Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study

BackgroundMultiple observational studies suggest a connection between the composition of the gut microbiota and hypothyroidism. However, it has yet to be determined whether the gut microbiota has a causal effect on hypothyroidism.MethodsTo investigate the connection between the gut microbiota and hypothyroidism, two-sample Mendelian randomization was performed using data from a genome-wide association study meta-analysis (n = 18,430) conducted by the MiBioGen consortium. Summary statistics for hypothyroidism (26,342 cases and 59,827 controls) were obtained using the data from the FinnGen consortium R8 release data. To investigate the causal link between the gut microbiota and hypothyroidism, various methods, including MR-Egger, weighted median, weighted model, simple model, MR-PRESSO, and inverse variance weighted (IVW), were employed. The bacteria that were causally linked to hypothyroidism in forward Mendelian randomization analysis were subjected to reverse Mendelian randomization analysis. Cochran’s Q statistics were utilized to gauge the heterogeneity of the instrumental variables.ResultsThe results indicated that Akkermansia had a positive impact on hypothyroidism, with an odds ratio of 0.84 (95% CI 0.74–0.95, p = 0.01) based on the inverse variance-weighted estimates. Additionally, Anaerostipes (OR = 1.17, 95% CI 1.01–1.36, p = 0.04), Butyrivibrio (OR = 0.93, 95% CI 0.88–0.99, p = 0.02), Holdemania (OR = 0.89, 95% CI 0.81–0.99, p = 0.03), Intestinimonas (OR = 1.13, 95% CI 1.02–1.26, p = 0.03), Ruminiclostridium5 (OR = 1.19, 95% CI 1.01–1.41, p = 0.04), and Ruminococcaceae UCG-011 (OR = 0.91, 95% CI 0.84–0.99, p = 0.03) were identified. The gut microbiota was not significantly affected by hypothyroidism, as indicated by the results of the reverse MR analysis. There was no significant variation in the instrumental variables or horizontal pleiotropy.ConclusionThe findings of this study using two-sample Mendelian randomization indicate a causal relationship between Akkermansia and hypothyroidism. Increased Akkermansia inhibits the onset and progression of hypothyroidism. Additional randomized controlled experiments are necessary to elucidate the beneficial impact of probiotics on hypothyroidism and their distinct protective mechanisms

PALMD regulates aortic valve calcification via altered glycolysis and NF-κB-mediated inflammation

Recent genome-wide association and transcriptome-wide association studies have identified an association between the PALMD locus, encoding palmdelphin, a protein involved in myoblast differentiation, and calcific aortic valve disease (CAVD). Nevertheless, the function and underlying mechanisms of PALMD in CAVD remain unclear. We herein investigated whether and how PALMD affects the pathogenesis of CAVD using clinical samples from CAVD patients and a human valve interstitial cell (hVIC) in vitro calcification model. We showed that PALMD was upregulated in calcified regions of human aortic valves and calcified hVICs. Furthermore, silencing of PALMD reduced hVIC in vitro calcification, osteogenic differentiation, and apoptosis, whereas overexpression of PALMD had the opposite effect. RNA-Seq of PALMD-depleted hVICs revealed that silencing of PALMD reduced glycolysis and nuclear factor-κB (NF-κB)–mediated inflammation in hVICs and attenuated tumor necrosis factor α–induced monocyte adhesion to hVICs. Having established the role of PALMD in hVIC glycolysis, we examined whether glycolysis itself could regulate hVIC osteogenic differentiation and inflammation. Intriguingly, the inhibition of PFKFB3-mediated glycolysis significantly attenuated osteogenic differentiation and inflammation of hVICs. However, silencing of PFKFB3 inhibited PALMD-induced hVIC inflammation, but not osteogenic differentiation. Finally, we showed that the overexpression of PALMD enhanced hVIC osteogenic differentiation and inflammation, as opposed to glycolysis, through the activation of NF-κB. The present study demonstrates that the genome-wide association– and transcriptome-wide association–identified CAVD risk gene PALMD may promote CAVD development through regulation of glycolysis and NF-κB–mediated inflammation. We propose that targeting PALMD-mediated glycolysis may represent a novel therapeutic strategy for treating CAVD

Effect of Enhanced Squeezing Needle Structure on the Jetting Performance of a Piezostack-Driven Dispenser.

Advanced dispensing technology is urgently needed to improve the jetting performance of fluid to meet the requirements of electronic product integration and miniaturization. In this work, an on-off valve piezostack-driven dispenser was used as a study object to investigate the effect of needle structure on jetting performance. Based on fluid dynamics, we investigated nozzle cavity pressure and jet velocity during the dispensing process using theoretical simulation for needles with and without a side cap. The results showed that the needle with a side cap had larger jet velocity and was capable of generating 8.27 MPa of pressure in the nozzle cavity, which was 2.39 times larger than the needle without a side cap. Further research on the influence of the nozzle and needle structural parameters showed that a nozzle conic angle of 85°-105°, needle conic angle of 10°-35°, and side clearance of 0.1-0.3 mm produced a dispenser with a large jet velocity and stable performance, capable of dispensing microscale droplets. Finally, a smaller droplet diameter of 0.42 mm was achieved in experiments using a glycerol/ethanol mixture, with a variation range of ± 4.61%

Mother-infant interactions and regional brain volumes in infancy: an MRI study

Background: It is generally agreed that the human brain is responsive to environmental influences, and that the male brain may be particularly sensitive to early adversity. However, this is largely based on retrospective studies of older children and adolescents exposed to extreme environments in childhood. Less is understood about how normative variations in parent-child interactions are associated with the development of the infant brain in typical settings. Method: To address this, we used magnetic resonance imaging to investigate the relationship between observational measures of mother-infant interactions and regional brain volumes in a community sample of 3-6 month old infants (N=39). In addition, we examined whether this relationship differed in male and female infants. Results: We found that lower maternal sensitivity was correlated with smaller subcortical grey matter volumes in the whole sample, and that this was similar in both sexes. However, male infants who showed greater levels of positive communication and engagement during early interactions had smaller cerebellar volumes. Conclusion These preliminary findings suggest that variations in mother-infant interaction dimensions are associated with differences in infant brain development. Although the study is cross-sectional and causation cannot be inferred, the findings reveal a dynamic interaction between brain and environment that may be important when considering interventions to optimize infant outcomes

Imperialism, immigration and identity : deterministic and symbolic violence in the southeast Asian American novel.

The main aim of this paper is to join the long-term debate within the field of Asian American studies, on how Asia is defined in the Asian-American context as the field continually renews itself in response to changing patterns of Asian immigration to the United States, by focusing on Southeast Asian-American literature. This is especially relevant in today’s global climate of mass consumerism, ease of travel, and transnational activities that bring about greater diversity in the Asian American population and community. Early anthologies and critiques tend to privilege writers from Chinese, Japanese and Filipino Asian groups, and with the most recent wave of Asian migrants of Southeast Asian descent, there is a need for a renewed interest in Southeast Asian-American literature so as to modernise and refine perspectives on Asian diasporas, transnationalism, immigration and assimilation, cultural, social and economic alienation, as well as marginalization and the western gaze.Bachelor of Art