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The long-lasting infection of high-risk type (type 16 or type 18) human papillomavirus (HPV) is the main cause of gynecological and urinary malignancies. Given the high mortality rate after surgery, the development of a new molecular therapy would be of value to clinicians. The aim of the present study was to achieve targeted inactivation of the viral E6 gene in keratinocytes using the reprogrammed CRISPR-Cas13a system. To accomplish this, a reprogrammed CRISPR-Cas13a system, targeting both the HPV16/18 E6 genes was constructed using a guide RNA expressing vector. The expression levels of E6 protein were measured using western blot analysis after transfection of the vector into E6-transformed keratin oocytes. Cell proliferation was analyzed using CCK-8 assays and cell apoptosis was evaluated using Hoechst 33258 staining and ELISAs examining caspase-3 levels. The results indicated that both the HPV16/18 E6 genes can be inactivated using the CRISPR-Cas13a system. Furthermore, silencing E6 inhibited cell proliferation (14±1.8% on average) and induced apoptosis (80.2±3.2% on average) in E6-transformed keratinocytes but not in normal keratinocytes. In conclusion, results of the present study demonstrate that the reprogrammed CRISPR-Cas13a system has the potential for inactivating HPV E6 gene functions. [ABSTRACT FROM AUTHOR]

Introduction: Hyaluronic acid (HA) fillers, popular for facial cosmetic enhancements, pose risks of vascular complications like skin necrosis due to arterial blockage, necessitating effective treatments such as hyperbaric oxygen therapy (HBOT)., Methodology: This study presents a series of cases where measurements of transcutaneous oxygen pressure (TcPO 2 ) informed the application of HBOT for skin necrosis induced by HA., Clinical Presentation and Outcomes: In cases 1 and 3, following the injection of HA, potential skin necrosis was observed. In addition to standard treatment, TcPO 2 revealed values below 40 mmHg, indicating tissue hypoxia. Treatment with HBOT increased TcPO 2 levels to above 200 mmHg, suggesting that HBOT could correct the hypoxia. Monitoring TcPO 2 levels also aided in determining the optimal time to discontinue HBOT. In cases 2 and 4, patients received standard treatment, resulting in TcPO 2 levels above 40 mmHg, indicating adequate tissue oxygenation, and no additional HBOT was administered. All four patients mentioned above showed good clinical recovery., Conclusion: This study investigates the application of TcPO 2 measurement technology in aiding decisions on whether to utilize HBOT in the treatment of complications arising from HA fillers, as well as in optimizing HBOT protocols., Competing Interests: The authors report no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Neuronal intranuclear inclusion disease (NIID) is a rare chronic progressive neurodegenerative disease, with complex and diverse clinical manifestations and pathological eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous systems and visceral organs. Improvements in diagnostic methods such as skin biopsy and gene testing are helpful in revealing the clinical and genetic characters of NIID., Materials and Methods: We presented two cases of NIID diagnosed by using NOTCH2NLC gene testing and skin biopsy. Diffusion weighted imaging (DWI) showed high linear intensity in corticomedullary junction. We also reviewed all the published NIID cases with positive NOTCH2NLC GGC repeat expansion and skin biopsy results in PubMed., Results: Patient 1 was a 63-year-old male who carried 148 GGC repeats and presented with progressive tremor and limb weakness. Patient 2 was a 62-year-old woman who carried 131 GGC repeats and presented with tremors, memory loss and headaches. The most common clinical manifestation of 63 NIID patients in this study was cognitive impairment, followed by tremors. In our study, almost all the patients were from East Asia, the male to female ratio was 1:1.26, with an age of onset of 54.12 ± 14.12 years, and an age of diagnosis of 60.03 ± 12.21 years. Symmetrical high signal intensity at the corticomedullary junction on DWI were revealed in 80.96% of the patients. For the GGC repeat numbers, the majority of GGC repeats were in the 80-119 intervals, with few GGC repeats above 160. The number of GGC repetitions was significantly higher in patients presented with muscle weakness than in other clinical manifestations., Conclusion: NIID is a neurodegenerative disease caused by aberrant polyglycine (polyG) protein aggregation. NIID mostly occurs in the elderly population in East Asia, with cognitive dysfunction as the most common symptom. Staging NIID based on clinical presentation is inappropriate because most patients with NIID have overlapping symptoms. In our study, there was no significant correlation between the number of GGC repeats and different phenotypes except for muscle weakness. Abnormal trinucleotides repeat and PolyG protein aggregation maybe common pathogenic mechanism in neurodegenerative diseases and cerebrovascular diseases, which needs to be confirmed by more studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhao, Yang, Wang, Yang, Zhang, Qi, Pan and Yu.)

We demonstrate that α-aryl cyclic vinylogous esters are competent substrates in the direct intermolecular Pd-catalyzed asymmetric allylic alkylation, enabling a straightforward enantioselective synthesis of 6-allyl-6-aryl-3-ethoxycyclohex-2-en-1-ones, common motifs embedded in numerous structurally diverse natural products. As an initial demonstration of the utility of this protocol, the first catalytic enantioselective total synthesis of (+)-oxomaritidine and an improved five-step catalytic enantioselective synthesis of (-)-mesembrine have been completed divergently.