Z-ligustilide reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling pathways

Purpose: To investigate the effect of Z-ligustilide (Z-lig) on cisplatin-induced nephrotoxicity and examine whether NRF2 signaling mediates the underlying mechanism of action.Methods: Human proximal tubular epithelial cells (HK-2) were pretreated with 20 or 100 μM Z-lig for 2 h, followed by 10 μM cisplatin treatment for 24 h. Cell viability was measured using (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A commercial kit was used todetermine lactate dehydrogenase (LDH) release. Apoptosis was determined by flow cytometry while Western blotting was used to evaluate protein levels. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) were assessed by enzymelinked immunosorbent assay (ELISA).Results: Cisplatin decreased HK-2 cell viability and increased LDH release, while Z-lig increased cell viability and decreased LDH release in a dose-dependent manner (p < 0.05). Moreover, Z-lig reduced cisplatin-induced apoptosis (p < 0.01), and alleviated cellular oxidative stress caused by cisplatin (p < 0.05). Furthermore, Z-lig activated NRF2/HO-1 signaling in cells treated with cisplatin (p < 0.05).Conclusion: Z-lig reduces cisplatin-induced nephrotoxicity via activation of NRF2/HO-1 signaling. Thus, Z-lig is a potential drug for the treatment of nephrotoxicity caused by cisplatin. Keywords: Z-ligustilide, Cisplatin, Nephrotoxicity, Oxidative stress, Apoptosis, Nuclear factor erythroid 2-related factor 2, Heme oxygenase-

Evaluating the value of new metro lines using route diversity measures: the case of Hong Kong's Mass Transit Railway system

The Mass Transit Railway (MTR) serves as the backbone of the Hong Kong public transportation network and continues to be expanded in phases. Nevertheless, occasional but severe disruptions have raised concerns about whether the proposed MTR expansions will benefit the system resilience. To assess the value of each stage of MTR network expansion, it is key to identify the distributive effects of new metro lines on both accessibility and resilience. This paper applies the route diversity index, a relatively new accessibility indicator, to assess the effects of new lines and evaluate their spatial distribution, variation, and changes at nodal, dyadic, and network levels. The results indicate that the effects on accessibility and resilience will differ between each stage of MTR expansion. On the accessibility front, the benefits of reduced travel times and increased route diversity will be successively extended to more districts with each MTR expansion, and the spatial equity will also be improved gradually by the expansion, especially in isolated regions such as the northern and western New Territories. In contrast, on the resilience front, although the overall network vulnerability will be reduced, the vulnerability of certain parts of the network will be increased, which might necessitate additional resources to protect these stations. However, some new lines will reduce this vulnerability and provide a complementary solution to enhance network resilience. Overall, the insights from this study could assist in cost-effective resource allocation and informed decision-making for the prioritization of future railway investments and cost-effective resource allocation

Underwater dual manipulators-Part I: Hydrodynamics analysis and computation

1098-1103This paper introduces two 4-DOF underwater manipulators mounted on autonomous underwater vehicle (AUV) with grasping claws, such that the AUV can accomplish the underwater task by using dual manipulators. Mechanical design of the manipulator is briefly presented and the feature of the simple structure of dual manipulators is simulated by using Solid Works. In addition, the hydrodynamics of the manipulator is analyzed, considering drag force, added mass and buoyancy. Then, hydrodynamic simulations of the manipulator are conducted by using 3-D model with Adams software, from which the torque of each joint is calculated. This paper presents an integrated result of computed torques by combining the theoretical calculation and simulation results, which is instrumental in determining the driving torque of the manipulators

An Uncertainty-aware Hybrid Approach for Sea State Estimation Using Ship Motion Responses

Situation awareness is essential for autonomous ships. One key aspect is to estimate the sea state in a real-time manner. Considering the ship as a large wave buoy, the sea state can be estimated from motion responses without extra sensors installed. This task is challenging since the relationship between the wave and the ship motion is hard to model. Existing methods include a wave buoyanalogy (WBA) method, which assumes linearity between wave and ship motion, and a machine learning (ML) approach. Since the data collected from a vessel in the real world is typically limited to a small range of sea states, the ML method might suffer from catastrophic failure when the encountered sea state is not in the training dataset. This paper proposes a hybrid approach that combined the two methods above. The ML method is compensated by the WBA method based on the uncertainty of estimation results and, thus, the catastrophic failure can be avoided. Real-world historical data from the Research Vessel (RV) Gunnerus are applied to validate the approach. Results show that the hybrid approach improves estimation accuracy.acceptedVersio

Arsenic and Cadmium Accumulation in Soil as Affected by Continuous Organic Fertilizer Application: Implications for Clean Production

As and Cd in soil can be assimilated and accumulated by vegetables and can be subsequently ingested by humans. Contradictory effects of organic fertilizer application on As and Cd accumulation in soil have been reported in previous studies. An eight-year greenhouse study was conducted on a sandy loam soil in Beijing, China to investigate the effects of organic fertilizer application rate on soil properties, and As and Cd accumulation in soil. The contamination risk of pak choi grown after eight years’ application of organic fertilizer was also evaluated. Soil organic carbon increased 3.0–3.8 times with low, medium and high rates of fertilizer application in 2018 compared to the initial soil. Organic fertilizer application significantly increased soil nutrients and microbial biomass while it mildly affected soil pH. The bioavailability of As/Cd has decreased after eight years’ application of organic fertilizer. Pak choi crop harvested from all three treatments in 2018 did not pose a threat to human health, even for life-time consumption. Soil total As content significantly decreased with organic fertilizer application, mainly due to the lower As content in the applied fertilizer than that in soil. Continuous application of clean organic fertilizer can be adopted to reduce the contamination risk of highly contaminated soil in the soil–plant system

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Carbon nanotube-induced phase and stability engineering: A strained cobalt-doped WSe2/MWNT heterostructure for enhanced hydrogen evolution reaction

Efficient evolution of hydrogen with inexpensive, highly active and long-term stable catalysts in a wide pH range holds tremendous promise for clean energy. Here, we report the synthesis of a cobalt-doped tungsten selenide/multiwalled carbon nanotube (Co-WSe 2 /MWNT) heterostructure for the first time, wherein the MWNTs act as an efficient topological template for the nucleation and growth of curved Co-WSe 2 nanosheets with abundant accessible active sites. Furthermore, we demonstrate that the MWNT induced curvature strain not only promotes the predominant 1T phase of active Co-WSe 2 , but also enhances its anti-oxidative stability. Further study indicates that the as-prepared catalyst exhibits efficient electrocatalytic HER in both acidic and alkaline environments with high activity and long-term stability

Molecular dynamics simulation in the interlayer of mixed-layer clays due to hydration and swelling mechanism

The swelling behavior of clay minerals is widely known for its importance in soil and environmental sciences and its detrimental effects in engineering fields. Although more than 70 percent of all clays are of mixed-layer types, the vast majority of the previous experiments and simulations are focused on pure clays, which cause the swelling mechanism of the widespread mixed-layer clay (MLC) and its role in soils are little understood, especially the most common illite-montmorillonite (I-M) mixed-layer clay (MLC). This paper reports on a molecular dynamics (MD) study of the differences in swelling behavior between I-M MLCs containing K+ and Na+ and Na-montmorillonite (MMT). It captures the evolution of quantitative properties such as basal spacing d, interaction energy, and many hydrogen bonds in the clay interlayer, increasing hydration for the first time through the scripts. It is found that MLCs have smaller swellings than Na-MMT due to the asymmetric interlayer charges and mixed counterions in the I-M interlayer. However, in terms of the interaction energy for the in-depth reason of swelling, it is found that the clay-clay interaction energy and the clay-ion interaction energy drop, while the clay-water interaction energy increases with increasing hydration. In addition, the attractive interaction of clay-bound water seriously promotes swelling, and it is mainly composed of Coulomb interaction and Van der Waals interaction. The higher the K+ concentration, the more noticeable these phenomena are. Besides, it is also reported that the number and distribution mechanism of hydrogen bonds in MLCs are very different from that of pure clay. This work provides insight into the molecular mechanism for initial swelling and clay-bound water interaction in widespread MLCs. This will help to decipher its specific role in soils and minimize clay swelling

Seismic Response of Immersed Tunnel Subject to Oblique Incidence of SV Wave

In view of the near-field seismic action, considering that oblique incidence of seismic waves is more realistic than vertical incidence, the seismic response of the Hong Kong–Zhuhai–Macao immersed tunnel subjected to an obliquely incident SV wave is investigated. Using the finite element method and time-domain wave method, the seismic input is transformed into an equivalent node load with a viscous–spring artificial boundary, and a three-dimensional simulation technology for SV waves of oblique incidence is presented. A half-space numerical example is given to demonstrate the accuracy of the proposed simulation technology. Taking the stress field formed by the self-weight stress and hydrostatic pressure as the initial state of the dynamic response analysis, the static–dynamic coupling numerical simulation of the seismic response of a soil-immersed tunnel system is realized. The results show that the amplification in the vertical and longitudinal response of the tunnel, due to the oblique incidence, reaches maximum when the incident angle is close to the critical angle. Furthermore, the horizontal response and incident angle show the inverse relation and tend to be stable. In addition, the oblique incidence also causes asymmetric shearing in symmetric parts of the tunnel. The root of the shear key easily produces tensile cracks, while the end angle of the shear key is prone to stress concentration and local damage. Thus, the impact of oblique incidence should be considered in the seismic design, and attention should be paid to the optimization of the end angle of the shear key and the configuration of anti-crack reinforcement at the root of shear key to meet the seismic requirements

The complete chloroplast genome of Camellia leyeensis (theaceae)

Camellia leyeensis Chang ＆ Y. C. Zhong is a plant belonging to the genus Camellia. To determine its correct taxonomic status and better understand its molecular phylogenetic and genetic diversity, we studied the chloroplast genome of this species. Here, we report and characterize the complete chloroplast (cp) genome of C. leyeensis by using Illumina paired-end sequencing data. The chloroplast genome was determined to be 157,063 bp in length with a GC content of 37.30%. The genome contained 136 genes, including 91 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The sequence contained a large single-copy region (LSC, 86,661 bp), a small single-copy region (SSC, 18,284 bp), and two inverted repeat sequences (IRs, 26,059 bp, each). The GC content of the IR regions (42.96%) was higher than that of the SSC region (30.6%) and LSC region (35.31%). Phylogenetic analysis suggested that Camellia leyeensis is closely related to C. anlungensis with 96% bootstrap support. This chloroplast genome would be helpful for the phylogeny and conservation of Camellia