The ARK2N-CK2 complex initiates transcription-coupled repair through enhancing the interaction of CSB with lesion-stalled RNAPII.

Transcription is extremely important for cellular processes but can be hindered by RNA polymerase II (RNAPII) pausing and stalling. Cockayne syndrome protein B (CSB) promotes the progression of paused RNAPII or initiates transcription-coupled nucleotide excision repair (TC-NER) to remove stalled RNAPII. However, the specific mechanism by which CSB initiates TC-NER upon damage remains unclear. In this study, we identified the indispensable role of the ARK2N-CK2 complex in the CSB-mediated initiation of TC-NER. The ARK2N-CK2 complex is recruited to damage sites through CSB and then phosphorylates CSB. Phosphorylation of CSB enhances its binding to stalled RNAPII, prolonging the association of CSB with chromatin and promoting CSA-mediated ubiquitination of stalled RNAPII. Consistent with this finding, Ark2n-/- mice exhibit a phenotype resembling Cockayne syndrome. These findings shed light on the pivotal role of the ARK2N-CK2 complex in governing the fate of RNAPII through CSB, bridging a critical gap necessary for initiating TC-NER.

PP2A inhibition causes synthetic lethality in BRCA2-mutated prostate cancer models via spindle assembly checkpoint reactivation.

Mutations in the BRCA2 tumor suppressor gene have been associated with an increased risk of developing prostate cancer. One of the paradoxes concerning BRCA2 is the fact that its inactivation affects genetic stability and is deleterious for cellular and organismal survival, while BRCA2-mutated cancer cells adapt to this detriment and malignantly proliferate. Therapeutic strategies for tumors arising from BRCA2 mutations may be discovered by understanding these adaptive mechanisms. In this study, we conducted forward genetic synthetic viability screenings in Caenorhabditis elegans brc-2 (Cebrc-2) mutants and found that Ceubxn-2 inactivation rescued the viability of Cebrc-2 mutants. Moreover, loss of NSFL1C, the mammalian ortholog of CeUBXN-2, suppressed the spindle assembly checkpoint (SAC) activation and promoted the survival of BRCA2-deficient cells. Mechanistically, NSFL1C recruited USP9X to inhibit the polyubiquitination of AURKB and reduce the removal of AURKB from the centromeres by VCP, which is essential for SAC activation. SAC inactivation is common in BRCA2-deficient prostate cancer patients, but PP2A inhibitors could reactivate the SAC and achieve BRCA2-deficient prostate tumor synthetic lethality. Our research reveals the survival adaptation mechanism of BRCA2-deficient prostate tumor cells and provides different angles for exploring synthetic lethal inhibitors in addition to targeting DNA damage repair pathways.

Evaluation of the intervention effect of conventional and peer AIDS voluntary counseling and testing services among young students / 中国学校卫生

Objective@#To explore the influence of two voluntary counseling and testing(VCT) services on young students acquired immune deficiency syndrome(AIDS) related knowledge and behaviour, so as to provide a new idea for further improvement and promotion of VCT services.@*Methods@#From April 2017 to December 2018, the sample size,selected from 12 patrol and fixed monitoring sites in colleges in Guangzhou, was calculated by non inferiority trial, and the students who received services at the same period were 1∶1 matched. A total of 113 students received conventional VCT and 186 recerived peer VCT services. The Chi square test was used to analyse the difference of AIDS related knowledge and behavior before and after intervention, and a survey was conducted on satisfaction.@*Results@#After young students received conventional VCT services, the overall awareness rate of AIDS basic knowledge increased from 80.53% to 93.75%, and the frequency of condom use every time during heterosexual sexual activity in the past year increased by 29.17 percentage points ( χ 2=4.49,4.10, P <0.05). After young students received peer VCT services, the awareness rate of the Four Frees and One Care Policy increased from 34.95% to 58.26%, the rates of homosexual anal sex and more than or equal to 2 sexual partners in the past half a year decreased by 14.84 and 29.43 percentage points, respectively( χ 2=15.69, 4.82, 10.97, P <0.05).@*Conclusion@#After young students receive two modes of VCT services respectively, the AIDS related knowledge and behavior have been improved, and the influence of the two VCT services has different advantages. The combination of conventional VCT and peer education might be a more effective way of AIDS intervention.

Development and utility of a close contact information management system for the COVID-19 pandemic.

BACKGROUND: Since the outbreak started in 2019, COVID-19 pandemic has a significant global impact. Due to the highly infective nature of SARS-CoV-2, the COVID-19 close contacts are at significant risk of contracting COVID-19. China's experience in successfully controlling COVID-19 emphasized the importance of managing close contacts because this strategy helps to limit potential infection sources, prevent the unconscious spread of COVID-19 and thus control this pandemic. As a result, to understand and consider the management of close contacts may be beneficial to other countries. However, managing close contacts is challenging owing to the huge number of close contacts and a lack of appropriate management tools and literature references. METHODS: A new system called the COVID-19 Close Contact Information Management System was developed. Here we introduced the design, use, improvement and achievements of this system. RESULTS: This system was designed from the standpoint of the Centers for Disease Control and Prevention in charge of managing close contacts. Two main functions and eight modules/themes were ultimately formed after two development stages. The system introduces what information need to be collected in the close contact management. Since the system allows information flow across cities, the geographical distance and administrative regional boundaries are no longer obstacles for managing close contacts, which promotes the management of each close contact. Moreover, when this system is used in conjunction with other data tools, it provides data assistance for understanding the COVID-19 characteristics and formulating targeted COVID-19 control policies. To date, the system has been widely used in Guangdong Province for over 1 year and has recorded tens of thousands of pieces of data. There is sufficient practical experience to suggest that the system is capable of meeting the professional work requirements for close contact management. CONCLUSIONS: This system provides a new way to manage close contacts and restrict the spread of COVID-19 by combining information technology with disease prevention and control strategies in the realm of public health. We hope that this system will serve as an example and guide for those anticipating similar work in other countries in response to current and future public health incidents.

The effect of cardiovascular disease and acute cardiac injury on fatal COVID-19: a meta-analysis.

BACKGROUND: With the continuance of the global COVID-19 pandemic, cardiovascular disease (CVD) and cardiac injury have been suggested to be risk factors for severe COVID-19. OBJECTIVE: The aim is to evaluate the mortality risks associated with CVD and cardiac injury among hospitalized COVID-19 patients, especially in subgroups of populations in different countries. METHODS: A comprehensive systematic literature search was performed using 9 databases from November 1, 2019 to November 9, 2020. Meta-analyses were performed for CVD and cardiac injury between non-survivors and survivors of COVID-19. RESULTS: Although the prevalence of CVD in different populations was different, hospitalized COVID-19 patients with CVD were at a higher risk of fatal outcomes (OR = 2.72; 95% CI 2.35-3.16) than those without CVD. Separate meta-analyses of populations in four different countries also reached a similar conclusion that CVD was associated with an increase in mortality. Cardiac injury was common among hospitalized COVID-19 patients. Patients with cardiac injury had a significantly higher mortality risk than those without cardiac injury (OR = 13.25; 95% CI: 8.56-20.52). CONCLUSIONS: Patients' CVD history and biomarkers of cardiac injury should be taken into consideration during the hospital stay and incorporated into the routine laboratory panel for COVID-19.