Overexpression of Lias Gene Alleviates Cadmium-Induced Kidney Injury in Mice Involving Multiple Effects: Metabolism, Oxidative Stress, and Inflammation.

Oxidative stress is an important mechanism underlying toxicity induced by cadmium (Cd) exposure. However, there are significant differences of the antioxidant baseline in different populations. This means that different human has different intensity of oxidative stress in vivo after exposure to toxicants. LiasH/H mouse is a specific model which is created by genetically modifying the Lias 3'-untranslated region (3'-UTR). LiasH/H mice express high levels of LA and have high endogenous antioxidant capacity which is approximately 150% higher than wild-type C57BL/6 J mice (WT, Lias+/+). But more importantly, they have dual roles of metal chelator and antioxidant. Here, we applied this mouse model to evaluate the effect of endogenous antioxidant levels in the body on alleviating Cd-induced renal injury including Cd metabolism, oxidative stress, and inflammation. In the experiment, mice drank water containing Cd (50 mg/L), for 12 weeks. Many biomarkers of Cd metabolism, oxidative stress, inflammation, and major pathological changes in the kidney were examined. The results showed overexpression of the Lias gene decreased Cd burden in the body of mice, mitigated oxidative stress, attenuated the inflammatory response, and subsequent alleviated cadmium-induced kidney injury in mice.

The prevalence of oropharyngeal dysphagia in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: Oropharyngeal dysphagia (OD) in chronic obstructive pulmonary disease (COPD) patients seriously influence the long-term prognosis of COPD patients. The aim of this study was to assess the prevalence and risk factors of OD in patients with COPD through a systematic review and meta-analysis of observational studies. METHODS: We identified all observational studies on the prevalence of OD in COPD patients by searching PubMed, Embase, the Cochrane Library, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), China National Knowledge Infrastructure (CNKI), the China Biomedical Literature Service System (CBM), the Wanfang Database, and the WeiPu (VIP) databases from database establishment to 1 December 2020. RESULTS: Results of the meta-analysis showed that the prevalence of OD in COPD patients was 32.7% (95%CI=30.1, 35.4, I2=91.5%). Dyspnea, gastroesophageal reflux disease(GERD), xerostomia, sputum bacteria, poor physical capacity, poor quality of life, and high CRP level are the risk factors for OD in COPD patients. CONCLUSION: : The prevalence of OD in COPD patients is high. There were some differences in OD among COPD patients with different sex, ages, continents, evaluation methods, patient source and COPD exacerbation.

Effect of nitrilotriacetic acid and tea saponin on the phytoremediation of Ni by Sudan grass (Sorghum sudanense (Piper) Stapf.) in Ni-pyrene contaminated soil.

Phytoremediation is commonly used in the remediation of soils co-contaminated by heavy metals and polycyclic aromatic hydrocarbons (PAHs) because of its economy and effectiveness. Sudan grass (Sorghum sudanense (Piper) Stapf.) has well-developed roots and strong tolerance to heavy metals, so it has been widely concerned. In this study, nitrilotriacetic acid (NTA) and tea saponin (TS) were used as enhancers and combined with Sudan grass for improving the remediation efficiency of Ni-pyrene co-contaminated soil. The results of the pot experiment in soils showed that enhancers promoted the enrichment of Ni in plants. With the function of enhancers, more inorganic and water-soluble Ni were converted into low-toxic phosphate-bonded and residual Ni, so as to reinforce the tolerance of Sudan grass to Ni. In the pot experiment based on vermiculite, it was found that enhancers increased the accumulation of Ni in cell wall by 49.71-102.73%. Enhancers also had the positive effect on the relative abundance of Proteobacteria, Patescibacteria and Bacteroidetes that could tolerate heavy metals at phylum level. Simultaneously, the study found that pyrene reduced the exchangeable Ni in soils. More Ni entered the organelles and transfer to more high-toxic forms in Sudan grass when pynere coexisted. The study manifested that enhancers improved the phytoremediation effect of Ni significantly, yet the co-existence of pyrene weakened the process. Our results provided meaningful references for remediating actual co-contaminated soil of heavy metals and PAHs.

Prediction of drug efficacy from transcriptional profiles with deep learning.

Drug discovery focused on target proteins has been a successful strategy, but many diseases and biological processes lack obvious targets to enable such approaches. Here, to overcome this challenge, we describe a deep learning-based efficacy prediction system (DLEPS) that identifies drug candidates using a change in the gene expression profile in the diseased state as input. DLEPS was trained using chemically induced changes in transcriptional profiles from the L1000 project. We found that the changes in transcriptional profiles for previously unexamined molecules were predicted with a Pearson correlation coefficient of 0.74. We examined three disorders and experimentally tested the top drug candidates in mouse disease models. Validation showed that perillen, chikusetsusaponin IV and trametinib confer disease-relevant impacts against obesity, hyperuricemia and nonalcoholic steatohepatitis, respectively. DLEPS can generate insights into pathogenic mechanisms, and we demonstrate that the MEK-ERK signaling pathway is a target for developing agents against nonalcoholic steatohepatitis. Our findings suggest that DLEPS is an effective tool for drug repurposing and discovery.

Mobile Robot Indoor Positioning Based on a Combination of Visual and Inertial Sensors.

Multi-sensor integrated navigation technology has been applied to the indoor navigation and positioning of robots. For the problems of a low navigation accuracy and error accumulation, for mobile robots with a single sensor, an indoor mobile robot positioning method based on a visual and inertial sensor combination is presented in this paper. First, the visual sensor (Kinect) is used to obtain the color image and the depth image, and feature matching is performed by the improved scale-invariant feature transform (SIFT) algorithm. Then, the absolute orientation algorithm is used to calculate the rotation matrix and translation vector of a robot in two consecutive frames of images. An inertial measurement unit (IMU) has the advantages of high frequency updating and rapid, accurate positioning, and can compensate for the Kinect speed and lack of precision. Three-dimensional data, such as acceleration, angular velocity, magnetic field strength, and temperature data, can be obtained in real-time with an IMU. The data obtained by the visual sensor is loosely combined with that obtained by the IMU, that is, the differences in the positions and attitudes of the two sensor outputs are optimally combined by the adaptive fade-out extended Kalman filter to estimate the errors. Finally, several experiments show that this method can significantly improve the accuracy of the indoor positioning of the mobile robots based on the visual and inertial sensors.

Nickel uptake and distribution in Agropyron cristatum L. in the presence of pyrene.

PAHs affect the uptake of heavy metal by plants. The uptake pathway, distribution and detoxification of nickel (Ni) in Agropyron cristatum L. (A. cristatum) were investigated in the presence of pyrene in this study. Most of Ni was adsorbed on the cell wall in the insoluble phosphate (57.31-72.18%) form and pectate and protein integrated (38.27-38.98%) form. Ni was transferred to the organelle (from 37.84% to 40.52%) in the presence of pyrene. The concentration of Ni in A. cristatum decreased by 27.42%; it was affected by the ATP production inhibitor and 29.49% by the P-type ATPase inhibitor. The results indicated that the uptake of Ni related closely to the synthesis and decomposition of ATP and was an active uptake process. Contents of phytochelatins (PCs) in A. cristatum in Ni contaminated soils increased by 19.97%, and an additional 4.13% increase occurred in the presence of pyrene when compared to single Ni contamination. The content of malic acid in A. cristatum was the highest for 262.78 mg g-1 in shoots and 46.81 mg g-1 in roots with Ni contamination. Besides, acetic acid in shoots and roots increased by 40.25% and 102.63% with Ni contamination, and by 61.59% and 185.71% with Ni-pyrene co-contamination. This study preliminarily explored the inhibitory mechanism of pyrene on plant uptake of Ni.

Quantitative combination of natural anti-oxidants prevents metabolic syndrome by reducing oxidative stress.

Insulin resistance and abdominal obesity are present in the majority of people with the metabolic syndrome. Antioxidant therapy might be a useful strategy for type 2 diabetes and other insulin-resistant states. The combination of vitamin C (Vc) and vitamin E has synthetic scavenging effect on free radicals and inhibition effect on lipid peroxidation. However, there are few studies about how to define the best combination of more than three anti-oxidants as it is difficult or impossible to test the anti-oxidant effect of the combination of every concentration of each ingredient experimentally. Here we present a math model, which is based on the classical Hill equation to determine the best combination, called Fixed Dose Combination (FDC), of several natural anti-oxidants, including Vc, green tea polyphenols (GTP) and grape seed extract proanthocyanidin (GSEP). Then we investigated the effects of FDC on oxidative stress, blood glucose and serum lipid levels in cultured 3T3-L1 adipocytes, high fat diet (HFD)-fed rats which serve as obesity model, and KK-ay mice as diabetic model. The level of serum malondialdehyde (MDA) in the treated rats was studied and Hematoxylin-Eosin (HE) staining or Oil red slices of liver and adipose tissue in the rats were examined as well. FDC shows excellent antioxidant and anti-glycation activity by attenuating lipid peroxidation. FDC determined in this investigation can become a potential solution to reduce obesity, to improve insulin sensitivity and be beneficial for the treatment of fat and diabetic patients. It is the first time to use the math model to determine the best ratio of three anti-oxidants, which can save much more time and chemical materials than traditional experimental method. This quantitative method represents a potentially new and useful strategy to screen all possible combinations of many natural anti-oxidants, therefore may help develop novel therapeutics with the potential to ameliorate the worldwide metabolic abnormalities.