Differences in the relative strength and role of the stream wise and cross-stream turbulent eddies in fire spread and the relative importance of some terms of the TKE budget over others at each of the measurement heights have been discussed, based on fire intensity and the surface-fire environment. Shear production and buoyancy production in sub-canopy surface fires are found to be more substantial near the canopy top for more intensefires, while their magnitudes decrease with decreasing fire intensity. For low-intensity sub-canopy fires, the buoyancy production is considerably lower than the shear production near the canopy top, though the latter is mostly attributed to the background canopy turbulence. In a heading grassland fire, shear production dominates buoyancy production close to the surface and appears to be inconsequential beyond a certain height relative to the flame length, while buoyancy production increases with height thereby becoming substantial further away from the surface. In all sub-canopy fires, buoyancy production seems to dominate shear production at the mid-canopy height. The turbulent transport term appears to follow a coherent pattern during fire-front passage when the fire intensity is higher, both within the canopy and in a grassland environment. For intense sub-canopy surface fires, a noticeable loss in TKE due to its expulsion to the atmospheric boundary layer aloft via the transport term is compensated by a gain due to TKE influx via the transport term. In the grassland fire,10 liter drainage collection pot the transport term shows similar behavior until a certain height. These differences also inform the vertical length scales associated with fire induced turbulent flow in their respective environments.
While such length scales have been quantified and studied in no-fire conditions in previous studies , this study takes a step in the direction of quantifying length scales in the presence of a fire, which can inform smoke dispersion in different environments. Model developers can utilize the knowledge of relatively important or less important terms associated with each height to simplify their models or adjust their model complexity depending on the vegetative environment. This will lead to decreased model computational costs without loss of physical understanding. In conjunction with simplified models, the turbulence dynamics presented in this study can also be applied towards understanding the physics of ember transport and estimating the horizontal distance covered by embers lofted by the fire plume before they land to generate spot fires. Another step in the direction of simplifying the governing equations would involve parameterizing fire-atmosphere interactions via a modified flux-gradient approach . The authors plan on using this data to obtain better estimates of the eddy diffusivity in the presence of a fire that will account for the non-local turbulence in the canopy and the coupling between shear and buoyancy. Furthermore, it must be noted that there are limitations associated with the averaging scheme used for examining coherent motions: a larger averaging window delocalizes the coherent motions in time, while a smaller window makes it difficult to separate the mean terms from the turbulent fluctuations. The findings of this study could be augmented by inferences drawn from a wavelet transform on the temperature and velocity signals, which the authors are currently working on. With the help of a suitable window in the time domain, a wavelet transform could disassemble the signal into its component frequencies while achieving the best localization in time, thereby providing insights into the corresponding coherent motions and their temporal evolution.
The issue fibrosis and cancer are two major causes of high human morbidity and mortality worldwide. Although there are multiple therapies for cancer, including chemotherapy, oncologic surgery, and radiation therapy, an effective therapeutic strategy is needed.Among these therapeutic strategies, chemotherapy is the main tool for curing various cancers. The therapeutic resistance of anticancer drugs, such as 5‐fluorouracil, gemcitabine, gefitinib, and trastuzumab, has been widely observed in the clinic.However, due to the lack of effective therapeutic drugs, tissue fibrosis still threatens human health. Although some drugs exhibit antifibrotic effects, including angiotensin‐ converting enzyme inhibitors, aldosterone inhibitors, statins, angiotensin II type 1 receptor blockers, endothelin receptors, β‐blockers, acetylsalicylic acid, and matrix metalloproteinase inhibitors, none of them are specifically designed to target fibrosis, and the related side effects limit their clinical use for treating fibrosis.Thus, antifibrotic and anticancer treatments are extremely urgent, and new therapeutic drugs should be designed based on specific targets that contribute to the progression of fibrosis and tumors. Epithelial‐mesenchymal transition is a reversible terminal differentiation process in which epithelial cells shed their properties and acquire a more mesenchymal phenotype.EMT is a fundamental process widely involved in the development and the progression of various diseases, and there are mainly three types of EMZ. Type I EMT is involved in embryonic development and organ formation. Type II EMT is critical for wound healing and fibrosis. Type III EMT contributes to the progression and metastasis of tumors.Extensive studies revealed that EMT profoundly contributed to the production of myofibroblasts, which are the major cells producing massive amounts of collagen that leads to the deposition of collagen in the development of fibrosis.In addition, EMT confers increased motility and invasiveness in epithelial‐derived tumor cells and promotes tumor metastasis.
Therefore, fibrosis and tumors share the common process of EMT, and drugs that specifically target EMT may exhibit both antifibrosis and antitumor effects, which will provide an effective strategy against fibrosis and tumors. Small molecules have a long history of acting as drugs for the treatment of hypertension, infections, heart failure, diabetes, asthma, rhinitis, and tumors and comprise approximately 75% of the anticancer drugs approved by the FDA from 1981 to 2014.Recently, many small molecules target EMT and exhibit good therapeutic effects on retarding progressive tissue fibrosis and cancer in experimental conditions.In addition, it is worth noting that many small molecules, such as tivantinib, trametinib, linsitinib, nintedanib, and binimetinib, are in ongoing clinical trials for the treatment of tumors.2 These cases show promising prospects for treating fibrosis and cancer, which encourages researchers to find effective small molecule drugs for treating fibrosis and cancer. In this review, we describe some important transcription factors, signaling pathways, RNA‐binding proteins and microRNAs and several novel regulators that contribute to EMT and further present some small molecules that exhibit therapeutic effects against EMT. Targeting these mediators with these compounds may be a promising therapeutic strategy to treat fibrosis and cancer.Several excellent reviews have discussed the mechanisms of EMT well.Briefly, histological and pathological analyses show that epithelial cells are present in single cell layers or multil-layers and show apical‐basal polarity. Epithelial cells not only interact with the basement membrane with integrins but also communicate with each other via specialized intercellular junctions, including desmosomes, subapical tight junctions, adherens junctions and scattered gap junctions. These interactions help maintain epithelium integrity and function. However, some stimuli drive EMT in pathological conditions. During the process of EMT, epithelial cell‐cell junctions are dissolved,10 liter drainage pot and the epithelial cells lose their apical‐basal polarity and acquire front‐rear polarity. In addition, the cytoskeletal architecture is reorganized, and E‐cadherin expression is replaced by N‐cadherin expression, which enhances cell motility and invasiveness. In fibrosis, mesenchymal‐like cells transform into myofibroblasts, which can be activated to produce excessive collagen, and in tumors, these mesenchymal‐like cells migrate along with the circulatory system to a secondary location where they form a secondary tumor via mesenchymal‐epithelial transition .It is worth noting that tissue fibrosis and tumors share the common process of EMT, which suggests that targeting EMT may be an effective strategy to treat both fibrosis and tumors . EMT is regulated by various mediators such as transcription factors, signaling pathways, RNA‐binding proteins, and miRNAs. In addition, there are many small molecules that exhibit effective therapeutic effects on tissue fibrosis and tumors by suppressing EMT via targeting these mediators.The NF‐κB signaling pathway is widely involved in multiple cellular activities, such as cell proliferation, apoptosis, invasion, and inflammation. NF‐κB plays a vital role in the inflammation of tissue fibrosis, and inhibiting NF‐κB activity reduced inflammation and enhanced recovery from CCl4‐induced liver fibrosis.In addition, NF‐κB contributed to inflammation, apoptosis, growth, migration, and invasion of cancer cells.Recently, it was found that the mediator of RNA polymerase II transcription, subunit 28 modulated EMT through NF‐κB in human breast cancer cells, which suggests that the NF‐κB signaling pathway also plays a key role in the process of EMT.Therefore, targeting the NF‐κB signaling pathway may be a good choice to treat fibrosis and tumors. Osthole, a dominant component in Cnidium monnieri Cuss., exhibited various biological activities including neuroprotective, osteogenic, cardiovascular protective, immunomodulatory, hepatoprotective, and antimicrobial effects. Osthole was found to block TGF‐β1‐induced EMT, adhesion, migration, and invasion by the inactivation of the NF‐κB/Snail pathways in A549 cells .In addition, osthole also attenuated insulin‐like growth factor‐ 1‐induced EMT by the PI3K/Akt pathway and inhibited hepatocyte growth factor‐induced EMT via the c‐Met/Akt/ mTOR pathway in human brain cancer cells.Pterostilbene is a stilbene containing in blueberries hat effectively blocked the EMT in breast cancer stem cells by the NF‐κB/miR‐488 circuit.Moreover, pterostilbene negatively regulated EMT and inhibited triple‐negative breast cancer metastasis via inducing the expression of miR‐205.
The sclerotia of Polyporus umbellatus Fries is widely used to promote urination and prevent dampness.Our previous studies systematically demonstrated that ergosta‐4,6,8,22‐tetraen‐3‐one isolated from Polyporus umbellatus Fries showed significant antitumor, diuretic, and renoprotective effects.Our recent study demonstrated that ergone inhibited NF‐κB signaling and α‐SMA expression in 5/6 nephrectomised and unilateral ureteral obstruction rats.The Wnt signaling pathway is an evolutionarily conserved developmental signaling cascade that plays a critical role in regulating organ development and tissue homeostasis. Leucine‐rich repeat‐containing G protein‐coupled receptor 5 is a novel functional marker in glioma stem cells that promotes EMT by activating the Wnt/β‐catenin signaling pathway.Sry‐like high‐mobility group box 8 regulated cancer stem‐like properties and cisplatin‐induced EMT by the Wnt/β‐catenin signaling pathway in tongue squamous cell carcinoma.In addition, bone marrow mesenchymal stromal cells suppressed EMT by inhibiting the Wnt/β‐catenin signaling pathway in silica‐induced pulmonary fibrosis.Our previous study showed the activation of the canonical Wnt/β‐catenin signaling pathway accompanied by the upregulation of proinflammatory and pro‐oxidative protein expression in the NF‐κB signaling pathway and downregulation of the anti‐inflammatory Nrf2 signaling pathway in patients with chronic kidney disease compared with the Nrf2 signaling pathway in healthy controls.Many compounds inhibit the Wnt signaling pathway, and these compounds may suppress EMT in cancer and fibrosis .FH535, a β‐catenin/Tcf inhibitor, not only increased radio‐sensitivity but also suppressed EMT in the radioresistant KYSE‐150R esophageal cancer cell line, which indicated that inhibitors of the Wnt signaling pathway might be effective anticancer agents with the potential to be anticancer drugs.In addition, it was reported that FH535 alleviated multiple types of cancer, including colorectal cancer, gastric cancer, and hepatocellular carcinoma.Isoquercitrin, a bio-active flavonoid from Bidens bipinnata L., inhibited the Wnt/β‐catenin signaling pathway and hepatocyte growth factor/scatter factor‐induced EMT in NBT‐II cells.In addition, salinomycin was previously used as an antibiotic and also showed significant anticancer activity by suppressing EMT. Salinomycin‐inhibited EMT by suppressing the Wnt/β‐catenin signaling pathway in epithelial ovarian cancer cells, indicating that small molecules targeting the Wnt/β‐catenin signaling pathway might have anticancer properties by reversing EMT.Poria cocos is a well‐known fungus that exhibits an effective therapeutic effect to improve kidney function in clinic.Our previous studies have confirmed that extracts of the surface layer of Poria cocos show remarkable antihyperlipidemic, diuretic, and renoprotective effects.Recently, our group isolated more than 90 triterpenoid compounds from the surface layer of Poria cocos, some of which exhibited significant antifibrotic properties.New triterpenoids, including poricoic acid ZC, poricoic acid ZD, and poricoic acid ZE, significantly downregulated the expression of Wnt1, active β‐catenin, Snail, Twist, MMP‐7, PAI‐1, and FSP1 in HK‐2 cells induced by TGF‐β1 and angiotensin II and mice with unilateral ureteral occlusion. Moreover, new triterpenoids, including poricoic acid ZG and poricoic acid ZH, improved renal fibrosis by targeting the phosphorylation of Smad3 signaling and the Wnt/β‐catenin signaling pathway. Alismatis rhizome , the dried rhizome of Alisma orientale Juzep, exhibited diuretic, antihyperlipidemic, and renoprotective effects that were also confirmed by our previous studies.Our recent study demonstrated that triterpenoid was the main component of AR,30 and further study showed that the novel tetracyclic triterpenoid 25‐O‐methylalisol F inhibited EMT by suppressing the Wnt/β‐catenin signaling pathway as well as the phosphorylation of Smad3 signaling in both NRK‐52E and NRK‐49F cell. Additionally, it was also observed that ergone inhibited extracellular matrix accumulation in HK‐2 cells and attenuated podocyte injury through inhibiting the activation of the Wnt/β‐catenin signaling pathway induced by angiotensin II.Taken together, these data indicate that tetracyclic triterpenoid and steroid compounds show significant antifibrotic properties in renal fibrosis.