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Lassa virus (LASV) is an enveloped, negative-sense RNA virus that causes Lassa hemorrhagic fever. Successful entry of LASV requires the viral glycoprotein 1 (GP1) to undergo a receptor switch from its primary receptor alpha-dystroglycan (α-DG) to its endosomal receptor lysosome-associated membrane protein 1 (LAMP1). A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor switch. To test the hypothesis that other non-conserved residues also contribute to receptor switch, we constructed a series of mutant LASV GP1 proteins and tested them for binding to LAMP1. Four residues, L84, K88, L107, and H170, were identified as critical for receptor switch. Substituting any of the four residues with the corresponding lymphocytic choriomeningitis virus (LCMV) residue (L84 âN, K88E, L10F, and H170S) reduced the binding affinity of LASV GP1 for LAMP1. Moreover, all mutations caused decreases in glycoprotein precursor (GPC)-mediated membrane fusion at both pH 4.5 and 5.2. The infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types, while L107F and H170S had only mild effects on infectivity. Using biolayer light interferometry assay, we found that all four mutants had decreased binding affinity to LAMP1, in the order of binding affinity being L84 âN â> âL107F â> âK88E â> âH170S. The four amino acid loci identified for the first time in this study have important reference significance for the in-depth investigation of the mechanism of receptor switching and immune escape of LASV occurrence and the development of reserve anti-LASV infection drugs.
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Objective: Pyriform fossa (PF) branchial apparatus anomalies (PFBAA) are rare congenital third or fourth branchial apparatus anomalies (TBAA or FBAA). This article summarizes our paradigm in managing this condition by combining endoscopic procedures and open neck surgery. Methods: A retrospective review was undertaken concerning PFBAA cases treated at our tertiary medical institution between July 2020 and November 2023. Data were collected from case records. Three sequential steps were implemented: (1) direct laryngoscopy to identify internal orifice (IO), with injection of methylene blue into it; (2) open neck surgery to resect all inflammatory tissues, focusing on the ligation of the sinus tract out of PF; and (3) plasma coblation of IO mucosa. Results: In total, 7 cases (4 men and 3 women) were included (28-67 years old, median age 53). Presenting symptoms were various, with 6 lesions on the left and 1 on the right side. Preoperative (PO) fiberoptic laryngoscopy identified IO in 6 patients, while PO barium esophageal study identified outflow from PF in 4 patients. A preliminary diagnosis of PFBAA could be established in all cases (2 TBAA and 5 FBAA cases). Direct laryngoscopy after general anesthesia identified IO in all cases (2 on the base of PF and 5 on the apex of PF). All the surgical procedures were successful, with uneventful recovery in all the patients. No postoperative complications were observed. All the patients resumed oral fluid intake after confirmation of no pharyngeal fistula by barium esophageal study on the seventh postoperative day. The duration of follow-up was between 6 and 40 months (with a median duration of 27 months). No recurrence was observed. Conclusion: Open neck surgery, assisted by endoscopic dyeing of sinus tracts and plasma coblation of IO mucosa, is a suitable treatment for PFBAA in adults. This paradigm is effective and safe for senior surgeons.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and its subvariants (such as BQ.1, XBB and the latest variants, including XBB.1.16, EG.5, and BA.2.86), as the dominant variants, currently account for almost all new infections in the world due to their high transmissibility and immune escape ability. Omicron-specific mRNA vaccines showed great potential to protect against Omicron infections. However, whether the vaccine could provide long-term protection is unknown. Toward this goal, we evaluated the immunogenicity of a preclinical Omicron (BA.1)-specific mRNA vaccine (SOmicron-6P) in different animal models. SOmicron-6P induced the highest levels of antibody titers at 1-2 weeks in different animals after the second dose. Even 9 months after the immunization, we observed modest neutralizing activity against Omicron subvariants in macaques. In addition, immunological memory cells can be rapidly reactivated upon stimulation. SOmicron-6P at concentrations higher than 10 µg effectively protected hamsters from BA.1 challenge 253 days after the first immunization, which could be attributed to the reactivation of immune systems. In addition, the toxicity tests conducted in rats revealed a highly favorable biosafety profile for SOmicron-6P, even at high dosages. Our data suggest that the Omicron-specific mRNA vaccine is highly effective and safe in animal models and provides long-term immunologic protection against SARS-CoV-2 Omicron infections.
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Background: Ischemic stroke has the characteristics of high morbidity, mortality, and recurrence rate. This study aimed to describe and assess the burden of ischemic stroke in Asia based on the global burden of disease (GBD) 2019 data and provide a crucial scientific foundation for the prevention and control of this life-threatening disease. Method: This study used the GBD 2019 data to assess the burden of ischemic stroke. The indicators used in this study were derived from the following methods: (i) the incidence of ischemic stroke was estimated using the disability model for the global burden of disease study-mixed effects regression (DisMod-MR), a Bayesian meta-regression disease modeling tool; (ii) the non-specific codes of all available data on mortality were corrected and used to estimate mortality rates for ischemic stroke and the cause of death ensemble model was used to estimate mortality rates; and (iii) the disability-adjusted life years (DALYs) is the sum of years lived with disability (YLD) and the years of life lost (YLL), which quantifies the health loss due to specific diseases and injuries. In addition, the joinpoint regression model was adopted to analyze the temporal trend of ischemic stroke from 1990 to 2019 in Asia. Result: This study found an increase in the burden of ischemic stroke in 2019 compared to 1990. Moreover, the age-standardized incidence rate (ASIR) of ischemic stroke showed a gradual upward trend over the specific period. The age-standardized mortality rate (ASMR) showed a downward trend in Asia from 1990 to 2019. The burden of ischemic stroke was more concentrated on older age groups, particularly those older than 65 years. East Asia had the highest burden of ischemic stroke compared to other regions in Asia. Particularly, China, India, Indonesia, and Japan had the highest burdens of ischemic stroke among the Asian countries and regions. However, the population with the highest burden of ischemic stroke was still the elderly group. Conclusion: Based on our study, it is evident that the burden of ischemic stroke exists substantially and exhibits variations in the aspects of age, gender, and geographical region in Asia. Without targeted implementation of population-wide primary strategies for prevention and control, the burden of ischemic stroke is likely to worsen significantly in the future.
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Objective@#To investigate the status quo and causes of left behind children’s sexual problems and behaviors during puberty, and to provide relevant educational intervention strategies.@*Methods@#A total of 2 305 left-behind students from 3 township middle schools in Jinhu County, Huai'an were selected to send out questionnaires to understand their common sexual problems, sexual behaviors, assess to sexual knowledge, and help.@*Results@#About 30.02% of the respondents had menstruation/spermatorrhea trouble, 45.99% had acne trouble. 20.00% had early love confusion, 10.02% had masturbation confusion. The percentage of girls with early love confusion was higher than that of boys, and that of high school students was higher than that of junior high school students; the percentage of boys with masturbation confusion was higher than that of girls, and that of high school students was higher than that of junior high school students (P<0.05). 11.97% reported verbal harassment, 16.92% had been asked to fall in love, 10.02% had been kissed, 5.99% had been sexually touched, 1.00% had been forced to have sex, 17.01% had masturbation, 7.90% had same-sex sexual activities, 6.94% had sexual behaviors, and the proportion of girls who had been teased by speech, asked to fall in love, kissed and stroked was higher than that of boys, and the proportion of boys who had been stroked was higher than that of boys (P<0.05). The proportion of sexual intercourse, sexual activity and sexual behavior was higher than that of female (P<0.05). The proportion of high school students who had masturbation, homosexual activities and sexual behaviors was higher than that of middle school students (P<0.05). In terms of access to sexual knowledge, 43.99% through the school classroom, 35.01% through books, 23.99% through the Internet, 17.01% through parents and elders. Compared with boys, girls had higher proportion of acquiring sexual knowledge from books and parents’ elders, high school students have higher proportion of acquiring sexual knowledge from school classroom and books, junior high school students have higher proportion of acquiring sexual knowledge from parents’ elders (P<0.05). After the left behind children encountered sexual problems, 31.02% from the Internet/books, and 30.02% from their yellow videos/novels. Compared with boys, girls had higher proportion of seeking help from parents (P<0.05). Compared with high school students, junior high school students had higher proportion of seeking help from parents and teachers (P<0.05).@*Conclusion@#Adolescent left-behind children are generally confused about sexual physiology and their sexual behavior is relatively open. Schools and families need to strengthen sexual health education for left-behind children to help them form scientific and healthy sexual concepts and attitudes and resolve their sexual confusion.