Advancing CAR-based immunotherapies in solid tumors: CAR- macrophages and neutrophils

Macrophages and neutrophils are the main components of the innate immune system and play important roles in promoting angiogenesis, extracellular matrix remodeling, cancer cell proliferation, and metastasis in the tumor microenvironment (TME). They can also be harnessed to mediate cytotoxic tumor killing effects and orchestrate effective anti-tumor immune responses with proper stimulation and modification. Therefore, macrophages and neutrophils have strong potential in cancer immunotherapy. In this review, we briefly outlined the applications of macrophages or neutrophils in adoptive cell therapies, and focused on chimeric antigen receptor (CAR)-engineered macrophages (CAR-Ms) and neutrophils (CAR-Ns). We summarized the construction strategies, the preclinical and clinical studies of CAR-Ms and CAR-Ns. In the end, we briefly discussed the limitations and challenges of CAR-Ms and CAR-Ns, as well as future research directions to extend their applications in treating solid tumors

Reduced expression of IA channels is associated with post-ischemic seizures

Purpose Post-stroke seizures are considered as a major cause of epilepsy in adults. The pathophysiologic mechanisms resulting in post-stroke seizures are not fully understood. The present study attempted to reveal a new mechanism underlying neuronal hyperexcitability responsible to the seizure development after ischemic stroke. Methods Transient global ischemia was produced in adult Wistar rats using the 4-vessel occlusion (4-VO) method. The spontaneous behavioral seizures were defined by the Racine scale III – V. The neuronal death in the brain was determined by hematoxylineosin staining. The expression levels of A-type potassium channels were analyzed by immunohistochemical staining and western blotting. Results We found that the incidence of spontaneous behavioral seizures increased according to the severity of ischemia with 0% after 15-min ischemia and ~50% after 25- min ischemia. All behavioral seizures occurred with 48 hrs after ischemia. Morphological analysis indicated that brain damage was not correlated with behavioral seizures. Immunohistochemical staining showed that the expression levels of the A-type potassium channel subunit Kv4.2 was significantly reduced in ischemic brains with behavioral seizures, but not in ischemic brains without seizures. In addition, rats failing to develop spontaneous behavioral seizures within 2 days after ischemia were more sensitive to bicuculline-induced seizures at 2 months after ischemia than control rats. Meanwhile, Kv4.2 expression was decreased in brain at 2 months after ischemia. Conclusion Our results demonstrated the reduction of Kv4.2 expression might contribute to the development of post-ischemic seizures and long-term increased seizure susceptibility after ischemia. The mechanisms underlying post-stroke seizures and epilepsy is unknown so far. The down-regulation of IA channels may explained the abnormal neuronal hyperexcitability responsible for the seizure development after ischemic stroke

Impact of COVID-19 on transportation and logistics: a case of China

Recent research has shown that the COVID-19 pandemic has holistically affected the financial and industrial sectors of China, in a considerably adverse manner. This paper aims to examine the impact of the COVID-19 virus on the transportation and logistics sector in China. In this regard, the study opted for a quantitative method of research design, along with primary data collection. The explanatory variable here is the COVID-19 virus, whereas, the dependent variables are air freight, ocean freight, and land freight. The data analysis technique used is the Structural Equation Modelling (SEM) analysis, comprising of the Confirmatory Factor Analysis (CFA) and the path assessment method. A structured survey questionnaire was also used, and the survey questionnaire scale was set from strongly agree to disagree strongly. The findings revealed that the effect of COVID-19 on air freight is statistically negative and significant. Moreover, the impact of COVID-19 on land freight is statistically negative and significant, whereas the effect of COVID-19 is statistically insignificant in the context of ocean freight, particularly during the period of the COVID-19 pandemic. Therefore, keeping these results in consideration, policymakers can enhance their support, so as to increase the performance of the logistics and transportation sector in China

KidneyRegNet: A Deep Learning Method for 3DCT-2DUS Kidney Registration during Breathing

This work proposed a novel deep registration pipeline for 3D CT and 2D U/S kidney scans of free breathing, which consists of a feature network, and a 3D-2D CNN-based registration network. The feature network has handcraft texture feature layers to reduce the semantic gap. The registration network is encoder-decoder structure with loss of feature-image-motion (FIM), which enables hierarchical regression at decoder layers and avoids multiple network concatenation. It was first pretrained with retrospective datasets cum training data generation strategy, then adapted to specific patient data under unsupervised one-cycle transfer learning in onsite application. The experiment was on 132 U/S sequences, 39 multiple phase CT and 210 public single phase CT images, and 25 pairs of CT and U/S sequences. It resulted in mean contour distance (MCD) of 0.94 mm between kidneys on CT and U/S images and MCD of 1.15 mm on CT and reference CT images. For datasets with small transformations, it resulted in MCD of 0.82 and 1.02 mm respectively. For large transformations, it resulted in MCD of 1.10 and 1.28 mm respectively. This work addressed difficulties in 3DCT-2DUS kidney registration during free breathing via novel network structures and training strategy.Comment: 15 pages, 8 figures, 9 table

Vaccaria hypaphorine alleviates lipopolysaccharide-induced inflammation via inactivation of NFκB and ERK pathways in Raw 264.7 cells

10.1186/s12906-017-1635-1BMC Complementary and Alternative Medicine17112

The effect of salt stress on the chlorophyll level of the main sand-binding plants in the shelterbelt along the Tarim Desert Highway

Based on the fact that only high saline water irrigated to the shelterbelt along the Tarim Desert Highway, the experiment about three species with six degree of salinity was carried out to analyze the relation between chlorophyll content and salt stress. The results show that: (1) the chlorophyll content of tree species decreases with aggravating the salt stress, which explains that salt stress can affect chlorophyll accumulation of three plants; (2) from chlorophyll content with different salinity, the chlorophyll content of three shrubs also has twice obvious decrease, which indicates that some plants adapt to salt stress. We divided salt resistance of the plant into three grades, namely the slight salt resistance, the heavy salt resistance and the extreme salt resistance; and (3) according to the experimental results, the salt stress of each plant was divided, which can provide theoretical guidance for constructing the shelterbelt along the Tarim Desert Highway

Model-free adaptive iterative learning control of melt pool width in wire arc additive manufacturing

© 2020, Springer-Verlag London Ltd., part of Springer Nature. Wire arc additive manufacturing (WAAM) is a Direct Energy Deposition (DED) technology, which utilize electrical arc as heat source to deposit metal material bead by bead to make up the final component. However, issues like the lack of assurance in accuracy, repeatability and stability hinder the further application in industry. Therefore, a Model Free Adaptive Iterative Learning Control (MFAILC) algorithm was developed to be applied in WAAM process in this study. The dynamic process of WAAM is modelled by adaptive neuro fuzzy inference system (ANFIS). Based on this ANFIS model, simulations are performed to demonstrate the effectiveness of MFAILC algorithm. Furthermore, experiments are conducted to investigate the tracking performance and robustness of the MFAILC controller. This work will help to improve the forming accuracy and automatic level of WAAM

Effects of Electroacupuncture on Chronic Unpredictable Mild Stress Rats Depression-Like Behavior and Expression of p-ERK/ERK and p-P38/P38

We investigate the antidepressant-like effect and mechanism of electroacupuncture (EA) on a chronic unpredictable mild stress rats depression-like behavior. In our study, depression in rats was induced by unpredictable chronic mild stress (UCMS) and isolation for four weeks. Male Sprague-Dawley rats were randomly divided into four groups: Normal, Model, EA, and Sham EA. EA treatment was administered for two weeks, once a day for five days a week. Two acupoints, Yintang (EX-HN3) and Baihui (GV20), were selected. For sham EA, acupuncture needles were inserted shallowly into the acupoints: EX-HN3 and GV20. No electrostimulator was connected. The antidepressant-like effect of the electroacupuncture treatment was measured by sucrose intake test, open field test, and forced swimming test in rats. The protein levels of phosphorylated extracellular regulated protein kinases (p-ERK1/2)/ERK1/2 and p-P38/P38 in the hippocampus (HP) were examined by Western blot analysis. Our data demonstrate that EA treatment decreased the immobility time of forced swimming test and improved the sucrose solution intake in comparison to unpredictable chronic mild stress and placebo sham control. Electroacupuncture may act on depression by enhancing p-ERK1/2 and p-p38 in the hippocampus