Nephrol. 2012, 7, 427‐436) inhibited phosphorylation of JNK, ERK and p38 MAPK signalling pathways, and priming signal of the NLRP3 inflammasome; and (Free Radic Biol Med. 2013, 61, 285‐297) blunted NLRP3 inflammasome activation through SIRT1‐ and SIRT3‐mediated autophagy induction, in renal tissues or cultured macrophages. In conclusion, Tris DBA effectively ameliorated the mouse IgAN model and targeted signalling pathways downstream of ICs‐mediated interaction, which is a novel immunomodulatory strategy. Further development of Tris DBA as a therapeutic candidate for IgAN is warranted.
Journal Article
Changes in the Bacterial Microbiota in Gut, Blood, and Lungs following Acute LPS Instillation into Mice Lungs
Previous reports have shown that the gastrointestinal (GI) bacterial microbiota can have profound effects on the lungs, which has been described as the \"gut-lung axis\". However, whether a \"lung-gut\" axis exists wherein acute lung inflammation perturbs the gut and blood microbiota is unknown.
Adult C57/Bl6 mice were exposed to one dose of LPS or PBS instillation (n=3 for each group) directly into lungs. Bacterial microbiota of the bronchoalveolar lavage fluid, blood, and cecum were determined using 454 pyrotag sequencing and quantitative polymerase chain reaction (qPCR) at 4 through 168 hours post-instillation. We then investigated the effects of oral neomycin and streptomycin (n=8) on the microbiota at 4 and 24 hours post LPS instillation versus control treatment (n=5 at baseline and 4 hours, n=7 at 24 hours).
At 24 hours post LPS instillation, the total bacterial count was significantly increased in the cecum (P<0.05); whereas the total bacterial count in blood was increased at 4, 48, and 72 hours (P<0.05). Antibiotic treatment reduced the total bacteria in blood but not in the cecum. The increase in total bacteria in the blood correlated with Phyllobacteriaceae OTU 40 and was significantly reduced in the blood for both antibiotic groups (P<0.05).
LPS instillation in lungs leads to acute changes in the bacterial microbiota in the blood and cecum, which can be modulated with antibiotics.
Journal Article