Effects of forskolin and cholera toxin on cyclic AMP release in a neurotensin-secreting rat C-cell line

The effects of forskolin and cholera toxin on the regulation of cAMP release were studied in a neurotensin-secreting rat C-cell line. The interaction of these agents with norepinephrine, a potent neurotensin secretagogue, was also investigated. Forskolin stimulated cAMP release 10(2)-10(3) fold while it increased neurotensin release 2-3 fold. Cholera toxin caused a 10(2)-10(3) fold increase in cAMP release and had no effect on neurotensin release. We conclude that the 44-2 C-cells provide a new model for studying the regulation of the concomitant (via forskolin) or independent (via cholera toxin) secretion of cyclic AMP and/or neurotensin.     

Ontogeny of the response to growth hormone-releasing factor

Primary cell cultures were prepared from fetal, neonatal and adult rat pituitaries and evaluated for their ability to secrete growth hormone (GH) in response to growth hormone-releasing factor (GRF). Pituitary cells prepared from fetuses at days 19 and 21 of gestation, neonatal animals at the day of birth (day 0) or the following day (day 1) and peripubertal male rats showed full dose response curves to GRF with maximal GH release when stimulated with 1 X 10(-10) M rat GRF. At this concentration of GRF, the amount of GH released was not different from that elicited by activation of adenylate cyclase with 1 X 10(-5) M forskolin. In contradistinction, a preparation of cells from fetuses at day 18 of gestation did not show the same release of GH when challenged with 1 X 10(-10) M GRF and forskolin (0.057 +/- 0.001, compared to 0.076 +/- 0.003 micrograms/10(5) cells per 4.5 h), although the cells clearly responded to both secretagogues (basal levels of GH, 0.029 +/- 0.002 micrograms/10(5) cells per 4.5 h). While cells prepared from fetuses at day 21 of gestation or from animals after birth released 5-10% of their total cellular GH content, those prepared from 18- and 19-day fetuses released as much as 40% of their total GH suggesting there is a maturation of intracellular GH processing that occurs late in gestation. The results show that, in late pregnancy, the rat fetal pituitary is highly responsive to growth hormone-releasing factor and suggest that this peptide participates in regulating GH levels during the perinatal period.     

Modulation of hepatic level of microsomal testosterone 7 alpha-hydroxylase, P-450a (P450IIA), by thyroid hormone and growth hormone in rat liver

The effects of thyroid hormone and growth hormone on microsomal testosterone 7 alpha-hydroxylase, P-450a, were studied to understand the interaction of these hormone-mediated regulations in rats. In Western blots using anti-P-450a IgG, 1.7-fold higher content of P-450a was observed in livers of female than male adult rats, while no appreciable sex-related difference was detected in prepubertal rats and rats of 24 months of age. Treatment with n-propyl-2-thiouracil or thyroidectomy of male rats increased by 2-fold the hepatic content of P-450a, but neither regimen had a significant effect on the content in female rats. Levels of P-450a in both sexes of thyroidectomized rats were decreased by the supplementation of triiodothyronine (T3, 50 micrograms per kg, i.p. for 7 days) to levels similar to that observed in normal male rats. Hypophysectomy also caused an increase in microsomal P-450a content in male rats. Continuous infusion of human growth hormone, which mimicked the female secretion, further significantly increased the content in hypophysectomized rats to a level similar to that observed in normal female rats. In contrast, hepatic level of P-450a in hypophysectomized male and female rats was reduced by intermittent injection, which mimicked the male secretion. Clear suppression on the level of hepatic P-450a was also observed by the treatment of hypophysectomized rats with 5 or 50 micrograms/kg of T3 and of hGH-infused hypophysectomized rat with 50 micrograms/kg of T3.(ABSTRACT TRUNCATED AT 250 WORDS)     

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology     

无花果曲霉发酵生产β-葡萄糖苷酶的动力学分析

在7L生物反应器的分批发酵中,通过对无花果曲霉UV-29液态发酵茵丝体的生长、基质消耗（以总糖计）及β-葡萄糖苷酶产生的特性研究,发现总糖是无花果曲霉生长的限制性基质;β-葡萄糖苷酶的增长趋势明显滞后于细胞生长的增长趋势,其发酵过程属于部分相关模型,即Ga—den提出的Ⅱ型发酵;基于logistic方程,建立了发酵动力学模型,同时对实验数据与模型进行了验证比较,模型计算值与实验数据拟合良好。在7L生物反应器的最大茵体生物量（干重）达到1．17g／100mL,β-葡萄糖苷酶最高酶活达到22．25IU／mL。     

Effects of dissolved organic matter from sewage sludge on the atrazine sorption by soils

The effects of dissolved organic matter (DOM), water soluble organic matter derived from sewage sludge, on the sorption of atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-trazine) by soils were studied using a batch equilibrium technique. Six paddy soils, chosen so as to have different organic carbon contents, were experimented in this investigation. Atrazine sorption isotherms on soils were described by the linear equation, and the distribution coefficients without DOM (Kd) or with DOM (Kd*) were obtained. Generally, the values of Kd*/Kd initially insoil-solution system form. Critical concentrations of DOM (DOMnp) were obtained where the value of Kd* was equal to Kd. The presence of DOM with concentrations lower than DOMnp promoted atrazine sorption on soils (Kd* ＞ Kd), whereas the presence of DOM with concentrations higher than DOMnp tended to inhibit atrazine sorption (Kd* ＜ Kd). Interestingly, DOMnp for tested soils was negatively correlated to the soil organic carbon content, and the maximum of Kd*/Kd (i.e.Kmax) correlated positively with the maximum of DOM sorption on soil (Xmax). Further investigations showed that the presence of hydrophobic fraction of DOM evidently promoted the atrazine sorption on soils, whereas the presence of hydrophilic DOM fraction obviously tended to inhibit the atrazine sorption. Interactions of soil surfaces with DOM and its fractions were suggested to be the major processes determining atrazine sorption on soils. The results of this work provide a reference to the agricultural use of organic amendment such as sewage sludge for improving the availability of atrazine in soils.     

mRNA差别显示技术及其在生命科学中的应用

ｍＲＮＡ表达水平的变化决定细胞的功能状态,个体发育、细胞增殖分化与凋谢、生理刺激和药物治疗等过程,都会出现ｍＲＮＡ 表达水平的变化。阐明这种变化有助于揭示细胞生理过程的分子机制。该技术无需更多的背景资料,可快速有效地分离表达水平出现差别的基础,这些基因编剧编码的功能多肽在细胞生理过程中扮演着重要角色。     

改良早期预警评分对转院转运工作影响的临床研究

目的 研究改良早期预警（MEWS）评分对转院转运工作的影响.方法 在转院转运工作中应用MEWS评分系统对患者进行病情评估,对比其应用前（对照组）、应用后（研究组）转院患者转运途中病情恶化的发生率、患者或家属满意度及医生、护士对实施MEWS评分转运管理模式前（对照组）、后（研究组）满意度的变化.结果 转院患者转运途中病情恶化发生率由应用前（对照组）的10.63%降至应用后（研究组）的3.74%,应用前、后比较差异有显著统计学意义（P＜0.01）;患方满意度则由96%提高至99%,医护人员对实施MEWS评分转运管理模式前、后的满意度由应用前的83.3%提高至应用后的95%,应用前、后比较均有显著性意义（P＜0.05）.结论 MEWS评分能对转院患者的病情进行比较客观、准确的评估,提高了医务人员的质量和医疗干预意识,从而有效降低转院患者转运途中的病情恶化发生率和提高院前医患双方的满意度,是转院转运工作中简便、快捷、客观、实用的病情评估方法和模式,值得推广应用.