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Sulfur is an essential nutrient for plant growth and development. Sulfate transporters (Sultrs) are critical for sulfate (SO42-) uptake from the soil by the roots in higher plants. However, knowledge about Sultrs in apples (Malus domestica) is scarce. Here, nine putative MdSultrs were identified and classified into two groups according to the their phylogenetic relationships, gene structures, and conserved motifs. Various cis-regulatory elements related to abiotic stress and plant hormone responsiveness were found in the promoter regions of MdSultrs. These MdSultrs exhibited tissue-specific expression patterns and responded to low sulfur (S), abscisic acid (ABA), indole-3-acetic acid (IAA), and methyl jasmonate (MeJA), wherein MdSultr3;1a was especially expressed in the roots and induced by low S. The uptake of SO42- in cultivated apples depends on the roots of its rootstock, and MhSultr3;1a was isolated from Malus hupehensis roots used as a rootstock. MhSultr3;1a shared 99.85% homology with MdSultr3;1a and localized on the plasma membrane and nucleus membrane. Further function characterization revealed that MhSultr3;1a complemented an SO42- transport-deficient yeast mutant and improved the growth of yeast and apple calli under low S conditions. The MhSultr3;1a-overexpressing apple calli had a higher fresh weight compared with the wild type (WT) under a low-S treatment because of the increased SO42- and cysteine (Cys) content. These results demonstrate that MhSultr3;1a may increase the content of SO42- and Cys to meet the demands of S-containing compounds and improve their growth under S-limiting conditions.

PurposeThis study aimed to clarify the effect of early glucocorticoid (GC) application on achieving minimal manifestation (MM) status or better in the treatment of myasthenia gravis (MG) in the early clinical phase.MethodsA retrospective analysis was performed using data from 336 patients with MG who received GC therapy from January 2015 to September 2022 in the Zhengzhou University Henan Institute of Medical and Pharmaceutical Sciences Myasthenia Gravis Biobank (ZMB). Patients were divided into two groups: the early mono-GC group (treated with GC within 6 months of MG onset) and the delayed mono-GC group.ResultsKaplan–Meier analysis showed that the early mono-GC group achieved MM status earlier and more frequently than the delayed mono-GC group (log-rank test, p = 0.0082; hazard ratio [HR], 1.66; p = 0.011). The early mono-GC group had a lower maintenance oral GC dose than the delayed mono-GC group. In multivariate Cox regression analysis, early mono-GC (HR, 1.50; p = 0.043), early-onset MG (EOMG) (HR, 1.74; p = 0.034), and ocular MG (OMG) (HR, 1.90; p = 0.007) were associated with MM status or better. In conclusion, early mono-GC, EOMG, and OMG were positive predictors of treatment goals. In EOMG, OMG, and acetylcholine receptor antibody-positive MG (AChR-MG) subgroups, the maintenance oral GC doses in the early mono-GC group were significantly lower than the doses in the delayed mono-GC group (p < 0.05).ConclusionEarly intervention with GC led to better long-term outcomes and reduced the necessary maintenance dose of oral GC for patients with MG. EOMG and OMG were positive predictors of MM status or better with mono-GC.

Myasthenia gravis (MG) is characterized by autoimmune damage to the postsynaptic membrane of the neuromuscular junction (NMJ) with impaired postsynaptic acetylcholine receptor (AChR) aggregation. Low-density lipoprotein receptor-related protein 4 (LRP4) plays an important role in AChR aggregation at endplate membranes via the Agrin–LRP4–muscle-specific receptor tyrosine kinase (MuSK) cascade. Sorting nexin 17 (SNX17) regulates the degradation and recycling of various internalized membrane proteins. However, whether SNX17 regulates LRP4 remains unclear. Therefore, we examined the regulatory effects of SNX17 on LRP4 and its influence on AChR aggregation in MG. We selected C2C12 myotubes and induced LRP4 internalization via stimulation with anti-LRP4 antibody and confirmed intracellular interaction between SNX17 and LRP4. SNX17 knockdown and overexpression confirmed that SNX17 promoted MuSK phosphorylation and AChR aggregation by increasing cell surface LRP4 expression. By establishing experimental autoimmune MG (EAMG) mouse models, we identified that SNX17 upregulation improved fragmentation of the AChR structure at the NMJ and alleviated leg weakness in EAMG mice. Thus, these results reveal that SNX17 may be a novel target for future MG therapy.

Limited load capacity is the bottleneck for the practical application of mobile multi-joint legged robots. And improving the efficiency of the drive system is a key factor in improving the load capacity. To improve the efficiency of mobile robots, in this paper, a new kind of actuator that imitates the driving mechanism of human muscles is innovatively designed and validated through experiments. The proposed actuator consists of a single power source and multiple plunger pistons, and imitates the configuration of a human muscle, to improve the efficiency and load capacities. The design proposed here represents a new class of driving methods. The actuator selects the most appropriate combination of the effective areas of plunger pistons like the human muscles, to ensure that the maximal output force aligns with the load force. To validate that the new actuator can improve the efficiency of hydraulic systems of mobile robots, a robotic arm incorporating a prototype of the new actuator was designed. The proposed system was validated through a series of experiments. The experiments show that the bionic actuator can adjust the flow rate of the system input by adjusting the number and size of the motion units involved in the work, and with the change in load force, it changes the output force by recruiting different motion units, which indicates good controllability. The results reported herein reveal that the application of bionics to the design of robotic actuator can significantly improve the efficiency and overall performance of the robots, and this biomimetic approach can be applied to a variety of robots.

This study aimed to establish a cell-based assay (CBA) for the detection of agrin antibodies (Agrin-Ab) to explore the clinical features of agrin antibody-positive Chinese patients with myasthenia gravis (Agrin-MG). We developed a CBA based on the human full-length agrin protein expressed in HEK293T cells for the reliable and efficient detection of Agrin-Ab. Clinical data and serum samples were collected from 1948 MG patients in 26 provinces in China. The demographic and clinical features of Agrin-MG patients were compared with those of other MG patient subsets. Eighteen Agrin-MG cases were identified from 1948 MG patients. Nine patients were Agrin-Ab positive, and nine were AChR-Ab and Agrin-Ab double-positive (Agrin/AChR-MG). Eleven (61.11%) patients were males older than 40 years of age. The initial symptom in 13 (81.25%) cases was ocular weakness. Occasionally, the initial symptom was limb-girdle weakness (two cases) or bulbar muscle weakness (one case). Agrin-MG patients demonstrated slight improvement following treatment with either acetylcholinesterase inhibitor or prednisone; however, the combination of the two drugs could effectively relieve MG symptoms. In China, Agrin-MG demonstrated seropositivity rates of 0.92%. These patients were commonly middle-aged or elderly men. The patients usually presented weakness in the ocular, bulbar, and limb muscles, which may be combined with thymoma. These patients have more severe diseases, although the combination of pyridostigmine and prednisone was usually effective in relieving symptoms.