Lipidomics based on liquid chromatography-high resolution mass spectrometry reveals the protective role of peroxisome proliferator-activated receptor alpha on kidney stone formation in mice treated with glyoxylate

Few studies have examined the relationship between lipid metabolism and kidney stone formation, particularly the role of key lipid regulatory factors in kidney stone formation. We evaluated the effect of the lipid regulatory factor-peroxisome proliferator-activated receptor alpha on the formation of renal stones in mice by injecting them with glyoxylate followed by treatment with either a peroxisome proliferator-activated receptor alpha agonist fenofibrate or an antagonist GW6471 (GW). Liquid chromatography coupled with trapped ion mobility spectrometry-quadrupole-time-of-flight mass spectrometry-based lipidomics was used to determine the lipid profile in the mouse kidneys. Histological and biochemical analyses showed that the mice injected with glyoxylate exhibited crystal precipitation and renal dysfunction. Crystallization decreased significantly in the fenofibrate group, whereas it increased significantly in the GW group. A total of 184 lipids, including fatty acyls, glycerolipids, glycerophospholipids, and sphingolipids differed significantly between the mice in the model and control groups. Peroxisome proliferator-activated receptor alpha activity negatively correlated with glyoxylate-induced kidney stone formation in mice, which may be related to improved fatty acid oxidation, maintenance of ceramide/complex sphingolipids cycle balance, and alleviation of disorder in phospholipid metabolism.     

Dynamical Behavior of a Stochastic Nutrient-Plankton Food Chain Model with L\''{e}vy Jumps

In aquatic ecosystem, plankton populations are easily affected by environmental fluctuations due to the unpredictability of many physical factors. To better understand how environmental fluctuations influence plankton populations, in this paper, we propose and investigate a stochastic nutrient-plankton food chain model with L$\acute{\rm e}$vy jumps. Firstly, by constructing a suitable Lyapunov function, we prove that the stochastic model has a unique global positive solution for any given positive initial value. Then, we establish sufficient conditions for the persistence and extinction of plankton. Finally, we provide some numerical simulations to illustrate the analytical results.     

Uniqueness of Limit Cycles in a Predator-Prey Model with Sigmoid Functional Response

In this paper, we prove that a predator-prey model with sigmoid functional response and logistic growth for the prey has a unique stable limit cycle, if the equilibrium point is locally unstable. This extends the results of the literature where it was proved that the equilibrium point is globally asymptotically stable, if it is locally stable. For the proof, we use a combination of three versions of Zhang Zhifen''s uniqueness theorem for limit cycles in Li$\acute{\rm e}$nard systems to cover all possible limit cycle configurations. This technique can be applied to a wide range of differential equations where at most one limit cycle occurs.     

Dynamics Behavior of a Stochastic Predator-Prey Model with Stage Structure for Predator and L\''{e}vy Jumps

In order to study the effects of external environmental noise on the interaction dynamics between predator and prey populations, in this paper, we develop a predator-prey model with the stage structure for predator and L$\acute{\rm e}$vy noise. By constructing an appropriate Lyapunov function, we first prove that the proposed model exists the uniqueness of global positive solution. Then, we analyze the persistence and extinction of the proposed model. Finally, we perform some numerical simulations to verify the correctness of the theoretical results.     

QSAR‐based targeting anaplastic lymphoma kinase (ALK) variants with noncognate inhibitors in pediatric acute lymphoblastic leukemia

Human anaplastic lymphoma kinase (ALK) is a potential target for the treatment of pediatric acute lymphoblastic leukemia. However, a number of residue mutations in ALK kinase domain have been observed to cause drug resistance in pediatric acute lymphoblastic leukemia chemotherapy. Here, a chemometrics quantitative structure‐activity relationship predictor was developed using a structure‐based panel of kinase‐inhibitor activity data. The predictor was validated rigorously through internal cross‐validation and external blind test to ensure its statistical reliability, which was then used to computationally construct a systematic activity profile of 13 noncognate kinase inhibitors against both wild‐type ALK^wt and cancer‐related variants ALK^vt. It is revealed that most noncognate inhibitors exhibit weak potency on ALK^wt, but some of them are able to selectively target ALK^vt over ALK^wt. The chemometrics findings were then evaluated by using a kinase inhibition protocol; results showed that few noncognate inhibitors are 2‐ to 5‐fold higher potent against ALK variant than wild‐type kinase.     

Tackling COVID-19 Using Antiviral Nanocoating's—Recent Progress and Future Challenges

In the current situation of the global coronavirus disease 2019 (COVID-19) pandemic, there is a worldwide demand for the protection of regular handling surfaces from viral transmission to restrict the spread of COVID-19 infection. To tackle this challenge, researchers and scientists are continuously working on novel antiviral nanocoatings to make various substrates capable of arresting the spread of such pathogens. These nanocoatings systems include metal/metal oxide nanoparticles, electrospun antiviral polymer nanofibers, antiviral polymer nanoparticles, graphene family nanomaterials, and etched nanostructures. The antiviral mechanism of these systems involves depletion of the spike glycoprotein that anchors to surfaces by the nanocoating and makes the spike glycoprotein and viral nucleotides inactive; however, the nature of the interaction between the spike proteins and virus depends on the type of nanostructure and a surface charge over the coating surface. In this article, the current scenario of COVID-19 and how it can be tackled using antiviral nanocoatings from the further transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with their different mode of action, are discussed. Additionally, it is also highlighted different types of nanocoatings developed for various substrates to encounter transmission of SARS-CoV-2, future research areas along with the current challenges related to it, and how these challenges can be resolved.     

Zero-Hopf Bifurcation at the Origin and Infinity for a Class of Generalized Lorenz System

In this paper, the zero-Hopf bifurcations are studied for a generalized Lorenz system. Firstly, by using the averaging theory and normal form theory, we provide sufficient conditions for the existence of small amplitude periodic solutions that bifurcate from zero-Hopf equilibria under appropriate parameter perturbations. Secondly, based on the Poincar{\''e} compactification, the dynamic behavior of the generalized Lorenz system at infinity is described, and the zero-Hopf bifurcation at infinity is investigated. Additionally, for the above theoretical results, some related illustrations are given by means of the numerical simulation.     

A liquid chromatography-tandem mass spectrometry method for comprehensive determination of metabolites in the purine pathway of rat plasma and its application in anti-gout effects of Lycium ruthenicum Murr.

It has been proved that purine metabolites are implicated in various biological syndromes and disorders. Therefore, the realization of panoramic detection of purine metabolites will be of great significance to the pathogenesis of purine metabolic disorders. In the present study, an ultra-high performance liquid chromatography with tandem mass spectrometry method was developed for the comprehensive quantification of purine metabolites in rat plasma. The 17 purine metabolites were separated and quantified in the short running time of 15 min. The proposed method was strictly validated by applying SeraSub solution as a matrix and proved to be linear (R² ≥ 0.9944), accurate (the recoveries of all analytes ranged from 85.3% to 103.0%, with relative standard deviation values ≤ 9.3%), and precise (the intra- and inter-day precisions were less than 10.8% and 12.4%, respectively). The method was then successfully applied to the qualification of the endogenous purine metabolites in acute gouty arthritis rats, as well as colchicine and anthocyanin-intervened rats. Results showed that uric acid, xanthine, hypoxanthine, and xanthine were considered the key factors of acute gouty arthritis. The established method and measurement of purines in rat plasma might help the investigation of the action mechanisms between purine disorders and related diseases.     

纳米和微米一水草酸钙对Vero细胞毒性的浓度效应

采用扫描电子显微镜(SEM)、激光共聚焦显微镜(LSM)和流式细胞仪等技术比较了纳米级和微米级一水草酸钙(COM)对非洲绿猴肾上皮细胞(Vero)的毒性差异。结果显示,尺寸为100 nm和6μm的COM晶体都能引起Vero细胞活力下降、乳酸脱氢酶(LDH)释放量升高、透明质酸(HA)表达量增多、溶酶体完整性降低、线粒体膜电位下降、细胞死亡率升高和细胞周期滞留,表明这些晶体对Vero细胞都有损伤作用且呈现浓度依赖性,但纳米COM的毒性及其在细胞表面的粘附量均大于微米COM晶体。