Cyclin C Mediates Stress-Induced Mitochondrial Fission and Apoptosis

Mitochondria are dynamic organelles that undergo constant fission and fusion cycles. In response to cellular damage, this balance is shifted dramatically toward fission. Cyclin C-Cdk8 kinase regulates transcription of diverse gene sets. Using knockout mouse embryonic fibroblasts (MEFs), we demonstrate that cyclin C directs the extensive mitochondrial scission induced by the anticancer drug cisplatin or oxidative stress. This activity is independent of transcriptional regulation, as Cdk8 is not required for this activity. Furthermore, adding purified cyclin C to unstressed permeabilized MEF cultures induced complete mitochondrial fragmentation that was dependent on the fission factors Drp1 and Mff. To regulate fission, a portion of cyclin C translocates from the nucleus to the cytoplasm, where it associates with Drp1 and is required for its enhanced mitochondrial activity in oxidatively stressed cells. In addition, although HeLa cells regulate cyclin C in a manner similar to MEF cells, U2OS osteosarcoma cultures display constitutively cytoplasmic cyclin C and semifragmented mitochondria. Finally, cyclin C, but not Cdk8, is required for loss of mitochondrial outer membrane permeability and apoptosis in cells treated with cisplatin. In conclusion, this study suggests that cyclin C connects stress-induced mitochondrial hyperfission and programmed cell death in mammalian cells

Research on the Current Situation and Strategies for Enhancing the Development and Capacity of Food Safety Inspection and Testing Institutions ——A Case Study of Zhejiang Province

Food is vital to the people, and safety comes first in food. Food safety is crucial to people's livelihood, economic development, and social stability. It represents people's aspiration for a better life and grabs great public attention. In recent years, while China has achieved significant progress in food safety, the situation remains severe, with incidents such as excessive residues of agricultural and veterinary drugs, as well as illegal addition of toxic and harmful substances. As an important technical support for ensuring food safety, food safety inspection and testing institutions also exhibit a mixed bag of performance. Problems such as inadequate personnel management, improper use of facilities and equipment, weak legal awareness resulting in issuance of false reports have frequently occurred, seriously disrupting the normal order of the inspection and testing market and affecting the authority and accuracy of food safety testing. Based on the capacity verification of inspection and testing organizations in Zhejiang Province in recent years, this paper studies the typical problems faced by food inspection and testing institutions in terms of management level and testing capabilities, analyzes the root causes in depth, and proposes specific strategies from three aspects: Strengthening the main responsibility of inspection and testing institutions, combining regulatory departments with supervision and guidance, and enhancing industry self-discipline, aiming to continuously improve their inspection and testing capabilities, promote the high-quality development of food inspection and testing institutions, and effectively ensure the safety of every bite of food

Influence of Sex on Cognition and Peripheral Neurovascular Function in Diabetic Mice

Cognition impairment and peripheral neuropathy (DPN) are two major complications of diabetes. The aim of the present study is to investigate the effect of sex differences on cognition and DPN in diabetic mice. Male and female BKS.Cg

LTBI-negative close contacts of tuberculosis are more likely to develop the disease: enlightenment and lessons from a cluster outbreak

BackgroundTuberculosis (TB) prevention and control among groups living together, such as students, workers, older adults in nursing homes, and prisoners, present many challenges due to their particular age and environmental factors, which can make them more susceptible to TB clusters with significant societal impact. This study aimed to evaluate a TB cluster outbreak epidemic in a university and provide suggestions for improving TB control strategies for groups living together.MethodsPulmonary TB screening and close-contact investigation were conducted using acid-fast staining, sputum culture, GeneXpert testing, tuberculin skin testing (TST), interferon-gamma release assay (IGRA), and chest computed tomography (CT). GraphPad Prism 9.5.1 was utilized for data analysis. Collected epidemic data were comprehensively analyzed by rate comparison.ResultsThe TB cluster outbreak epidemic was identified with an index case confirmed positive. The initial screening was conducted on potential close contacts of the index case, and the TST’s positive rate (diameter ≥ 5 mm) and strong positive rate (diameter ≥ 15 mm) among these close contacts were 65.60% (21/32) and 34.40% (11/32), respectively. Moreover, the latent TB infection (LTBI) rate (diameter ≥ 10 mm) was 43.75% (14/32), and the IGRA’s positive rate was 9.30% (3/32). Chest CT scans did not reveal any abnormalities. Surprisingly, 5 of the close contacts developed active TB in the second screening, accompanied by changes from negative to positive TST and/or IGRA results, after 3 months of follow-up. Accordingly, we expanded the screening scope to include another 28 general contacts. We found that the positive rate (78.00%, 25/32), strong positive rate (50.00%, 16/32), and LTBI rate (62.50%, 20/32) of the 32 close contacts were significantly higher than those of the additional general contacts (28.00%, 8/28; 14.3%, 4/28; 25.00%, 7/28), as indicated by p < 0.05.ConclusionIn the event of an epidemic TB outbreak, it is essential to rapidly identify the source of infection and initiate timely screening of close contacts. The initial screening should be focused on individuals without LTBI, who are at higher risk of developing TB. In purified protein derivative-negative individuals living in groups, additional vaccination or revaccination with Bacille Calmette-Guérin may help prevent cluster outbreaks of TB

Metagenomic surveillance and comparative genomic analysis of Chlamydia psittaci in patients with pneumonia

Chlamydia psittaci, a strictly intracellular bacterium, is an underestimated etiologic agent leading to infections in a broad range of animals and mild illness or pneumonia in humans. In this study, the metagenomes of bronchoalveolar lavage fluids from the patients with pneumonia were sequenced and highly abundant C. psittaci was found. The target-enriched metagenomic reads were recruited to reconstruct draft genomes with more than 99% completeness. Two C. psittaci strains from novel sequence types were detected and these were closely related to the animal-borne isolates derived from the lineages of ST43 and ST28, indicating the zoonotic transmissions of C. psittaci would benefit its prevalence worldwide. Comparative genomic analysis combined with public isolate genomes revealed that the pan-genome of C. psittaci possessed a more stable gene repertoire than those of other extracellular bacteria, with ~90% of the genes per genome being conserved core genes. Furthermore, the evidence for significantly positive selection was identified in 20 virulence-associated gene products, particularly bacterial membrane-embedded proteins and type three secretion machines, which may play important roles in the pathogen-host interactions. This survey uncovered novel strains of C. psittaci causing pneumonia and the evolutionary analysis characterized prominent gene candidates involved in bacterial adaptation to immune pressures. The metagenomic approach is of significance to the surveillance of difficult-to-culture intracellular pathogens and the research into molecular epidemiology and evolutionary biology of C. psittaci

Targeting cyclin B1 inhibits proliferation and sensitizes breast cancer cells to taxol

Background Cyclin B1, the regulatory subunit of cyclin-dependent kinase 1 (Cdk1), is essential for the transition from G2 phase to mitosis. Cyclin B1 is very often found to be overexpressed in primary breast and cervical cancer cells as well as in cancer cell lines. Its expression is correlated with the malignancy of gynecological cancers. Methods In order to explore cyclin B1 as a potential target for gynecological cancer therapy, we studied the effect of small interfering RNA (siRNA) on different gynecological cancer cell lines by monitoring their proliferation rate, cell cycle profile, protein expression and activity, apoptosis induction and colony formation. Tumor formation in vivo was examined using mouse xenograft models. Results Downregulation of cyclin B1 inhibited proliferation of several breast and cervical cancer cell lines including MCF-7, BT-474, SK-BR-3, MDA-MB-231 and HeLa. After combining cyclin B1 siRNA with taxol, we observed an increased apoptotic rate accompanied by an enhanced antiproliferative effect in breast cancer cells. Furthermore, control HeLa cells were progressively growing, whereas the tumor growth of HeLa cells pre-treated with cyclin B1 siRNA was strongly inhibited in nude mice, indicating that cyclin B1 is indispensable for tumor growth in vivo. Conclusion Our data support the notion of cyclin B1 being essential for survival and proliferation of gynecological cancer cells. Concordantly, knockdown of cyclin B1 inhibits proliferation in vitro as well as in vivo. Moreover, targeting cyclin B1 sensitizes breast cancer cells to taxol, suggesting that specific cyclin B1 targeting is an attractive strategy for the combination with conventionally used agents in gynecological cancer therapy

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

Informing patients about intermittent urinary catheterization in transcultural patient-nurse interactions

Summary: The aim of this study was to explore the methods of informing patients about intermittent urinary catheterization performed by a nurse who has a different cultural background than the patient. It was vital to find out beneficial methods of providing information to the patients and how to consider the patient’s cultural background in this process. The theoretical framework used in this study was Joyce Newman Giger and Ruth Davidhizar’s (2008) “Transcultural Assessment Model”. The study pointed out that difficulties appear in the intermittent urinary catheterization information provision if there is no common language between the patient and the nurse, since written materials and IT-based program information is always combined with oral interaction. Therefore, the communication difficulties were the most significant result of the study. Cultural awareness among nurses enhances the nurses’ ability to provide culturally competent care

US-PRC technology transfer through joint venture : a case study of China/Tech

M.S.John R. McIntyr

Takayasu arteritis presenting with massive cerebral ischemic infarction in a 35-year-old woman: a case report

INTRODUCTION: Takayasu arteritis is a relatively rare type of large-vessel arteritis that primarily affects the aorta and its major branches, the coronary arteries, and the pulmonary arteries. Depending on the different groups of blood vessels involved in the disease process, the clinical presentation of Takayasu arteritis varies. Here we report a case of a woman presenting with a debilitating massive cerebral ischemic infarct that turned out to be a relatively rare first presentation of Takayasu arteritis. CASE PRESENTATION: A 35-year-old Chinese woman presented to the Emergency Department with left hemiparesis, pain and numbness of her arms and weak radial pulses. Her laboratory results showed an elevated C-reactive protein and erythrocyte sedimentation rate, and subsequent digital subtraction angiography demonstrated narrowing and occlusion of the major branches of her aortic arch. We report the case of a patient with Takayasu arteritis presenting with a massive cerebral ischemic infarct and review the current literature on this topic. CONCLUSION: Takayasu arteritis is a relatively rare disease with various and sometimes devastating clinical manifestations, such as massive cerebral ischemic infarction as in our case. Currently, there are multiple diagnostic tools and treatment options available, and more under investigation. Early, appropriate diagnosis and initiation of proper therapy could avoid further progression and reduce complications of the disease