BackgroundZipf's law and Heaps' law are two representatives of the scaling concepts, which play a significant role in the study of complexity science. The coexistence of the Zipf's law and the Heaps' law motivates different understandings on the dependence between these two scalings, which has still hardly been clarified.Methodology/Principal FindingsIn this article, we observe an evolution process of the scalings: the Zipf's law and the Heaps' law are naturally shaped to coexist at the initial time, while the crossover comes with the emergence of their inconsistency at the larger time before reaching a stable state, where the Heaps' law still exists with the disappearance of strict Zipf's law. Such findings are illustrated with a scenario of large-scale spatial epidemic spreading, and the empirical results of pandemic disease support a universal analysis of the relation between the two laws regardless of the biological details of disease. Employing the United States domestic air transportation and demographic data to construct a metapopulation model for simulating the pandemic spread at the U.S. country level, we uncover that the broad heterogeneity of the infrastructure plays a key role in the evolution of scaling emergence.Conclusions/SignificanceThe analyses of large-scale spatial epidemic spreading help understand the temporal evolution of scalings, indicating the coexistence of the Zipf's law and the Heaps' law depends on the collective dynamics of epidemic processes, and the heterogeneity of epidemic spread indicates the significance of performing targeted containment strategies at the early time of a pandemic disease.

Networks PACS 89.65.-s -Social and economic systemsRecently, the analysis of temporal features of complex communication networks, especially the human contact networks, have received a boost with the advance of information technology, e.g., wireless communication. Newly created digital instruments not only reshape our daily life, but also record tremendous digital data produced by human daily activities, which can be utilized to analyze human behaviors [17][18][19][20]. WiFi, as a ubiquitous wireless accessing technology, has been widely deployed in human p-1

Context: Heart failure (HF) is one of the most serious diseases worldwide. Astragaloside IV (ASI) is widely used for the treatment of cardiovascular disease in China. Objective: To evaluate the protective effect of ASI on the HF in a Sprague-Dawley rat model of left coronary artery ligation, and investigate the angiogenesis-related mechanisms. Materials and methods: Left coronary artery was ligated to induce a rat model of HF, and the rats were treated with vehicle (saline) or different doses of ASI (0.1, 0.3 and 1 mg/kg/day) by oral gavage for 6 weeks. Cardiac function was evaluated by echocardiography. Infarct size was determined by triphenyltetrazolium chloride staining. Cardiac vascular density was analyzed by microangiography. Real-time PCR, Western blot and chromatin immunoprecipitation were performed to investigate the mechanisms. Results: ASI treatment improved the body weight and survival rate of HF rats, as well as the cardiac function of HF rats, with significantly improved ejection fraction (75.27 ± 5.75% vs. 36.26 ± 4.14%) and fractional shortening (45.39 ± 3.66% vs. 17.88 ± 1.32%). ASI reduced the infarct size of the HF rats by 47%. ASI promoted angiogenesis, with increased vascular density (2.08fold) and induced mRNA expression of CD31 (1.81-fold) and VEGF (2.70-fold) in the ischemic heart. Furthermore, ASI induced the phosphorylation of JAK (1.89-fold) and STAT3 (2.95-fold), as well as the activity of VEGF promoter which was regulated by STAT3. Discussion and conclusions: ASI alleviated HF by promoting angiogenesis through JAK-STAT3 pathway, providing novel alternative strategies to prevent HF in the future.

This study retrospectively evaluated the effectiveness and safety of traditional Chinese medicine Shenqilixin Formula (SQLXF) as an adjunctive intervention for treating patients with chronic heart failure (CHF).This retrospective study included 135 patients with CHF. They were allocated to a treatment group or a control group according to the different treatments they received. Seventy five patients in the treatment group underwent SQLXF plus routine treatment, while 60 subjects in the control group received routine treatment only. The primary outcome was cardiac function. It was measured by the left ventricular end diastolic diameter (LVDD), left ventricular ejection fraction (LVEF), cardiac output (CO), every cardiac output (ECO), and cardiac index (CI). The secondary outcome included motor function. It was measured by the standard 6-MinuteWalk Test (6MWT). In addition, adverse events (AEs) were also recorded.Compared to subjects in the control group, patients in the treatment group revealed greater effectiveness in cardiac function, measured by LVEF (P < .05), CO (P < .05), and ECO (P < .05), and motor function, measured by the 6MWT scale (P < .05). Moreover, no significant differences of AEs were found between the 2 groups.SQLXF as an adjunctive therapy to routine treatment may help to improve both cardiac and motor function in patients with CHF.

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease (ESRD) worldwide. SGLT2 inhibitors are clinically effective in halting DKD progression. However, the underlying mechanisms remain unclear. The serum and kidneys of mice with DKD were analyzed using liquid chromatography with tandem mass spectrometry (LC–MS/MS)-based metabolomic and proteomic analyses. Three groups were established: placebo-treated littermate db/m mice, placebo-treated db/db mice and EMPA-treated db/db mice. Empagliflozin (EMPA) and placebo (10 mg/kg/d) were administered for 12 weeks. EMPA treatment decreased Cys-C and urinary albumin excretion compared with placebo by 78.60% and 57.12%, respectively (p < 0.001 in all cases). Renal glomerular area, interstitial fibrosis and glomerulosclerosis were decreased by 16.47%, 68.50% and 62.82%, respectively (p < 0.05 in all cases). Multi-omic analysis revealed that EMPA treatment altered the protein and metabolic profiles in the db/db group, including 32 renal proteins, 51 serum proteins, 94 renal metabolites and 37 serum metabolites. Five EMPA-related metabolic pathways were identified by integrating proteomic and metabolomic analyses, which are involved in renal purine metabolism; pyrimidine metabolism; tryptophan metabolism; nicotinate and nicotinamide metabolism, and glycine, serine and threonine metabolism in serum. In conclusion, this study demonstrated metabolic reprogramming in mice with DKD. EMPA treatment improved kidney function and morphology by regulating metabolic reprogramming, including regulation of renal reductive stress, alleviation of mitochondrial dysfunction and reduction in renal oxidative stress reaction.