Chrysophanol protects against doxorubicin-induced cardiotoxicity by suppressing cellular PARylation

The clinical application of doxorubicin(DOX) in cancer chemotherapy is limited by its lifethreatening cardiotoxic effects. Chrysophanol(CHR), an anthraquinone compound isolated from the rhizome of Rheum palmatum L., is considered to play a broad role in a variety of biological processes.However, the effects of CHR’s cardioprotection in DOX-induced cardiomyopathy is poorly understood. In this study, we found that the cardiac apoptosis, mitochondrial injury and cellular PARylation levels were significantly increased in H9 C2 cells treated by Dox, while these effects were suppressed by CHR. Similar results were observed when PARP1 activity was suppressed by its inhibitors 3-aminobenzamide(3 AB)and ABT888. Ectopic expression of PARP1 effectively blocked this CHR’s cardioprotection against DOX-induced cardiomyocyte injury in H9 C2 cells. Furthermore, pre-administration with both CHR and 3 AB relieved DOX-induced cardiac apoptosis, mitochondrial impairment and heart dysfunction in Sprague–Dawley rat model. These results revealed that CHR protects against DOX-induced cardiotoxicity by suppressing cellular PARylation and provided critical evidence that PARylation may be a novel target for DOX-induced cardiomyopathy.

Quantifying temporal changes in Tornionjoki river ice breakup dates and spring temperatures in Lapland since 1802

Cryophenological records （i.e. observational series of freeze and breakup dates of ice） are of great importance when assessing the environmental variations in cold regions. Here we employed the extraordinarily long observational records of river ice breakup dates and air temperatures in northern Fennoscandia to examine their interrelations since 1802. Historical observations, along with modern data, comprise the informational setting for this analysis carried out using t-test. Temperature history of April-May season was used as cli- matic counterpart for the breakup timings. Both records （temperature and breakup） showed seven sub-periods during which their local means were distinctly different relative to preced- ing and subsequent sub-periods. The starting and ending years of these sub-periods oc- curred in temporal agreement. The main findings of this study are summarized as follows： （1） the synchrony between the temperature and river ice breakup records ruled out the possibility that the changes would have occurred due to quality of the historical series （i.e. inhomoge- neity problems often linked to historical time-series）; （2） the studied records agreed to show lower spring temperatures and later river ice breakups during the 19th century, in comparison to the 20th century conditions, evidencing the prevalence of cooler spring temperatures in the study region, in agreement with the concept of the Little Ice Age （1570-1900） climate in North-West Europe; （3） the most recent sub-period demonstrate the highest spring tem- peratures with concomitantly earliest river ice breakups, showing the relative warmth of the current springtime climate in the study region in the context of the past two centuries; （4） the effects of anthropogenic changes in the river environment （e.g. construction and demolition of dams） during the 20th century should be considered for non-climatic variations in the breakup records; （5） this study emphasizes the importance of multi-centurial （i.e. historical） cryo- phenological information for highly interesting viewpoints of climate and environmental his- tory.

Identification and attribute analysis of key stakeholders who influence multidrug-resistant tuberculosis prevention and control in China

Background There could be various stakeholders who influencing multidrug-resistant tuberculosis(MDR-TB)policy development and implementation,yet their attributes and roles remain unclear in practice.This study aimed to identify key stakeholders in the process of policy-making for MDR-TB control and prevention and to analyse the attributes and relationships of the stakeholders,providing evidence for further policy research on MDR-TB control.Methods This study was conducted from October 2018 to March 2019 and applied the stakeholder analysis guidelines and domestic stakeholder analysis.An initial candidate stakeholder list was developed by policy scanning.Ten experts were invited to identify these candidate stakeholders.The major attribute of these stakeholders were analysed using the Michell scoring method.Based on these results,the intertwined relationships among groups of stakeholders were analysed and mapped through a systematic scan of the policy and literature on MDR-TB control,as well as information obtained from the interviews.Results A list of 21 types of candidate stakeholders was developed after a literature review and policy scanning,of which 11 received 100%approval.After expert evaluation and identification(the total expert authority was 0.80),19 categories of stakeholders were approved and included in the stakeholder analysis.We categorized all of the stakeholders into three groups:(i)definitive stakeholders who are mainly involved in administrative departments and the Provincial Center for Disease Control and Prevention(CDC);(ii)expectant stakeholders who are mainly involved with MDR-TB patients,clinical departments of TB hospitals at different levels,community health care facilities,prefectural CDC and charity organizations;and(iii)latent stakeholders who mainly involved family members and neighbours of MDR-TB patients and TB related products manufacturers.Government departments and higher-level CDCs have strong decision-making power in developing MDR-TB control policies whereas the recommendations from service providers and the concerns of patients should be considered.Conclusions The MDR-TB prevention system was a multistakeholder cooperation system that was mainly led by government stakeholders.Enhancing communications with front-line service providers and patients on their unmet needs and evidence-based suggestions would highly benefit policy-making of MDR-TB prevention and control.

Isolation and Growth Characteristics of SARS-CoV-2 in Vero Cell

Dear Editors,The coronavirus disease 2019(COVID-19),caused by SARS-CoV-2,broke out in early December 2019 has escalated into a global pandemic(Lai et al.2020).Till the May 20 th 2020,more than 4,700,000 people were infected and the number is still increasing especially in Europe,North America and Asia(https://covid19.who.int/).