Artemisinin (Art) is isolated from Artemisia annua L. and known as the most effective antimalaria drugs. Previous studies demonstrated that it could exert an immune‐regulatory effect on autoimmune ...diseases. In this study, we first investigated its potential role in tubulointerstitial inflammation and fibrosis in rats with 5/6 nephrectomy. Subtotal nephrectomized (SNx) rats were orally administered Art (100 mg·kg
−1·d
−1) for 16 weeks. Blood and urine samples were collected for biochemical examination. Kidney tissues were collected for immunohistochemistry and Western blot analyses. Ang II‐induced injury of the human kidney 2 (HK‐2) cells was used for in vitro study. It was shown that Art could significantly attenuate the renal function decline in SNx rats compared with control. More importantly, Art treatment significantly reduced the tubulointerstitial inflammation and fibrosis, as demonstrated by the evaluation of renal pathology. Furthermore, Art inhibited the activation of NLRP3 inflammasome and NF‐κB in the kidneys. In in vitro study, Art pretreatment could significantly prevent the activation of NLRP3 inflammasome and NF‐κB in Ang II‐treated HK‐2 cells, while BAY11‐7082 (an inhibitor of NF‐κB) significantly inhibited Ang II‐induced NLRP3 inflammasome activation. This study suggested that Art could provide renoprotective role by attenuating the tubulointerstitial inflammation and fibrosis in SNx rats by downregulating the NF‐κB/NLRP3 signaling pathway.
We found that artemisinin (Art) treatment significantly prevents renal function decline and tubulointerstitial fibrosis in 5/6 nephrectomized rats by inhibiting NF‐κB/NLRP3 pathway. Our findings highlight the therapeutic potential of Art in preventing the progression of chronic kidney disease (CKD).
Due to rising energy prices and environmental concerns, the energy efficiency of urban rail transit has attracted much attention from both researchers and practitioners in recent years. Timetable ...optimization and energy-efficient driving, as two mainly used train operation methods in relation to the tractive energy saving, make major contributions in reducing the energy consumption that has been studied for a long time. Generally speaking, timetable optimization synchronizes the accelerating and braking actions of trains to maximize the utilization of regenerative energy, and energy-efficient driving optimizes the speed profile at each section to minimize the tractive energy consumption. In this paper, we present a fully comprehensive survey on energy-efficient train operation for urban rail transit. First, a general energy consumption distribution of urban rail trains is described. Second, the current literature on timetable optimization and energy-efficient driving is reviewed. Finally, according to the review work, it is concluded that the integrated optimization method jointly optimizing the timetable and speed profile has become a new tendency and ought to be paid more attention in future research.
It is known that the Allen-Chan equations satisfy the maximum principle. Is this true for numerical schemes？ To the best of our knowledge, the state-of-art stability framework is the nonlinear energy ...stability which has been studied extensively for the phase field type equations. In this work, we will show that a stronger stability under the infinity norm can be established for the implicit-explicit discretization in time and central finite difference in space. In other words, this commonly used numerical method for the Allen-Cahn equation preserves the maximum principle.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Integrating the internet and financial services gives people the luxury to reduce financial stress and anxiety by giving consumers more power over their financial situation. Likewise, the adoption of ...environmental technologies helps improve environmental quality, which positively impacts mental and physical health and thus increases the sense of well-being and happiness. Therefore, the main focus of the study is to analyze the influence of financial services and environmental technologies on happiness. For analyzing the short and long-run impacts of financial services and environmental technologies on happiness, we have utilized the ARDL model and QARDL models. The findings of the ARDL model confirm the positive influence of financial services, environmental technologies, national income, financial development, and education on happiness in the short and long term. Similarly, the QARDL model also suggests the favorable long-run effects of financial services and environmental technologies on happiness at most quantiles. The long-run Wald test confirms the asymmetric influence of all variables on happiness, while in the short-term, excluding education, all other variables exert asymmetric impacts on happiness. Thus, to promote happiness, policymakers should try to increase the role of internet-based financial services and increases investment in research and development activities to enhance environment-related technologies. However, the study is limited to China, it should be expanded to other regions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diabetic nephropathy (DN) is a leading cause of renal failure, whereas the effective and early diagnostic biomarkers are still lacking.
Fourteen cytokines and chemokines mRNA were detected in urinary ...extracellular vesicles (EVs) from the screening cohort including 4 healthy controls (HC), 4 diabetes mellitus (DM) and 4 biopsy-proven DN patients, and was validated in another 16 HC and 15 DM and 28 DN patients. Correlation analysis was performed between the candidate biomarkers and clinic parameters as well as kidney histological changes. The findings were also confirmed in DN rat model with single injection of STZ.
The number of small EVs secreted in urine was increased in DN patients compared to DM patients and healthy controls, with expression of AQP1 (a marker of proximal tubules) and AQP2 (a marker of distal/collecting tubules). Small EVs derived CCL21 mRNA increased significantly in DN patients and correlated with level of proteinuria and eGFR. Interestingly, elevated CCL21 mRNA from urine small EVs was observed in DN patients with normal renal function and could discriminate early DN patients from DM more efficiently compared to eGFR and proteinuria. CCL21 also showed an accurate diagnostic ability in distinguishing incipient from overt DN. Histologically, CCL21 mRNA expression increased progressively with the deterioration of tubulointerstitial inflammation and showed the highest level in nodular sclerosis group (class III) in DN patients. Remarkable infiltration of CD3 positive T cells including both CD4 and CD8 positive T cell population were observed in DN patients with high-CCL21 expression. Besides, accumulation of CD3 positive T cells correlated with level of urinary small EVs derived CCL21 and co-localized with CCL21 in the tubulointerstitium in DN patients. Finally, the correlation of CCL21 expression in renal cortex and urinary small EVs was confirmed in STZ-induced DN rat model.
Urinary small EVs derived CCL21 mRNA may serve as early biomarker for identifying DN linked with pathogenesis. CCL21 mRNA mediated T cell infiltration may constitute the key mechanism of chronic inflammation in DN.
Dysregulated inflammation is a complicated pathological process involved in various diseases, and the treatment of inflammation-linked disorders currently represents an enormous global burden. ...Extracellular vesicles (EVs) are nanosized, lipid membrane-enclosed vesicles secreted by virtually all types of cells, which act as an important intercellular communicative medium. Considering their capacity to transfer bioactive substances, both unmodified and engineered EVs are increasingly being explored as potential therapeutic agents or therapeutic vehicles. Moreover, as the nature's own delivery tool, EVs possess many desirable advantages, such as stability, biocompatibility, low immunogenicity, low toxicity, and biological barrier permeability. The application of EV-based therapy to combat inflammation, though still in an early stage of development, has profound transformative potential. In this review, we highlight the recent progress in EV engineering for inflammation targeting and modulation, summarize their preclinical applications in the treatment of inflammatory disorders, and present our views on the anti-inflammatory applications of EV-based nanotherapeutics.
Albuminuria contributes to the development and progression of chronic kidney disease by inducing tubulointerstitial inflammation (TI) and fibrosis. However, the exact mechanisms of TI in response to ...albuminuria are unresolved. We previously demonstrated that NLRP3 and inflammasomes mediate albumin-induced lesions in tubular cells. Here, we further investigated the role of endocytic receptors and lysosome rupture in NLRP3 inflammasome activation. A murine proteinuric nephropathy model was induced by albumin overload as described previously. The priming and activation signals for inflammasome complex formation were evoked simultaneously by albumin excess in tubular epithelial cells. The former signal was dependent on a albumin-triggered NF-κB pathway activation. This process is mediated by the endocytic receptor, megalin and cubilin. However, the silencing of megalin or cubilin inhibited the albumin-induced NLRP3 signal. Notably, subsequent lysosome rupture and the corresponding release of lysosomal hydrolases, especially cathepsin B, were observed in tubular epithelial cells exposed to albumin. Cathepsin B release and distribution are essential for NLRP3 signal activation, and inhibitors of cathepsin B suppressed the NLRP3 signal in tubular epithelial cells. Taken together, our findings suggest that megalin/cubilin and lysosome rupture are involved in albumin-triggered tubular injury and TI. This study provides novel insights into albuminuria-induced TI and implicates the active control of albuminuria as a critical strategy to halt the progression of chronic kidney disease.
NLRP3 inflammasome activation is involved in albuminuria-induced renal injury.
The inhibition of megalin/cubilin or lysosomal cathepsin B reduced albuminuria-induced NLRP3 inflammasome activation.
Megalin/cubilin and lysosome rupture is involved in albumin-triggered tubular injury and TI.
This study provides novel insights into albuminuria-induced TI and implicates the active control of albuminuria as a critical strategy to halt the progression of CKD.
A metal‐ and oxidant‐free electrochemical method for preparing selenomethyl‐substituted cyclic ethers or lactones via difunctionalization of olefines is presented. A series of ...selenomethyl‐substituted cyclic ethers, particularly 9‐ and 11‐ membered, selenomethyl‐substituted lactones (4‐6 membered), and selenomethyl‐substituted phthalides can be obtained via this reaction. This method features convenient operation, an electron as oxidant, and ammonium iodide as electrolyte, thereby making it a green synthesis method.
Improving the stability of sensitive catalytic systems is an emerging research topic in the catalysis field. However, the current design of heterogeneous catalysts mainly improves their catalytic ...performance. This paper presents a single‐atom catalyst (SAC) strategy to improve the cobalt‐catalysed fluorination of acyl chlorides. A stable Co−F intermediate can be formed through the oxidative fluorination of Co1−N4@NC SAC, which can replace the unstable high‐valent cobalt catalytic system and avoid the use of phosphine ligands. In the SAC system, KF can be employed as a fluorinating reagent to replace the AgF, which can be applied to various substrates and scale‐up conversion with high turnover numbers (TON=1.58×106). This work also shows that inorganic SACs have tremendous potential for organofluorine chemistry, and it provides a good reference for follow‐up studies on the structure‐activity relationship between catalyst design and chemical reaction mechanisms.
A Co single‐atom catalyst was synthesized via thermal decomposition of a zeolitic imidazolate framework (ZIF). The Co1−N4@NC catalyst generated a stable Co−F intermediate in situ through an oxidative fluorination pathway to replace the substitution fluorination of the unstable high‐valent Co system. In the presence of Co−F intermediates, KF can be used to replace AgF. Co1−N4@NC exhibited ultrahigh catalytic activity for the fluorination of acyl chlorides.
Given rising energy prices and environmental concerns, train energy-efficient operation techniques are paid more attention as one of the effective methods to reduce operation costs and energy ...consumption. Generally speaking, the energy-efficient operation technique includes two levels, which optimize the timetable and the speed profiles among successive stations, respectively. To achieve better performance, this paper proposes to optimize the integrated timetable, which includes both the timetable and the speed profiles. First, we provide an analytical formulation to calculate the optimal speed profile with fixed trip time for each section. Second, we design a numerical algorithm to distribute the total trip time among different sections and prove the optimality of the distribution algorithm. Furthermore, we extend the algorithm to generate the integrated timetable. Finally, we present some numerical examples based on the operation data from the Beijing Yizhuang subway line. The simulation results show that energy reduction for the entire route is 14.5%. The computation time for finding the optimal solution is 0.15 s, which implies that the algorithm is fast enough to be used in the automatic train operation (ATO) system for real-time control.
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