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Phthalic acid esters (PAEs) are a group of compounds widespread in the environment. To investigate the occurrence and accumulation characteristics of PAEs, surface water samples were collected from the Three Gorges Reservoir area, China. The total concentrations of 11 analyzed PAEs (∑11PAEs) in the collected water samples ranging from 197.7 to 1,409.3 ng/L (mean ± IQR: 583.1 ± 308.4 ng/L). While DEHP was the most frequently detected PAE, DnBP and DnNP were the most predominant PAEs in the analyzed water samples with a mean contribution of 63.3% of the ∑11PAEs. The concentrations of the ∑11PAEs in the water samples from the upper reaches of the Yangtze River were significantly higher than those from the middle reaches. To better understand the transport and fate of the PAEs, seven detected PAEs were modeled by Quantitative Water Air Sediment Interaction (QWASI). The simulated and measured values were close for most PAEs, and differences are within one order of magnitude even for the worst one. For all simulated PAEs, water and particle inflow were main sources in the reservoir, whereas water outflow and degradation in water were important removal pathways. The contribution ratios of different sources/losses varied from PAEs, depending on their properties. The calculated risk quotients of DnNP in the Three Gorges Reservoir area whether based on monitoring or simulating results were all far exceeded the safety threshold value, implying the occurrence of this PAE compound may cause potential adverse effects for the aquatic ecology of the Three Gorges Reservoir area.
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Surveillance de l'environnement , Esters , Acides phtaliques , Polluants chimiques de l'eau , Acides phtaliques/analyse , Chine , Polluants chimiques de l'eau/analyse , Esters/analyse , Rivières/composition chimique , Modèles chimiquesRÉSUMÉ
BACKGROUND: The modification of N6-methyladenosine (m6A) plays a pivotal role in tumor by altering both innate and adaptive immune systems through various pathways, including the regulation of messenger RNA. The YTH domain protein family, acting as "readers" of m6A modifications, affects RNA splicing, stability, and immunogenicity, thereby playing essential roles in immune regulation and antitumor immunity. Despite their significance, the impact of the YTH domain protein family on tumor initiation and progression, as well as their involvement in tumor immune regulation and therapy, remains underexplored and lacks comprehensive review. CONCLUSION: This review introduces the molecular characteristics of the YTH domain protein family and their physiological and pathological roles in biological behavior, emphasizing their mechanisms in regulating immune responses and antitumor immunity. Additionally, the review discusses the roles of the YTH domain protein family in immune-related diseases and tumor resistance, highlighting that abnormal expression or dysfunction of YTH proteins is closely linked to tumor resistance. KEY POINTS: This review provides an in-depth understanding of the YTH domain protein family in immune regulation and antitumor immunity, suggesting new strategies and directions for immunotherapy of related diseases. These insights not only deepen our comprehension of m6A modifications and YTH protein functions but also pave the way for future research and clinical applications.
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Immunomodulation , Immunothérapie , Tumeurs , Humains , Tumeurs/immunologie , Tumeurs/thérapie , Immunothérapie/méthodes , Protéines de liaison à l'ARN/immunologie , Protéines de liaison à l'ARN/génétique , Facteurs d'épissage des ARN/génétique , Facteurs d'épissage des ARN/immunologieRÉSUMÉ
Olfactory functioning involves multiple cognitive processes and the coordinated actions of various neural systems. Any disruption at any stage of this process may result in olfactory dysfunction, which is consequently widely used to predict the onset and progression of diseases, such as Alzheimer's Disease (AD). Although the underlying mechanisms have not yet been fully unraveled, apparent changes were observed in olfactory brain areas form patients who suffer from AD by means of medical imaging and electroencephalography (EEG). Olfactory dysfunction holds significant promise in detecting AD during the preclinical stage preceding mild cognitive impairment (MCI). Owing to the strong specificity, olfactory tests are prevalently applied for screening in community cohorts. And combining olfactory tests with other biomarkers may further establish an optimal model for AD prediction in studies of specific olfactory dysfunctions and improve the sensitivity and specificity of early AD diagnosis.
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The dysregulation of Angiotensin-converting enzyme 2 (ACE2) in central nervous system is believed associates with COVID-19 induced cognitive dysfunction. However, the detailed mechanism remains largely unknown. In this study, we performed a comprehensive system genetics analysis on hippocampal ACE2 based on BXD mice panel. Expression quantitative trait loci (eQTLs) mapping showed that Ace2 was strongly trans-regulated, and the elevation of Ace2 expression level was significantly correlated with impaired cognitive functions. Further Gene co-expression analysis showed that Ace2 may be correlated with the membrane proteins in Calcium signaling pathway. Further, qRT-PCR confirmed that SARS-CoV-2 spike S1 protein upregulated ACE2 expression together with eight membrane proteins in Calcium Signaling pathway. Moreover, such elevation can be attenuated by recombinant ACE2. Collectively, our findings revealed a potential mechanism of Ace2 in cognitive dysfunction, which could be beneficial for COVID-19-induced cognitive dysfunction prevention and potential treatment.
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Background: Epilepsy is associated with the immune system and metabolism; however, its etiology remains insufficiently understood. Here, we aim to elucidate whether circulating immune cell profiles and metabolites impact the susceptibility to epilepsy. Methods: We used publicly available genetic data and two-sample Mendelian randomization (MR) analyses to establish causal relationships and mediating effects between 731 immune cells and 1,400 metabolites associated with epilepsy. Sensitivity analyses were conducted to detect heterogeneity and horizontal pleiotropy in the study results. Results: MR analysis examining the relationship between immune cells, metabolites, and epilepsy revealed significant causal associations with 28 different subtypes of immune cells and 14 metabolites. Besides, the mediation effects analysis revealed that eight metabolites mediated the effects of six types of immune cells on epilepsy and that 3-hydroxyoctanoylcarnitine (2) levels exhibited the highest mediating effect, mediating 15.3% (95%CI, -0.008, -30.6%, p = 0.049) of the effect of DN (CD4-CD8-) AC on epilepsy. 1-(1-enyl-stearoyl)-2-linoleoyl-GPE (p-18:0/18:2) levels (95%CI, 0.668, 10.6%, p = 0.026) and X-12544 levels (95%CI, -15.1, -0.856%, p = 0.028) contributed 5.63 and 8%, respectively, to the causal effect of FSC-A on myeloid DC on epilepsy. Conclusion: This study revealed a significant causal link between immune cells, metabolites, and epilepsy. It remarkably enhances our understanding of the interplay between immune responses, metabolites, and epilepsy risk, providing insights into the development of therapeutic strategies from both immune and metabolic perspectives.
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Purpose: Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15-0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Patients and Methods: A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction. Results: Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62-0.79), anxiety level (OR, 0.77; 95% CI, 0.62-0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56-0.98) were identified as significant predictors associated with patient satisfaction. Conclusion: A subanesthetic dose of esketamine (0.15-0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery. Clinical Trial Registration: ChiCTR2400080363.
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Dexmédétomidine , Hypnotiques et sédatifs , Kétamine , Rémifentanil , Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Analgésiques/administration et posologie , Analgésiques/pharmacologie , Anesthésie , Dexmédétomidine/administration et posologie , Dexmédétomidine/pharmacologie , Relation dose-effet des médicaments , Méthode en double aveugle , Hypnotiques et sédatifs/administration et posologie , Hypnotiques et sédatifs/pharmacologie , Kétamine/administration et posologie , Kétamine/pharmacologie , Lipectomie , Études prospectives , Rémifentanil/administration et posologie , Rémifentanil/pharmacologieRÉSUMÉ
BACKGROUND: The interplay between inflammation, immune dysregulation, and the onset of neurological disorders, including epilepsy, has become increasingly recognized. Interleukin (IL)-6, a pro-inflammatory cytokine, is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients. The role of IL-6 receptor (IL6R) blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes. AIM: To explore the potential of IL6R blockade in reducing the risk of epilepsy and investigate whether this pathway might also influence associated psychiatric and neuropsychiatric conditions due to neuroinflammation. METHODS: Mendelian randomization (MR) analysis employing single nucleotide polymorphisms (SNPs) in the vicinity of the IL6R gene (total individuals = 408225) was used to evaluate the putative causal relationship between IL6R blockade and epilepsy (total cases/controls = 12891/312803), focal epilepsy (cases/controls = 7526/399290), and generalized epilepsy (cases/controls = 1413/399287). SNP weights were determined by their effect on C-reactive protein (CRP) levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects. To address potential outlier and pleiotropic influences, sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions. RESULTS: The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk [inverse variance weighting: Odds ratio (OR): 0.827; 95% confidence interval (CI): 0.685-1.000; P = 0.05]. Subtype analysis showed variability, with no significant effect observed in generalized, focal, or specific childhood and juvenile epilepsy forms. Beyond the primary inflammatory marker CRP, the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy, hinting at possible links to neuroinflammation, psychiatric symptoms, and associated mental disorders. CONCLUSION: The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence, likely mediated via complex neuroinflammatory pathways. These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy. The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.
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Background: Solid pseudopapillary tumor of the pancreas (SPT) is a rare low-grade malignant tumor predominantly observed in young women without significant clinical symptoms. While most SPTs occur in the pancreatic region, rare cases have occurred in the retroperitoneum, making the diagnosis of ectopic SPTs difficult. Case presentation: Herein, we report a rare case of an extrapancreatic solid SPT with superior mesenteric artery (SMA) involvement in a 47-year-old man together with a literature review to provide context with clinical information, CT and a literature review. Conclusions: This case may provide a practical approach for the diagnosis of ectopic SPT, especially for patients with vascular invasion.
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Background: Patients with fractures of the proximal humerus often local complications and failures attributed to osteoporosis. Currently, there is a lack of straight forward screening methods for assessing the extent of local osteoporosis in the proximal humerus. This study utilizes machine learning techniques to establish a diagnostic approach for evaluating local osteoporosis by analyzing the patient's demographic data, bone density, and X-ray ratio of the proximal humerus. Methods: A cohort comprising a total of 102 hospitalized patients admitted during the period spanning from 2021 to 2023 underwent random selection procedures. Resulting in exclusion of 5 patients while enrolling 97 patients for analysis encompassing patient demographics, shoulder joint anteroposterior radiographs, and bone density information. Using the modified Tingart index methodology involving multiple measurements denoted as M1 through M4 obtained from humeral shafts. Within this cohort comprised 76 females (78.4 %) and 21 males (21.6 %), with an average age of 73.0 years (range: 43-98 years). There were 25 cases with normal bone density, 35 with osteopenia, and 37 with osteoporosis. Machine learning techniques were used to randomly divide the 97 cases into training (n = 59) and validation (n = 38) sets with a ratio of 6:4 using stratified random sampling. A decision tree model was built in the training set, and significant diagnostic indicators were selected, with the performance of the decision tree evaluated using the validation set. Multinomial logistic regression methods were used to verify the strength of the relationship between the selected indicators and osteoporosis. Results: The decision tree identified significant diagnostic indicators as the humeral shaft medullary cavity ratio M2/M4, age, and gender. M2/M4 ≥ 1.13 can be used as an important screening criterion; M2/M4 < 1.13 was predicted as local osteoporosis; M2/M4 ≥ 1.13 and age ≥83 years were also predicted as osteoporosis. M2/M4 ≥ 1.13 and age <64 years or males aged between 64 and 83 years were predicted as the normal population; M2/M4 ≥ 1.13 and females aged between 64 and 83 years were predicted as having osteopenia. The decision tree's accuracy in the training set was 0.7627 (95 % CI (0.6341, 0.8638)), and its accuracy in the test set was 0.7895 (95 % CI (0.6268, 0.9045)). Multinomial logistic regression results showed that humeral shaft medullary cavity ratios M2/M4, age, and gender in X-ray images were significantly associated with the occurrence of osteoporosis. Conclusion: Utilizing X-ray data of the proximal humerus in conjunction with demographic information such as gender and age enable the prediction of localized osteoporosis, facilitating physicians' rapid comprehension of osteoporosis in patients and optimization of clinical treatment plans. Level of evidence: Level IV retrospective case study.
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A copper-catalyzed trifluoromethylation of benzene-linked 1,7-dienes with 1-trifluoromethyl-1,2-benziodoxole via a radical cascade cyclization process for the synthesis of mono- and bis-trifluoromethylated benzoxepines is developed. The selectivity depends on substituents on the double bond of the allyl group in 1,7-dienes. The large-scale operation and late-stage functionalization of bioactive molecules reveal the promising utility of this protocol.
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The spatial organization characteristics and redox status of the extracellular space (ECS) are crucial in the development of brain diseases. However, it remains a challenge to simultaneously capture dynamic changes in microstructural features and redox states at the submicron level within the ECS. Here, we developed a reversible glutathione (GSH)-responsive nanoprobe (RGN) for mapping the spatial organization features and redox status of the ECS in brain tissues with nanoscale resolution. The RGN is composed of polymer nanoparticles modified with GSH-responsive molecules and amino-functionalized methoxypoly(ethylene glycol), which exhibit exceptional single-particle brightness and excellent free diffusion capability in the ECS of brain tissues. Tracking single RGNs in acute brain slices allowed us to dynamically map spatial organizational features and redox levels within the ECS of brain tissues in disease models. This provides a powerful super-resolution imaging method that offers a potential opportunity to study the dynamic changes in the ECS microenvironment and to understand the physiological and pathological roles of the ECS in vivo.
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Encéphale , Espace extracellulaire , Glutathion , Nanoparticules , Oxydoréduction , Encéphale/métabolisme , Encéphale/imagerie diagnostique , Animaux , Espace extracellulaire/métabolisme , Espace extracellulaire/composition chimique , Glutathion/composition chimique , Glutathion/métabolisme , Nanoparticules/composition chimique , Souris , Polyéthylène glycols/composition chimiqueRÉSUMÉ
Purpose: Owing to substantial interfraction motion in cervical cancer, plan-of-the-day (PotD) adaptive radiation therapy may be of benefit to patients. Implementation is limited by uncertainty over how to generate the planning target volumes (PTVs). We compared published methods on our own patients. Methods and Materials: Forty patients each had 3 planning scans with variable bladder filling and daily cone beam computed tomographies (cone beam CTs) during radiation therapy; 5 to 11 cone beam CTs were selected to represent interfraction motion. Clinical target volumes (CTVs) and organs at risk were contoured following EMBRACE-II guidelines. A literature search identified 30 adaptive and nonadaptive solutions to PTV generation, which we applied to our patients. PTV sizes and mean coverage of the daily CTV were determined. For 11 patients, the clinically implemented, subjectively edited plan library was also investigated. Results: Eleven studies assessed 15 PotD strategies against nonadaptive comparators on a median of 14 patients (range, 9-23). Some PotD approaches applied margin recipes to the CTV on each planning scan, some modeled the CTV against bladder volume, and others applied incremental isotropic margins to the CTV with a single planning scan. Generally, coverage improved as PTV size increased. The fixed isotropic margin required to provide 100% coverage of all patients was 44 mm, with a mean PTV size of 3316 cm3. The PotD strategy with the best coverage was a 2-plan library formed by modeling the CTV against bladder volume with extrapolation; it provided 98% mean coverage with 1419-cm3 mean PTV size. A 3-plan library consisting of the CTV on each planning scan with 10-mm margin provided 96% mean coverage with 1346-cm3 mean PTV size. The clinically implemented solution that employed subjective extrapolation had mean 100% coverage and 1282-cm3 PTV size on the 11-patient subset. Coverage provided by the best nonadaptive strategies was not statistically superior to the best PotD strategy (P = .13), but PTVs were larger (P = .02). Conclusions: We identified a modeled 2-plan method and a simple 3-plan method, both of which provided excellent coverage with small PTVs compared with nonadaptive strategies.
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Background: Transarterial chemo(embolization) is preferred for treating unresectable hepatocellular carcinoma (uHCC); however, because of emerging immune-targeted therapies, its efficacy is at stake. This systematic review pioneers to evaluate the clinical efficacy and safety of transarterial chemo(embolization) combined with immune-targeted therapy for uHCC patients. Methods: PubMed, Embase, and Cochrane Library were searched for studies comparing immune-targeted therapy with or without transarterial chemo(embolization) until 31 May 2024. The complete response (CR) rate, objective response rate (ORR), and disease control rate (DCR) were considered to be the primary outcomes calculated for the clinical outcomes of transarterial chemo(embolization) combined with immune-targeted therapy, along with progression-free survival (PFS) and overall survival (OS). The incidence of treatment-related severe adverse events was set as the major measure for the safety outcome. Results: Sixteen studies, encompassing 1,789 patients receiving transarterial chemo(embolization) plus immune-targeted therapy and 1,215 patients receiving immune-targeted therapy alone, were considered eligible. The combination of transarterial chemo(embolization) and immune-targeted therapy demonstrated enhanced outcomes in CR (OR = 2.12, 95% CI = 1.35-3.31), ORR (OR = 2.78, 95% CI = 2.15-3.61), DCR (OR = 2.46, 95% CI = 1.72-3.52), PFS (HR = 0.59, 95% CI = 0.50-0.70), and OS (HR = 0.51, 95% CI = 0.44-0.59), albeit accompanied by a surge in ALT (OR = 2.17, 95% CI = 1.28-3.68) and AST (OR = 2.28, 95% CI = 1.42-3.65). The advantages of additional transarterial chemo(embolization) to immune-targeted therapy were also verified in subgroups of first-line treatment, intervention techniques, with or without extrahepatic metastasis, Child-Pugh grade A or B, and with or without tumor thrombus. Conclusion: The combination of transarterial chemo(embolization) and immune-targeted therapy seems to bolster local control and long-term efficacy in uHCC, albeit at the expense of hepatic complications. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier 474669.
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Carcinome hépatocellulaire , Chimioembolisation thérapeutique , Tumeurs du foie , Humains , Carcinome hépatocellulaire/thérapie , Carcinome hépatocellulaire/immunologie , Tumeurs du foie/thérapie , Tumeurs du foie/immunologie , Tumeurs du foie/mortalité , Chimioembolisation thérapeutique/méthodes , Chimioembolisation thérapeutique/effets indésirables , Immunothérapie/méthodes , Immunothérapie/effets indésirables , Association thérapeutique , Résultat thérapeutique , Thérapie moléculaire cibléeRÉSUMÉ
ABSTRACT: Sepsis is a life-threatening organ dysfunction that occurs due to a dysregulated host response to infection. Septic-associated liver injury (SALI) has been closely linked to the prognosis and mortality of sepsis. Recent investigations have delved into the gut-liver axis and its association with SALI, identifying its pivotal role in the gut microbiota. Bacterial translocation and the onset of SALI can occur due to an imbalance in the gut microbiota, impairing the function of the gut barrier. Moreover, their metabolites might exacerbate or initiate SALI by modulating immune responses. Nevertheless, interventions to restore the balance of the gut microbiota, such as the administration of probiotics, fecal microbiota transplantation, or dietary adjustments, may ameliorate SALI and enhance the prognosis and survival rates of septic patients. This review aimed to elucidate the function of the gut microbiota in the genesis and procession of SALI and its potential therapeutic value, offering a deeper understanding of the pathogenesis and therapeutic avenues for SALI.
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Phillygenin (PHI) is an active ingredient derived from the leaf of Forsythia suspensa that has been found to alleviate inflammation and peroxidation response. Avian infectious bronchitis (IB) is a major threat to poultry industry viral respiratory tract disease that infected with infectious bronchitis virus (IBV). This study investigated the protection of PHI to CEK cell and broiler's tracheal injury triggered by avian infectious bronchitis virus (IBV). The results showed that IBV infection did not cause serious clinical symptoms and slowing-body weight in PHI-treated broilers. The expression of virus loads, pro-inflammation factors (IL-6, TNF-α, and IL-1ß) in CEK cell, and tracheas were decreased compared to the IBV group, exhibiting its potent anti-inflammation. Mechanistically, the study demonstrated that the inhibition of TLR7/MyD88/NF-κB pathway was mainly involved in the protection effect of PHI to inflammation injury. Interestingly, a higher abundance of Firmicutes and Lactobacillus in respiratory tract was observed in PHI-treated broilers than in the IBV group. Significant differences were observed between the IBV group and PHI-treated group in the Ferroptosis, Tryptophan metabolism, and Glutathione metabolism pathways. PHI exhibited potent protection effect on IBV infection and alleviated inflammation injury, mainly through inhibiting TLR7/MyD88/NF-κB pathway. The study encourages further development of PHI, paving the way to its clinical use as a new candidate drug to relieve IBV-induced respiratory symptoms.
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Poulets , Infections à coronavirus , Virus de la bronchite infectieuse , Facteur de différenciation myéloïde-88 , Facteur de transcription NF-kappa B , Maladies de la volaille , Récepteur de type Toll-7 , Animaux , Facteur de transcription NF-kappa B/métabolisme , Facteur de différenciation myéloïde-88/métabolisme , Maladies de la volaille/traitement médicamenteux , Maladies de la volaille/microbiologie , Maladies de la volaille/métabolisme , Récepteur de type Toll-7/métabolisme , Infections à coronavirus/traitement médicamenteux , Infections à coronavirus/médecine vétérinaire , Microbiote/effets des médicaments et des substances chimiques , Transduction du signal/effets des médicaments et des substances chimiquesRÉSUMÉ
Corn leaf aphids (Rhopalosiphum maidis) are highly destructive pests of maize (Zea mays) that threaten growth and seed yield, but resources for aphid resistance are scarce. Here, we identified an aphid-resistant maize mutant, resistance to aphids 1 (rta1), which is allelic to LIGULELESS1 (LG1). We confirmed LG1's role in aphid resistance using the independent allele lg1-2, allelism tests and LG1 overexpression lines. LG1 interacts with, and increases the stability of ZINC-FINGER PROTEIN EXPRESSED IN INFLORESCENCE MERISTEM (ZIM1), a central component of the jasmonic acid (JA) signalling pathway, by disturbing its interaction with the F-box protein CORONATINE INSENSITIVE 1a (COI1a). Natural variation in the LG1 promoter was associated with aphid resistance among inbred lines. Moreover, a loss-of-function mutant in the LG1-related gene SPL8 in the dicot Arabidopsis thaliana conferred aphid resistance. This study revealed the aphid resistance mechanism of lg1, providing a theoretical basis and germplasm for breeding aphid-resistant crops.
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The activation of PP5 is essential for a variety of cellular processes, as it participates in a variety of biological pathways by dephosphorylating substrates. However, activation of PP5 by small molecules has been a challenge due to its native "self-inhibition" mechanism, which is controlled by the N-terminal TPR domain and the C-terminal αJ helix. Here, we reported the discovery of DDO-3733, a well-identified TPR-independent PP5 allosteric activator, which facilitates the dephosphorylation process of downstream substrates. Considering the negative regulatory effect of PP5 on heat shock transcription factor HSF1, pharmacologic activation of PP5 by DDO-3733 was found to reduce the HSP90 inhibitor-induced heat shock response. These results provide a chemical tool to advance the exploration of PP5 as a potential therapeutic target and highlight the value of pharmacological activation of PP5 to reduce heat shock toxicity of HSP90 inhibitors.
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Glycerol electrooxidation reaction (GOR) to produce value-added chemicals, such as formic acid, could make more efficient use of abundant glycerol and meet future demand for formic acid as a fuel for direct or indirect formic acid fuel cells. Non-noble metal Cu-based catalysts have great potential in electro-reforming glycerol to formic acid. However, the high activity, selectivity and stability of Cu based catalysts in GOR cannot be achieved simultaneously. Here, we used ozone-assisted electrocatalyst to convert glycerol to formic acid under alkaline conditions, the onset potential was reduced by 60 mV, the Faraday efficiency (FE) reached 95%. The catalyst has excellent stability within 300 h at the current density of 10 mA cm-2. The electron spin resonance proved that ozone produced superoxide anion during the GOR. In situ Raman spectroscopy, electrochemical studies showed that glycerol can be activated with ozone in GOR, and the C-C bond can be broken to reduce the polymerization of glycerol on the catalyst surface, so as to produce more formic acid at a lower voltage. Moreover, the removal of dissolved O3 from water can be up to 100% after 30 minutes of GOR reaction at a solubility of 50 mg L-1 as measured by UV-VIS spectrophotometry.
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African swine fever (ASF), caused by ASF virus (ASFV), is a highly infectious and severe hemorrhagic disease of pigs that causes major economic losses. Currently, no commercial vaccine is available and prevention and control of ASF relies mainly on early diagnosis. Here, a novel automated double antigen sandwich chemiluminescent immunoassay (DAgS-aCLIA) was developed to detect antibodies against ASFV p72 (p72-Ab). For this purpose, recombinant p72 trimer was produced, coupled to magnetic particles as carriers and labeled with acridinium ester as a signal trace. Finally, p72-Ab can be sensitively and rapidly measured on an automated chemiluminescent instrument. For quantitative analysis, a calibration curve was established with a laudable linearity range of 0.21 to 212.0 ng/mL (R2 = 0.9910) and a lower detection limit of 0.15 ng/mL. For qualitative analysis, a cut-off value was set at 1.50 ng/mL with a diagnostic sensitivity of 100.00% and specificity of 98.33%. Furthermore, antibody response to an ASF gene-deleted vaccine candidate can be accurately quantified using this DAgS-aCLIA, as evidenced by early seroconversion as early as 7 days post-immunization and high antibody levels. Compared with available enzyme-linked immunosorbent assays, this DAgS-aCLIA demonstrated a wider linearity range of 4 to 16-fold, and excellent analytical sensitivity and agreement of over 95.60%. In conclusion, our proposed DAgS-aCLIA would be an effective tool to support ASF epidemiological surveillance.IMPORTANCEAfrican swine fever virus (ASFV) is highly contagious in wild boar and domestic pigs. There is currently no vaccine available for ASF, so serological testing is an important diagnostic tool. Traditional enzyme-linked immunosorbent assays provide only qualitative results and are time and resource consuming. This study will develop an automated chemiluminescent immunoassay (CLIA) that can quantitatively and qualitatively detect antibodies to ASFV p72, greatly reducing detection time and labour-intensive operation, and improving detection sensitivity and linearity range. This novel CLIA would serve as a reliable and convenient tool for ASF pandemic surveillance and vaccine development.