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The biogenesis of functional forms of chloroplast ribosomal RNAs (rRNAs) is crucial for the translation of chloroplast mRNAs into polypeptides. However, the molecular mechanisms underlying the proper processing and maturation of chloroplast rRNA species are poorly understood. Through a genetic approach, we isolated and characterized an Arabidopsis mutant, α1-4, harboring a missense mutation in the plastid chaperonin-60α1 gene. Using allelism tests and transgenic manipulation, we determined functional redundancy among ptCPN60 subunits. The ptCPN60α1S57F mutation caused specific defects in the formation of chloroplast rRNA species, including 23S, 5S, and 4.5S rRNAs, but not 16S rRNAs. Allelism tests suggested that the dysfunctional ptCPN60α1S57F competes with other members of the ptCPN60 family. Indeed, overexpression of the ptCPN60α1S57F protein in wild-type plants mimicked the phenotypes observed in the α1-4 mutant, while increasing the endogenous transcriptional levels of ptCPN60α2, ß1, ß2, and ß3 in the α1-4 mutant partially mitigated the abnormal fragmentation processing of chloroplast 23S, 5S, and 4.5S rRNAs. Furthermore, we demonstrated functional redundancy between ptCPN60ß1 and ptCPN60ß2 in chloroplast rRNA processing through double-mutant analysis. Collectively, our data reveal a novel physiological role of ptCPN60 subunits in generating the functional rRNA species of the large 50S ribosomal subunit in Arabidopsis chloroplasts.
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AIMS: The objective of this study was to investigate the correlation between serum 25 hydroxyvitamin D [25(OH)D] levels and insulin resistance, as well as metabolic associated fatty liver disease (MAFLD) in newly diagnosed with type 2 diabetes mellitus(T2DM) patients. METHOD: A retrospective analysis was conducted on 491 T2DM patients who were newly diagnosed between January 2017 and August 2022 at Peking University International Hospital. These patients were categorized into three groups based on their 25(OH)D levels. RESULTS: The prevalence of MAFLD was significantly elevated in both the Vitamin D(VD) deficiency group and the VD insufficiency group compared to the VD sufficiency group (χ2 = 6.51, p<0.05). The patients in the VD sufficiency group had lower levels of insulin resistanceï¼as assessed by the homeostasis model assessment when compared to the VD deficiency group and the VD insufficiency group (F = 8.61ï¼p < 0.05). Additionally, the VD sufficiency group demonstrated higher levels of ß cell function in comparison to the other two groups(p<0.05ï¼ respectively). (2) A significant negative correlation was observed between 25(OH)D levels and insulin resistance, as assessed by the homeostasis model assessment in T2DM patients(r=-0.33ï¼p<0.05 for females; r=-0.32ï¼p<0.05 for males). (3) In male patients, 25(OH)D was identified as a protective factor against MAFLD(OR = 0.42;95%CI:0.19-0.95;p<0.05). Meanwhileï¼in female patients, 25(OH)D was also associated with a reduced risk of MAFLD(OR = 0.35;95%CI 0.17-0.89;p<0.05). Additionally, the study determined that the threshold values for 25(OH)D were 15.06 ng/ml in female patients and 18.79 ng/ml in male patients for predicting MAFLD. CONCLUSION: In newly diagnosed with T2DM patients, the level of 25(OH)D may be related to insulin resistance and ß cell secretion function independently and VD deficiency is an independent risk factor for MAFLD in patients with newly diagnosed T2DM.
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Lipid droplets (LDs) are composed of a core of neutral lipids wrapped by a phospholipid (PL) monolayer containing several hundred proteins that vary between different cells or organisms. How LD proteins target to LDs is still largely unknown. Here, we show that RNAi knockdown or gene mutation of let-767, encoding a member of hydroxysteroid dehydrogenase (HSD), displaced the LD localization of three well-known LD proteins: DHS-3 (dehydrogenase/reductase), PLIN-1 (perilipin), and DGAT-2 (diacylglycerol O-acyltransferase 2), and also prevented LD growth in Caenorhabditis elegans. LET-767 interacts with ARF-1 (ADP-ribosylation factor 1) to prevent ARF-1 LD translocation for appropriate LD protein targeting and lipid homeostasis. Deficiency of LET-767 leads to the release of ARF-1, which further recruits and promotes translocation of ATGL-1 (adipose triglyceride lipase) to LDs for lipolysis. The displacement of LD proteins caused by LET-767 deficiency could be reversed by inhibition of either ARF-1 or ATGL-1. Our work uncovers a unique LET-767 for determining LD protein targeting and maintaining lipid homeostasis.
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Oxidorreductasas de Alcohol , Proteínas de Caenorhabditis elegans , Gotas Lipídicas , Homeostasis , Lipasa/genética , Proteínas Asociadas a Gotas Lipídicas/metabolismo , Gotas Lipídicas/metabolismo , Metabolismo de los Lípidos/genética , Lípidos , Lipólisis/fisiología , Proteínas/metabolismo , Caenorhabditis elegans , Animales , Oxidorreductasas de Alcohol/metabolismo , Proteínas de Caenorhabditis elegans/metabolismoRESUMEN
State transition is a fundamental light acclimation mechanism of photosynthetic organisms in response to the environmental light conditions. This process rebalances the excitation energy between photosystem I (PSI) and photosystem II through regulated reversible binding of the light-harvesting complex II (LHCII) to PSI. However, the structural reorganization of PSI-LHCI, the dynamic binding of LHCII, and the regulatory mechanisms underlying state transitions are less understood in higher plants. In this study, using cryoelectron microscopy we resolved the structures of PSI-LHCI in both state 1 (PSI-LHCI-ST1) and state 2 (PSI-LHCI-LHCII-ST2) from Arabidopsis thaliana. Combined genetic and functional analyses revealed novel contacts between Lhcb1 and PsaK that further enhanced the binding of the LHCII trimer to the PSI core with the known interactions between phosphorylated Lhcb2 and the PsaL/PsaH/PsaO subunits. Specifically, PsaO was absent in the PSI-LHCI-ST1 supercomplex but present in the PSI-LHCI-LHCII-ST2 supercomplex, in which the PsaL/PsaK/PsaA subunits undergo several conformational changes to strengthen the binding of PsaO in ST2. Furthermore, the PSI-LHCI module adopts a more compact configuration with shorter Mg-to-Mg distances between the chlorophylls, which may enhance the energy transfer efficiency from the peripheral antenna to the PSI core in ST2. Collectively, our work provides novel structural and functional insights into the mechanisms of light acclimation during state transitions in higher plants.
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Arabidopsis , Complejo de Proteína del Fotosistema I , Complejo de Proteína del Fotosistema I/metabolismo , Microscopía por Crioelectrón , Proteína 1 Similar al Receptor de Interleucina-1/metabolismo , Complejos de Proteína Captadores de Luz/química , Complejos de Proteína Captadores de Luz/metabolismo , Clorofila/metabolismo , Arabidopsis/metabolismoRESUMEN
Ampelopsis grossedentata, commonly known as "Vine Tea" and well-recognized for its rich flavonoid content, is mainly distributed in the southern regions of the Yangtze River basin in China. These regions include Hunan, Hubei, Jiangxi, and Guizhou provinces. Vine Tea is mainly consumed as an herbal tea and has garnered attention for its reported health benefits, including antioxidant, anti-inflammatory, anti-tumor, anti-diabetic, and neuroprotective properties. It has been used to alleviate coughs and sore throats (Zhang et al., 2021; Wang et al., 2017; Gao et al., 2009). In the Zhangjiajie region of Hunan province alone, the Vine Tea planting area reached 7,670.5 hectares and produced commercial goods worth 1.417 billion RMB in 2022. In May 2021, leaf margins and veins fading to yellowing mottling, and crumpling of leaf blades in the shape of a boat symptoms were found in ~16% of Vine Tea plants in the Sanjiakuan Township, Yongding District, Zhangjiajie region (29°15'E, 110°30' N) (Figure 1a, b, c). (Figure 1a, b, c). Phytoplasma-like microbial cells (small oval shaped bacterial cells, around 1000 nm in size) were observed in sieve tube cells in the phloem of diseased leaves using transmission electron microscopy. No such cell was observed in the phloem of healthy leaves (Figure 2a, b). To investigate the potential association between phytoplasma and the observed symptoms of the diseased plants, total DNA was isolated from ten diseasedeaves and compared with ten healthy leaves from the same field using SteadyPure Plant Genomic DNA Extraction Kit. The isolated DNAs were analyzed first in a direct PCR using universal phytoplasma primer pair R16mF2/R16mR1 targeting the 16S rRNA gene (Gundersen and Lee 1996) and specific pair rpF1/rpR1 (Lee et al. 1998) targeting the DNA fragment encoding partial ribosomal proteins (rp) L22 (complete) and S3 and S19 (partial). The initial amplified products were used as templates and further amplified by nested PCR respectively with primer pair R16F2n/R16R2 for the 16S rRNA gene (Lee et al. 1998) and the rpF2/rpR2 primer pair for the rp gene (Martini et al. 2007). No amplification was obtained with DNA from healthy leaf samples using any of the four primer pairs. The amplified fragments from diseased leaves by nested PCR were cloned and sequenced (Qingke Biotech, China). The obtained sequences have been deposited in GenBank with accession numbers OR282806 for the 16S rRNA gene and GenBank OR353012 for the rp gene. BLASTn analysis revealed that the partial 16S rRNA gene sequence in our sample shared 99.4% nucleotide sequence identity with 'Candidatus Phytoplasma sp.' (MW364378) and 'Peony yellows phytoplasma' (KY814723) of the 16SrI group. Similarly, our rp gene sequence shared 99.6% nucleotide identity with the rpI group of phytoplasma such as the 'Balsamine virescence phytoplasma' (JN572890) and 'Paulownia witches'-broom phytoplasma' (HM146079). Phylogenetic analysis of the 16S rRNA and rp sequences using MEGA version 7.0 revealed that the phytoplasma strain associated with A. grossedentata yellow leaf syndrome in our study site belonged to the 16SrI (Candidatus Phytoplasma asteris) group of phytoplasma (Figure 3a, b). Using the interactive online phytoplasma classification tool iPhyClassifier (Zhao et al., 2009), virtual restriction fragment length polymorphism (RFLP) analysis of the 16S rRNA gene sequences showed our strain having a distinct RFLP map but was closest to that of the onion yellow phytoplasma 16SrI-B subgroup (GenBank accession number: AP006628), with a similarity coefficient of 0.94 (Figure 4a, b). To confirm phytoplasma transmission, healthy plants were inoculated with three scions of infected plants of A. grossedentata. After 16 days, the new leaves of the inoculated A. grossedentata showed yellow leaf symptoms (Figure 5a, b, c), akin to the symptoms originally observed in the field, and the outer contour of the leaf margin appeared chlorotic. After 26 days, primer pairs R16mF2/R16R1 and R16F2n/R16R2 were used for nested PCR detection of phytoplasma in symptomatic A. grossedentata leaves. Phytoplasma was detected in the first and second leaves of symptomatic branches and leaves while negative control showed no amplification. Sequencing of the amplified fragments showed 100% nucleotide identity to the strain from the grafting source. Our results indicated that the pathogen and the disease can be transmitted by tissue grafting, consistent with the biological characteristics of phytoplasma, and further confirmed that the phytoplasma was the pathogen of yellow leaf syndrome of A. grossedentata. Toour knowledge, this is the first report of phytoplasma of group 16SrI affecting A. grossedentata.
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Purpose: To explore the association between thyroid parameters and subclinical atherosclerosis (AS) in hospitalised euthyroid patients with type 2 diabetes mellitus (T2DM). Patients and Methods: A retrospective analysis was conducted involving 1245 inpatients with T2DM. Free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH) levels were measured, and carotid artery ultrasonography was performed. Thyroid hormone (TH) sensitivity was evaluated using thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free triiodothyronine/free thyroxine ratio (FT3/FT4). Results: In inpatients with T2DM having normal thyroid function, the incidence of subclinical AS declined with increasing levels of FT3, FT4, and FT3/FT4 (P trend < 0.05). Logistic regression analysis revealed that FT4 (OR, 0.914; 95% CI, 0.845-0.989), FT3 (OR, 0.374; 95% CI, 0.277-0.504), and FT3/FT4 (OR, 0.036; 95% CI, 0.013-0.061) were independently associated with subclinical AS (P < 0.05). However, TSH, TFQI, TSHI, and TT4RI levels were not associated with subclinical AS (P > 0.05). FT3/FT4 demonstrated superior predictive accuracy for subclinical AS than that of FT3 or FT4 alone (P < 0.001), with a cutoff point of 0.25. Conclusion: In euthyroid inpatients with T2DM, subclinical AS exhibited negative correlation with FT3, FT4, and FT3/FT4 levels, independent of other risk factors for AS. Additionally, FT3/FT4 ratio had a good predictive value for subclinical AS.
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Stroke is the second-leading cause of death and the leading cause of disability in much of the world. In particular, China faces the greatest challenge from stroke, since the population is aged quickly. In decades of clinical trials, no neuroprotectant has had reproducible efficacy on primary clinical end points, because reperfusion is probably a necessity for neuroprotection to be clinically beneficial. Fortunately, the success of thrombolysis and endovascular thrombectomy has taken us into a reperfusion era of acute ischaemic stroke (AIS) therapy. Brain cytoprotective agents can prevent detrimental effects of ischaemia, and therefore 'freeze' ischaemic penumbra before reperfusion, extend the time window for reperfusion therapy. Because reperfusion often leads to reperfusion injury, including haemorrhagic transformation, brain oedema, infarct progression and neurological worsening, cytoprotective agents will enhance the efficacy and safety of reperfusion therapy by preventing or reducing reperfusion injuries. Therefore, reperfusion and cytoprotective agents are a mutually beneficial pair in AIS therapy. In this review, we outline critical pathophysiological events causing cell death within the penumbra after ischaemia or ischaemia/reperfusion in the acute phase of AIS, focusing on excitotoxicity and free radicals. We discuss key pharmacological targets for cytoprotective therapy and evaluate the recent advances of cytoprotective agents going through clinical trials, highlighting multitarget cytoprotective agents that intervene at multiple levels of the ischaemic and reperfusion cascade.
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OBJECTIVE: This study aims to explore the correlation between central and peripheral thyroid resistance indices and diabetic retinopathy(DR) in patients with type 2 diabetes mellitus (T2DM), so as to provide a clinical basis for the prevention and treatment of diabetic retinopathy. METHODS: This study retrospectively analyzed 1249 euthyroid patients with T2DM hospitalized in the Department of Endocrinology, Peking University International Hospital from January 2017 to June 2022, including 852 males and 397 females, with an average age of 54.73 ± 13.40 years. According to the degree of DR, the patients were divided into three groups including the no diabetic retinopathy (NDR) group, non-proliferative diabetic retinopathy (NPDR) group and proliferative diabetic retinopathy (PDR) group. RESULTS: Free thymidine (FT4), thyroid stimulating hormone (TSH), thyroid feedback quantile index (TFQI), thyrotropin-T4 resistance index (TT4RI), thyroid stimulating hormone index (TSHI) and free triiodothyronine/free thyroxine (FT3/FT4) levels among the three groups were significantly different, with the NDR group having lowest TSH, TFQI, TT4QI, TSHI and the highest in the PDR group (all p < 0.05). Logistic regression showed that after adjusting for age, body mass index (BMI), sex, diabetes duration, blood pressure, blood lipid, HbA1c, lower level of FT4 was an independent risk factor for DR, high level of TSH, TFQI, TSHI and TT4RI were independent risk factors for DR. Central and peripheral thyroid sensitivity indices have predictive value for DR, the overall predictive accuracy of FT3/FT4 was 0.61 (95%CI 0.57, 0.65), the overall predictive accuracy of TFQI was 0.66(95%CI 0.63, 0.70), the overall predictive accuracy of TSHI was 0.66(95%CI 0.62, 0.68), the overall predictive accuracy of TT4RI was 0.63 (95%CI 0.59, 0.66). CONCLUSION: The reduction of central and peripheral thyroid hormone sensitivity is an independent risk factor for DR. These results can help predict the risk of the occurrence and development of DR, which may provide a clinical basis for the prevention and treatment of DR in T2DM patients.
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Diabetes Mellitus Tipo 2 , Enfermedades de la Retina , Femenino , Masculino , Humanos , Adulto , Persona de Mediana Edad , Anciano , Glándula Tiroides , Diabetes Mellitus Tipo 2/complicaciones , Estudios Retrospectivos , Tirotropina , Triyodotironina , China/epidemiologíaRESUMEN
Background: According to the 2023 guidelines for treating non-small-cell lung cancer (NSCLC), first-line treatment and recently developed agents for the treatment of epidermal growth factor (EGFR) mutation-positive locally advanced or metastatic NSCLC were compared in this meta-analysis. Treatment regimens involved in the included studies included first, second, and third-generation tyrosine kinase inhibitors (TKIs), TKIs plus chemotherapy, TKIs plus angiogenesis inhibitors, and platinum-containing doublet chemotherapy with or without bevacizumab. Considering the varying efficacy and safety of drugs in people of different ethnic origins, the optimal regimen should be determined, and the safety of first-line treatments should be assessed in the Asian population specifically. Methods: PubMed, Embase, the Cochrane Library, Web of Science, and the China National Knowledge Infrastructure (CNKI) were systematically searched to retrieve reports on randomized controlled trials (RCTs) with research data published from inception to 1 February 2023. Adopting Asian patient populations as the target (including studies in which Asian patients accounted for more than 50% of the sample), a network meta-analysis (NMA) was conducted for comparison of treatment regimens and treatments were ranked based on the surface under the cumulative ranking curve (SUCRA). Results: A total of 19 RCTs involving 5,824 patients and covering 14 treatment regimens were included. The primary outcome measure examined in this study was progression-free survival (PFS); other outcome measures examined were overall survival (OS), disease control rate (DCR), objective response rate (ORR), occurrence of any adverse events (AE), occurrence of adverse events of grade 3 or above (≥3AE), and occurrence of serious adverse events (SAE). In terms of PFS, all regimens including TKIs (as a monotherapy or in combination with other therapies), as well as bevacizumab (Bev) plus chemotherapy (Ch) were found to be significantly superior to basic chemotherapy (HRs: 0.09-0.61, p < 0.05 in all cases compared with Ch alone). The highest-ranking therapies were erlotinib (Erl) plus Bev (SUCRA: 0.94) and Erl plus ramucirumab (Ram) (SUCRA: 0.93). Regarding OS, no significant differences was observed between first-line treatment strategies; the top four treatments based on SUCRA, in rank order, were Bev + Ch (0.87), gefitinib (Gef) plus Ch (0.81), dacomitinib (Dac) (0.79), and osimertinib (Osi) (0.69). Additionally, there were no significant differences between first-line treatment strategies in terms of DCR. Regarding ORR, the top three treatments based on SUCRA were Erl + Bev (0.85), Erl + Ram (0.76), and Gef + Ch (0.74). No significant difference between first-line treatment strategies was observed in terms of the risk of AE. However, based on SUCRA, Erl ranked highest on avoidance of ≥ 3AE (0.97), and Osi ranked highest on avoidance of SAE (0.91). Conclusion: Based on these analyses of survival benefits, tumor burden response, and safety, furmonertinib (Fur), Osi, and aumolertinib (Aum) may represent the best treatment regimen options for Asian patients, significantly prolonging survival (as measured by median PFS/OS), eliciting a greater tumor burden response, and exposing patients to a lower risk of adverse events. Although Erl + Bev and Erl + Ram are associated with the best survival benefits in terms of PFS, further clinical studies are still needed to identify ways to reduce the risk of adverse events. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42023407994, identifier CRD42023407994.
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This paper uses the tourism heat footprint (THF) and a structural vector autoregressive model to investigate how tourism has affected the urban heat island effect in Macao, a typical urban tourism destination. The dynamic relationships between the THF, heat island intensity (HII), and quarterly average temperature (QAT) are investigated. The impulse response function and variance decomposition analysis are used to assess if a long-term causal relationship exists between the three indicators. The results show the following. (1) The hotel industry in Macao is the source of energy consumption and heat release. (2) A Granger causality relationship exists between the THF and QAT but not between the THF and HII. (3) The interaction effect between the growth rate of the THF and QAT is manifested as shocks with the same frequency and regular periodic fluctuations. (4) The heat island effect of this tourism destination is reflected in an increase in local temperature due to the energy consumption and heat release by tourists. Based on the results, policy implications for a sustainable tourism city are provided.
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Analyzing collaborations on energy research in the hotel industry has important implications for promoting the research performance in this field. The Web of Science Core Collection from 1984 to 2022 was used to analyze the research contributions and cooperation networks and clusters at three levels: macro (national level), meso (institutional level), and micro (key authors and papers) using a bibliometric approach. The results show the following. (1) The cooperative relationship is the closest between China and the United States. Developed countries in Europe exhibit more academic cooperation. (2) There is a significant regional imbalance in the cooperation between universities. Leading universities rely on their strengths in energy research or hotel management and are often highly productive institutions. (3) The breadth of the authors' cooperation is insufficient. Collaborative research dominated by productive authors tends to focus on practical issues in the local hotel industry. The collaboration between experts from different disciplines benefits from the complementary advantages of these experts. (4) Hotel energy research has evolved from single-disciplinary research in the early days to interdisciplinary research in recent years. This paper provides visualizations of current conditions and deficiencies in existing research collaborations and provides a reference for analyzing the potential of research cooperation.
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Cardiac autonomic neuropathy has a high prevalence in type 2 diabetes, which increases the risk of cardiovascular system disorders. CpG oligodeoxynucleotide (CpG-ODN), a Toll-like receptor 9 (TLR9) ligand, has been shown to have cardioprotection and cellular protection. Our previous work showed that P2Y12 in stellate ganglia (SG) is involved in the process of diabetic cardiac autonomic neuropathy (DCAN). Here, we aim to investigate whether CpG-ODN 1826 plays a protective role in DCAN and whether this beneficial protection involves regulation of the P2Y12-mediated cardiac sympathetic injury. Our results revealed that CpG-ODN 1826 activated TLR9 receptor, improved the abnormal blood pressure (BP), heart rate (HR), heart rate variability (HRV) and sympathetic nerve discharge (SND) activity in diabetic rats and reduced the up-regulated NF-κB, P2Y12 receptor, TNF-α and IL-1ß in SG. Meanwhile, CpG-ODN 1826 significantly decreased the elevated ATP, nuclear receptor coactivator 4 (NCOA4), iron, ROS and MDA levels and increased GPX4 and GSH levels. In addition, CpG-ODN 1826 contributes to maintain normalization of mitochondrial structure in SG. Overall, CpG-ODN 1826 alleviates the sympathetic excitation and abnormal neuron-glial signal communication via activating TLR9 receptors to achieve a balance of autonomic activity and relieve the DCAN in rats. The mechanism may involve the regulation of P2Y12 receptor in SG by reducing ATP release and NF-κB expression, which counteract neuroinflammation and ferroptosis mediated by activated P2Y12 in SG.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Ratas , Animales , FN-kappa B/metabolismo , Receptor Toll-Like 9/metabolismo , Antagonistas del Receptor Purinérgico P2Y , Diabetes Mellitus Experimental/metabolismo , Ganglio Estrellado/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Oligodesoxirribonucleótidos/farmacología , Oligodesoxirribonucleótidos/uso terapéutico , Adenosina Trifosfato/metabolismoRESUMEN
Plant growth is coordinately controlled by various environmental and hormonal signals, of which light and gibberellin (GA) signals are two critical factors with opposite effects on hypocotyl elongation. Although interactions between the light and GA signaling pathways have been studied extensively, the detailed regulatory mechanism of their direct crosstalk in hypocotyl elongation remains to be fully clarified. Previously, we reported that ABA INSENSITIVE 4 (ABI4) controls hypocotyl elongation through its regulation of cell-elongation-related genes, but whether it is also involved in GA signaling to promote hypocotyl elongation is unknown. In this study, we show that promotion of hypocotyl elongation by GA is dependent on ABI4 activation. DELLAs interact directly with ABI4 and inhibit its DNA-binding activity. In turn, ABI4 combined with ELONGATED HYPOCOTYL 5 (HY5), a key positive factor in light signaling, feedback regulates the expression of the GA2ox GA catabolism genes and thus modulates GA levels. Taken together, our results suggest that the DELLA-ABI4-HY5 module may serve as a molecular link that integrates GA and light signals to control hypocotyl elongation.
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Proteínas de Arabidopsis , Arabidopsis , Giberelinas/metabolismo , Hipocótilo/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Luz , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismoRESUMEN
Stroke is a leading cause of adult disability worldwide, and better drugs are needed to promote functional recovery after stroke. Growing evidence suggests the critical role of network excitability during the repair phase for stroke recovery. Here, we show that ß-hydroxybutyrate (ß-HB), an essential ketone body (KB) component, is positively correlated with improved outcomes in patients with stroke and promotes functional recovery in rodents with stroke during the repair phase. These beneficial effects of ß-HB depend on HDAC2/HDAC3-GABA transporter 1 (GAT-1) signaling-mediated enhancement of excitability and phasic GABA inhibition in the peri-infarct cortex and structural and functional plasticity in the ipsilateral cortex, the contralateral cortex, and the corticospinal tract. Together with available clinical approaches to elevate KB levels, our results offer a clinically translatable means to promote stroke recovery. Furthermore, GAT-1 can serve as a pharmacological target for developing drugs to promote functional recovery after stroke.
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Cuerpos Cetónicos , Accidente Cerebrovascular , Humanos , Proteínas Transportadoras de GABA en la Membrana PlasmáticaRESUMEN
Adenosine triphosphate (ATP) acts on P2 purinergic receptors as an extracellular signaling molecule. P2 purinergic receptors include P2X ionotropic receptors and P2Y metabotropic receptors. Satellite glial cells (SGCs) and macrophages express P2X and P2Y receptors. Inflammatory cytokines and pro-nociceptive mediators are released by activated macrophages and SGCs, which can act on neurons to promote excitability and firing. In the primary sensory ganglia, in response to signals of injury, SGCs and macrophages accumulate around primary sensory neurons, forming a macrophage-SGC-neuron triad. In addition to affecting the pathological alterations of inflammation-related neuropathic pain, inflammatory cytokines and pro-nociceptive mediators are released by the action of ATP on P2X and P2Y receptors in macrophages and SGCs. Macrophages and SGCs work together to enhance and prolong neuropathic pain. The macrophage-SGC-neuron triad communicates with each other through ATP and other inflammatory mediators and maintains and promotes the initiation and development of inflammation related-neuropathic pain. This article is part of the Special Issue on "Purinergic Signaling: 50 years".
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Macrófagos , Neuralgia , Neuroglía , Enfermedades Neuroinflamatorias , Receptores Purinérgicos P2 , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2/fisiología , Neuralgia/metabolismo , Neuralgia/patología , Macrófagos/metabolismo , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , Neuroglía/metabolismo , Neuroglía/patología , Humanos , Animales , RatonesRESUMEN
Apples, as a typical agricultural product with high added value, play a significant role in increasing farmers' income and promoting regional economic growth. They have become one of the main ways for farmers to develop agricultural and sideline products in China's Loess Plateau and Bohai Rim region. Based on panel data for provinces from 2007 to 2020, this study used stochastic frontier analysis to calculate the technical efficiency of apple production in China's major apple-producing areas and then introduced urbanization rate as the threshold variable. Based on the quantity, quality, and structure of the rural labor force, the threshold model was used to empirically analyze the effect of labor transfer at different stages of urbanization on industrial technical efficiency in the main apple-producing areas. The results showed that labor transfer had an obvious negative effect on apple production. The labor transfer at the national level has had an obvious negative impact on the output of the apple industry, and the impact of labor transfer on the technical efficiency of China's apple industry is significantly different; that is, the impact of labor outflow on the technical efficiency of apple production is different in different regions. In some areas, the technical efficiency of production in the main apple-producing areas can be significantly improved. Finally, the proportion of the labor force showed significant differences in its effect on technical efficiency in different stages of urbanization.
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Malus , Agricultura , Urbanización , Desarrollo Económico , Eficiencia , ChinaRESUMEN
This paper discusses the compensation standard for exhaust pollution and devises a compensation mechanism for Macao's tourism-related transport sector based on an integration of chemical exergy and universal exergy, using data on gasoline consumption by automobile sector retrieved from the transportation industry. The results reveal that: (1) the exergy values of air pollutant emissions increased from 1.53 × 1012 kJ in 2010 to 2.03 × 1012 kJ in 2019 (an increase of 1.33 times), and the exergy of CO, NOx, and SO2 emissions accounted for 77.5%, 20.4% and 2.1% of total exhaust emissions in Macao respectively. (2) In 2019, the monetary value of emission exergy, and the environmental costs of air pollution, were 1.7 times greater than in 2010. (3) If Light Rail Transit is compensated for, then the mean interval's values of the upper and lower limits of the compensation standard are 0.55 USD and 0.05 USD, respectively. When gasoline tax is used as a means of compensation it is necessary to raise its rate by about 8% based on the tax rate. A three-stage bargaining game model is used to provide evidence that this compensation standard is practical and acceptable.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Atmosféricos/análisis , Gasolina , Macao , Turismo , Contaminación del Aire/análisis , Emisiones de Vehículos/análisisRESUMEN
Ferroptosis is an inflammatory programmed cell death process that is dependent on iron deposition and lipid peroxidation. The P2X7 receptor not only is involved in the pain process but also is closely related to the onset of depression. Gallic acid (3,4,5-trihydroxybenzoic acid), which is naturally found in a variety of plants, exhibits anti-inflammatory, antioxidant, and analgesic effects. This study established a rat model with the comorbidity of chronic constrictive injury (CCI) plus chronic unpredictable mild stress (CUMS) to explore the role and mechanism of gallic acid in the treatment of pain and depression comorbidity. Our experimental results showed that pain and depression-like behaviors were more obvious in the chronic constriction injury (CCI) plus chronic unpredictable mild stimulation (CUMS) group than they were in the sham operation group, and the P2X7-reactive oxygen species (ROS) signaling pathway was activated. The tissue iron concentration was increased, and mitochondrial damage was observed in the CCI plus CUMS group. These results were alleviated with gallic acid treatment. Therefore, we speculate that gallic acid inhibits the ferroptosis of the spinal microglia by regulating the P2X7-ROS signaling pathway and relieves the behavioral changes in rats with comorbid pain and depression.
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Dolor Crónico , Ferroptosis , Neuralgia , Ratas , Animales , Dolor Crónico/tratamiento farmacológico , Ratas Sprague-Dawley , Receptores Purinérgicos P2X7 , Depresión/tratamiento farmacológico , Ácido Gálico/farmacología , Ácido Gálico/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Neuralgia/metabolismo , Médula Espinal/metabolismo , ComorbilidadRESUMEN
The exponential random graph model (ERGM) is an effective approach for testing the dynamic and local processes of a network. This paper explores the structure of stakeholders' partnerships in a tourism waste management network using high-order dependency ERGMs based on relational data obtained from a field survey in Motuo County, China. The results reveal that (1) the network has many edges, indicating a tight network; (2) the geometrically weighted edge distribution shows a high transitive effect of the network; (3) the structural effect is more significant than the attribute effect; (4) there is a good agreement between the simulation results and observations, suggesting a tourism waste network with close connections and collaborative division of labor. These findings indicate that different groups of stakeholders have been extensively involved in tourism waste management in Motuo County. The edgewise shared partners formed by stakeholders of different groups increase the information transmission efficiency of the network. The results have implications for tourism waste management, specifically for promoting sustainability transitions via network governance.
Asunto(s)
Turismo , Administración de Residuos , Simulación por Computador , Proyectos de Investigación , ChinaRESUMEN
The comorbid mechanism of depression and chronic pain has been a research hotspot in recent years. Until now, the role of purinergic signals in the comorbid mechanism of depression and chronic pain has not been fully understood. This review mainly summarizes the research results published in PubMed during the past 5 years and concludes that purinergic signaling is a potential therapeutic target for comorbid depression and chronic pain, and the purinergic receptors A1, A2A, P2X3, P2X4, and P2X7and P2Y6, P2Y1, and P2Y12 may be important factors. The main potential pathways are as follows: A1 receptor-related G protein-dependent activation of introverted K+ channels (GIRKs), A2A receptor-related effects on the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and MAPK/nuclear factor-κB (NF-κB) pathways, P2X3 receptor-related effects on dorsal root ganglia (DRG) excitability, P2X4 receptor-related effects on proinflammatory cytokines and inflammasome activation, P2X7 receptor-related effects on ion channels, the NLRP3 inflammasome and brain-derived neurotrophic factor (BDNF), and P2Y receptor-related effects on the phospholipase C (PLC)/inositol triphosphate (IP3)/Ca2+ signaling pathway. We hope that the conclusions of this review will provide key ideas for future research on the role of purinergic signaling in the comorbid mechanism of depression and chronic pain.