METHODS: Cell counting kit 8(CCK8), 5-ethynyl-2'-deoxyuridine (EdU), transwell and wound healing assays were conducted to study the influence of ZnC in the proliferating, invading and migrating processes of CRC cell lines (HCT116, LOVO) in vitro. The antitumor activity ZnC as well as its effects on tumor immune microenvironment were then assessed using CRC subcutaneous tumors in the C57BL/6 mouse model.
RESULTS: According to CCK8, EdU, transwell and wound healing assays, ZnC inhibited CRC cell lines in terms of proliferation, invasion and migration. ZnC could inhibit miR-570 for up-regulating PD-L1 expression. In vivo experiments showed that gavage (100 mg/kg, once every day) of ZnC inhibited the tumor growth of CRC, and the combination of ZnC and anti-PD1 therapy significantly improved the efficacy exhibited by anti-PD1 in treating CRC. In addition, mass cytometry results showed that immunosuppressive cells including regulatory T cells (tregs), bone marrow-derived suppressor cells (MDSC), and M2 macrophages decreased whereas CD8+ T cells elevated after adding ZnC.
CONCLUSIONS: The present study reveals that ZnC slows the progression of CRC by inhibiting CRC cells in terms of proliferation, invasion and migration, meanwhile up-regulating PD-L1 expression via inhibiting miR-570. The ZnC-anti-PD1 co-treatment assists in synergically increasing anti-tumor efficacy in CRC therapy.
RESULTS: In this study, phylogeography of a mangrove tree Sonneratia alba was studied by sequencing three chloroplast fragments and seven nuclear genes. A low level of genetic diversity at the population level was detected across its range, especially at the range margins, which was mainly attributed to the steep sea-level drop and associated climate fluctuations during the Pleistocene glacial periods. Extremely small effective population size (Ne) was inferred in populations from both eastern and western Malay Peninsula (44 and 396, respectively), mirroring the fragility of mangrove plants and their paucity of robustness against future climate perturbations and human activity. Two major genetic lineages of high divergence were identified in the two mangrove biodiversity centres: the Indo-Malesia and Australasia regions. The estimated splitting time between these two lineages was 3.153 million year ago (MYA), suggesting a role for pre-Pleistocene events in shaping the major diversity patterns of mangrove species. Within the Indo-Malesia region, a subdivision was implicated between the South China Sea (SCS) and the remaining area with a divergence time of 1.874 MYA, corresponding to glacial vicariance when the emerged Sunda Shelf halted genetic exchange between the western and eastern coasts of the Malay Peninsula during Pleistocene sea-level drops. Notably, genetic admixture was observed in populations at the boundary regions, especially in the two populations near the Malacca Strait, indicating secondary contact between divergent lineages during interglacial periods. These interregional genetic exchanges provided ample opportunity for the re-use of standing genetic variation, which could facilitate mangrove establishment and adaptation in new habitats, especially in the context of global climate changes.
CONCLUSION: Phylogeogrpahic analysis in this study reveal that Pleistocene sea-level fluctuations had profound influence on population differentiation of the mangrove tree S. alba. Our study highlights the fragility of mangrove plants and offers a guide for the conservation of coastal mangrove communities experiencing ongoing changes in sea-level.
RESULTS: Restriction-site associated DNA sequencing (RAD-seq) was employed to isolate sex-specific SNP markers for S. paramamosain. A total of 335.6 million raw reads were obtained from 20 individuals, of which 204.7 million were from 10 females and 130.9 million from 10 males. After sequence assembly and female-male comparison, 20 SNP markers were identified to be sex-specific. Furthermore, ten SNPs in a short sequence (285 bp) were confirmed heterozygous in females and homozygous in males in a large population by PCR amplification and sequencing. Subsequently, a female-specific primer was successfully designed according to the female-specific nucleotide which could amplify an expected band from females but not from males. Thus, a rapid and effective method for molecular sexing in S. paramamosain was developed, meanwhile, this method could successfully identify the sex of S. tranquebarica and S. serrata. Finally, nine and four female-specific SNP markers were detected in S. tranquebarica and S. serrata, respectively.
CONCLUSIONS: Sex-specific SNP markers were firstly identified in crab species and showed female heterogamety and male homogamety, which provided strong genetic evidence for a WZ/ZZ sex determination system in mud crabs S. paramamosain, S. tranquebarica and S. serrata. These findings will lay a solid foundation for the study of sex determination mechanism, sex chromosome evolution, and the development of mono-sex population in crustaceans.
OBJECTIVE: This research aims to determine factors influencing students' behavioural intention to use Rain Classroom.
METHODS: In this cross-sectional and correlational investigation, 1138 medical students from five medical universities in Guangxi Province, China, made up the sample. This study added self-efficacy (SE), motivation (MO), stress (ST), and anxiety (AN) to the UTAUT framework. This study modified the framework by excluding actual usage variables and focusing only on intention determinants. SPSS-26 and AMOS-26 were used to analyze the data. The structural equation modelling technique was chosen to confirm the hypotheses.
RESULTS: Except for facilitating conditions (FC), all proposed factors, including performance expectancy (PE), effort expectancy (EE), social influence (SI), self-efficacy (SE), motivation (MO), anxiety (AN), and stress (ST), had a significant effect on students' behavioural intentions to use Rain Classroom.
CONCLUSIONS: The research revealed that the proposed model, which was based on the UTAUT, is excellent at identifying the variables that influence students' behavioural intentions in the Rain Classroom. Higher education institutions can plan and implement productive classrooms.
METHODS: Multistage sampling was used to recruit registered nurses from Hunan province in China. Registered nurses who identified themselves as experiencing adverse events from nine tertiary hospitals were included in this study. Participants were recruited to complete a survey on the second victim experience and support tool, the simplified coping style questionnaire, and the professional quality of life scale. The stress coping theory was used to develop the framework in this study. The structural equation modelling approach was used for conducting the mediating effects analysis via IBM SPSS Statistics 26.0 and Mplus 8.3.
RESULTS: In total, 67% (n = 899) of nurses reported a second victim experience during their careers. In a bivariate analysis, both second-victims experiences and coping styles were significantly associated with their professional quality of life. The results showed that the effects of second victim experiences on their professional quality of life were fully mediated by coping styles. A total of 10 significantly indirect pathways were estimated, ranging from -0.243 to 0.173.
CONCLUSIONS: Second-victim experiences are common among nurses in this study. Since the mediating effects of coping styles were clarified in this study, it is imperative to promote the perception of negative coping styles and encourage nurses to adopt more positive coping styles with adequate support systems.
METHODS: We define effective vaccine coverage (EVC) of measles as the proportion of a population vaccinated with measles-containing vaccine (MCV) and effectively protected against measles infection. A quantitative evaluation of EVC throughout the life course of Malaysian birth cohorts was conducted accounting for both vaccine efficacy (VE) and between-dose correlation (BdC). Measles vaccination coverage was sourced from WHO-UNICEF estimates of Malaysia's routine immunisation coverage and supplementary immunisation activities (SIAs). United Nations World population estimates and projections (UNWPP) provided birth cohort sizes stratified by age and year. A step wise joint Bernoulli distribution was used to proportionate the Malaysian population born between 1982, the first year of Malaysia's measles vaccination programme, and 2021, into individuals who received zero dose, one dose and multiple doses of MCV. VE estimates by age and doses received are then adopted to derive EVC. A sensitivity analysis was conducted using 1000 random combinations of BdC and VE parameters.
RESULTS: This study suggests that no birth cohort in the Malaysian population has achieved > 95% population immunity (EVC) conferred through measles vaccination since the measles immunisation programme began in Malaysia.
CONCLUSION: The persistence of measles in Malaysia is due to pockets of insufficient vaccination coverage against measles in the population. Monitoring BdC through immunisation surveillance systems may allow for the identification of susceptible subpopulations (primarily zero-dose MCV individuals) and increase the coverage of individuals who are vaccinated with multiple doses of MCV. This study provides a tool for assessment of national-level population immunity of measles conferred through vaccination and does not consider subnational heterogeneity or vaccine waning. This tool can be readily applied to other regions and vaccine-preventable diseases.
RESEARCH DESIGN AND METHODS: 71 children with diabetes mellitus (43 diagnosed before 6 months of age, and 28 diagnosed between 6 months and 3 years of age who were negative for diabetes-associated autoantibodies) underwent genetic testing with a combination strategy of Sanger sequencing, chromosome microarray analysis and whole exome sequencing. They were categorized into four groups according to the age of onset of diabetes (at or less than 6 months, 6 to 12 months, 1 to 2 years, 2 to 3 years) to investigate the correlation between genotype and phenotype.
RESULTS: Genetic abnormalities were identified in 39 of 71 patients (54.93%), namely KCNJ11 (22), ABCC8 (3), GCK (3), INS (3), BSCL2 (1) and chromosome abnormalities (7). The majority (81.40%, 35/43) of neonatal diabetes diagnosed less than 6 months of age and 33.33% (3/9) of infantile cases diagnosed between 6 and 12 months of age had a genetic cause identified. Only 11.11% (1/9) of cases diagnosed between 2 and 3 years of age were found to have a genetic cause, and none of the 10 patients diagnosed between 1 and 2 years had a positive result in the genetic analysis. Vast majority or 90.48% (19/21) of patients with KCNJ11 (19) or ABCC8 (2) variants had successful switch trial from insulin to oral sulfonylurea.
CONCLUSIONS: This study suggests that genetic testing should be given priority in diabetes cases diagnosed before 6 months of age, as well as those diagnosed between 6 and 12 months of age who were negative for diabetes-associated autoantibodies. This study also indicates significant impact on therapy with genetic cause confirmation.