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The survival and suppressive function of regulatory T (Treg) cells rely on various intracellular metabolic and physiological processes. Our study demonstrates that Vps34 plays a critical role in maintaining Treg cell homeostasis and function by regulating cellular metabolic activities. Disruption of Vps34 in Treg cells leads to spontaneous fatal systemic autoimmune disorder and multi-tissue inflammatory damage, accompanied by a reduction in the number of Treg cells, particularly eTreg cells with highly immunosuppressive activity. Mechanistically, the poor survival of Vps34-deficient Treg cells is attributed to impaired endocytosis, intracellular vesicular trafficking and autophagosome formation, which further results in enhanced mitochondrial respiration and excessive ROS production. Removal of excessive ROS can effectively rescue the death of Vps34-deficient Treg cells. Functionally, acute deletion of Vps34 within established Treg cells enhances anti-tumor immunity in a malignant melanoma model by boosting T-cell-mediated anti-tumor activity. Overall, our results underscore the pivotal role played by Vps34 in orchestrating Treg cell homeostasis and function towards establishing immune homeostasis and tolerance.
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Background: Tai Chi is an increasingly utilized aerobic rehabilitation exercise in the field of cardiovascular disease (CVD). However, there remains debate regarding its effects on physiological function and mental health in patients with coronary heart disease (CHD). This study aims to investigate the impact of Tai Chi-based rehabilitation exercises on physical and psychological health outcomes for CHD patients. Methods: By collecting data from 12 databases up to December 2022, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the effects of Tai Chi on the physical function and psychological health among CHD patients. Results: We analyzed twenty qualified studies involving 2095 patients. Meta-analyses revealed that compared with conventional therapy groups, those who participated in Tai Chi-based interventions demonstrated significant improvements in physical function as measured by six-minute walk test (6MWT) [mean difference (MD) = 56.40, 95% confidence interval (CI) (38.50, 74.29), p < 0.01], maximal oxygen consumption ( VO 2 max) [standardized mean difference (SMD) = 0. 57, 95% CI (0.12, 1.03), p = 0.01], New York Heart Association (NYHA) class [relative risk (RR) = 1.34, 95% CI (1.18, 1.53), p < 0.01] and physical health components (PHC) [SMD = 1.23, 95% CI (0.76, 1.69), p < 0.01]. Additionally, Tai Chi participants showed greater improvement than control groups across various psychological parameters including anxiety scales [SMD = -0.80, 95% CI (-1.33, -0.28), p = 0.003], depression scales [SMD = -0.77, 95% CI (-1.32, -0.23), p = 0.005] and mental health components (MHC) [SMD = 1.27, 95% CI (0.76, -1.78), p < 0.01]. The GRADEpro (Grade Guideline Development Tool) indicated evidence levels ranging from very low to moderate. Conclusions: The present meta-analysis demonstrates that mind-body rehabilitation exercises based on Tai Chi can improve both physical and psychological health outcomes for CHD patients. These findings suggest that this exercise pattern may be a potential option for cardiovascular rehabilitation. PROSPERO Registration: The protocol for this systematic review and meta-analysis has been registered with PROSPERO International Prospective Systematic Reviews (No: CRD42022370021, http://www.crd.york.ac.uk/PROSPERO).
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BACKGROUND: Cliffs are recognized as one of the most challenging environments for plants, characterized by harsh conditions such as drought, infertile soil, and steep terrain. However, they surprisingly host ancient and diverse plant communities and play a crucial role in protecting biodiversity. The Taihang Mountains, which act as a natural boundary in eastern China, support a rich variety of plant species, including many unique to cliff habitats. However, it is little known how cliff plants adapt to harsh habitats and the demographic history in this region. RESULTS: To better understand the demographic history and adaptation of cliff plants in this area, we analyzed the chromosome-level genome of a representative cliff plant, T. rupestris var. ciliata, which has a genome size of 769.5 Mb, with a scaffold N50 of 104.92 Mb. The rapid expansion of transposable elements may have contributed to the increasing genome and its ability to adapt to unique and challenging cliff habitats. Comparative analysis of the genome evolution between Taihangia and non-cliff plants in Rosaceae revealed a significant expansion of gene families associated with oxidative phosphorylation, which is likely a response to the abiotic stresses faced by cliff plants. This expansion may explain the long-term adaptation of Taihangia to harsh cliff environments. The effective population size of the two varieties has continuously decreased due to climatic fluctuations during the Quaternary period. Furthermore, significant differences in gene expression between the two varieties may explain the varied leaf phenotypes and adaptations to harsh conditions in different natural distributions. CONCLUSION: Our study highlights the extraordinary adaptation of T. rupestris var. ciliata, shedding light on the evolution of cliff plants worldwide.
Subject(s)
Adaptation, Physiological , Chromosomes, Plant , Genome, Plant , China , Chromosomes, Plant/genetics , Adaptation, Physiological/genetics , Rosaceae/genetics , Rosaceae/physiology , Ecosystem , Evolution, MolecularABSTRACT
Natural killer (NK) cells play a crucial role in immune response against viral infections and tumors. However, further investigation is needed to better understand the key molecules responsible for determining the fate and function of NK cells. In this study, we made an important discovery regarding the involvement of the Hippo kinases Mst1 and Mst2 as novel regulators in maintaining mouse NK cell homeostasis. The presence of high Mst1 and Mst2 (Mst1/2) activity in NK cells is essential for their proper development, survival and function in a canonical Hippo signaling independent mode. Mechanistically, Mst1/2 induce cellular quiescence by regulating the processes of proliferation and mitochondrial metabolism, thereby ensuring the development and survival of NK cells. Furthermore, Mst1/2 effectively sense IL-15 signaling and facilitate the activation of pSTAT3-TCF1, which contributes to NK cell homeostasis. Overall, our investigation highlights the crucial role of Mst1/2 as key regulators in metabolic reprogramming and transcriptional regulation for mouse NK cell survival and function, emphasizing the significance of cellular quiescence during NK cell development and functional maturation.
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Homeostasis , Killer Cells, Natural , Protein Serine-Threonine Kinases , Serine-Threonine Kinase 3 , Animals , Humans , Mice , AMP-Activated Protein Kinases , Cell Proliferation , Cell Survival , Hippo Signaling Pathway , Interleukin-15/metabolism , Killer Cells, Natural/metabolism , Killer Cells, Natural/immunology , Mice, Inbred C57BL , Mitochondria/metabolism , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , Signal Transduction , STAT3 Transcription Factor/metabolism , Transcription, GeneticABSTRACT
By conducting a mixed-design experiment using simplified accident handling tasks performed by two-person teams, this study examined the effects of automation function and condition (before, during, and after malfunction) on human performance. Five different and non-overlapping functions related to human information processing model were considered and their malfunctions were set in a first-failure way. The results showed that while the automation malfunction impaired task performance, the performance degradation for information analysis was more severe than response planning. Contrary to other functions, the situation awareness for response planning and response implementation tended to increase during malfunctioning and decrease after. In addition, decreased task performance reduced trust in automation, and malfunctions in earlier stages of information processing resulted in lower trust. Suggestions provided for the design and training related to automation emphasise the importance of high-level cognitive support and the benefit of involving automation error handling in training.
The effects of automation function and malfunction on human performance are important for design and training. The experimental results in this study revealed the significance of high-level cognitive support. Also, introducing automation error handling in training can be helpful in improving situation awareness of the teams.
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Automation , Task Performance and Analysis , Humans , Male , Female , Adult , Young Adult , Man-Machine Systems , Trust , AwarenessABSTRACT
Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is a central nervous system demyelinating disease. Current therapy methods, however, have limited effect on acute attacks except for intravenous methylprednisolone (IVMP). Efgartigimod is a first-in-class novel human immunoglobulin G1 (IgG1) Fc fragment approved for the treatment of generalized myasthenia gravis. Its capacity to rapidly decrease serum IgG levels, including pathogenic autoantibodies, positions it as a potentially effective option for managing the acute phase of NMOSD. Case presentation: We report the case of a 59-year-old female patient with acute NMOSD, presenting with vision loss and numbness in all four limbs. Despite an initial inadequate response to intravenous methylprednisolone (IVMP), the addition of Efgartigimod to her treatment regimen led to rapid improvement, notably including a significant reduction in serum aquaporin-4 antibody titers, total IgG levels, and inflammation cytokine levels. Furthermore, no adverse events were reported during a four-month follow-up period. Conclusion: As an adjunct to glucocorticoid therapy, Efgartigimod has proven effective and safe for this patient. However, to ascertain its potential as a novel therapeutic option for acute NMOSD, larger-scale prospective clinical trials are required.
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â¢Four newly recorded species of Podostemaceae from southern China were identified by molecular and morphological evidence.â¢17 plastomes of Podostemaceae were newly sequenced and two novel polymorphic barcodes (ccsA and ndhA) detected.â¢Our findings reveal greater species richness (15 species from five genera) of Podostemaceae in China and supply molecular resources for research on taxonomy and phylogenomics of this enigmatic aquatic family.
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BACKGROUND: Interest in the evolution of climatic niches, particularly in understanding the potential adaptive responses of species under climate change, has increased both theoretically and within macroecological studies. These studies have provided valuable insights into how climatic traits of species influence their niche evolution. In this study, we aim to investigate whether niche conservatism plays a role in the species diversification of Nymphaea, a group of aquatic plants with a cosmopolitan distribution that is facing severe habitat loss. We will use climatic models and phylogenetic data for 23 species to reconstruct Nymphaea's niche evolution, measure niche overlap, and assess disparity through time while testing for evolutionary models. RESULTS: There was a lot of overlap in niches both within and between groups, especially for species that can be found in many places. The breadth and peaks of the niche profile varied depending on the bioclimatic variables, which suggested that the species evolved differently to cope with changes in climate. The analysis also showed that evolutionary changes happened across the phylogeny, with weak to moderate signals. The morphological disparity index (MDI) values indicated that there were disparities within subclades over time but not between or among them. Niche reconstruction and evolution analysis revealed both convergent and divergent evolution among various variables. For example, N. immutabilis, N. atrans, N. violancea, and N. nouchali evolved towards intermediate temperatures for bio2 and bio3 (isothermity) while moving towards extreme temperatures for bio8 and bio9 (wettest and driest average quarterly temperatures). CONCLUSION: Our study will improve our understanding of how changes in climatic niches are potentially driving the evolution of Nymphaea. It has significant scientific implications for the limits, assemblages, evolution, and diversification of species. This information is crucial for the ongoing efforts of conservation and management, particularly considering the inevitable effects of climate change.
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Biological Evolution , Climate , Ecosystem , Phylogeny , South America , Australia , Africa , Climate ChangeABSTRACT
Eichhornia crassipes is an aquatic plant in tropical and subtropical regions, renowned for its notorious invasive tendencies. In this study, we assembled the complete mitogenome of E. crassipes into a single circle molecule of 397,361 bp. The mitogenome has 58 unique genes, including 37 protein-coding genes (PCGs), 18 tRNA genes, three rRNA genes, and 47 % GC content. Sixteen (6.93 %) homologous fragments, ranging from 31 bp to 8548 bp, were identified, indicating the transfer of genetic material from chloroplasts to mitochondria. In addition, we detected positive selection in six PCGs (ccmB, ccmC, ccmFC, nad3, nad4 and sdh4), along with the identification of 782 RNA editing sites across 37 mt-PCGs. These findings suggest a potential contribution to the robust adaptation of this invasive plant to the stressful environment. Lastly, we inferred that phylogenetic conflicts of E. crassipes between the plastome and mitogenome may be attributed to the difference in nucleotide substitution rates between the two organelle genomes. In conclusion, our study provided vital genomic resources for further understanding the invasive mechanism of this species and exploring the dynamic evolution of mitogenomes within the monocot clade.
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Eichhornia , Genome, Mitochondrial , Phylogeny , Eichhornia/genetics , Introduced Species , RNA, Transfer/genetics , Base Composition , RNA Editing , Genome, PlantABSTRACT
Background: The knowledge of normalâappearing cortical gray matter (NAGM) in multiple sclerosis (MS) remains unclear. In this study, we aimed to identify diagnostic biomarkers and explore the immune infiltration characteristics of NAGM in MS through bioinformatic analysis and validation in vivo. Methods: Differentially expressed genes (DEGs) were analyzed. Subsequently, the functional pathways of the DEGs were determined. After screening the overlapping DEGs of MS with two machine learning methods, the biomarkers' efficacy and the expression levels of overlapping DEGs were calculated. Quantitative reverse transcription polymerase chain reaction (qRTâPCR) identified the robust diagnostic biomarkers. Additionally, infiltrating immune cell populations were estimated and correlated with the biomarkers. Finally, the characteristics of immune infiltration of NAGM from MS were evaluated. Results: A total of 98 DEGs were identified. They participated in sensory transduction of the olfactory system, synaptic signaling, and immune responses. Nine overlapping genes were screened by machine learning methods. After verified by ROC curve, four genes, namely HLAâDRB1, RPS4Y1, EIF1AY and USP9Y, were screened as candidate biomarkers. The mRNA expression of RPS4Y1 and USP9Y was significantly lower in MS patients than that in the controls. They were selected as the robust diagnostic biomarkers for male MS patients. RPS4Y1 and USP9Y were both positively correlated with memory B cells. Moreover, naive CD4+ T cells and monocytes were increased in the NAGM of MS patients compared with those in controls. Conclusions: Low expressed Yâlinked genes, RPS4Y1 and USP9Y, were identified as diagnostic biomarkers for MS in male patients. The inhomogeneity of immune cells in NAGM might exacerbate intricate interplay between the CNS and the immune system in the MS.
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Plant terrestrialization (i.e. the transition to a terrestrial environment) is a significant evolutionary event that has been intensively studied. While certain plant lineages, particularly in angiosperms, have re-adapted to freshwater habitats after colonizing terrene, however, the molecular mechanism of the terrestrial-freshwater (T-F) transition remains limited. Here, the basal monocot Araceae was selected as the study object to explore the T-F transition adaptation mechanism by comparative genomic analysis. Our findings revealed that the substitution rates significantly increased in the lineage of freshwater Araceae, which may promote their adaptation to the freshwater habitat. Additionally, 20 gene sets across all four freshwater species displayed signs of positive selection contributing to tissue development and defense responses in freshwater plants. Comparative synteny analysis showed that genes specific to submerged plants were enriched in cellular respiration and photosynthesis. In contrast, floating plants were involved in regulating gene expression, suggesting that gene and genome duplications may provide the original material for plants to adapt to the freshwater environment. Our study provides valuable insights into the genomic aspects of the transition from terrestrial to aquatic environments in Araceae, laying the groundwork for future research in the angiosperm.
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Araceae , Biological Evolution , Genome , Fresh Water , Plants , Chromosomes , PhylogenyABSTRACT
AIM:To study the effect of tarsal gland massage combined with medication in treatment of meibomian gland dysfunction (MGD).METHODS:Totally 100 patients (189 eyes) with MGD were selected in our hospital from December 2014 to December 2016.The patients were randomly divided into control group and observation group.Patients in the control group were treated with routine drugs,while the patients in the observation group were treated with routine massage.We observed and compared the clinical efficacy of two groups of patients before treatment,1 wk,1 and 3mo after treatment for the subjective symptoms,tear film break-up time,tear secretion test,ocular surface disease index,corneal staining score of the patients in the 3 groups.RESULTS:The total effective rate of the observation group was 93.6%,which was significantly higher than that of the control group (P< 0.05).Two groups of patients after treatment of subjective symptoms,ocular surface disease index,corneal staining score decreased,tear break-up time,Schirmer test was increased compared with before treatment (P<0.05).The decrease of subjective symptoms,ocular surface disease index,corneal staining score,the increase of tear film break-up time,tear secretion test in the observation group were higher than those in the control group (P<0.05).CONCLUSION:Massage combined with medication can improve the clinical efficacy of MGD.
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<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of incising spinal pia mater to relieve pressure and unilateral open-door laminoplasty with internal screw fixation for treatment of the dated spinal cord injury.</p><p><b>METHODS</b>From March, 2009 to July, 2010, 16 cases with chronic cervical cord injury underwent spinal dura mater incision and unilateral open-door laminoplasty with internal screw fixation. Nerve functions of pre- and postoperation were evaluated by Frankel classification and the Japanese Orthopaedic Association (JOA) scale.The improvement rate of JOA score at the indicated time was recorded.</p><p><b>RESULTS</b>Postoperative Frankel classification rating of 16 patients improved obviously.JOA scores at the 1st month, 3rd month, 6th month, and 12th month after surgery were 7.9 ± 2.3, 8.5 ± 1.6, 8.9 ± 2.1, and 12.4 ± 2.5, respectively, and significantly increased compared with that prior to surgery (5.5 ± 0.6). At the end of follow-up period, JOA score was significantly higher than that of pre-treatment (P<0.05). The recovery was relatively rapid during the first 3 months following the surgery, then entered a platform period.</p><p><b>CONCLUSION</b>It is effective for patients with dated spinal cord injury to undergo spinal decompression and laminoplasty.</p>