3-Hydroxyisobutyryl-CoA hydrolase involved in isoleucine catabolism regulates triacylglycerol accumulation in Phaeodactylum tricornutum

Since methylmalonyl-CoA epimerase appears to be absent in the majority of photosynthetic organisms, including diatoms, (S)-methylmalonyl-CoA, the intermediate of isoleucine (Ile) catabolism, cannot be metabolized to (R)methylmalonyl-CoA then to succinyl-CoA. In this study, propionyl-CoA carboxylase (PCC) RNAi silenced strains and 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) overexpression strains were constructed to elucidate the Ile degradation pathway and its influence on lipid accumulation in Phaeodactylum tricornutum based on growth, neutral lipid content and metabolite profile analysis. Knockdown of PCC disturbed the metabolism of Ile through propionyl-CoA to methylmalonyl-CoA, as illustrated by much higher Ile content at day 6. However, Ile decreased to comparable levels to the wild-type at day 10. PCC silencing redirected propionyl-CoA to acetyl-CoA via a modified beta-oxidation pathway, and transcript levels for some branched-chain amino acid (BCAA) degradation-related genes, especially HIBCH, significantly upregulated in the PCC mutant, which enhanced the BCAA degradations and thus resulted in higher triacylglycerol (TAG) content. Overexpression of HIBCH accelerates Ile degradation and results in a lowered Ile content in the overexpression strains, thus enhancing carbon skeletons to the tricarboxylic acid cycle and giving rise to increasing TAG accumulation. Our study provides a good strategy to obtain high-lipid-yield transgenic diatoms by modifying the propionyl-CoA metabolism. This article is part of the themed issue &#39;The peculiar carbon metabolism in diatoms&#39;.</p

Potential contribution of anti-p200 autoantibodies to mucosal lesions in anti-p200 pemphigoid

Anti-p200 pemphigoid is a relatively rare subepidermal autoimmune bullous disease (AIBD), which was firstly reported by Detlef Zillikens, Takashi Hashimoto and others in 1996. Skin lesions are considered as the major clinical features of this disease, with occasional involvement of mucosal lesions. The mechanism of mucosal lesions involved in anti-p200 pemphigoid is still unclear. In the present study, we aimed to analyze published data on cases and case series of anti-p200 pemphigoid with mucosal lesions and explored the potential contribution of anti-p200 autoantibodies to mucosal lesions. A total of 32 papers that comprised 52 anti-p200 pemphigoid patients with various mucosal lesions were included in this review. Oral lesions were involved in 75.0% patients, followed by genital lesions (26.9%) and ocular lesions (11.54%). Only one patient had psoriasis, 26.9% patients had multiple mucosal lesions, and 30.8% cases had comorbidity of other AIBDs, particularly anti-laminin (LM) 332-type mucous membrane pemphigoid (MMP). In comparison with anti-LM332-type MMP, anti-BP180-type MMP and epidermolysis bullosa acquisita, higher frequency of genital lesions was identified as a unique character of anti-p200 pemphigoid with mucosal lesions. These results indicated that anti-p200 autoantibodies might contribute to mucosal lesions in a pattern different from other MMP-related autoantibodies, although its pathogenetic mechanisms are still unclear

Coniferyl ferulate alleviate xylene-caused hematopoietic stem and progenitor cell toxicity by Mgst2

Xylene exposure is known to induce toxicity in hematopoietic stem and progenitor cells (HSPCs), leading to bone marrow suppression and potential leukemogenesis. However, research on the gene expression profiles associated with xylene-induced toxicity in HSPCs, and effective therapeutic interventions, remains scarce. In our study, we employed single-cell RNA sequencing to capture the transcriptomic shifts within bone marrow HSPCs both prior to and following treatment with coniferyl ferulate (CF) in a mouse model of xylene-induced hematotoxicity. Subsequently, we pinpointed CF as a targeted agent using SPR-LC/MS analysis. This enabled us to confirm the link between the gene Mgst2 and specific cellular subtypes. Our data revealed that CF significantly countered the reduction of both monocyte and neutrophil progenitor cells, which are commonly affected by xylene toxicity. Through targeted analysis, we identified Mgst2 as a direct molecular target of CF. Notably, Mgst2 is preferentially expressed in neutrophil progenitor cells and is implicated in mitochondrial metabolic processes. By selectively inhibiting Mgst2 in bone marrow, we observed amelioration of xylene-induced hematotoxic effects. In summary, our findings suggest that coniferyl ferulate can mitigate the detrimental impact of xylene on hematopoietic stem and progenitor cells by targeting Mgst2, particularly within subpopulations of neutrophil progenitors. This discovery not only advances our comprehension of the cellular response of HSPCs to xenobiotic stressors like xylene but also identifies CF and Mgst2 as potential therapeutic targets for alleviating xylene-induced hematotoxicity

Stability on Adaptive NN Formation Control with Variant Formation Patterns and Interaction Topologies

The formation task achieved by multiple robots is a tough issue in practice, because of the limitations of the sensing abilities and communicating functions among them. This paper investigates the decentralized formation control in case of parameter uncertainties, bounded disturbances, and variant interactions among robots. To design decentralized controller, a formation description is firstly proposed, which consists of two aspects in terms of formation pattern and interaction topology. Then the formation control using adaptive neural network (ANN) is proposed based on the relative error derived from formation description. From the analysis on stability of the formation control under invariant/variant formation pattern and interaction topology, it is concluded that if formation pattern is of class C k , k ≥1, and interaction graph is connected and changed with finite times, the convergence of the formation control is guaranteed, so that robots must form the formation described by the formation pattern

Kinematic Analysis and Optimization of a New Compliant Parallel Micromanipulator

In this paper, a new three translational degrees of freedom (DOF) compliant parallel micromanipulator (CPM) is proposed, which has an excellent accuracy of parallel mechanisms with flexure hinges. The system is established by a proper selection of hardware and analyzed via the derived pseudo-rigid-body model. In view of the physical constraints imposed by both the piezoelectric actuators and flexure hinges, the CPM's reachable workspace is determined analytically, where a maximum cylinder defined as an usable workspace can be inscribed. Moreover, the optimal design of the CPM with the consideration of the usable workspace size and global dexterity index simultaneously is carried out by utilizing the approaches of direct search method, genetic algorithm (GA), and particle swarm optimization (PSO), respectively. The simulation results show that the PSO is the best method for the optimization, and the results are valuable in the design of a new micromanipulator