Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise.

JOURNAL/nrgr/04.03/01300535-202503000-00028/figure1/v/2024-06-17T092413Z/r/image-tiff Spinal cord injury necessitates effective rehabilitation strategies, with exercise therapies showing promise in promoting recovery. This study investigated the impact of rehabilitation exercise on functional recovery and morphological changes following thoracic contusive spinal cord injury. After a 7-day recovery period after spinal cord injury, mice were assigned to either a trained group (10 weeks of voluntary running wheel or forced treadmill exercise) or an untrained group. Bi-weekly assessments revealed that the exercise-trained group, particularly the voluntary wheel exercise subgroup, displayed significantly improved locomotor recovery, more plasticity of dopaminergic and serotonin modulation compared with the untrained group. Additionally, exercise interventions led to gait pattern restoration and enhanced transcranial magnetic motor-evoked potentials. Despite consistent injury areas across groups, exercise training promoted terminal innervation of descending axons. In summary, voluntary wheel exercise shows promise for enhancing outcomes after thoracic contusive spinal cord injury, emphasizing the role of exercise modality in promoting recovery and morphological changes in spinal cord injuries. Our findings will influence future strategies for rehabilitation exercises, restoring functional movement after spinal cord injury.

Carbon emissions in China's steel industry from a life cycle perspective: Carbon footprint insights.

China is the most important steel producer in the world, and its steel industry is one of the most carbon-intensive industries in China. Consequently, research on carbon emissions from the steel industry is crucial for China to achieve carbon neutrality and meet its sustainable global development goals. We constructed a carbon dioxide (CO2) emission model for China's iron and steel industry from a life cycle perspective, conducted an empirical analysis based on data from 2019, and calculated the CO2 emissions of the industry throughout its life cycle. Key emission reduction factors were identified using sensitivity analysis. The results demonstrated that the CO2 emission intensity of the steel industry was 2.33 ton CO2/ton, and the production and manufacturing stages were the main sources of CO2 emissions, accounting for 89.84% of the total steel life-cycle emissions. Notably, fossil fuel combustion had the highest sensitivity to steel CO2 emissions, with a sensitivity coefficient of 0.68, reducing the amount of fossil fuel combustion by 20% and carbon emissions by 13.60%. The sensitivities of power structure optimization and scrap consumption were similar, while that of the transportation structure adjustment was the lowest, with a sensitivity coefficient of less than 0.1. Given the current strategic goals of peak carbon and carbon neutrality, it is in the best interest of the Chinese government to actively promote energy-saving and low-carbon technologies, increase the ratio of scrap steel to steelmaking, and build a new power system.

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202505000-00029/figure1/v/2024-07-28T173839Z/r/image-tiff Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Meta-analysis of the effect of exercise intervention on cognitive function in elderly patients with type 2 diabetes mellitus.

OBJECTIVE: Cognitive dysfunction is a common complication of diabetes after central nervous system involvement. The impact of exercise, as an important non-pharmacological intervention strategy, on cognitive function remains controversial. Thus, we conducted a meta-analysis to assess the impact of exercise on cognitive function of elderly patients with type2 diabetes mellitus (T2DM). METHODS: We computer searched PubMed, Web of Science, Embase, CINAHL, Cochrane Library, CNKI, Wanfang date, and VIP, and traced back the references included in the literature from 1974 to July 2024. We used RevMan5.4 software for data analysis, and also conducted sensitivity, subgroup, and publication bias analyses. RESULTS: Eight eligible studies with a combined total of 747 elderly patients with T2DM were included. Meta-analysis showed that the combined effect size of exercise intervention on cognitive improvement in elderly patients with T2DM was significant [SMD = 0.65, 95% CI (0.48, 0.82), P < 0.01]. The following three factors had significant effects on the overall cognitive function of participants: subgroups (MoCA group [MD = 2.22 95% CI (1.26, 3.18), P < 0.01] and MMSE group [MD = 1.81, 95% CI (0.71,2.90), P = 0.001]); intervention times (3-month intervention [MD = 3.14, 95% CI (2.50, 3.78), P < 0.01], 6-month intervention [SMD = 0.32, 95% CI (0.12. 0.52), P = 0.002], and > 6 month intervention [SMD = 0.21, 95% CI (0.45, 0.81), P < 0.01]); intervention forms (single exercise [SMD = 0.21, 95% CI (0.45, 0.81), P < 0.01] and multiple exercise [SMD = 0.86, 95% CI ( 0.39,1.33), P < 0.0001]). CONCLUSION: Exercise intervention may improve cognitive function in elderly patients with T2DM.

Airway tryptase levels inform the lack of clinical efficacy of the tryptase inhibitor MTPS9579A in asthma.

BACKGROUND: Tryptase, a mast cell protease, has been identified as a potential therapeutic target in managing patients with refractory asthma. We assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of MTPS9579A, an anti-tryptase antibody, in a phase 2a randomized trial for patients with uncontrolled asthma and a phase 1c trial to understand activity within the lower respiratory tract. METHODS: Phase 2a patients (n = 134) received 1800 mg MTPS9579A or placebo intravenously every 4 weeks for 48 weeks. The primary endpoint was time to the first composite exacerbation event. Phase 1c patients (n = 27) received one intravenous dose of 300 or 1800 mg MTPS9579A or placebo. Both trials measured MTPS9579A concentrations and effects on tryptase in serum and nasal lining fluid; phase 1c also analyzed bronchial lining fluid. RESULTS: MTPS9579A did not meet the primary endpoint (hazard ratio = 0.90; 95% CI: 0.55-1.47; p = 0.6835); exacerbation rates in the placebo group were low. Serum and nasal MTPS9579A pharmacokinetics and tryptase levels were consistent with data from healthy volunteers. However, in phase 1c patients, compared to nasal levels, MTPS9579A bronchial concentrations were 6.8-fold lower, and bronchial active and total tryptase levels were higher (119-fold and 30-fold, respectively). Pharmacokinetic/pharmacodynamic modeling predicted intravenous doses of 3800 mg every 4 weeks would be necessary to achieve 95% active tryptase inhibition from baseline. CONCLUSIONS: The MTPS9579A dose tested in the phase 2a study was insufficient to inhibit tryptase in bronchial lining fluid, likely contributing to the observed lack of efficacy.

Acarbose enhances the efficacy of immunotherapy against solid tumours by modulating the gut microbiota.

The crucial role of gut microbiota in shaping immunotherapy outcomes has prompted investigations into potential modulators. Here we show that oral administration of acarbose significantly increases the anti-tumour response to anti-PD-1 therapy in female tumour-bearing mice. Acarbose modulates the gut microbiota composition and tryptophan metabolism, thereby contributing to changes in chemokine expression and increased T cell infiltration within tumours. We identify CD8+ T cells as pivotal components determining the efficacy of the combined therapy. Further experiments reveal that acarbose promotes CD8+ T cell recruitment through the CXCL10-CXCR3 pathway. Faecal microbiota transplantation and gut microbiota depletion assays indicate that the effects of acarbose are dependent on the gut microbiota. Specifically, acarbose enhances the efficacy of anti-PD-1 therapy via the tryptophan catabolite indoleacetate, which promotes CXCL10 expression and thus facilitates CD8+ T cell recruitment, sensitizing tumours to anti-PD-1 therapy. The bacterial species Bifidobacterium infantis, which is enriched by acarbose, also improves response to anti-PD-1 therapy. Together, our study endorses the potential combination of acarbose and anti-PD-1 for cancer immunotherapy.

The regulatory mechanism of natural polysaccharides in type 2 diabetes mellitus treatment.

Diabetes is a complex, multifactorial disease that is caused by a pathological combination of insulin resistance and pancreatic islet dysfunction. Polysaccharides are extensively dispersed in nature and have a very complicated structure with various biological properties. Natural polysaccharides have potentially extraordinary beneficial health effects on managing metabolic diseases such as diabetes, obesity and cardiovascular disease. Thus, a systematic review of the latest research into and possible regulatory mechanisms of natural polysaccharides for type 2 diabetes mellitus treatment is of great significance for a better understanding of their pharmaceutical value. We discuss the regulatory mechanisms of natural polysaccharides for the treatment of diabetes, and especially their role in reshaping dysfunctional gut microbiota. Natural polysaccharides could be developed as new and safe antidiabetic drugs, and detailed mechanistic studies could further clarify the molecular targets of polysaccharides in the treatment of diabetes.

Tissue inhibitor of metalloproteinase (TIMP)-1 predicts failure of recovery of ejection fraction in acute heart failure with reduced ejection fraction.

BACKGROUND: Heart failure (HF) with improved ejection fraction (HFimpEF) is a recently identified phenotype of HF, which had better cardiovascular outcomes compared with persistent HF with reduced ejection fraction (HFrEF). The present study aimed to investigate the predictive value of tissue inhibitor of metalloproteinase (TIMP)-1 and matrix metalloproteinases-9 (MMP-9) in the recovery of left ventricular ejection fraction (LVEF). METHODS: Subjects who presented with acute decompensated HF and reduced LVEF of ≤40% were eligible for this study. HFimpEF was defined by a follow-up LVEF >40% and a ≥10% improvement in LVEF. Overnight fasting N-terminal pro-brain natriuretic peptide (NT-proBNP), MMP-9 and TIMP-1 were measured within 24 hours before discharge. The study participants were followed for up to 5 years. RESULTS: Among a total of 91 participants (70.1±16.2 years, baseline LVEF 28.9±7.6%), 19 (20.8%) of them had HFimpEF and 72 (79.2%) had persistent HFrEF at 6 months. The receiver operating characteristic curve analyses showed the area under curve measures for TIMP-1, MMP-9 and NT-proBNP in the prediction of HFimpEF were 0.69, 0.52 and 0.65, respectively. TIMP-1 was negatively correlated with HFimpEF as continuous variables (OR per 1-SD and 95% CI 0.99 (0.98 to 1.00)) and categorical variables (cut-off value 200.68 ng/mL, OR and 95% CI 0.16 (0.05 to 0.54)) after adjustment of confounding factors. During a mean follow-up duration 34.8 months, patients with HFimpEF will have better long-term survival than those with persistent HFrEF. CONCLUSIONS: In subjects with decompensated HFrEF, TIMP-1, but not MMP-9 was associated with the reverse remodelling in LVEF. In addition, patients with HFimpEF would have better long-term survival.

Mixture effect of parental exposure to triazophos and fenvalerate on the early development of zebrafish offspring.

Triazophos (TRI) and fenvalerate (FEN) have been extensively used in the world and frequently coexist in the water environments, might pose health risk to aquatic species. However, investigations of their mixture toxic effects on offspring after parental exposure have been neglected, especially for aquatic vertebrates such fish. To address this knowledge gap, parental zebrafish (F0 generation) were exposed to TRI, FEN and their mixture for 60 days, as well as the embryos (F1 generation) were hatched without or with continued corresponding exposures at the same concentrations until 7 days post fertilization. The results exhibited that exposure to TRI and FEN altered the expression levels of biomarkers associated with several biological processes, such as apoptosis and inflammatory response. Compared to individual exposure in the F1 generation, the co-exposure to TRI and FEN resulted in increased the expression of T4 and cc-chem mRNA and decreased the expression of ROS, trα, il-8, and gpx mRNA when the F0 generation was similarly exposed. These results revealed that the co-exposure to TRI and FEN has detrimental effects on fish progeny following parental exposure, even if the progeny are not directly exposed to the pesticides, and such negative effects may be intensified if the offspring continue to be exposed. This study enhances the understanding of the harmful impacts of parental exposure to the pesticide mixture on descendants and holds implications for the ecological risk assessment of pesticide mixtures in aquatic vertebrates. Further mechanistic studies are necessary to gain a deeper insight into the mixture effects of pesticides and other kinds of pollutants on subsequent offspring following parental exposure.

The temporal trend and disparity in short-term health impacts of fine particulate matter in California (2006-2019).

Most epidemiological studies assume that the relationship between short-term air pollution exposure and health outcomes is constant over time, which ignores potential changes in population composition and particulate matter emission sources. Limited studies have assessed changes in the relationship between fine particulate matter (PM2.5) and adverse health outcomes over time, with mixed results. Additionally, there is a need to identify which subgroups are disproportionately impacted over time by PM2.5-related health consequences. Therefore, we aimed to examine whether temporal trends exist in the relationships between daily PM2.5 exposure and circulatory and respiratory acute care utilization in California from 2006 to 2019. We further assessed whether certain subpopulations are more susceptible to PM2.5 exposure by demographic characteristics and extreme wildfire frequency. Daily PM2.5 concentrations estimated from a stacked ensemble model and daily cause-specific acute care utilization and demographic data from the California Department of Health Care Access and Information. We analyzed this relationship using modified two-stage Bayesian hierarchical models, where we first did not consider temporal trends, then stratified by two periods, and finally flexibly considered non-linear changes over time. Increases in circulatory (0.56 %; 95 % credible interval (CI): 0.17 %, 0.96 %) and respiratory acute care utilization risk (2.61 %; 95%CI: 2.29 %, 2.94 %) were found with every 10 µg/m3 increase in PM2.5 on the same day and previous two days. These risks were found to increase over time, where 0.13 % (95%CI: 0.02 %, 0.22 %) and 1.40 % (95%CI: 1.24 %, 1.54 %) increases were identified for circulatory and respiratory acute care utilizations, respectively, from the first (2006-2012) to second period (2013-2019). Differences by age, sex, race/ethnicity, and extreme wildfire frequency were noted. These findings confirm that air pollution guidelines should consider the dynamic nature of epidemiological dose-response and can provide insight for targeted air pollution control and adaptation policies designed to reduce PM2.5 exposure, particularly for the most susceptible subpopulations.

Main-group element-boosted oxygen electrocatalysis of Cu-N-C sites for zinc-air battery with cycling over 5000 h.

Developing highly active and durable air cathode catalysts is crucial yet challenging for rechargeable zinc-air batteries. Herein, a size-adjustable, flexible, and self-standing carbon membrane catalyst encapsulating adjacent Cu/Na dual-atom sites is prepared using a solution blow spinning technique combined with a pyrolysis strategy. The intrinsic activity of the Cu-N4 site is boosted by the neighboring Na-containing functional group, which enhances O2 adsorption and optimizes the rate-determining step of O2 activation (*O2 → *OOH) during the oxygen reduction reaction process. Meanwhile, the Cu-N4 sites are encapsulated within carbon nanofibers and anchored by the carbon matrix to form a C2-Cu-N4 configuration, thereby reinforcing the stability of the Cu centers. Moreover, the introduction of Na-containing functional groups on the carbon atoms significantly reduces the positive charge on their outer shell C atoms, rendering the carbon skeletons less susceptible to corrosion by oxygen species and further preventing the dissolution of Cu centers. Under these multi-type regulations, the zinc-air battery with Cu/Na-carbon membrane catalyst as the air cathode demonstrates long-term discharge/charge cycle stability of over 5000 h. This considerable stability improvement represents a critical step towards developing Cu-N4 active sites modified with the neighboring main-group metal-containing functional groups to overcome the durability barriers of zinc-air batteries for future practical applications.

Genetically defined neuron types underlying visuomotor transformation in the superior colliculus.

The superior colliculus (SC) is a conserved midbrain structure that is important for transforming visual and other sensory information into motor actions. Decades of investigations in numerous species have made the SC and its nonmammalian homologue, the optic tectum, one of the best studied structures in the brain, with rich information now available regarding its anatomical organization, its extensive inputs and outputs and its important functions in many reflexive and cognitive behaviours. Excitingly, recent studies using modern genomic and physiological approaches have begun to reveal the diverse neuronal subtypes in the SC, as well as their unique functions in visuomotor transformation. Studies have also started to uncover how subtypes of SC neurons form intricate circuits to mediate visual processing and visually guided behaviours. Here, we review these recent discoveries on the cell types and neuronal circuits underlying visuomotor transformations mediated by the SC. We also highlight the important future directions made possible by these new developments.

On-chip multifunctional metasurfaces with full-parametric multiplexed Jones matrix.

On-chip metasurface for guided wave radiation works as an upgrade of conventional grating couplers, enriching the interconnection between guided wave and free-space optical field. However, the number of controllable parameters in equivalent Jones matrix of on-chip metasurface is limited that restricts the channels for multiplexing. Here, a supercell design based on detour phase and geometric phase has been proposed to reach full-parametric modulation of Jones matrix. As proof of concept, four independent sets of amplitude-phase channels have been experimentally demonstrated through a single on-chip metasurface. Moreover, through joint modulation of three phase mechanisms including detour phase, geometric phase and propagation phase, the Jones matrix could be decoupled from forward- and backward-propagating guided waves for direction multiplexing. This work paves the way for guided wave radiation towards high-capacity multiplexing and may further extend its application in optical communications, optical displays and augmented/virtual reality.

Crotonylation of NAE1 Modulates Cardiac Hypertrophy via Gelsolin Neddylation.

BACKGROUND: Cardiac hypertrophy and its associated remodeling are among the leading causes of heart failure. Lysine crotonylation is a recently discovered posttranslational modification whose role in cardiac hypertrophy remains largely unknown. NAE1 (NEDD8 [neural precursor cell expressed developmentally downregulated protein 8]-activating enzyme E1 regulatory subunit) is mainly involved in the neddylation modification of protein targets. However, the function of crotonylated NAE1 has not been defined. This study aims to elucidate the effects and mechanisms of NAE1 crotonylation on cardiac hypertrophy. METHODS: Crotonylation levels were detected in both human and mouse subjects with cardiac hypertrophy through immunoprecipitation and Western blot assays. Tandem mass tag (TMT)-labeled quantitative lysine crotonylome analysis was performed to identify the crotonylated proteins in a mouse cardiac hypertrophic model induced by transverse aortic constriction. We generated NAE1 knock-in mice carrying a crotonylation-defective K238R (lysine to arginine mutation at site 238) mutation (NAE1 K238R) and NAE1 knock-in mice expressing a crotonylation-mimicking K238Q (lysine to glutamine mutation at site 238) mutation (NAE1 K238Q) to assess the functional role of crotonylation of NAE1 at K238 in pathological cardiac hypertrophy. Furthermore, we combined coimmunoprecipitation, mass spectrometry, and dot blot analysis that was followed by multiple molecular biological methodologies to identify the target GSN (gelsolin) and corresponding molecular events contributing to the function of NAE1 K238 (lysine residue at site 238) crotonylation. RESULTS: The crotonylation level of NAE1 was increased in mice and patients with cardiac hypertrophy. Quantitative crotonylomics analysis revealed that K238 was the main crotonylation site of NAE1. Loss of K238 crotonylation in NAE1 K238R knock-in mice attenuated cardiac hypertrophy and restored the heart function, while hypercrotonylation mimic in NAE1 K238Q knock-in mice significantly enhanced transverse aortic constriction-induced pathological hypertrophic response, leading to impaired cardiac structure and function. The recombinant adenoviral vector carrying NAE1 K238R mutant attenuated, while the K238Q mutant aggravated Ang II (angiotensin II)-induced hypertrophy. Mechanistically, we identified GSN as a direct target of NAE1. K238 crotonylation of NAE1 promoted GSN neddylation and, thus, enhanced its protein stability and expression. NAE1 crotonylation-dependent increase of GSN promoted actin-severing activity, which resulted in adverse cytoskeletal remodeling and progression of pathological hypertrophy. CONCLUSIONS: Our findings provide new insights into the previously unrecognized role of crotonylation on nonhistone proteins during cardiac hypertrophy. We found that K238 crotonylation of NAE1 plays an essential role in mediating cardiac hypertrophy through GSN neddylation, which provides potential novel therapeutic targets for pathological hypertrophy and cardiac remodeling.

Recent progress in electrochemical C-N coupling: metal catalyst strategies and applications.

Electrochemical C-N coupling reactions hold significant importance in the fields of organic chemistry and green chemistry. Conventional methods for constructing C-N bonds typically rely on high temperatures, high pressures, and other conditions that are energy-intensive and prone to generating environmental pollutants. In contrast, the electrochemical approaches employ electrical energy as the driving force to achieve C-N bond formation under ambient conditions, representing a more environment-friendly and sustainable alternative. The notable advantages of electrochemical C-N coupling include high efficiency, good selectivity, and mild reaction conditions. Through rational design of corresponding electrocatalysts, it is possible to achieve efficient C-N bond coupling at low potentials. Moreover, the electrochemical methods allow for precise control over reaction conditions, thereby avoiding side reactions and by-products that are common for conventional methods, improving both selectivity and product purity. Despite the extensive research efforts devoted to exploring the potential of electrochemical C-N coupling, the design of efficient and stable metal catalysts remains a significant challenge. In this review, we summarize and evaluate the latest strategies developed for designing metal catalysts, and their application prospects for different nitrogen sources such as N2 and NOx. We delineate how the control over nanoscale structures, morphologies, and electronic properties of metal catalysts can optimize their performance in C-N coupling reactions, and discuss the performances and advantages of single-metal catalysts, bimetallic catalysts, and single-atom catalysts under various reaction conditions. By summarizing the latest research achievements, particularly in the development of high-efficiency catalysts, the application of novel catalyst materials, and the in-depth study of reaction mechanisms, this review aims to provide insights for future research in the field of electrochemical C-N coupling, and demonstrates that rationally designed metal catalysts could not only enhance the efficiency and selectivity of electrochemical C-N coupling reactions, but also offer conceptual frameworks for other electrochemical reactions.

Rapid Synthesis of Sb2Si2Te6 under High Pressure with a Modulated Microstructure.

Over the past decades, thermoelectric materials have advanced significantly, yet materials such as Sb2Si2Te6, which are challenging to synthesize chemically, often require lengthy and complex preparation processes, hindering their development. In this work, we prepare polycrystalline Sb2Si2Te6 bulk from elemental precursors using a high-pressure synthesis (HPS) method. This method offers significant advantages in efficiency and preparation duration. The applied pressure promotes an isotropic microstructure and regulates the thermoelectric properties by controlling precipitate contents, grain size, and twinning. Although an increase in thermal conductivity, mostly due to the notable increase in electrical conductivity, leads to less favorable thermal conductivity near room temperature compared to samples prepared using conventional methods, a beneficial reversal occurs at high temperatures. The polycrystalline Sb2Si2Te6 sample synthesized at 2 GPa demonstrates a peak ZT value of 1.1 at 773 K, outperforming most pristine Sb2Si2Te6 materials. This work demonstrates an efficient strategy for optimizing Sb2Si2Te6 performance and offers a new synthesis pathway for other challenging thermoelectric materials.

BMSCs-Derived Extracellular VesiclemiR-29a-3p Improved the Stability of Rat Myasthenia Gravis by Regulating Treg/Th17 Cells.

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disorder. Microvesicle-derived miRNAs have been implicated in autoimmune diseases. However, the role of microvesicle-derived miR-29a-3p in MG remains poorly understood. This study aimed to investigate the therapeutic effect and mechanism of miR-29a-3p derived from stem cell microvesicles (MVs) on experimental autoimmune myasthenia gravis (EAMG) rats. METHODS: EAMG was induced in rats by injection of the subunit of the rat nicotinic anti-acetylcholine receptor (AChR) R97-116 peptide.Besides the control group, EAMG rats were randomly allocated into the EAMG model group, MV group, MV-NC-agomir group, and MV- miR-29a-3p-agomir group. RESULTS: Our results found that BMSCs-MV promoted miR-29a-3p expression in gastrocnemius of EAMG rats. Bone marrow mesenchymal stem cells (BMSCs) derived microvesicle miR-29a-3p improved the hanging ability and swimming time of EMGA rats and weakened the degree of muscle fiber atrophy. Furthermore, microvesicles from miR-29a-3p overexpressing BMSCs reduced the content of AchR-Ab in the serum of EAMG rats. BMSC-derived microvesicle miR-29a-3p further suppressed the expression of IFN-γ and enhanced the IL-4 and IL-10 in the serum of EAMG rats by restoring the Th17/Treg cells balance. DISCUSSION: BMSCs-derived microvesicle miR-29a-3p improved the stability of rat myasthenia gravis by regulating Treg/Th17 cells. It may be an effective treatment for MG.

Case investigation on the construction mode of rural landscapes in the Qinghai Tibet Plateau, Mengda National Nature Reserve.

It is vital and challenging to coordinate the protection of natural reserves with rural construction. The rural structure and function were divided during the creation of natural reserves on the Qinghai Tibet Plateau (QTP), throwing the rural structure and functional system and its constituent parts out of balance. According to current research results on the construction mode of rural landscapes, the creation of rural landscapes is unable to address the requirements of villages and encourage the creation of protected areas. Therefore, it has become urgently necessary to conduct research on the rural landscape construction model of the QTP natural reserve. This study focuses on the case study of the construction mode of rural landscapes in the Mengda National Nature Reserve (MNNR) in the QTP. The inherent hierarchical structure relationships between rural landscape types, units and elements were identified. The basic characteristics of residential, production and cultural landscapes and their interdependent structural relationships were described. According to the evidence collected from literature, the rural landscape complex model and spatial optimisation strategy in the MNNR were proposed. It is believed that the rural residential, production and cultural landscape structures of the MNNR cannot effectively realise its living, production and culture function. From a spatial structure level, a rural landscape construction model was proposed based on production landscapes, residential landscapes as characteristics and cultural landscapes as the source. This model is based on agricultural landscapes, features the village and village dwellings and originates from temple landscapes, forming a comprehensive landscape unit that relies on and supports each other among production, residential and cultural landscapes. Emphasising the structural construction of infrastructure, such as transportation roads, network routes, tourism routes and water and electricity networks between the system and the external environment, is essential for promoting the circular relationship between the agricultural community complex in Dazhuang Village and the external system. The model is beneficial to balance the relationship between the rural landscape structure and MNNR function and promote the sustainable development of the relationship between the nature reserve and rural areas.

CD133+/ABCC5+ cervical cancer cells exhibit cancer stem cell properties.

Objective: This study explores the correlation between Forkhead box M1 (FOXM1) and ATP-binding cassette subfamily C member 5 (ABCC5) in relation to paclitaxel resistance in cervical cancer. It aims to identify potential cervical cancer stem cell markers, offering fresh perspectives for developing therapeutic strategies to overcome paclitaxel chemoresistance in cervical cancer. Methods: Paclitaxel-resistant Hela cells (Hela/Taxol) were developed by intermittently exposing Hela cells to progressively increasing concentrations of paclitaxel. We assessed the biological properties of both Hela and Hela/Taxol cells using various assays: cell proliferation, clonogenic, cell cycle, apoptosis, scratch, and transwell. To determine which markers better represent tumor stem cells, we analyzed various known and potential stem cell markers in combination. Flow cytometry was employed to measure the proportion of positive markers in both parental and drug-resistant cell lines. Following statistical analysis to establish relative stability, CD133+ABCC5+ cells were sorted for further examination. Subsequent tests included sphere-forming assays and Western blot analysis to detect the presence of the stem cell-specific protein Sox2, aiding in the identification of viable cervical cancer stem cell markers. Results: The Hela/Taxol cell line exhibited significantly enhanced proliferation, migration, and invasion capabilities compared to the Hela cell line, alongside a marked reduction in apoptosis rates (P < 0.01). Notably, proportions of CD44+, CD24+CD44+, ABCC5+, CD24+CD44+ABCC5+, CD44+ABCC5+, CD24+CD44+FOXM1+, CD44+FOXM1+, CD133+ABCC5+, and CD133+FOXM1+ were significantly higher (P < 0.05). Furthermore, the size and number of spheres formed byCD133+ABCC5+ cells were greater in the sorted Hela/Taxol line (P < 0.01), with increased expression of the stem cell marker Sox2 (P < 0.001). Conclusion: The Hela/Taxol cells demonstrate increased tumoral stemness, suggesting that CD133+ABCC5+ may serve as a novel marker for cervical cancer stem cells.

Unveiling chlorine's role: How it shapes the formation and light-activated oxygen dynamics of chlorophenol-derived environmental persistent free radicals.

Environmental persistent free radicals (EPFRs) derived from chlorophenols, triggered by light or heat exposure, pose significant ecological concerns, yet the impact of chlorine substituents on EPFRs formation and reactivity remains inadequately understood. Through an intentional synthesis of chlorophenol-derived EPFRs with varying chlorine contents and positioning, we elucidated the role of chlorine in the photoactivation of molecular oxygen. Our combined experimental and theoretical analysis reveals that these EPFRs are primarily oxygen-centered phenoxy radicals, establishing a direct link between chlorine substitution patterns and their ability to activate molecular oxygen under visible light. Increased chlorine content enhances EPFRs formation by elevating the positive charge on the phenolic hydroxyl group's hydrogen atom, facilitating its removal. Moreover, the capability of EPFRs to activate molecular oxygen was directly correlated with chlorine content, with 2,3,5,6-tetrachlorophenol-derived EPFRs showcasing the highest activity. This activity is attributed to their structural propensity for TCSQ·- species generation. Furthermore, our study established a significant correlation between the toxicity and activity of EPFRs, emphasizing the critical role of halogen substituents in determining the reactivity of EPFRs. These insights contribute to our understanding of their environmental and toxicological ramifications, underscoring the imperative for continued research aimed at mitigating their detrimental impacts.