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Human mitochondrial DNA (mtDNA) encodes 37 essential genes and plays a critical role in mitochondrial and cellular functions. mtDNA is susceptible to damage by endogenous and exogenous chemicals. Damaged mtDNA molecules are counteracted by the redundancy, repair, and degradation of mtDNA. In response to difficult-to-repair or excessive amounts of DNA lesions, mtDNA degradation is a crucial mitochondrial genome maintenance mechanism. Nevertheless, the molecular basis of mtDNA degradation remains incompletely understood. Recently, mitochondrial transcription factor A (TFAM) has emerged as a factor in degrading damaged mtDNA containing abasic (AP) sites. TFAM has AP-lyase activity, which cleaves DNA at AP sites. Human TFAM and its homologs contain a higher abundance of Glu than that of the proteome. To decipher the role of Glu in TFAM-catalyzed AP-DNA cleavage, we constructed TFAM variants and used biochemical assays, kinetic simulations, and molecular dynamics (MD) simulations to probe the functional importance of E187 near a key residue K186. Our previous studies showed that K186 is a primary residue to cleave AP-DNA via Schiff base chemistry. Here, we demonstrate that E187 facilitates β-elimination, key to AP-DNA strand scission. MD simulations showed that extrahelical confirmation of the AP lesion and the flexibility of E187 in TFAM-DNA complexes facilitate AP-lyase reactions. Together, highly abundant Lys and Glu residues in TFAM promote AP-DNA strand scission, supporting the role of TFAM in AP-DNA turnover and implying the breadth of this process across different species.

In higher eukaryotes, mitochondria play multiple roles in energy production, signaling, and biosynthesis. Mitochondria possess multiple copies of mitochondrial DNA (mtDNA), which encodes 37 genes that are essential for mitochondrial and cellular function. When mtDNA is challenged by endogenous and exogenous factors, mtDNA undergoes repair, degradation, and compensatory synthesis. mtDNA degradation is an emerging pathway in mtDNA damage response and maintenance. A key factor involved is the human mitochondrial genome maintenance exonuclease 1 (MGME1). Despite previous biochemical and functional studies, controversies exist regarding the polarity of MGME1-mediated DNA cleavage. Also, how DNA sequence may affect the activities of MGME1 remains elusive. Such information is not only fundamental to the understanding of MGME1 but critical for deciphering the mechanism of mtDNA degradation. Herein, we use quantitative assays to examine the effects of substrate structure and sequence on the DNA-binding and enzymatic activities of MGME1. We demonstrate that MGME1 binds to and cleaves from the 5'-end of single-stranded DNA substrates, especially in the presence of 5'-phosphate, which plays an important role in DNA binding and optimal cleavage by MGME1. In addition, MGME1 tolerates certain modifications at the terminal end, such as a 5'-deoxyribosephosphate intermediate formed in base excision repair. We show that MGME1 processes different sequences with varying efficiencies, with dT and dC sequences being the most and least efficiently digested, respectively. Our results provide insights into the enzymatic properties of MGME1 and a rationale for the coordination of MGME1 with the 3'-5' exonuclease activity of DNA polymerase γ in mtDNA degradation.

ObjectiveTo analyze and compare the vestibular function of posterior canal cupulolithiasis and canalolithiasis.MethodsThe results of posterior cupulolithiasis in 45 cases, posterior canalolithiasis in 122 cases and 19 healthy controls were analyzed retrospectively.ResultsThe abnormal rates of vHIT in the canalolithiasis group and the cupulolithiasis group were 42.6 and 37.8%, respectively, both higher than those in the control group (both p 0.05). 84.4% of canalolithiasis and 65.0% of cupulolithiasis had abnormal VEMP results, with no significant differences in abnormality rates or sides (both p > 0.05). Abnormal results of VEMPs did not show any correlation with side (p > 0.05). The results of pc-ca and pc-cu were both abnormal in 14 cases and 7 cases, and there was no correlation between the site and side of the injury (all p > 0.05).ConclusionThe results of vHIT and VEMP in pc-cu and pc-ca were partially abnormal, but they did not show any correlation with side of BPPV. It can be considered that there are scattered vestibular peripheral organ damage in both groups.

In higher eukaryotic cells, mitochondria are essential subcellular organelles for energy production, cell signaling, and the biosynthesis of biomolecules. The mitochondrial DNA (mtDNA) genome is indispensable for mitochondrial function because it encodes protein subunits of the electron transport chain and a full set of transfer and ribosomal RNAs. MtDNA degradation has emerged as an essential quality control measure to maintain mtDNA and to cope with mtDNA damage resulting from endogenous and environmental factors. Among all types of DNA damage known, abasic (AP) sites, sourced from base excision repair and spontaneous base loss, are the most abundant endogenous DNA lesions in cells. In mitochondria, AP sites trigger rapid DNA loss; however, the mechanism and molecular factors involved in the process remain elusive. Herein, we demonstrate that the stability of AP sites is reduced dramatically upon binding to a major mtDNA packaging protein, mitochondrial transcription factor A (TFAM). The half-life of AP lesions within TFAM-DNA complexes is 2 to 3 orders of magnitude shorter than that in free DNA, depending on their position. The TFAM-catalyzed AP-DNA destabilization occurs with nonspecific DNA or mitochondrial light-strand promoter sequence, yielding DNA single-strand breaks and DNA-TFAM cross-links. TFAM-DNA cross-link intermediates prior to the strand scission were also observed upon treating AP-DNA with mitochondrial extracts of human cells. In situ trapping of the reaction intermediates (DNA-TFAM cross-links) revealed that the reaction proceeds via Schiff base chemistry facilitated by lysine residues. Collectively, our data suggest a novel role of TFAM in facilitating the turnover of abasic DNA.

Background and purpose: Pancreatic neuroendocrine tumor (pNET) is a rare tumor. At present, there is still a lack of large-scale clinical research data to summarize the clinical effect of minimally invasive technology in the treatment of pNET. This study analyzed the clinical data of pNET patients undergoing surgical treatment, in order to provide reference for the surgical treatment of pNET. Methods: The clinical data of 118 patients with well-differentiated pNET undergoing minimally invasive surgery admitted by the Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center from September 2018 to July 2022 were retrospectively analyzed. The patients were divided into robot group (n=17) and laparoscopic group (n=101) according to the minimally invasive operation mode. According to the surgical resection mode, they were divided into regular resection group (n=86) and local resection group (n=32). The clinical data of operation and postoperation were collected and analyzed. Results: Of the 118 patients who underwent minimally invasive surgery on pNET included in this study, 17 were in the robot group, and 101 were in the laparoscopic group. There were 32 cases in local resection group and 86 cases in regular resection group. There was no significant difference between robot group and laparoscopic group in operation time and intraoperative bleeding (P>0.05). The operation time of local resection group [(145.3±55.5) min] was significantly shorter compared with regular resection group [(247.4±94.7) min](P 0.05). The incidence of postoperative b-pancreatic fistula was higher in the local resection group than in the regular resection group (P

Resource management is an important part of nursing management. Nursing team management will directly affect the stability of the nursing team, and then affect the overall development of the hospital. In recent years, with the development of modern medical technology and changes in the hospital environment, private hospitals are under increasing pressure, and the shortage of resources for nurses in private hospitals is becoming increasingly prominent. In this paper, the dynamic management of nursing resource recruitment, with the purpose of a full range of training and transfer the nurse resources rationally, to achieve the optimal use, the optimal distribution and optimal service, thereby alleviating the deficiency of nursing resource in private hospitals, improve the ability of handling emergency manpower deployment, improve nurses' satisfaction and patient satisfaction, improve service quality, eventually improve the market competitiveness, improve the efficiency of the hospital. (人力资源管理是护理管理的重要组成部分, 护理队伍的管理将直接影响护理团队的稳定性, 进而影响医院的整体发展。随着现代医学技术的发展和就医环境的变化, 私立医院护士人力资源短缺问题日益突出。本文总结了动态人力资源管理在私立医院护理管理中的应用经验, 通过护理人力资源的动态管理进行有目的的招聘、全方位的培训、合理调动护士资源, 达到最优使用、最优分配、最优服务, 进而缓解私立医院护理人力资源的不足, 提高应急人力调配处理能力, 提高护士满意度和患者满意度, 提升服务质量, 最终提高市场竞争力。)