Experimental study and mechanism analysis on bioeffects by nanosecond electromagnetic pulses

The athermal bioeffects caused by nanosecond electromagnetic pulses with body cells was studied by using a broad band transverse EM-wave cell (BTEM CELL). The experimental system and preliminary mechanism analysis were presented.     

Regulation of GABAB receptors by histamine and neuronal activity in the isolated spinal cord of neonatal opossum in culture.

The aim of these experiments has been to analyse the properties of receptors for the transmitter gamma-aminobutyric acid (GABA) in developing mammalian nervous system. Changes in responses of GABAB receptors have been measured after alterations of the chemical environment and the level of electrical activity. We have previously shown that when the central nervous system (CNS) of the new-born opossum, Monodelphis domestica, is cultured for three to five days in the presence of histidine, inhibition by baclofen, a GABAB agonist, disappears (Stewart et al. 1991). We have now investigated whether histidine acts indirectly by way of conversion to histamine. As with histidine, culture with 150 microM histamine for five days virtually abolished the inhibition by baclofen. The effects of histidine, as well as histamine, were blocked by mepyramine, a histamine H1-receptor antagonist, and by ranitidine, an H2-antagonist. Tetrodotoxin (TTX), which blocks all electrical activity, protected preparations from the action of histidine but not histamine. Our results suggest that histidine is converted to histamine, which reduces the efficacy of GABAB agonists. We conclude that, in the developing mammalian CNS, transmitter levels and electrical activity can selectively influence the properties of receptors.     

A new method for estimating gross phosphorus mineralization and immobilization rates in soils

Phosphorus availability in soils is controlled by both the sizes of P pools and the transformation rates among these pools. Rates of gross P mineralization and immobilization are poorly known due to the limitations of available analytical techniques. We developed a new method to estimate P transformation rates in three forest soils and one grassland soil representing an Alfisol, an Ultisol, and Andisol, and a Mollisol. Three treatments were applied to each soil in order to separate the processes of mineral P solubilization, organic P mineralization, and solution P immobilization. One set of soils was retained as control, a second set was irradiated with -rays to stop microbial immobilization, and a third was irradiated and then autoclaved, also stop phosphatase activity. All three sets of samples were then incubated with anion exchange resin bags under aerobic conditions. Differences in resin P among the three treatments were used to estimate gross P mineralization and immobilization rates. Autoclaving did not affect resin-extractable P in any of the soils. Radiation did not alter resin-extractable P in the forest soils but increased resin-extractable P in the grassland soil. This increase was corrected in the calculation of potential P transformation rates. Effects of radiation on phosphatase activity varied with soils but was within 30% of the original values. Rates of P gross mineralization and immobilization ranged from 0.6–3.8 and 0–4.3 mg kg-soil^-1 d^-1, respectively, for the four soils. The net rates of solubilization of mineral P in the grassland soil were 7–10 times higher than the rates in forest soils. Mineralization of organic P contributed from 20–60% of total available P in the acid forest soils compared with 6% in the grassland soil, suggesting that the P mineralization processes are more important in controlling P availability in these forest ecosystems. This new method does not require an assumption of equilibrium among P pools, and is safer and simpler in operation than isotopic techniques.     

EPR studies of spin-labeled bovine plasma amine oxidase: the nature of the substrate-binding site.

The carbonyl cofactor of bovine plasma amine oxidase (EC 1.4.3.6), recently shown to be 6-hydroxydopa (also known as topa), has been spin labeled to the extent of one label per enzyme dimer molecule, using 4-amino-2,2,6,6-tetramethylpiperidine-N-oxyl (4-amino-TEMPO) and 4-hydrazino-TEMPO followed by reduction with borohydride. By studying the EPR spectra of the labeled enzyme, it has been deduced that there is no magnetic interaction between the copper and the spin label, and that the spin label is at least 1.3 nm distant from the copper(II) ion in the resting enzyme. The bound label is strongly immobilized, is in a sterically constricted environment, and is not accessible to small anions. Removal of the copper does not alter the EPR spectrum of the label. The results are similar to results for porcine plasma amine oxidase, and show that the copper is not close to, and does not directly interact with, the topa-bound substrate.     

龟纹瓢虫幼虫的食物搜索行为

本试验采用Nakamuta(1982)装置研究龟纹瓢虫Propylea japonica(Thunberg)幼虫的食饵搜索行为,结果表明:1.五种刺激均能激发搜索行为由广域型转换为地域集中型;2.摄食时间与GUT呈正相关;3.摄食的最后一个食饵大小决定GUT的长短;4.摄食后0—15秒的搜索速度小、弯曲角度大.     

CRISPR/Cas9-induced structural variations expand in T lymphocytes in vivo

CRISPR/Cas9 has been adapted to disrupt endogenous genes in adoptive T-lymphocyte therapy to prevent graft-versus-host disease. However, genome editing also generates prevalent deleterious structural variations (SVs), including chromosomal translocations and large deletions, raising safety concerns about reinfused T cells. Here, we dynamically monitored the progression of SVs in a mouse model of T-cell receptor (TCR)-transgenic T-cell adoptive transfer, mimicking TCR T therapeutics. Remarkably, CRISPR/Cas9-induced SVs persist and undergo clonal expansion in vivo after three weeks or even two months, evidenced by high enrichment and low junctional diversity of identified SVs post infusion. Specifically, we detected 128 expanded translocations, with 20 615 as the highest number of amplicons. The identified SVs are stochastically selected among different individuals and show an inconspicuous locus preference. Similar to SVs, viral DNA integrations are routinely detected in edited T cells and also undergo clonal expansion. The persistent SVs and viral DNA integrations in the infused T cells may constantly threaten genome integrity, drawing immediate attention to the safety of CRISPR/Cas9-engineered T cells mediated immunotherapy.     

A multi-label learning model for predicting drug-induced pathology in multi-organ based on toxicogenomics data

Drug-induced toxicity damages the health and is one of the key factors causing drug withdrawal from the market. It is of great significance to identify drug-induced target-organ toxicity, especially the detailed pathological findings, which are crucial for toxicity assessment, in the early stage of drug development process. A large variety of studies have devoted to identify drug toxicity. However, most of them are limited to single organ or only binary toxicity. Here we proposed a novel multi-label learning model named Att-RethinkNet, for predicting drug-induced pathological findings targeted on liver and kidney based on toxicogenomics data. The Att-RethinkNet is equipped with a memory structure and can effectively use the label association information. Besides, attention mechanism is embedded to focus on the important features and obtain better feature presentation. Our Att-RethinkNet is applicable in multiple organs and takes account the compound type, dose, and administration time, so it is more comprehensive and generalized. And more importantly, it predicts multiple pathological findings at the same time, instead of predicting each pathology separately as the previous model did. To demonstrate the effectiveness of the proposed model, we compared the proposed method with a series of state-of-the-arts methods. Our model shows competitive performance and can predict potential hepatotoxicity and nephrotoxicity in a more accurate and reliable way. The implementation of the proposed method is available at https://github.com/RanSuLab/Drug-Toxicity-Prediction-MultiLabel.     

间充质干细胞治疗新型冠状病毒肺炎研究进展及相关临床试验难点

当前新型冠状病毒肆虐,全球确诊患者超过3 500万例,累计死亡患者超过50万例,对于突发疫情,临床尚缺乏有效特异性治疗,新型冠状病毒已成为危害人类健康、社会发展的主要公共卫生问题。间充质干细胞具有抗炎和免疫调节功能,可降低重症患者体内由冠状病毒引发的细胞因子风暴,改善患者肺部纤维化,促进损伤肺组织修复,有望降低新冠肺炎的死亡率。目前已开展多项间充质干细胞治疗新型冠状病毒肺炎临床试验,初步证实了间充质干细胞应用在新冠肺炎方面的安全及有效性。在间充质干细胞治疗新冠肺炎取得进展的同期,还应看到该疗法独有特点及疫情严峻形势对临床试验开和及评价带来的问题与挑战,包括临床试验方案设计、干细胞质量管理以及治疗中的伦理考量。只有对其加以重视,才能保证在严峻疫情下安全有效地开展间充质干细胞治疗新型冠状病毒肺炎的临床试验。     

IL1RN promotes osteoblastic differentiation via interacting with ITGB3 in osteoporosis

The occurrence and progress of osteoporosis(OP)are partially caused by impaired osteoblast differentiation.Interleukin-I receptor antagonist(IL1RN)is an immune ...