Current Status of Radical Cystectomy on High-risk Nonmuscle Invasive Bladder Cancer

Nonmuscle invasive bladder cancer (NMIBC) is mainly composed of three different types of tumors: papillary urothelial carcinoma is limited to the mucosal layer (Ta), high-grade carcinoma in situ is limited to the epithelial layer (CIS) and tumors invading the submucosa or lamina propria (T1). The standard treatment for NMIBC is complete transurethral resection of bladder tumors (TURBT) with or without intravesical instillation therapies. However, some high-risk patients are at risk of tumor progression and therefore require more aggressive treatment. Studies have reported that delayed cystectomy can lead to a significant reduction in survival benefits. Therefore, for these NMIBC patients who are at high risk of disease progression, when to abandon conservative treatment and choose cystectomy is one of the biggest challenges. This article reviews the current application status and future directions of radical cystectomy as the initial treatment on NMIBC patients

Research and experiment of a current-limiting HVDC circuit breaker

Existing mechanical HVDC circuit breakers (CB) are capable of interrupting HVDC currents within several tens of milliseconds, but this is too slow to satisfy the requirements of a reliable HVDC grid. HVDC CB based on semiconductors can easily overcome the limitations of operating speed, but need large number of the series (parallel) connection of electronic switching devices. To overcome these shortcomings, this paper introduces a topology of hybrid CB; this paper first describes the principle of hybrid CB; then a control strategy of fault pre-treatment is also proposed, that is, the ‘pre-action and action (or recovery)’ of the switches, in order to improve the breaking speed of the hybrid CB and the equalising circuit of its solid-state switch has been designed. The proposed topology and control strategy do not produce loss in the normal operation of CB, and instantaneous trigger solid-state switch with quickly cutting short-circuit current during short-circuit faults; at last the simulation and experiment of the hybrid HVDC CB have also been done. The results turn out when a short circuit occurs, the hybrid HVDC CB can quickly break the short-circuit current; the buffer circuit can be provided for the release of the stored energy circuit

DNA Phosphorothioate Modification Plays a Role in Peroxides Resistance in Streptomyces lividans

DNA phosphorothioation, conferred by dnd genes, was originally discovered in the soil-dwelling bacterium Streptomyces lividans, and thereafter found to exist in various bacterial genera. However, the physiological significance of this sulfur modification of the DNA backbone remains unknown in S. lividans. Our studies indicate that DNA phosphorothioation has a major role in resistance to oxidative stress in the strain. Although Streptomyces species express multiple catalase/peroxidase and organic hydroperoxide resistance genes to protect them against peroxide damage, a wild type strain of S. lividans exhibited two-fold to 10-fold higher survival, compared to a dnd- mutant, following treatment with peroxides. RNA-seq experiments revealed that, catalase and organic hydroperoxide resistance gene expression were not up-regulated in the wild type strain, suggesting that the resistance to oxidative stress was not due to the up-regulation of these genes by DNA phosphorothioation. Quantitative RT-PCR analysis was conducted to trace the expression of the catalase and the organic hydroperoxide resistance genes after peroxides treatments. A bunch of these genes were activated in the dnd- mutant rather than the wild type strain in response to peroxides. Moreover, the organic hydroperoxide peracetic acid was scavenged more rapidly in the presence than in the absence of phosphorothioate modification, both in vivo and in vitro. The dnd gene cluster can be up-regulated by the disulfide stressor diamide. Overall, our observations suggest that DNA phosphorothioate modification functions as a peroxide resistance system in S. lividans

Unraveling shared risk factors for diabetic foot ulcer: a comprehensive Mendelian randomization analysis

Introduction Diabetic foot ulcer (DFU) stands as a severe diabetic lower extremity complication, characterized by high amputation rates, mortality, and economic burden. We propose using Mendelian randomization studies to explore shared and distinct risk factors for diabetic lower extremity complications.Research design and methods We selected uncorrelated genetic variants associated with 85 phenotypes in five categories at the genome-wide significance level as instrumental variables. Genetic associations with DFU, diabetic polyneuropathy (DPN), and diabetic peripheral artery disease (DPAD) were obtained from the FinnGen and UK Biobank studies.Results Body mass index (BMI) emerged as the only significant risk factor for DPAD, DPN, and DFU, independent of type 2 diabetes, fasting glucose, fasting insulin, and HbA1c. Educational attainment stood out as the sole significant protective factor against DPAD, DPN, and DFU. Glycemic traits below the type 2 diabetes diagnosis threshold showed associations with DPAD and DPN. While smoking history exhibited suggestive associations with DFU, indicators of poor nutrition, particularly total protein, mean corpuscular hemoglobin, and mean corpuscular volume, may also signal potential DFU occurrence.Conclusions Enhanced glycemic control and foot care are essential for the diabetic population with high BMI, limited education, smoking history, and indicators of poor nutrition. By focusing on these specific risk factors, healthcare interventions can be better tailored to prevent and manage DFU effectively

S100A9-/- alleviates LPS-induced acute lung injury by regulating M1 macrophage polarization and inhibiting pyroptosis via the TLR4/MyD88/NFκB signaling axis

Acute lung injury (ALI) is characterized by pulmonary diffusion abnormalities that may progress to multiple-organ failure in severe cases. There are limited effective treatments for ALI, which makes the search for new therapeutic avenues critically important. Macrophages play a pivotal role in the pathogenesis of ALI. The degree of macrophage polarization is closely related to the severity and prognosis of ALI, and S100A9 promotes M1 polarization of macrophages. The present study assessed the effects of S100A9-gene deficiency on macrophage polarization and acute lung injury. Our cohort study showed that plasma S100A8/A9 levels had significant diagnostic value for pediatric pneumonia and primarily correlated with monocyte-macrophages and neutrophils. We established a lipopolysaccharide (LPS)-induced mouse model of acute lung injury and demonstrated that knockout of the S100A9 gene mitigated inflammation by suppressing the secretion of pro-inflammatory cytokines, reducing the number of inflammatory cells in the bronchoalveolar lavage fluid, and inhibiting cell apoptosis, which ameliorated acute lung injury in mice. The in vitro and in vivo mechanistic studies demonstrated that S100A9-gene deficiency inhibited macrophage M1 polarization and reduced the levels of pulmonary macrophage chemotactic factors and inflammatory cytokines by suppressing the TLR4/MyD88/NF-κB signaling pathway and reversing the expression of the NLRP3 pyroptosis pathway, which reduced cell death. In conclusion, S100A9-gene deficiency alleviated LPS-induced acute lung injury by inhibiting macrophage M1 polarization and pyroptosis via the TLR4/MyD88/NFκB pathway, which suggests a potential therapeutic strategy for the treatment of ALI

LncRNAs Expression Signatures of Renal Clear Cell Carcinoma Revealed by Microarray

<div><h3>Background</h3><p>Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. They are aberrantly expressed in many types of cancers. In this study, we described lncRNAs profiles in 6 pairs of human renal clear cell carcinoma (RCCC) and the corresponding adjacent nontumorous tissues (NT) by microarray.</p> <h3>Methodology/Principal Findings</h3><p>With abundant and varied probes accounting 33,045 LncRNAs in our microarray, the number of lncRNAs that expressed at a certain level could be detected is 17157. From the data we found there were thousands of lncRNAs that differentially expressed (≥2 fold-change) in RCCC tissues compared with NT and 916 lncRNAs differentially expressed in five or more of six RCCC samples. Compared with NT, many lncRNAs were significantly up-regulated or down-regulated in RCCC. Our data showed that down-regulated lncRNAs were more common than up-regulated ones. ENST00000456816, X91348, BC029135, NR_024418 were evaluated by qPCR in sixty-three pairs of RCCC and NT samples. The four lncRNAs were aberrantly expressed in RCCC compared with matched histologically normal renal tissues.</p> <h3>Conclusions/Significance</h3><p>Our study is the first one to determine genome-wide lncRNAs expression patterns in RCCC by microarray. The results displayed that clusters of lncRNAs were aberrantly expressed in RCCC compared with NT samples, which revealed that lncRNAs differentially expressed in tumor tissues and normal tissues may exert a partial or key role in tumor development. Taken together, this study may provide potential targets for future treatment of RCCC and novel insights into cancer biology.</p> </div