First-order turbulence closure schemes continue to be work-horse models for weather and climate simulations. The turbulent Prandtl number, which represents the dissimilarity between turbulent ...transport of momentum and heat, is a key parameter in such schemes. This paper reviews recent advances in our understanding and modeling of the turbulent Prandtl number in high-Reynolds number and thermally stratified atmospheric boundary layer (ABL) flows. Multiple lines of evidence suggest that there are strong linkages between the mean flow properties such as the turbulent Prandtl number in the atmospheric surface layer (ASL) and the energy spectra in the inertial subrange governed by the Kolmogorov theory. Such linkages are formalized by a recently developed cospectral budget model, which provides a unifying framework for the turbulent Prandtl number in the ASL. The model demonstrates that the stability-dependence of the turbulent Prandtl number can be essentially captured with only two phenomenological constants. The model further explains the stability- and scale-dependences of the subgrid-scale Prandtl number in large-eddy simulation. The connections between mean flow properties and microscale energy distributions shed novel insights into the breakdown of Monin-Obukhov similarity theory under strongly stable conditions.
•Recent advances in understanding and modeling of turbulent Prandtl number in the atmospheric boundary layer are reviewed.•A unifying framework for turbulent Prandtl number and its counterpart for large-eddy simulation is presented.•There are strong linkages between mean flow properties in the inertial sublayer and energy spectra in the inertial subrange.
Natural deep eutectic solvents (NaDESs) are considered a new type of green solvent with attractive application prospects in many fields because of their simple preparation, low cost, environmental ...friendliness, low volatility, high solvency capacity, designable structure, and easy biodegradability. Due to their biocompatibility, they are safe to use and are particularly suitable for natural product applications. In recent years, NaDESs have been used to extract phytonutrients (e.g., flavonoids, saponins, polysaccharides, alkaloids, quinones, phenolic acids, volatile oils, etc.) to improve their solubility, stability, and bioavailability. This review is intended to summarize and discuss recent progress in the field of natural products related to materials and preparation methods, physicochemical properties, enhancing extraction and separation, increasing solubility, improving stability and bioavailability, facilitating oral absorption of phytonutrients, and finally, highlighting the challenge for future work.
Population growth and industrial development have exacerbated environmental pollution of both land and aquatic environments with toxic and harmful materials. Luminescence-based chemical sensors ...crafted for specific hazardous substances operate on host-guest interactions, leading to the detection of target molecules down to the nanomolar range. Particularly, the luminescence-based sensors constructed on the basis of metal-organic frameworks (MOFs) are of increasing interest, as they can not only compensate for the shortcomings of traditional detection techniques, but also can provide more sensitive detection for analytes. Recent years have seen MOFs-based fluorescent sensors show outstanding advantages in the field of hazardous substance identification and detection. Here, we critically discuss the application of MOFs for the detection of a broad scope of hazardous substances, including hazardous gases, heavy metal ions, radioactive ions, antibiotics, pesticides, nitro-explosives, and some harmful solvents as well as luminous and sensing mechanisms of MOF-based fluorescent sensors. The outlook and several crucial issues of this area are also discussed, with the expectation that it may help arouse widespread attention on exploring fluorescent MOFs (LMOFs) in potential sensing applications.
Autophagy is a degradative pathway that delivers cellular components to the lysosome for degradation. The role of autophagy in cell differentiation is poorly understood. Here we show that CaMKII can ...directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy. Meanwhile, CaMKII can also promote K63-linked ubiquitination of inhibitor of differentiation 1/2 (Id-1/2) by catalyzing phosphorylation of Id proteins and recruiting TRAF-6. Ubiquitinated Id-1/Id-2 can then bind to p62 and be transported to autolysosomes for degradation. Id degradation promotes the differentiation of neuroblastoma cells and reduces the proportion of stem-like cells. Our study proposes a mechanism by which autophagic degradation of Id proteins can regulate cell differentiation. This suggests that targeting of CaMKII and the regulation of autophagic degradation of Id may be an effective therapeutic strategy to induce cell differentiation in neuroblastoma.
DNA hypermethylation and the silencing of tumor suppressor genes caused by DNA hypermethylation is considered as a molecular hallmark of many kinds of cancers. Procaine, a local anesthetic, has been ...shown as a potential DNA methylation inhibitor in some types of cancers. However, the influence of procaine on DNA methylation regulation as well as the biological function in gastric cancer is still unknown. We report here that procaine represses the DNA‐methylation level and promotes the proliferation arrest and apoptosis of gastric cancer cells. Global DNA methylation measurement demonstrates that procaine significantly reduces the global DNA methylation level. Analyses of the DNMTs expression and activity show procaine represses the activity, but not the expression, of DNMT1/DNMT3A. Further evidence on specific genes shows that procaine reduces the DNA methylation level in the promoter regions of CDKN2A and RARβ genes through abrogating the binding of DNMT1/DNMT3A toward these regions. This repression would not be reversed by the overexpression of DNMT1/DNMT3A. Moreover, RT‐qPCR and luciferase report assays demonstrate that procaine leads to the upregulation of CDKN2A and RARβ due to the activation of the promoter of these genes. In the end, we test the function of procaine toward gastric cancer cells and find that procaine has the growth inhibitory and apoptosis inducement effect toward gastric cancer cells. Collectively, our data not only uncovers the regulation mechanisms of procaine to DNA methylation but also suggests an anti‐tumor potential of procaine specific to the gastric carcinoma and provides a new therapeutic strategy for gastric carcinoma.
In this study, we investigated the influence of procaine on DNA methylation as well as on cell proliferation and apoptosis of gastric cancer cells. We found that procaine repressed the activity but not the expression of DNMT1 and DNMT3A. Further evidence showed that procaine increased the expression of CDKN2A and RARβ through activating the promoter activity of those genes, which is determined by the DNA methylation level. Functionally, procaine inhibited the proliferation and induced the apoptosis of gastric cancer cells. Our results describe a critical role of procaine in the expression of DNMT1 and some critical target genes and suggest the procaine treatment might be a new therapeutic strategy for gastric cancer.
Two cycles in one pot! The synthesis of biologically important phenanthridinones has been achieved by the one‐pot formation of CC and CN bonds through a palladium‐catalyzed dual CH activation, ...which involves four bond ruptures and two bond formations (see scheme). The conversion of phenanthridinones into natural product like derivatives further demonstrates the utility of this synthetic achievement.
Lysine crotonylation (Kcr) is a recently identified post‐translational modification (PTM) that is regulated by an acetyltransferase, p300. The p300‐catalyzed histone Kcr is able to stimulate ...transcription to a greater degree than the well‐studied histone lysine acetylation (Kac). Despite these progresses, the global Kcr substrates regulated by p300 remain largely unknown, hindering efforts to establish mechanistic links between Kcr and p300‐mediated phenotypes. Here, a quantitative proteomics study to characterize the p300‐regulated lysine crotonylome is reported. A total of 816 unique endogenous crotonylation sites are identified across 392 proteins, with 88 sites from 69 proteins being decreased by more than 0.7‐fold (log2 < 0.5) and 31 sites from 17 proteins being increased by more than 1.4‐fold (log2 > 0.5) in response to p300 knockout (KO). The most downregulated crotonylome alterations under p300 deficiency concern components of the nonsense‐mediated decay, infectious disease, and viral/eukaryotic translation pathways. Moreover, some p300‐targeted Kcr substrates are potentially linked to diseases such as cancer. Taken together, this study reveals the lysine crotonylome in response to p300, which sheds light on the role for lysine crotonylation in regulation of diverse cellular processes and provides new insights into mechanisms of p300 functions.
The pathogenesis of autoimmune diseases (AIDs) is not only attributed to genetic susceptibilities but also environmental factors, among which, disturbed gut microbiota has attracted increasing ...attention. Compositional and functional changes of gut microbiota have been reported in various AIDs, and increasing evidence suggests that disturbed gut microbiota contributes to their immunopathogenesis. The accepted mechanisms include abnormal microbial translocation, molecular mimicry, and dysregulation of both local and systemic immunity. Studies have also suggested microbiota-based classification models and therapeutic interventions for patients with AIDs. Further in-depth mechanistic studies on microbiota–autoimmunity interplay in AIDs are urgently needed and underway to explore novel and precise diagnostic biomarkers and develop disease and patient-tailored therapeutic strategies.
The compositional and functional changes of gut microbiota have been implicated in various autoimmune diseases (AIDs) by high-throughput techniques such as metagenomic sequencing.Correlation studies in humans and interventional studies in animal models have suggested that disturbed gut microbiota is involved in the immunopathogenesis of AIDs.The mechanisms of disturbed gut microbiota include abnormal microbial translocation, molecular mimicry, and dysregulation of both local and systemic immunity.In-depth deciphering of gut microbiota will help us to develop new microbiota-based assessments and interventions for patients with AIDs, which can help with their diagnosis, prognosis and treatment.
Imported malaria has been an important challenge for China. Fatality rates from malaria increased in China, particularly in Henan Province, primarily due to malpractice and misdiagnoses in healthcare ...institutions, and the level of imported malaria. This study aims to investigate the relationship between the state of diagnosis and subsequent complications among imported malaria cases at healthcare institutions, based on malaria surveillance data in Henan Province from 2012 to 2017.
A retrospective descriptive analysis was performed using data from the Centre for Disease Control and Prevention, Zhengzhou City, the capital of Henan Province. A decision tree method was exploited to provide valuable insight into the correlation between imported malaria cases and healthcare institutions.
From 2012 to 2017, there were 371 imported malaria cases, mostly in males aged between 20 and 50 years, including 319 Plasmodium falciparum cases. First visits of 32.3%, 19.9% and 15.9% malaria cases for treatment were to provincial, municipal and county healthcare institutions, respectively. The time interval between onset and initial diagnosis of 284 cases (76.5%) and the time interval between initial diagnosis and final diagnosis of 197 cases (53.1%) was no more than 72 h. An apparent trend was found that there were notably fewer patients misdiagnosed at first visit to healthcare institutions of a higher administrative level; 12.5% of cases were misdiagnosed in provincial healthcare institutions compared to 98.2% in private clinics, leading to fewer complications at healthcare institutions of higher administrative level due to correct initial diagnosis. In the tree model, the rank of healthcare facilities for initial diagnosis, and number of days between onset and initial diagnosis, made a major contribution to the classification of initial diagnosis, which subsequently became the most significant factor influencing complications developed in the second tree model. The classification accuracy were 82.2 and 74.1%, respectively for the tree models of initial diagnosis and complications developed.
Inadequate seeking medical care by imported malaria patients, and insufficient capacity to diagnose malaria by healthcare institutions of lower administrative level were identified as major factors influencing complications of imported malaria cases in Henan Province. The lack of connection between uncommon imported malaria cases and superior medical resources was found to be the crucial challenge. A web-based system combined with WeChat to target imported malaria cases was proposed to cope with the challenge.
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