Research progress in delineating the pathological mechanisms of GJB2-related hearing loss

Hearing loss is the most common congenital sensory impairment. Mutations or deficiencies of the GJB2 gene are the most common genetic cause of congenital non-syndromic deafness. Pathological changes such as decreased potential in the cochlea, active cochlear amplification disorders, cochlear developmental disorders and macrophage activation have been observed in various GJB2 transgenic mouse models. In the past, researchers generally believed that the pathological mechanisms underlying GJB2-related hearing loss comprised a K+ circulation defect and abnormal ATP-Ca2+ signals. However, recent studies have shown that K+ circulation is rarely associated with the pathological process of GJB2-related hearing loss, while cochlear developmental disorders and oxidative stress play an important, even critical, role in the occurrence of GJB2-related hearing loss. Nevertheless, these research has not been systematically summarized. In this review, we summarize the pathological mechanisms of GJB2-related hearing loss, including aspects of K+ circulation, developmental disorders of the organ of Corti, nutrition delivery, oxidative stress and ATP-Ca2+ signals. Clarifying the pathological mechanism of GJB2-related hearing loss can help develop new prevention and treatment strategies

Characterization of an aspartate aminotransferase encoded by YPO0623 with frequent nonsense mutations in Yersinia pestis

Yersinia pestis, the causative agent of plague, is a genetically monomorphic bacterial pathogen that evolved from Yersinia pseudotuberculosis approximately 7,400 years ago. We observed unusually frequent mutations in Y. pestis YPO0623, mostly resulting in protein translation termination, which implies a strong natural selection. These mutations were found in all phylogenetic lineages of Y. pestis, and there was no apparent pattern in the spatial distribution of the mutant strains. Based on these findings, we aimed to investigate the biological function of YPO0623 and the reasons for its frequent mutation in Y. pestis. Our in vitro and in vivo assays revealed that the deletion of YPO0623 enhanced the growth of Y. pestis in nutrient-rich environments and led to increased tolerance to heat and cold shocks. With RNA-seq analysis, we also discovered that the deletion of YPO0623 resulted in the upregulation of genes associated with the type VI secretion system (T6SS) at 26°C, which probably plays a crucial role in the response of Y. pestis to environment fluctuations. Furthermore, bioinformatic analysis showed that YPO0623 has high homology with a PLP-dependent aspartate aminotransferase in Salmonella enterica, and the enzyme activity assays confirmed its aspartate aminotransferase activity. However, the enzyme activity of YPO0623 was significantly lower than that in other bacteria. These observations provide some insights into the underlying reasons for the high-frequency nonsense mutations in YPO0623, and further investigations are needed to determine the exact mechanism

Causal relationship between gut microbiota and autoimmune thyroiditis: A mendelian study

Background: Autoimmune thyroiditis (AIT), also known as Hashimoto's thyroiditis (HT) or chronic lymphocytic thyroiditis, is a prevalent autoimmune disorder. Despite its high prevalence, the pathogenesis of AIT remains unclear. Previous studies have suggested a potential association between gut microbiota and AIT. However, whether this relationship is causal or coincidental remains uncertain. To address this gap in knowledge, our study aimed to investigate the potential causal association between gut microbiota and AIT using the two-sample Mendelian randomization (MR) method. Methods: Summary-level gut microbiota data comprising 211 taxa (131 genera, 35 families, 20 orders, 16 classes, and 9 phyla) were obtained from the comprehensive MiBioGen study. Genetic associations with 22 gastrointestinal diseases were extracted from the UK Biobank, FinnGen study, and various extensive GWAS studies. A meticulous MR analysis was conducted to evaluate the causal relationship between genetically predicted gut microbiota and these gastrointestinal diseases. Sensitivity analyses and tests for heterogeneity were systematically performed to validate the reliability of our findings. Results: Six gut microbiota species showed significant associations with AIT according to the IVW method. Among them, the following exhibited negative associations with AIT: family Alcaligenaceae, family Pasteurellaceae (ID: 3689), family Peptococcaceae, genus Lachnospira, genus Victivallis, and order Pasteurellales (ID: 3688). No evidence of pleiotropy or heterogeneity was detected. Conclusion: The MR analysis uncovered a causal relationship at the genetic prediction level between specific gut microbiota and AIT. These findings offer novel insights into the mechanisms governing the development of AIT mediated by gut microbiota. This knowledge could inform the design of future interventions, potentially involving microbiome-related strategies, to address the mechanisms associated with AIT development

An Ultrasonication-Assisted Cobalt Hydroxide Composite with Enhanced Electrocatalytic Activity toward Oxygen Evolution Reaction

A catalyst toward oxygen evolution reaction (OER) was synthesized by depositing cobalt hydroxide on carbon black. Ultrasonication was applied during precipitation to improve the performance of the catalyst. The ultrasonic-assisted process resulted in the refinement of the cobalt hydroxide particles from 400 nm to 50 nm, and the thorough incorporation of these particles with carbon black substrate. The resulting product exhibited enhanced OER catalytic activity with an onset potential of 1.54 V (vs. reversible hydrogen electrode), a Tafel slope of 18.18 mV/dec, and a stable OER potential at a current density of 10 mA cm−2, because of the reduced resistance of the catalyst and the electron transfer resistance

Experimental Study of the Flexural and Compression Performance of an Innovative Pultruded Glass-Fiber-Reinforced Polymer-Wood Composite Profile.

The plate of a pultruded fiber-reinforced polymer or fiber-reinforced plastic (FRP) profile produced via a pultrusion process is likely to undergo local buckling and cracking along the fiber direction under an external load. In this study, we constructed a pultruded glass-fiber-reinforced polymer-light wood composite (PGWC) profile to explore its mechanical performance. A rectangular cross-sectional PGWC profile was fabricated with a paulownia wood core, alkali-free glass fiber filaments, and unsaturated phthalate resin. Three-point bending and short column axial compression tests were conducted. Then, the stress calculation for the PGWC profile in the bending and axial compression tests was performed using the Timoshenko beam theory and the composite component analysis method to derive the flexural and axial compression rigidity of the profile during the elastic stress stage. The flexural capacity for this type of PGWC profile is 3.3-fold the sum of the flexural capacities of the wood core and the glass-fiber-reinforced polymer (GFRP) shell. The equivalent flexural rigidity is 1.5-fold the summed flexural rigidity of the wood core and GFRP shell. The maximum axial compressive bearing capacity for this type of PGWC profile can reach 1.79-fold the sum of those of the wood core and GFRP shell, and its elastic flexural rigidity is 1.2-fold the sum of their rigidities. These results indicate that in PGWC profiles, GFRP and wood materials have a positive combined effect. This study produced a pultruded composite material product with excellent mechanical performance for application in structures that require a large bearing capacity

Mechanical response and data-driven fatigue model of interlayer soils in track-bed considering multi-factor coupling effect

International audienc

Interactive Effects of Intertidal Elevation and Light Level on Early Growth of Five Mangrove Species under Sonneratia apetala Buch. Hamplantation Canopy: Turning Monocultures to Mixed Forests

The introduced Sonneratia apetala Buch. Hamplantation plantations have occupied more than 3800 ha in China. The prevalence, fast growth rate, and high seed production of S. apetala have raised concerns about the risks to native mangrove habitats. Efforts are required to convert these introduced monocultures to mixed or native forests. In this study, we examined native mangrove colonization in the introduced S. apetala plantations at the Qi’ao Island, Zhuhai, China. A 12-month field study was conducted to evaluate the effects of intertidal elevation and light level on the survival and early growth of five native mangrove species, viz., Bruguiera gymnorrhiza (L.) Savigny, Kandelia obovata Sheue, Liu & Yong, Aegiceras corniculatum (L.) Blanco, Avicennia marina (Forssk.) Vierh., and Rhizophora stylosa Griff.. Across intertidal elevations and light levels, the survival of B.gymnorrhiza was the highest. All the species had relatively higher survival rates under 30% canopy closure. Although the seedlings survived best at high intertidal elevation, the relative growth rate (RGR) was the highest at low intertidal elevation, and it was promoted by high light level. The stem height at low intertidal elevation was higher than that at high intertidal elevation, and it was the highest under 30% canopy closure. B. gymnorrhiza and R. stylosa at high intertidal elevation had relatively high leaf numbers, whereas K. obovata and A. marina showed a reverse tendency. The growth of stem diameter showed a decreasing trend initially and then increased with better performance at low intertidal elevations, and B. gymnorrhiza presented the best value under 30% canopy closure. Bruguiera gymnorrhiza showed the highest growth rate under similar conditions. Overall, intensive canopy thinning is an effective measure to promote native mangrove growth in S. apetala plantations. Additionally, increasing planting density especially at low intertidal elevations may improve native mangrove establishment and growth. Furthermore, Bruguiera gymnorrhiza is the best choice in the effort to plant native species in S. apetala plantations in the study area