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Eutrophic shallow lakes are generally considered as a contributor to the emission of nitrous oxide (N2O), while regional and global estimates have remained imprecise. This due to a lack of data and insufficient understanding of the multiple contributing factors. This study characterized the spatiotemporal variability in N2O concentrations and N2O diffusive fluxes and the contributing factors in Lake Wuliangsuhai, a typical shallow eutrophic and seasonally frozen lake in Inner Mongolia with cold and arid climate. Dissolved N2O concentrations of the lake exhibited a range of 4.5 to 101.2 nmol/L, displaying significant spatiotemporal variations. The lowest and highest concentrations were measured in summer and winter, respectively. The spatial distribution of N2O flux was consistent with that of N2O concentrations. Additionally, the hotspots of N2O emissions were detected within close to the main inflow of lake. The wide spatial and temporal variation in N2O emissions indicate the complexity and its relative importance of factors influencing emissions. N2O emissions in different lake zones and seasons were regulated by diverse factors. Factors influencing the spatial and temporal distribution of N2O concentrations and fluxes were identified as WT, WD, DO, Chl-a, SD and COD. Interestingly, the same factor demonstrated opposing effects on N2O emission in various seasons or zones. This research improves our understanding of N2O emissions in shallow eutrophic lakes in cold and arid areas.
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Monitoramento Ambiental , Lagos , Óxido Nitroso , Estações do Ano , Óxido Nitroso/análise , Lagos/química , China , Poluentes Atmosféricos/análise , Eutrofização , Análise Espaço-Temporal , Poluentes Químicos da Água/análiseRESUMO
Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells, leading to notable efficacy in patients with non-small cell lung cancer, melanoma, and other malignancies through immunotherapy utilization. However, secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression, resulting in reduced overall effectiveness of immune therapy. Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates, progression-free survival, and overall survival when secondary malignant tumors develop in the liver. Through Liu's retrospective analysis, valuable insights are provided for the future clinical management of these patients. Therefore, in patients with gastric cancer (GC), the occurrence of liver metastasis might be indicative of reduced efficacy of immunotherapy. Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.
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Directed differentiation of stem cells toward chondrogenesis in vitro and in situ to regenerate cartilage suffers from off-target differentiation and hypertrophic tendency. Here, we generated a cartilaginous organoid system from human expanded pluripotent stem cells (hEPSCs) carrying a COL2A1mCherry and COL10A1eGFP double reporter, enabling real-time monitoring of chondrogenesis and hypertrophy. After screening 2,040 FDA-approved drugs, we found that α-adrenergic receptor (α-AR) antagonists, especially phentolamine, stimulated chondrogenesis but repressed hypertrophy, while α2-AR agonists reduced chondrogenesis and induced hypertrophy. Phentolamine prevented cartilage degeneration in hEPSC cartilaginous organoid and human cartilage explant models and stimulated microfracture-activated endogenous skeletal stem cells toward hyaline-like cartilage regeneration without fibrotic degeneration in situ. Mechanistically, α2-AR signaling induced hypertrophic degeneration via cyclic guanosine monophosphate (cGMP)-dependent secretory leukocyte protease inhibitor (SLPI) production. SLPI-deleted cartilaginous organoid was degeneration resistant, facilitating large cartilage defect healing. Ultimately, targeting α2-AR/SLPI was a promising and clinically feasible strategy to regenerate cartilage via promoting chondrogenesis and repressing hypertrophy.
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OBJECTIVES: Endoscopic necrosectomy (EN) is a promising minimally invasive approach for treating infected walled-off pancreatic necrosis (WOPN). Multiple EN approaches are currently available, though criteria for selecting the optimal approaches are lacking. We aimed to propose a rational selection strategy of EN and to retrospectively evaluate its safety and effectiveness. METHODS: Altogether 101 patients who underwent EN for infected WOPN at a tertiary hospital between June 2009 and February 2023 were retrospectively included for analysis. Demographic characteristics, details of the EN procedures, procedure-related adverse events, and clinical outcomes were investigated. RESULTS: Among these 101 patients with WOPN, 56 (55.4%) underwent transluminal EN, 38 (37.6%) underwent percutaneous EN, and seven (6.9%) underwent combined approach, respectively. Clinical success was achieved in 94 (93.1%) patients. Seven (6.9%) experienced procedure-related adverse events, and seven (6.9%) died during the treatment period. During a median follow-up of 50 months, 5 (5.3%) of the 94 patients had disease recurrence, 17.0% (16/94) had new-onset diabetes mellitus, and 6.4% (6/94) needed oral pancreatic enzyme supplementation. The clinical success rate, procedure-related adverse event rate, and long-term follow-up outcomes were not significantly different among the three groups. High APACHE-II scores (≥15) and organ failure were identified as factors related to treatment failure. CONCLUSIONS: A selection strategy for EN approaches, based on the extent of necrosis and its distance from the gastrointestinal lumen (using a threshold of 15 mm), is safe and effective for treating infected WOPN in both short-term and long-term outcomes.
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The potential of forestation to mitigate climate warming depends largely on whether it can improve terrestrial carbon (C) storage. Changes in soil microbial stability can cause ecosystem C fluctuations. Unfortunately, it remains unclear whether forestation alters soil microbial stability with cascading effects on C storage in high-altitude ecosystems. In this study, a total of 14 typical planted forests were selected on the Tibetan Plateau. We showed that high-altitude forestation, particularly with poplars, altered the microbial diversity and potentially improved the stability of soil microbial communities. These changes were associated with soil C accumulation and potentially positive feedback on soil organic C storage. Variations in the microbial community stability were mostly caused by changes in soil bulk density and dissolved organic C. Superior network stability was found in fungal community rather than bacterial community. Additionally, there were strong interactions between bacterial and fungal communities that influenced soil C storage. These findings contribute to understand the differences and relationships between bacteria and fungi in plantation soils. This work reveals the potential of high-altitude forestation to mitigate climate warming through insights into the microbial-mediated mechanisms responsible for soil C storage in high-altitude ecosystems.
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Analysing the relationship between economic growth and carbon emissions may help China to determine how to reduce carbon emissions. This study examined 221 Chinese prefecture-level cities using data from 2003 to 2018 to investigate the possible inverted U-shaped relationship between carbon emissions and economic growth, based on per capita nighttime light brightness. This revealed a significant inverted U-shaped relationship between per capita nighttime and carbon emissions with a per capita GDP of 139.8 thousand Yuan corresponding to the turning point. For China to achieve its carbon emissions peak before 2030, the per capita GDP growth rate would need to be at least 6.6 %. Therefore, for help prefecture-level cities to achieve peak carbon, they must strive towards high-quality economic growth and accelerate transformation of economic growth modes to improve low-carbon pilot policies, and such projects should be implemented in more cities. Efforts to achieve peak should be accelerated first in eastern cities and later in western cities.
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Thousands of genes are activated in late 2-cell embryos, which means that numerous pre-mRNAs are generated during this time. These pre-mRNAs must be accurately spliced to ensure that the mature mRNAs are translated to functional proteins. However, little is known about the roles of pre-mRNA splicing and cellular factors modulating pre-mRNA splicing during early embryonic development. Here, we report that downregulation of SON, a large Ser/Arg (SR)-related protein, reduced embryonic development and caused deficient blastomere cleavage. These embryonic developmental defects result from dysregulated nuclear speckle organization and pre-mRNA splicing of a set of cell cycle-related genes. Furthermore, SON downregulation disrupted the transcriptome (2128 upregulated and 1399 downregulated) in 4-cell embryos. Increased H3K4me3, H3K9me3 and H3K27me3 levels were detected in 4-cell embryos after SON downregulation. Taken together, these results demonstrate that accurate pre-mRNA splicing is essential for early embryonic development and that SON plays important roles in nuclear speckle organization, pre-mRNA splicing, transcriptome establishment and histone methylation reprogramming during early embryonic development.
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The extracellular matrix (ECM) plays a crucial role in maintaining cell morphology and facilitating intercellular signal transmission within the human body. ECM has been extensively utilized for tissue injury repair. However, the consideration of factor gradients during ECM preparation has been limited. In this study, we developed a novel approach to generate sheet-like ECM with a continuous gradient of stromal cell-derived factor-1 (SDF1α). Briefly, we constructed fibroblasts to overexpress SDF1α fused with the collagen-binding domain (CBD-SDF1α), and cultured these cells on a slanted plate to establish a gradual density cell layer at the bottom surface. Subsequently, excess parental fibroblasts were evenly distributed on the plate laid flat to fill the room between cells. Following two weeks of culture, the monolayer cells were lyophilized to form a uniform ECM sheet possessing a continuous gradient of SDF1α. This engineered ECM material demonstrated its ability to guide oriented migration of human umbilical cord mesenchymal stem cells (hUCMSCs) on the ECM sheet. Our simple yet effective method holds great potential for advancing research in regenerative medicine.
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BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide(EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs. 12.3 months (hazard ratio [HR]: 0.38, 95% CI: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs. 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs. 14.7 months) and PFS (9.1 months vs. 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs. 13.7 months and median PFS of 9.8 months vs. 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs. 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs. 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION: Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
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INTRODUCTION: In addition to various techniques involved in catheter insertion, catheter placement location, lumen diameter and operation and management during continuous renal replacement therapy (CRRT), the design of the tip and side holes, as well as the position of the tip of the catheter, can also impact catheter function. Side-hole and step-tip catheters are commonly used during CRRT. However, there is insufficient evidence comparing their efficacy for CRRT in critically ill patients. And the optimal position of the tip of catheters is not well studied and remains controversial. This study was conducted to assess whether using a step-tip catheter could reduce the rate of catheter dysfunction compared with a side-hole catheter and whether inserting a longer catheter could reduce the incidence of catheter dysfunction and increase catheter survival time. METHODS AND ANALYSIS: A prospective, open-label, three-arm, parallel-group, single-centre randomised controlled trial will be conducted at West China Hospital of Sichuan University in China. An estimated sample of 378 participants receiving CRRT treatment will be recruited. Eligible patients will be randomly assigned to three groups to receive different dialysis catheters for the initiation of CRRT at a 1:1:1 ratio via a central randomisation system: group A, side-hole catheters (11Fr, 200 mm; GDHK-1120; Baxter International Inc., Deerfield, Illinois); group B, step-tip catheters (13Fr, 200 mm; GDHK-1320; Baxter International Inc.) and group C, step-tip catheters (13Fr, 250 mm; GDHK-1325; Baxter International Inc.). The femoral vein is the only vascular access. All catheters will be inserted under the guidance of ultrasound using the Seldinger method to reduce complications and trauma related to catheter insertion. The primary outcomes are the occurrence of catheter dysfunction and catheter survival time. Outcome assessors and data analysts will be blinded. All data will be analysed according to the group randomly assigned by an intention-to-treat analysis, in which catheters with missing data for the primary outcomes would be excluded. ETHICS AND DISSEMINATION: The trial protocol has been approved by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University (2023.1221). And the results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2300075107.
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Terapia de Substituição Renal Contínua , Unidades de Terapia Intensiva , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Terapia de Substituição Renal Contínua/métodos , Terapia de Substituição Renal Contínua/instrumentação , Estudos Prospectivos , China , Masculino , Estado Terminal/terapia , Desenho de Equipamento , Feminino , Cateteres de Demora/efeitos adversosRESUMO
Understanding the carbon cycling process and assessing the carbon sequestration potential in freshwater lakes relies heavily on their source-sink relationship. However, human activity and climate change have obscured the clarity of this relationship and its driving mechanisms, particularly in northern grassland lakes. This study focused on Hulun Lake, the largest grassland lake in northern China, to quantitatively analyze the carbon dioxide exchange flux (FCO2) at the water-air interface from 1963 to 2023. The analysis revealed significant seasonal, interannual, and decadal variations in the FCO2. Over the past 60 years, FCO2 varying significant in seasons and years has notably decreased, averaging 0.324 ± 0.106 gC·m-2·d-1. Notably, there was a qualitative change in FCO2 from "sink" (0.161 ± 0.109 gC·m-2·d-1) to "source" (-0.130 ± 0.087 gC·m-2·d-1)between 2019 and 2020. From 1963 to 2019, the lake acted as a CO2 source, releasing an average flux of 0.438 ± 0.111 gC·m-2·d-1. During this period, FCO2 was the highest in spring, followed by summer, and the lowest in autumn and winter when the lake was covered by ice. In 2020, the lake transitioned into a CO2 sink with an average FCO2 of -0.248 ± 0.042 gCm-2·d-1 from 2020 to 2023. During this period, FCO2 peaked in autumn, followed by summer and spring, and was lowest in winter when the lake was ice covered. A structural model equation (SEM) was employed to analyze the effects of various factors, including physical, chemical, and biological aspects, on FCO2 and the source-sink pattern of Hulun Lake. This study suggested that lake eutrophication, compounded by global warming, may be the primary driving force behind these changes. Rising temperatures and eutrophication enhanced the primary productivity of the lake. The amount of CO2 fixed through photosynthesis surpassed that emitted by respiration. Consequently, the eutrophication may alter the CO2 exchange pattern in Hulun Lake, shifting it from a "source" to a "sink".
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The presence of vacancy defects significantly impacts thermal properties of materials. In this research, we delve into the effects of vacancy defects on the thermal conductivity of ternary alloy BaAgBi, employing molecular dynamics simulations coupled with a deep neural network potential (NNP). Initially, we validate the precision of our NNP by comparing their predictions for energy, atomic forces, phonon dispersion curves, phonon density of states, and vacancy formation energy with density functional theory calculations, ensuring a high degree of accuracy. Our findings reveal that the reduction in thermal conductivity due to vacancies aligns with the Debye-Callaway model, with variations depending on the type of vacancy. Specifically, Ba vacancies result in the most notable decrement in thermal conductivity, attributable to their low phonon participation ratio and high lattice distortion, both factors that enhance phonon scattering. Besides, we find that the high energy barrier (â¼1.66 eV) indicates that Ba vacancies hardly migrate at 300 K. This study helps us understand how vacancies affect thermal conductivity in BaAgBi and how different vacancy types affect it.
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Aquifer leakage recharge poses a prevalent challenge in coalbed methane (CBM) development, severely impeding its efficient production. This study focuses on the Sanjiao Block, located on the eastern margin of the Ordos Basin, and provides a comprehensive evaluation of the impact of aquifer leakage recharge on CBM well productivity, employing hydrochemical characteristics and numerical simulation. Fisher's discriminant analysis reveals a close association between external water sources for CBM wells in the Taiyuan Formation and the hydrodynamic environment: in the western stagnant zone, hydrochemical characteristics resemble those from the Shanxi Formation; in the eastern strong runoff zone, water from the Taiyuan Formation directly contributes to CBM well development; in the central weak runoff zone, hydrochemical characteristics suggest mixed water sources from the Shanxi Formation and Taiyuan Formation. The numerical simulation employs orthogonal experiments to quantify the sensitivity of aquifer geological parameters to CBM production, ranked from strong to weak for aquifer types, leakage channel properties, and aquifer physical properties. The fundamental reason for disparities in the efficacy of leakage recharge lies in categorizing aquifers into finite and infinite recharges based on their water supply capacity. The properties of leakage channels, including the location and scale, manifest as effects on the magnitude and shape of gas production characteristics in infinite and finite recharge aquifers, respectively. Furthermore, a discriminant flowchart of CBM production is presented, delineating the production characteristics of CBM wells under the influence of aquifer leakage recharge into six patterns and illustrating their distribution in the study area. This discriminant process provides scientific guidance for analyzing CBM production characteristics and evaluating potential under the influence of aquifer leakage recharge.
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Accidental combustion and energy recovery of polyethylene terephthalate (PET) result in the formation of harmful organic substances and excessive emissions of CO2 and CO. This paper presents our recent efforts to unravel the formation mechanism of these harmful substances during the PET combustion process using thermal analysis and simulation calculations (DFT, CDFT, and ReaxFF). Our findings reveal that PET oxidative pyrolysis produces free radicals, harmful small molecule gases, and CO2. The interaction between aromatic free radicals and oxygen initiates unstable peroxy bonds, triggering uncontrollable chain exothermic reactions and producing oxygenated polycyclic aromatic hydrocarbon (OPAH) precursors. We propose a straightforward and eco-friendly free radical interlocking co-deposition inhibition strategy for PET by incorporating polycarbonate (PC). This strategy aims to facilitate green energy recovery by curbing OPAH formation and reducing CO2 and CO emissions during PET waste combustion. Our investigation into the oxidative pyrolysis of PET challenges conventional wisdom dominated by C-H bond fracture, paving the way for efficient, low-pollution green energy recovery.
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With the drying and warming of the climate and irrational grazing, various types of grasslands in Inner Mongolia have been degraded to different degrees, and different management modes will inevitably affect the plant diversity and vegetation carbon stock of soil grasslands. To clarify the changes and influencing factors of plant diversity and carbon stock in different types of grasslands under different management modes, plant species composition, aboveground biomass, and vegetation carbon were analyzed based on 18 sentinel monitoring stations across three different types of grasslands in Inner Mongolia. The results showed that grazing increased the dominance of typical grassland and desert grassland, whereas meadow grassland decreased, and the evenness index and Shannon Wiener diversity index increased less in meadow grassland and desert grassland. Grazing decreased graminaceous biomass in meadow grassland and typical grassland, whereas it increased in desert grassland. Above-ground vegetation and below-ground root carbon stocks were much higher than those in grazing areas, 1.5 and 1.2 higher, respectively, but vegetation carbon stocks in long-term grazing sites were significantly lower than those in short-term grazing. Further, the structural equations showed that the effects of geographic location, climatic factors, and soil factors on the biomass and vegetation carbon stocks of the three grassland types differed significantly. The results can provide a reference for the ecologically sustainable development of grassland and the optimization of management mode.
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Biodiversidade , Carbono , Pradaria , Poaceae , Carbono/análise , China , Poaceae/crescimento & desenvolvimento , Herbivoria , Animais , Biomassa , Conservação dos Recursos Naturais , Solo/químicaRESUMO
BACKGROUND: The intricate interplay between genetics and immunology often dictates the host's susceptibility to various diseases. This study explored the genetic causal relationship between natural killer (NK) cell-related traits and the risk of infection. METHODS: Single-nucleotide polymorphisms (SNPs) significantly associated with NK cell-related traits were selected as instrumental variables to estimate their genetic causal effects on infection. SNPs from a genome-wide association study (GWAS) on NK cell-related traits, including absolute cell counts, median fluorescence intensities reflecting surface antigen levels, and relative cell counts, were used as exposure instruments. Summary-level GWAS statistics of four phenotypes of infection were used as the outcome data. The exposure and outcome data were analyzed via the two-sample Mendelian randomization method. RESULTS: Each one standard deviation increase in the expression level of human leukocyte antigen (HLA)-DR on HLA-DR+ NK cells was associated with a lower risk of pneumonia (P < 0.05). An increased HLA-DR+ NK/CD3- lymphocyte ratio was related to a lower of risk of pneumonia (P < 0.05). Each one standard deviation increase in the absolute count of HLA-DR+ NK cells was associated with a lower risk of both bacterial pneumonia and pneumonia (P < 0.05). An increased HLA-DR+ NK/NK ratio was associated with a decreased risk of both pneumonia and bacterial pneumonia (P < 0.05). The results were robust under all sensitivity analyses. No evidence for heterogeneity, pleiotropy, or potential reverse causality was detected. Notably, our analysis did not reveal any significant associations between NK cell-related traits and other phenotypes of infection, including cellulitis, cystitis, and intestinal infection. CONCLUSIONS: HLA-DR+ NK cells could be a novel immune cell trait associated with a lower risk of bacterial pneumonia or pneumonia.
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Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Células Matadoras Naturais , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Células Matadoras Naturais/imunologia , Humanos , Antígenos HLA-DR/genética , Pneumonia Bacteriana/imunologia , Pneumonia Bacteriana/genética , FenótipoRESUMO
Skeletal muscle is a highly heterogeneous tissue, and its contractile proteins are composed of different isoforms, forming various types of muscle fiber, each of which has its own metabolic characteristics. It has been demonstrated that endurance exercise induces the transition of muscle fibers from fast-twitch to slow-twitch muscle fiber type. Herein, we discover a novel epigenetic mechanism for muscle contractile property tightly coupled to its metabolic capacity during muscle fiber type transition with exercise training. Our results show that an 8-week endurance exercise induces histone methylation remodeling of PGC-1α and myosin heavy chain (MHC) isoforms in the rat gastrocnemius muscle, accompanied by increased mitochondrial biogenesis and an elevated ratio of slow-twitch to fast-twitch fibers. Furthermore, to verify the roles of reactive oxygen species (ROS) and AMPK in exercise-regulated epigenetic modifications and muscle fiber type transitions, mouse C2C12 myotubes were used. It was shown that rotenone activates ROS/AMPK pathway and histone methylation enzymes, which then promote mitochondrial biogenesis and MHC slow isoform expression. Mitoquinone (MitoQ) partially blocking rotenone-treated model confirms the role of ROS in coupling mitochondrial biogenesis with muscle fiber type. In conclusion, endurance exercise couples mitochondrial biogenesis with MHC slow isoform by remodeling histone methylation, which in turn promotes the transition of fast-twitch to slow-twitch muscle fibers. The ROS/AMPK pathway may be involved in the regulation of histone methylation enzymes by endurance exercise.
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Histonas , Cadeias Pesadas de Miosina , Biogênese de Organelas , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Condicionamento Físico Animal , Espécies Reativas de Oxigênio , Animais , Histonas/metabolismo , Camundongos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Masculino , Cadeias Pesadas de Miosina/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Metilação , Fibras Musculares Esqueléticas/metabolismo , Epigênese Genética , Fibras Musculares de Contração Lenta/metabolismo , Resistência Física/fisiologia , Fibras Musculares de Contração Rápida/metabolismo , Músculo Esquelético/metabolismo , Linhagem Celular , Proteínas Quinases Ativadas por AMP/metabolismoRESUMO
The degradation of proteasomes or lysosomes is emerging as a principal determinant of programmed death ligand 1 (PDL1) expression, which affects the efficacy of immunotherapy in various malignancies. Intracellular cholesterol plays a central role in maintaining the expression of membrane receptors; however, the specific effect of cholesterol on PDL1 expression in cancer cells remains poorly understood. Cholesterol starvation and stimulation were used to modulate the cellular cholesterol levels. Immunohistochemistry and western blotting were used to analyze the protein levels in the samples and cells. Quantitative real-time PCR, co-immunoprecipitation, and confocal co-localization assays were used for mechanistic investigation. A xenograft tumor model was constructed to verify these results in vivo. Our results showed that cholesterol suppressed the ubiquitination and degradation of PDL1 in hepatocellular carcinoma (HCC) cells. Further mechanistic studies revealed that the autocrine motility factor receptor (AMFR) is an E3 ligase that mediated the ubiquitination and degradation of PDL1, which was regulated by the cholesterol/p38 mitogenic activated protein kinase axis. Moreover, lowering cholesterol levels using statins improved the efficacy of programmed death 1 (PD1) inhibition in vivo. Our findings indicate that cholesterol serves as a signal to inhibit AMFR-mediated ubiquitination and degradation of PDL1 and suggest that lowering cholesterol by statins may be a promising combination strategy to improve the efficiency of PD1 inhibition in HCC.