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1.
Heliyon ; 10(16): e35607, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39224360

RESUMEN

The human rights and mega sport events (SMEs) discourses gain massive importance and have grown immensely in recent years. Most of the time, the sports governance bodies are responsible for administration and management of these sport mega events. Keeping in consideration the situation regarding increasing involvement, the study focuses on the field of sport along with pleasure and basic rights. Through re-evaluation the commercial factors of sports, the mega governing bodies of sport (IOC & FIFA), and researchers discuss what is referred to commonly as Ruggie Principle, and both would be applied to IOC & FIFA practices, operation, and management regarding their events. This study is essential as it emphasizes the contribution and importance of carrying out human rights impact assessments, particularly in the context of hosting rights. The survey's findings reveal that human rights and due diligence assessments are integral components of organizations such as FIFA and the IOC. This study, being an empirical investigation, allowed us to arrive at some normative conclusions that had significant implications for practices and policy issues. Additionally, it laid the groundwork for future research in the crucial area of SMEs globally.

2.
Front Pharmacol ; 15: 1324509, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39246661

RESUMEN

Background: Chinese patent medicines are specialty preparations in China that are produced using traditional prescriptions processed by modern pharmaceutical technology. They contain complex ingredients and much attention is paid to their clinical safety. Demonstrating the clinical safety of Chinese patent medicines containing toxic ingredients in modern pharmacological studies has become one of the urgent issues to be solved for the safe use of clinical medicines. Objectives: The aim of this research is to evaluate the safety of Chinese patent medicines containing toxic ingredients by applying the risk-benefit assessment method. Additionally, a database of 'toxic ingredients-toxic Chinese herbal medicines-adverse reactions' will be established to explore the relationship between toxic ingredients and adverse reactions. This will lay the foundation for the rational clinical use of Chinese patent medicines containing toxic ingredients. Methods: 1) Establish a database of 'toxic Chinese herbal medicines-toxic ingredients-toxic Chinese patent medicines' to count the Chinese patent medicines containing toxic ingredients in the 2020 edition of Chinese Pharmacopoeia. 2) Filtered the clinical studies, extracted the drug-related ADEs, and analyzed the characteristics and correlations of these ADEs. 3) Finally, this section summarizes the causes of ADEs related to Chinese patent medicines containing toxic ingredients and extracts the main risk factors to provide a reference for further study. Outcomes: 1) There are four main types of Chinese patent medicines containing toxic ingredients. These include medicines with diester aconitine metabolites, mineral composition, Araceae metabolites, and hydrogen cyanide. 2) Digestive system, skin and its appendages, and allergic reactions were the main types of ADEs related to four types of Chinese patent medicines containing toxic ingredients. 3) There are four primary risk factors associated with the clinical use of Chinese patent medicines containing toxic ingredients: medicine, medication, individual and regulatory factors.

3.
Org Lett ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39248657

RESUMEN

A cooperative Rh(II)/Pd(0) dual-catalysis strategy that enabled divergent reactions of α-diazo 1,3-dicarbonyl compounds with allylic carbonates involving ketene versus carbene intermediates is described. The efficient synthesis of α-quaternary allylated ß-keto-esters was accomplished by the Rh(II)/Pd(0) dual-catalysis allylic alkylation of α-diazo 1,3-dicarbonyl compounds. Alternatively, an unprecedented (1+4) annulation of α-diazo 1,3-dicarbonyl compounds with 2-(hydroxymethyl)allyl carbonates via Rh(II)/Pd(0) dual catalysis was also successfully developed, affording a wide variety of α-quaternary tetrahydrofurans in good to high yields.

4.
Biodivers Data J ; 12: e129087, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39229385

RESUMEN

Background: As a genus within the Clavicipitaceae, Metarhizium exhibits rich morphological and ecological diversity, with a wide distribution and a variety of hosts. Currently, sixty-eight species of Metarhizium have been described. New information: A new species of Metarhizium, M.puerense (Hong Yu bis), was described in Pu'er City, Yunnan Province, south-western China. Based on morphological characteristics and multilocus phylogenetic analyses, Metarhiziumpuerense was confirmed to be phylogenetically related to M.album, but was clearly separated and formed a distinct branch. In contrast, the host of Metarhiziumalbum was plants and leafhoppers and that lepidopteran larvae were the host of M.puerense. The diagnostic features of M.puerense were solitary to multiple stromata and smooth-walled, cylindrical with rounded apices conidia.

5.
J Sport Health Sci ; : 100976, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39237062

RESUMEN

BACKGROUND: Deficits in quadriceps strength of the injured leg have been observed in patients following anterior cruciate ligament (ACL) reconstructions and may contribute to ACL re-injury risk. Single-leg forward hopping is a widely used task for assessing knee function in patients following ACL reconstructions as it has been shown not to be particularly challenging to the knee. This study aimed to quantify the effect of decreased quadriceps strength induced by a fatigue protocol on hopping performance and lower limb mechanics in single-leg forward, vertical, and backward hopping. METHODS: Thirty-four injury-free participants performed single-leg forward, vertical, and backward hopping on both legs pre- and post-fatigue, with 1 leg experiencing a fatigue protocol. Peak moments, power, and work of hip, knee, and ankle joints were quantified during the jumping phase. Hopping performance and bilateral asymmetries in performance were assessed. RESULTS: Single-leg backward hopping demonstrated the greatest knee moments, power, and work compared to forward and vertical hopping, regardless of leg and fatigue. Fatigue protocol resulted in significantly less knee moments, power, and work, and decreased performance of the fatigued leg among all tasks. Bilateral symmetries in hopping performance decreased in post-fatigue, with the greatest decrease in backward hopping. CONCLUSION: The greater sensitivity of the backward hopping to detect quadriceps fatigue suggests it may act as a better or at least an additional metric to evaluate quadriceps strength deficits. The findings may contribute to the development of a clinically applicable and valid strength assessment to monitor the rehabilitation progress in patients following ACL reconstructions.

6.
Nat Commun ; 15(1): 7738, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39232004

RESUMEN

China faces challenges in reaching its carbon neutrality goal by the year 2060 to meet the Paris Agreement and improving air quality simultaneously. Dramatic nitrogen emission reductions will be brought by this ambitious target, yet their impact on the natural ecosystem is not clear. Here, by combining two atmospheric chemistry models and two process-based terrestrial ecosystem models constrained using nationwide measurements, we show that atmospheric nitrogen deposition in China's terrestrial land will decrease by 44-57% following two emission control scenarios including one aiming at carbon neutrality. They consequently result in a pronounced shrinkage in terrestrial net ecosystem production, by 11-20% depending on models and emission scenarios. Our results indicate that the nitrogen emission reductions accompanying decarbonization would undermine natural carbon sinks and in turn set back progress toward carbon neutrality. This unintended impact calls for great concern about the trade-offs between nitrogen management and carbon neutrality.

7.
Int J Cancer ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39177486

RESUMEN

Locally advanced breast cancer (LABC) is challenging with limited treatment options. This study investigates the feasibility and long-term outcomes of upfront surgery compared to neoadjuvant chemotherapy (NAC) in a real-world cohort. This retrospective study analyzed 243 inoperable LABC patients (excluding T3N1M0) that underwent upfront surgery (n = 187) or NAC (n = 56) in matched groups. Disease-free survival (DFS) and overall survival (OS) are primary outcomes. Secondary outcomes included NAC response rate and subgroup analyses based on age, tumor stage, and treatment response. Survival was estimated using Kaplan-Meier methods with log-rank tests for comparisons. Cox proportional hazards models were used for subgroup analyses. With a median follow-up of 60.9 months, no significant difference emerged in 5-year OS (upfront surgery: 89.6%, NAC: 81.9%, p = .12) or 5-year DFS rates (73.0% vs. 67.1%, p = .24). Subgroup analyses revealed upfront surgery offered significantly better OS for patients under 60 (HR = 0.32; 95% CI: 0.10-0.96; p = .0429) and stage IIIA disease (HR = 0.22; CI: 0.06-0.86; p = .03). Upfront surgery showed a trend towards improved OS for tumors under 5 cm (HR = 0.37; 95% CI: 0.13-1.03; p = .056). Patients with progressive disease (PD) or stable disease (SD) after NAC had significantly worse DFS (HR = 0.27; 95% CI: 0.09-0.79; p = .017) and OS (HR = 0.09; 95% CI: 0.02-0.48; p = .004) compared to responders. Upfront surgery may be viable for LABC patients, particularly younger patients, those with stage IIIA disease, or smaller tumors. NAC response can inform treatment decisions. These findings highlight the need for personalized LABC treatment considering patient characteristics and NAC response.

8.
Front Plant Sci ; 15: 1403869, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39086918

RESUMEN

Kiwifruit bacterial canker, caused by Pseudomonas syringae pv. actinidiae (PSA), poses a grave threat to the global kiwifruit industry. In this study, we examined the role of microRNAs (miRNAs) in kiwifruit's response to PSA. Kiwifruit seedlings subjected to PSA treatment showed significant changes in both miRNA and gene expression compared to the control group. We identified 364 differentially expressed miRNAs (DEMs) and 7170 differentially expressed genes (DEGs). Further analysis revealed 180 miRNAs negatively regulating 641 mRNAs. Notably, two miRNAs from the miRNA482 family, miRNA-215-3p and miRNA-29-3p, were found to increase kiwifruit's sensitivity to PSA when overexpressed. These miRNAs were linked to the regulation of NBS-LRR target genes, shedding light on their role in kiwifruit's defence against PSA. This study offers insights into the miRNA482-NBS-LRR network as a crucial component in enhancing kiwifruit bioresistance to PSA infestation and provides promising candidate genes for further research.

9.
Opt Lett ; 49(15): 4210-4213, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090896

RESUMEN

The large-scale deployment of quantum secret sharing (QSS) in quantum networks is currently challenging due to the requirements for the generation and distribution of multipartite entanglement states. Here we present an efficient source-independent QSS protocol utilizing entangled photon pairs in quantum networks. Through the post-matching method, which means the measurement events in the same basis are matched, the key rate is almost independent of the number of participants. In addition, the unconditional security of our QSS against internal and external eavesdroppers can be proved by introducing an equivalent virtual protocol. Our protocol has great performance and technical advantages in future quantum networks.

10.
PNAS Nexus ; 3(8): pgae291, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39108300

RESUMEN

Atmospheric sulfate aerosols contribute significantly to air pollution and climate change. Sulfate formation mechanisms during winter haze events in northern China have recently received considerable attention, with more than 10 studies published in high-impact journals. However, the conclusions from in-field measurements, laboratory studies, and numerical simulations are inconsistent and even contradictory. Here, we propose a physically based yet simple method to clarify the debate on the dominant sulfate formation pathway. Based on the hazes evolving in the synoptic scale, first, a characteristic sulfate formation rate is derived using the Eulerian mass conservation equation constrained by in situ observations. Then, this characteristic value is treated as a guideline to determine the dominant sulfate formation pathway with a 0D chemical box model. Our observation-derived results establish a linkage between studies from laboratory experiments and chemical transport model simulations. A convergent understanding could therefore be reached on sulfate formation mechanisms in China's wintertime haze. This method is universal and can be applied to various haze conditions and different secondary products.

11.
ACS Nano ; 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39185844

RESUMEN

Sweat analysis has advanced from diagnosing cystic fibrosis and testing for illicit drugs to noninvasive monitoring of health biomarkers. This article introduces the rapid development of wearable and flexible sweat sensors, highlighting key milestones and various sensing strategies for real-time monitoring of analytes. We discuss challenges such as developing high-performance nanomaterial-based biosensors, ensuring continuous sweat production and sampling, achieving high sweat/blood correlation, and biocompatibility. The potential of machine learning to enhance these sensors for personalized healthcare is presented, enabling real-time tracking and prediction of physiological changes and disease onset. Leveraging advancements in flexible electronics, nanomaterials, biosensing, and data analytics, wearable sweat biosensors promise to revolutionize disease management, prevention, and prediction, promoting healthier lifestyles and transforming medical practices globally.

12.
Heliyon ; 10(15): e34991, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39157315

RESUMEN

Common cancer complications include bone cancer pain (BCP), which was not sufficiently alleviated by traditional analgesics. More safe and effective therapy was urgent needed. Metformin relieved osteoarthritis pain, but the analgesia of Metformin in BCP was not well studied. The study aimed to explore the Metformin-mediated analgesic effect and its molecular mechanisms in BCP rats. We demonstrated that Walker 256 cell transplantation into the medullary cavity of the tibia worsened mechanical allodynia in BCP rats, increased the expression of TGFß1 in the metastatic bone tissue, and raised the expression of TGFßRI and TRPV1 in the L4-6 dorsal root ganglion (DRG) of BCP rats. While, selectively blockade of TGFßRI by SD208 could obviously elevated the paw withdraw threshold (PWT) of BCP rats, together with decreased TRPV1 expression in L4-6 DRG. Notably, continuous Metformin treatment reduced TGFß1, TGFßRI and TRPV1 expression, and relieved mechanical allodynia of BCP rats in a long-term effect. In conclusion, these results illustrated that Metformin ameliorated bone cancer pain, and the downregulation of TGFß1-TGFßRI-TRPV1 might be a potential mechanism of Metformin-mediated analgesia in BCP.

13.
Environ Int ; 191: 108958, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39153386

RESUMEN

Regional budget assessments of methane (CH4) are critical for future climate and environmental management. CH4 emissions from rice cultivation (CH4-rice) constitute one of the most significant sources. However, previous studies mainly focus on historical emission estimates and lack consideration of future changes in CH4-rice under climate change or anthropogenic policy intervention, which hampers our understanding of long-term trends and the implementation of targeted emission reduction efforts. This study investigates the spatiotemporal variations of CH4-rice over the past two decades, using an integrated method to identify the major drivers and predict future emissions under climate change scenarios and policy perspectives. Results indicate that the CH4-rice emissions in China ranged between 6.21 and 6.57 Tg yr-1 over the past two decades, with a spatial distribution characterized by decreases in the south and increases in the north, associated with economic development, dietary shifts, technological advancements, and climate change. Factors such as the rate of straw added (RSA), fertilization, soil texture, temperature, and precipitation significantly influence CH4 emissions per unit rice production (CH4-urp), with RSA identified as the most significant tillage management factor, explaining 32 % of the variance. Lowering RSA to 8 % is beneficial for reducing CH4-urp. Scenario analysis indicates that under policies focusing on production or demand, CH4-rice is expected to increase by 0.3 % to 5.6 %, while adjusting RSA can reduce CH4-rice by 9.4 % to 10.0 %. Structural adjustments and regional cooperation serve as beneficial starting points for controlling and reducing CH4-rice in China, while optimizing industrial layouts contributes to regional development and CH4-rice control. Implementing policies related to maintaining field and crop yields can achieve a balance between rice supply and demand ahead of schedule. Dynamic adjustment of rice cultivation based on supply-demand balance can effectively reduce CH4-rice from excess rice production. By 2060, the reduction effect could reach 8.95 %-12.01 %. Introducing policy-driven tillage management measures as reference indicators facilitates the reduction of CH4-rice.

15.
Cell Biochem Biophys ; 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39154131

RESUMEN

Intrauterine adhesion (IUA) resulting from irreversible fibrotic repair of endometrium is the main cause of secondary infertility in women, and current therapeutic approaches to IUA are limited. Increasing evidence has suggested the important role of competitive endogenous RNA (ceRNA) in IUA pathologies. This study aimed to investigate the long noncoding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1)-associated ceRNA in IUA development. We harvested endometrial tissues from patients with or without IUA and extracted endometrial stromal cells (ESCs) from normal endometrial tissues. Transforming growth factor ß1 (TGF-ß1) was used to induce fibrosis in ESCs. The expression of transforming growth factor ß receptor 1 (TGFßR1), α-smooth muscle actin, phosphorylated suppressor of mother against decapentaplegic (p-Smad)2/3, collagen type I alpha 1, MALAT1, and microRNA (miR)-22-3p in endometrial tissues and ESCs was measured by reverse transcription quantitative polymerase chain reaction (RT-qPCR) or western blotting. Pearson's correlation analysis was conducted to assess the correlation between miR-22-3p expression or TGFßR1 and MALAT1 expression in endometrial tissues. The expression of TGFßR1 in ESCs was also evaluated by immunofluorescence staining. The location of MALAT1 was examined by fluorescence in situ hybridization. Luciferase reporter assays were performed to verify the binding relationship between MALAT1 or TGFßR1 and miR-22-3p. Cell viability was assessed via cell counting kit-8 assays. Our findings revealed that lncRNA MALAT1 and TGFßR1 were upregulated while miR-22-3p was downregulated in IUA endometrial tissues or TGF-ß1-stimulated ESCs, and lncRNA MALAT1 expression was negatively correlated with miR-22-3p expression while being positively correlated with TGFßR1 expression in IUA endometrial tissues. Additionally, lncRNA MALAT1 was mainly located in the cytoplasm of ESCs and directly targeted miR-22-3p to regulate TGFßR1 expression. Moreover, knockdown of lncRNA MALAT1 exerted anti-fibrotic effects on ESCs by targeting miR-22-3p, and miR-22-3p overexpression inhibited the fibrosis of ESCs by binding to TGFßR1 3'untranslated region. Collectively, lncRNA MALAT1 promotes endometrial fibrosis by sponging miR-22-3p to regulate TGFßR1 and Smad2/3, and inhibition of MALAT1 may represent a promising therapeutic option for suppressing endometrial fibrosis.

16.
Chemistry ; : e202402558, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39158512

RESUMEN

The high electrochemical reactivity of H2O molecules and zinc metal results in severe side reactions and dendrite formation on zinc anodes. Here we demonstrate that these issues can be addressed by using N-hydroxymethylacetamide (NHA) as additives in 2 M ZnSO4 electrolytes. The addition of NHA molecules, acting as both a hydrogen bond donor and acceptor, enables the formation of cyclic hydrogen bonding with H2O molecules. This interaction disrupts the existing hydrogen bonding networks between H2O molecules, hindering proton transport, and containing H2O molecules within the cyclic hydrogen bonding structure to prevent deprotonation. Additionally, NHA molecules show a preference for adsorption on the (101) crystal surface of zinc metal. This preferential adsorption reduces the surface energy of the (101) plane, facilitating the homogeneous Zn deposition along the (101) direction. Thus, the NHA enables Zn||Zn symmetric cell with a cycle lifespan of 1100 hours at 5 mA cm-2 and Zn||Cu asymmetric cell with a high Coulombic efficiency over 99.5%. Moreover, the NHA-modified Zn||AC zinc ion hybrid capacitor is capable of sustaining 15000 cycles at 2 A g-1. This electrolyte additive engineering presents a promising strategy to enhance the performance and broaden the application potential of zinc metal-based energy storage devices.

17.
BMC Med Res Methodol ; 24(1): 186, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39187791

RESUMEN

BACKGROUND: According to long-term follow-up data of malignant tumor patients, assessing treatment effects requires careful consideration of competing risks. The commonly used cause-specific hazard ratio (CHR) and sub-distribution hazard ratio (SHR) are relative indicators and may present challenges in terms of proportional hazards assumption and clinical interpretation. Recently, the restricted mean time lost (RMTL) has been recommended as a supplementary measure for better clinical interpretation. Moreover, for observational study data in epidemiological and clinical settings, due to the influence of confounding factors, covariate adjustment is crucial for determining the causal effect of treatment. METHODS: We construct an RMTL estimator after adjusting for covariates based on the inverse probability weighting method, and derive the variance to construct interval estimates based on the large sample properties. We use simulation studies to study the statistical performance of this estimator in various scenarios. In addition, we further consider the changes in treatment effects over time, constructing a dynamic RMTL difference curve and corresponding confidence bands for the curve. RESULTS: The simulation results demonstrate that the adjusted RMTL estimator exhibits smaller biases compared with unadjusted RMTL and provides robust interval estimates in all scenarios. This method was applied to a real-world cervical cancer patient data, revealing improvements in the prognosis of patients with small cell carcinoma of the cervix. The results showed that the protective effect of surgery was significant only in the first 20 months, but the long-term effect was not obvious. Radiotherapy significantly improved patient outcomes during the follow-up period from 17 to 57 months, while radiotherapy combined with chemotherapy significantly improved patient outcomes throughout the entire period. CONCLUSIONS: We propose the approach that is easy to interpret and implement for assessing treatment effects in observational competing risk data.


Asunto(s)
Modelos de Riesgos Proporcionales , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/terapia , Estudios Observacionales como Asunto/métodos , Simulación por Computador , Resultado del Tratamiento , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos
18.
Rev Sci Instrum ; 95(8)2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39162607

RESUMEN

This paper introduces a novel digital triangular-trapezoidal double-channel shaping algorithm to enhance the counting rate of resistive anode detectors. The algorithm is based on the trapezoidal shaping algorithm and improves it. At the extreme counting rate, the trapezoidal shaping algorithm cannot alleviate the pulse pileup, so the counting rate cannot meet the requirements of a high performance detector. The triangular-trapezoidal double-channel shaping algorithm is introduced in the resistance anode detector, which can replace the trapezoidal shaping filtering algorithm to process the output signal of the resistance anode detector and obtain the single photon position information. This improvement improves the counting rate of the resistor anode detector and reduces the resolution degradation caused by pulse pileup. The algorithm is simulated by System Generator software and implemented on FPGA (field programmable gate array). The triangular-trapezoidal double-channel shaping algorithm presented in this paper plays an important role in reducing electronic noise and pulse pileup. The algorithm is subjected to simulation testing, and it can recognize signals with a minimum pulse interval of 1 µs and counting rate up to 1000 kcps.

19.
Food Chem Toxicol ; 192: 114926, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39147356

RESUMEN

Valproic acid (VPA), a common antiepileptic drug, can cause liver steatosis after long-term therapy. However, an impact of ferroptosis on VPA-induced liver steatosis has not been investigated. In the study, treatment with VPA promoted ferroptosis in the livers of mice by elevating ferrous iron (Fe2+) levels derived from the increased absorption by transferrin receptor 1 (TFR1) and the decreased storage by ferritin (FTH1 and FTL), disrupting the redox balance via reduced levels of solute carrier family 7 member 11 (SLC7A11), glutathione (GSH), and glutathione peroxidase 4 (GPX4), and augmenting acyl-CoA synthetase long-chain family member 4 (ACSL4) -mediated lipid peroxide generation, accompanied by enhanced liver steatosis. All the changes were significantly reversed by co-treatment with an iron-chelating agent, deferoxamine mesylate (DFO) and a ferroptosis inhibitor, ferrostatin-1 (Fer-1). Similarly, the increases in Fe2+, TFR1, and ACSL4 levels, as well as the decreases in GSH, GPX4, and ferroportin (FPN) levels, were detected in VPA-treated HepG2 cells. These changes were also attenuated after co-treatment with Fer-1. It demonstrates that ferroptosis promotes VPA-induced liver steatosis through iron overload, inhibition of the GSH-GPX4 axis, and upregulation of ACSL4. It offers a potential therapy targeting ferroptosis for patients with liver steatosis following VPA treatment.


Asunto(s)
Coenzima A Ligasas , Hígado Graso , Ferroptosis , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Receptores de Transferrina , Ácido Valproico , Ferroptosis/efectos de los fármacos , Animales , Ácido Valproico/toxicidad , Ratones , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Coenzima A Ligasas/metabolismo , Coenzima A Ligasas/genética , Humanos , Hígado Graso/inducido químicamente , Hígado Graso/metabolismo , Masculino , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genética , Hierro/metabolismo , Ratones Endogámicos C57BL , Ferritinas/metabolismo , Glutatión/metabolismo , Células Hep G2 , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Hígado/efectos de los fármacos , Hígado/metabolismo
20.
Plant Commun ; : 101072, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39192582

RESUMEN

Plants utilize plasma membrane-localized pattern recognition receptors (PRRs) to perceive pathogen-associated molecular patterns (PAMPs) to activate broad-spectrum pattern-triggered immunity (PTI). However, the regulatory mechanism ensuring robust broad-spectrum plant immunity remains largely unknown. Here, we reveal the dual roles of the transcription factor WRKY8 in transcriptional regulation of PRR genes: repressing the nlp20/nlp24 receptor gene RLP23 whereas promoting the chitin receptor gene CERK1. Remarkably, SsNLP1 and SsNLP2, two nlp24 type PAMPs in the destructive fungal pathogen Sclerotinia sclerotiorum, activate two calcium-elicited kinases, CPK4 and CPK11 to phosphorylate WRKY8 and consequently release its inhibition on RLP23 expression to accumulate RLP23. Meanwhile, SsNLPs activate a RLCK type kinase, PBL19 to phosphorylate WRKY8 and consequently enhance the accumulation of CERK1. Intriguingly, RLP23 is repressed at late stage by PBL19-mediated phosphorylation of WRKY8, to avoid excessive immunity for normal growth. Our findings unveil a "killing two birds with one stone" strategy employed by plants to elicit robust broad-spectrum immunity, which is based on PAMP-triggered fine-tuning of a dual-role transcription factor to simultaneously amplify two PRRs recognizing PAMPs well conserved in a wide range of pathogens. Moreover, our results reveal a novel plant strategy based on fine-tuning of multiple PRR gene expression to balance the trade-off between growth and immunity.

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