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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 46(3): 435-443, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38953268

RESUMO

With the continuous development of identification technologies such as mass spectrometry,omics,and antibody technology,post-translational modification (PTM) has demonstrated increasing potential in medical research.PTM as a novel chemical modification method provides new perspectives for the research on diseases.Succinylation as a novel modification has aroused the interest of more and more researchers.The available studies about succinylation mainly focus on a desuccinylase named sirtuin 5.This enzyme plays a key role in modification and has been preliminarily explored in cardiovascular studies.This paper summarizes the influencing factors and regulatory roles of succinylation and the links between succinylation and other PTMs and reviews the research progress of PTMs in the cardiovascular field,aiming to deepen the understanding about the role of this modification and give new insights to the research in this field.


Assuntos
Doenças Cardiovasculares , Lisina , Processamento de Proteína Pós-Traducional , Doenças Cardiovasculares/metabolismo , Humanos , Lisina/metabolismo , Ácido Succínico/metabolismo
2.
Plant Dis ; 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003505

RESUMO

Turfgrasses are susceptible to a wide variety of ectotrophic root-infecting (ERI) fungi that cause root rot (Tredway et al., 2023). Among the root rot diseases, fairway patch, caused by Phialocephala bamuru P.T.W. Wong & C. Dong sp. nov., was recently identified and characterized in Australia infecting bermudagrass (Cynodon dactylon) and kikuyu (Pennisetum clandestinum) grass (Wong et al., 2015). Symptoms begin as small, 5-10 cm diameter patches of yellowed turf that may coalesce into larger areas of diseased grass. A characteristic sign of fairway patch is roots colonized by dark brown to black, ectotrophic mycelium. In June 2020, many tan colored, irregular-shaped patches ranging from 10-30 cm in diameter developed on a hard fescue (Festuca brevipila) cultivar 'Beacon' turfgrass field in North Brunswick, New Jersey, USA. The centers of these patches later died and became sunken or filled in partially by recovering hard fescue. The patches grew into tan irregular-shaped rings with diameters up to 3 m by Aug 2023. Symptoms were indicative of a root disease. Five 'Beacon' hard fescue soil cores at the interface of the symptomatic and non-symptomatic area were sampled in Aug 2023. Root and crown samples were observed under a dissecting microscope and dark ectotrophic hyphae were observed on both. Roots with visible ectotrophic mycelium were removed, rinsed in sterile water three times, cut into 5 mm pieces, and plated onto 10% potato dextrose agar amended with streptomycin and gentamicin at 100 mg/L (PDA+). The plates were incubated at 25°C in the dark for 5 days. The most abundant colonies being characteristic long, septate hyphae that were hyaline at the edge and dark brown to black in the center and resembled the fungus described in Wong et al., 2015. These colonies were subcultured onto PDA+ medium and selected for molecular identification. Other less abundant colonies could be identified using morphology after subcultured and had no record being pathogenic to turfgrass. To confirm the isolate's identity, its internal transcribed spacer (ITS) region was amplified in PCR using the ITS1F/ITS4 primers (Bellemain et al., 2010). The amplicon was then sequenced with both ITS1 and ITS4 primers by Sanger sequencing. Sequences were assembled (GenBank #PP000819). The consensus sequence was then BLASTn analyzed with default settings, and the result showed 99.64% sequence identity with P. bamuru (GenBank #MG195534.1). Koch's postulate was conducted in an environmentally controlled growth chamber. Six healthy 'Beacon' hard fescue plugs were sampled from the field. Three of the six plugs (treatment) were each inoculated with P. bamuru by placing 20 g of P. bamuru colonized millets beneath and around the plug before filling the pots with sand. The other three plugs (control) received the same treatment except the P. bamuru colonized millets were autoclaved. The pots were incubated in the growth chamber with a 16 h light period and 25/20°C day/night temperatures. Symptoms resembling those observed in the field appeared on the treatment pots after 21 days of incubation while the control pots remained healthy. The roots from the treatment pots were examined under the dissecting microscope to confirm the colonization of P. bamuru on the roots, and P. bamuru was reisolated and confirmed using the aforementioned morphological traits and molecular assays (GenBank #PP000820). This is the first report of a turfgrass root rot disease caused by P. bamuru in the United States. Further epidemiological, disease ecological, and pathogen biological studies are required to clarify the importance of this disease in the United States and establish proper disease containment or control measures.

3.
Pak J Med Sci ; 40(6): 1087-1092, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38952500

RESUMO

Objective: To investigate the effects of motivational interview education on psychological status, compliance behavior and quality of life in patients with malignant tumors combined with diabetes mellitus. Methods: This is a retrospective study. Eighty patients with malignant tumors combined with diabetes mellitus admitted at The Fourth Hospital of Hebei Medical University from January 2021 to June 2022 were included as subjects and divided into observation group and control group according to the intervention measures. Patients in the control group were given routine health education intervention, while those in the observation group were given motivational interviewing intervention on the basis of the control group. We compared the prognosis, cognitive function, quality of life, relief of cancer pain before intervention and three months after the intervention of the two groups were compared. Results: At three months after the intervention, the total remission rate of cancer pain in the observation group was higher than that in the control group(p<0.05), while the levels of FBG and 2hPG in the observation group were significantly lower than those in the control group(p<0.05). Self-Rating Anxiety Scale(SAS) and Self-rating depression scale(SDS) scores decreased in both groups three months after the intervention, with the level of reduction in the observation group being higher than that in the control group(p<0.05). The overall compliance was higher in the observation group than in the control group(p<0.05). Conclusion: Motivational interviewing leads to alleviate negative emotions, improve the psychological status, enhance compliance behavior and improve quality of life in patients with malignant tumors combined with diabetes mellitus.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38968020

RESUMO

Multivariate networks are commonly found in realworld data-driven applications. Uncovering and understanding the relations of interest in multivariate networks is not a trivial task. This paper presents a visual analytics workflow for studying multivariate networks to extract associations between different structural and semantic characteristics of the networks (e.g., what are the combinations of attributes largely relating to the density of a social network?). The workflow consists of a neuralnetwork- based learning phase to classify the data based on the chosen input and output attributes, a dimensionality reduction and optimization phase to produce a simplified set of results for examination, and finally an interpreting phase conducted by the user through an interactive visualization interface. A key part of our design is a composite variable construction step that remodels nonlinear features obtained by neural networks into linear features that are intuitive to interpret. We demonstrate the capabilities of this workflow with multiple case studies on networks derived from social media usage and also evaluate the workflow with qualitative feedback from experts.

5.
MedComm (2020) ; 5(7): e623, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38988495

RESUMO

This study aimed to identify the role of chromothripsis as a novel biomarker in the prognosis and differentiation diagnosis of pancreatic neuroendocrine neoplasms (pNENs). We conducted next-generation gene sequencing in a cohort of 30 patients with high-grade (G3) pNENs. As a reference, a similar analysis was also performed on 25 patients with low-grade (G1/G2) pancreatic neuroendocrine tumors (pNETs). Chromothripsis and its relationship with clinicopathological features and prognosis were investigated. The results showed that DNA damage response and repair gene alteration and TP53 mutation were found in 29 and 11 patients, respectively. A total of 14 out of 55 patients had chromothripsis involving different chromosomes. Chromothripsis had a close relationship with TP53 alteration and higher grade. In the entire cohort, chromothripsis was associated with a higher risk of distant metastasis; both chromothripsis and metastasis (ENETS Stage IV) suggested a significantly shorter overall survival (OS). Importantly, in the high-grade pNENs group, chromothripsis was the only independent prognostic indicator significantly associated with a shorter OS, other than TP53 alteration or pathological pancreatic neuroendocrine carcinomas (pNECs) diagnosis. Chromothripsis can guide worse prognosis in pNENs, and help differentiate pNECs from high-grade (G3) pNETs.

6.
Exp Ther Med ; 28(2): 302, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38873048

RESUMO

[This retracts the article DOI: 10.3892/etm.2020.8708.].

7.
Chem Sci ; 15(22): 8545-8556, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38846386

RESUMO

A new class of amphiphilic tetradentate platinum(ii) Schiff base complexes has been designed and synthesized. The self-assembly properties by exploiting the potential Pt⋯Pt interactions of amphiphilic platinum(ii) Schiff base complexes in the solution state have been systematically investigated. The presence of Pt⋯Pt interactions has further been supported by computational studies and non-covalent interaction (NCI) analysis of the dimer of the complex. The extent of the non-covalent Pt⋯Pt and π-π interactions could be regulated by a variation of the solvent compositions and the hydrophobicity of the complexes, which is accompanied by attractive spectroscopic and luminescence changes and leads to diverse morphological transformations. The present work represents a rare example of demonstration of directed cooperative assembly of amphiphilic platinum(ii) Schiff base complexes by intermolecular Pt⋯Pt interactions in solution with an in-depth mechanistic investigation, providing guiding principles for the construction of supramolecular structures with desirable properties using platinum(ii) Schiff base building blocks.

8.
Nat Commun ; 15(1): 5081, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38876991

RESUMO

Stomatal movement is vital for plants to exchange gases and adaption to terrestrial habitats, which is regulated by environmental and phytohormonal signals. Here, we demonstrate that hydrogen peroxide (H2O2) is required for light-induced stomatal opening. H2O2 accumulates specifically in guard cells even when plants are under unstressed conditions. Reducing H2O2 content through chemical treatments or genetic manipulations results in impaired stomatal opening in response to light. This phenomenon is observed across different plant species, including lycopodium, fern, and monocotyledonous wheat. Additionally, we show that H2O2 induces the nuclear localization of KIN10 protein, the catalytic subunit of plant energy sensor SnRK1. The nuclear-localized KIN10 interacts with and phosphorylates the bZIP transcription factor bZIP30, leading to the formation of a heterodimer between bZIP30 and BRASSINAZOLE-RESISTANT1 (BZR1), the master regulator of brassinosteroid signaling. This heterodimer complex activates the expression of amylase, which enables guard cell starch degradation and promotes stomatal opening. Overall, these findings suggest that H2O2 plays a critical role in light-induced stomatal opening across different plant species.


Assuntos
Peróxido de Hidrogênio , Luz , Estômatos de Plantas , Estômatos de Plantas/efeitos da radiação , Estômatos de Plantas/metabolismo , Estômatos de Plantas/fisiologia , Peróxido de Hidrogênio/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Arabidopsis/efeitos da radiação , Triticum/genética , Triticum/metabolismo , Triticum/fisiologia , Triticum/efeitos da radiação , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Transdução de Sinais , Fosforilação , Gleiquênias/metabolismo , Gleiquênias/efeitos da radiação , Gleiquênias/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética
9.
Sci Rep ; 14(1): 13834, 2024 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879709

RESUMO

Receptor Expression-Enhancing Protein 3 (REEP3) serves as a pivotal enzyme crucial for endoplasmic reticulum (ER) clearance during mitosis and is implicated in the advancement of diverse malignancies. Nonetheless, the biological role and mechanisms of REEP3 in pancreatic cancer patients, along with its interplay with immune infiltration, remain inadequately elucidated. In this study, we initially analyzed the differential expression of REEP3 between pancreatic cancer tissues and normal pancreas tissues using the Cancer Genome Atlas (TCGA), GTEx and Gene Expression Omnibus (GEO) databases. Subsequently, we utilized Kaplan-Meier analysis, Cox regression and ROC curve to determine the predictive value of REEP3 for the clinical outcomes of pancreatic cancer patients. Functional enrichment analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), were conducted to explore the potential signaling pathways and biological functions associated with pancreatic cancer. Furthermore, we investigated the PPI network, miRNA, RBP and transcription factor interactions of REEP3 using databases such as GeneMania, STRING, StarBase, KnockTK, ENCODE, Jaspar and hTFtarget. Lastly, the "ssGSEA" algorithm and TIMER database were employed to investigate the correlation between REEP3 expression and immune infiltration as well as immune checkpoints. The expression of REEP3 in pancreatic cancer showed a significantly higher level compared to that in normal tissues. ROC curve analysis indicated that REEP3 holds substantial diagnostic potential for pancreatic cancer patients. Elevated REEP3 expression correlated with unfavorable outcomes in terms of both overall survival and relapse-free survival, establishing it as a notable adverse prognostic marker in pancreatic cancer. Moreover, both univariate and multivariate Cox regression analyses demonstrated that REEP3 maintained an independent association with overall survival. Functional enrichment analyses revealed pathways significantly linked to REEP3, including cytoplasmic translation, wound healing, viral processes, regulation of cellular component size and actin filament organization. Additionally, REEP3 expression displayed a significant positive correlation with CD8+ T cells, B cells, natural killer cells, dendritic cells and macrophages. REEP3 is a potential diagnostic, prognostic marker and immunotherapeutic target for pancreatic cancer.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estimativa de Kaplan-Meier , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Prognóstico , Mapas de Interação de Proteínas , Curva ROC
10.
Biochem Biophys Res Commun ; 726: 150269, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-38909533

RESUMO

Mitochondrial dysfunction is implicated in a wide range of human disorders including many neurodegenerative and cardiovascular diseases, metabolic diseases, cancers, and respiratory disorders. Studies have suggested the potential of l-ergothioneine (ET), a unique dietary thione, to prevent mitochondrial damage and improve disease outcome. Despite this, no studies have definitively demonstrated uptake of ET into mitochondria. Moreover, the expression of the known ET transporter, OCTN1, on the mitochondria remains controversial. In this study, we utilise mass spectrometry to demonstrate direct ET uptake in isolated mitochondria as well as its presence in mitochondria isolated from ET-treated cells and animals. Mitochondria isolated from OCTN1 knockout mice tissues, have impaired but still detectable ET uptake, raising the possibility of alternative transporter(s) which may facilitate ET uptake into the mitochondria. Our data confirm that ET can enter mitochondria, providing a basis for further work on ET in the prevention of mitochondrial dysfunction in human disease.


Assuntos
Ergotioneína , Camundongos Knockout , Mitocôndrias , Ergotioneína/metabolismo , Ergotioneína/farmacologia , Animais , Mitocôndrias/metabolismo , Humanos , Camundongos , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/genética , Simportadores/metabolismo , Simportadores/genética
11.
Biomolecules ; 14(5)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38785996

RESUMO

Excitotoxicity is a common pathological process in neurological diseases caused by excess glutamate. The purpose of this study was to evaluate the effect of gypenoside XVII (GP-17), a gypenoside monomer, on the glutamatergic system. In vitro, in rat cortical nerve terminals (synaptosomes), GP-17 dose-dependently decreased glutamate release with an IC50 value of 16 µM. The removal of extracellular Ca2+ or blockade of N-and P/Q-type Ca2+ channels and protein kinase A (PKA) abolished the inhibitory effect of GP-17 on glutamate release from cortical synaptosomes. GP-17 also significantly reduced the phosphorylation of PKA, SNAP-25, and synapsin I in cortical synaptosomes. In an in vivo rat model of glutamate excitotoxicity induced by kainic acid (KA), GP-17 pretreatment significantly prevented seizures and rescued neuronal cell injury and glutamate elevation in the cortex. GP-17 pretreatment decreased the expression levels of sodium-coupled neutral amino acid transporter 1, glutamate synthesis enzyme glutaminase and vesicular glutamate transporter 1 but increased the expression level of glutamate metabolism enzyme glutamate dehydrogenase in the cortex of KA-treated rats. In addition, the KA-induced alterations in the N-methyl-D-aspartate receptor subunits GluN2A and GluN2B in the cortex were prevented by GP-17 pretreatment. GP-17 also prevented the KA-induced decrease in cerebral blood flow and arginase II expression. These results suggest that (i) GP-17, through the suppression of N- and P/Q-type Ca2+ channels and consequent PKA-mediated SNAP-25 and synapsin I phosphorylation, reduces glutamate exocytosis from cortical synaptosomes; and (ii) GP-17 has a neuroprotective effect on KA-induced glutamate excitotoxicity in rats through regulating synaptic glutamate release and cerebral blood flow.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico , Ácido Glutâmico , Gynostemma , Animais , Ácido Glutâmico/metabolismo , Ratos , Masculino , Gynostemma/química , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Ratos Sprague-Dawley , Sinaptossomos/metabolismo , Sinaptossomos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Ácido Caínico/toxicidade , Convulsões/induzido quimicamente , Convulsões/metabolismo , Convulsões/tratamento farmacológico , Convulsões/prevenção & controle , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Proteína 25 Associada a Sinaptossoma/metabolismo , Sinapsinas/metabolismo , Fosforilação/efeitos dos fármacos , Cálcio/metabolismo , Extratos Vegetais
12.
J Integr Med ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38789290

RESUMO

BACKGROUND: Hypertension, a prevalent disease, is a significant risk factor for coronary heart disease. Huoxue Qianyang Qutan Recipe (HQQR), a traditional Chinese herbal remedy, has been used for treating hypertension over several years. OBJECTIVE: This study assesses HQQR's efficacy for controlling blood pressure among patients with hypertension related to blood stasis, yang hyperactivity and phlegm. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: A randomized controlled trial was conducted at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, China, from July 2020 to June 2022. Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography. Participants aged 18-80 years, exhibiting traditional Chinese medicine syndromes of blood stasis, yang hyperactivity or phlegm, along with grades 1 or 2 hypertension, were randomly categorized into two groups. The intervention group was given HQQR granules alongside conventional hypertension treatment, while the control group was given placebo granules in addition to conventional treatment for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was clinic blood pressure, whereas secondary outcomes included metabolic indices (e.g., homeostasis model assessment of insulin resistance [HOMA-IR], total cholesterol [TC], low-density lipoprotein cholesterol and triglyceride), target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio [UACR]) and inflammation indices (interleukin-6 [IL-6] and high-sensitivity C-reactive protein [hs-CRP]). RESULTS: HQQR's primary components were identified as salvianolic acid B, emodin and ferulic acid. Of the 216 participants (108 in each group), compared to the control, the intervention group exhibited significant improvements (P < 0.001) in clinic systolic blood pressure ([136.24 ± 7.63] vs [130.06 ± 8.50] mmHg), clinic diastolic blood pressure ([84.34 ± 8.72] vs [80.46 ± 6.05] mmHg), home systolic blood pressure ([131.64 ± 8.74] vs [122.36 ± 8.45] mmHg) and home diastolic blood pressure ([78.47 ± 9.53] vs [71.79 ± 6.82] mmHg). HQQR demonstrated a reduction in ambulatory blood pressure (24-hour systolic blood pressure: [133.75 ± 10.49] vs [132.46 ± 8.84] mmHg and 24-hour diastolic blood pressure: [84.12 ± 8.01] vs [82.11 ± 7.45] mmHg) and an improvement in HOMA-IR ([4.09 ± 1.72] vs [3.98 ± 1.44]), TC ([4.66 ± 1.47] vs [3.75 ± 1.81] mmol/L) and UACR (75.94 [5.12, 401.12] vs 45.61 [4.26, 234.26]). Moreover, HQQR demonstrated a decrease in hs-CRP (1.46 [0.10, 10.53] vs 0.57 [0.12, 3.99] mg/L) and IL-6 (6.69 [2.00, 29.74] vs 5.27 [2.00, 9.73] pg/mL), with no reported side effects (P < 0.001). CONCLUSION: This study highlights the therapeutic potential of HQQR use in ameliorating blood pressure, glycolipid metabolism, and inflammation in patients with hypertension. TRIAL REGISTRATION: ChiCTR2000035092 (https://www.chictr.org.cn/). Please cite this article as: Xie J, Ma YL, Gui MT, Yao L, Li JH, Wang MZ, Zhou XJ, Wang YF, Zhao MY, Cao H, Lu B, Fu DY. Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension: A randomized, double-blind, placebo-controlled trial. J Integr Med. 2024; Epub ahead of print.

13.
Plant Divers ; 46(3): 406-415, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38798721

RESUMO

Bamboo plants are an essential component of tropical ecosystems, yet their vulnerability to climate extremes, such as drought, is poorly understood due to limited knowledge of their hydraulic properties. Cephalostachyum pergracile, a commonly used tropical bamboo species, exhibited a substantially higher mortality rate than other co-occurring bamboos during a severe drought event in 2019, but the underlying mechanisms remain unclear. This study investigated the leaf and stem hydraulic traits related to drought responses, including leaf-stem embolism resistance (P50leaf; P50stem) estimated using optical and X-ray microtomography methods, leaf pressure-volume and water-releasing curves. Additionally, we investigated the seasonal water potentials, native embolism level (PLC) and xylem water source using stable isotope. We found that C. pergracile exhibited strong resistance to embolism, showing low P50leaf, P50stem, and turgor loss point, despite its rapid leaf water loss. Interestingly, its leaves displayed greater resistance to embolism than its stem, suggesting a lack of effective hydraulic vulnerability segmentation (HVS) to protect the stem from excessive xylem tension. During the dry season, approximately 49% of the water was absorbed from the upper 20-cm-deep soil layer. Consequently, significant diurnal variation in leaf water potentials and an increase in midday PLC from 5.87 ± 2.33% in the wet season to 12.87 ± 4.09% in the dry season were observed. In summary, this study demonstrated that the rapid leaf water loss, high reliance on surface water, and a lack of effective HVS in C. pergracile accelerated water depletion and increased xylem embolism even in the typical dry season, which may explain its high mortality rate during extreme drought events in 2019.

14.
Adv Healthc Mater ; : e2400237, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691819

RESUMO

Food allergy is a prevalent, potentially deadly disease caused by inadvertent sensitization to benign food antigens. Pathogenic Th2 cells are a major driver for disease, and allergen-specific immunotherapies (AIT) aim to increase the allergen threshold required to elicit severe allergic symptoms. However, the majority of AIT approaches require lengthy treatments and convey transient disease suppression, likely due to insufficient targeting of pathogenic Th2 responses. Here, the ability of allergen-encapsulating nanoparticles to directly suppress pathogenic Th2 responses and reactivity is investigated in a mouse model of food allergy. NPs associate with pro-tolerogenic antigen presenting cells, provoking accumulation of antigen-specific, functionally suppressive regulatory T cells in the small intestine lamina propria. Two intravenous doses of allergen encapsulated in poly(lactide-co-glycolide) nanoparticles (NPs) significantly reduces oral food challenge (OFC)-induced anaphylaxis. Importantly, NP treatment alters the fates of pathogenic allergen-specific Th2 cells, reprogramming these cells toward CD25+FoxP3+ regulatory and CD73+FR4+ anergic phenotypes. NP-mediated reductions in the frequency of effector cells in the gut and mast cell degranulation following OFC are also demonstrated. These studies reveal mechanisms by which an allergen-encapsulating NP therapy and, more broadly, allergen-specific immunotherapies, can rapidly attenuate allergic responses by targeting pathogenic Th2 cells.

15.
Plant J ; 119(2): 645-657, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38761364

RESUMO

The interplay between microRNAs (miRNAs) and phytohormones allows plants to integrate multiple internal and external signals to optimize their survival of different environmental conditions. Here, we report that miR394 and its target gene LEAF CURLING RESPONSIVENESS (LCR), which are transcriptionally responsive to BR, participate in BR signaling to regulate hypocotyl elongation in Arabidopsis thaliana. Phenotypic analysis of various transgenic and mutant lines revealed that miR394 negatively regulates BR signaling during hypocotyl elongation, whereas LCR positively regulates this process. Genetically, miR394 functions upstream of BRASSINOSTEROID INSENSITIVE2 (BIN2), BRASSINAZOLEs RESISTANT1 (BZR1), and BRI1-EMS-SUPPRESSOR1 (BES1), but interacts with BRASSINOSTEROID INSENSITIVE1 (BRI1) and BRI1 SUPRESSOR PROTEIN (BSU1). RNA-sequencing analysis suggested that miR394 inhibits BR signaling through BIN2, as miR394 regulates a significant number of genes in common with BIN2. Additionally, miR394 increases the accumulation of BIN2 but decreases the accumulation of BZR1 and BES1, which are phosphorylated by BIN2. MiR394 also represses the transcription of PACLOBUTRAZOL RESISTANCE1/5/6 and EXPANSIN8, key genes that regulate hypocotyl elongation and are targets of BZR1/BES1. These findings reveal a new role for a miRNA in BR signaling in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Brassinosteroides , Regulação da Expressão Gênica de Plantas , Hipocótilo , MicroRNAs , Transdução de Sinais , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Brassinosteroides/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Hipocótilo/crescimento & desenvolvimento , Hipocótilo/genética , Hipocótilo/metabolismo , Plantas Geneticamente Modificadas , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/genética , Reguladores de Crescimento de Plantas/metabolismo , Proteínas Quinases
16.
Heliyon ; 10(9): e30575, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38765140

RESUMO

Synaptotagmin 4 (syt4) belongs to the synaptotagmin protein family, which has 17 and 28 family members in human and zebrafish, respectively. In zebrafish and rodents, syt4 is known to express abundantly in the entire central nervous system in the early developmental stages. In adult rodents, the gene expression shifts to be predominant in the cerebellum, mostly in Purkinje cells, a type of GABAergic neurons. However, there is no report of the expression pattern of syt4 in the adult zebrafish brain. Therefore, we hypothesize that the expression of syt4 is conserved in adult zebrafish and is specific to the GABAergic neurons, likely Purkinje cells, in the cerebellum. To examine the hypothesis, we first show that only one copy of syt4 gene remains in the zebrafish genome, and it is orthologous to the gene in other vertebrates. We further observe mammalian SYT4 antibody immunoreactive-like (mSYT4-ir) signals in several structures in the hindbrain including the medial divisions of the valvula cerebelli and the corpus cerebelli. In addition, our observations indicate the presence of mSYT4-ir signals in GABAergic neurons, most notably in the Purkinje cell layer of the molecular layer in the aforementioned structures. Conversely, mSYT4-ir signals are not observed in glutamatergic or cholinergic neurons. Therefore, we deduce that the syt4 gene in zebrafish exhibits a homologous expression pattern to those of previously studied vertebrate species, which is revealed by the positive immunoreactive-like signals of mammalian SYT4 antibodies.

17.
Nat Commun ; 15(1): 4379, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782888

RESUMO

The Taklamakan and Gobi Desert (TGD) region has experienced a pronounced increase in summer precipitation, including high-impact extreme events, over recent decades. Despite identifying large-scale circulation changes as a key driver of the wetting trend, understanding the relative contributions of internal variability and external forcings remains limited. Here, we approach this problem by using a hierarchy of numerical simulations, complemented by diverse statistical analysis tools. Our results offer strong evidence that the atmospheric internal variations primarily drive this observed trend. Specifically, recent changes in the North Atlantic Oscillation have redirected the storm track, leading to increased extratropical storms entering TGD and subsequently more precipitation. A clustering analysis further demonstrates that these linkages predominantly operate at the synoptic scale, with larger contributions from large precipitation events. Our analysis highlights the crucial role of internal variability, in addition to anthropogenic forcing, when seeking a comprehensive understanding of future precipitation trends in TGD.

18.
Artigo em Inglês | MEDLINE | ID: mdl-38728178

RESUMO

A Gram-negative, facultative anaerobic, non-motile and rod-shaped bacterium, designated 10c7w1T, was isolated from a human gastrointestinal tract. Colonies on agar plates were small, circular, smooth and beige. The optimal growth conditions were determined to be 37 °C, pH 7.0-7.5 and 0 % (w/v) NaCl. Comparative analysis of complete 16S rRNA gene sequences revealed that strain 10c7w1T showed the highest sequence similarity of 95.8 % to Ottowia beijingensis MCCC 1A01410T, followed by Ottowia thiooxydans (95.2 %) JCM 11629T. The average amino acid identity values between 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were above 60 % (71.4 and 69.5 %). The average nucleotide identity values between strain 10c7w1T and O. beijingensis MCCC 1A01410T and O. thiooxydans JCM 11629T were 76.9 and 72.5 %, respectively. The dominant fatty acids (≥10 %) were straight chain ones, with summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c) and C16 : 00 being the most abundant. Q-8 was the only respiratory quinone. The major polar lipids of strain 10c7w1T were phosphatidylethanolamine, diphosphatidylglycerol and unknown lipids. The DNA G+C content of strain 10c7w1T was 63.6 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic data, strain 10c7w1T is considered to represent a novel species within the genus Ottowia, for which the name Ottowia cancrivicina sp. nov. is proposed. The type strain is 10c7w1T (=MCCC 1H01399T=KCTC 92200T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , Estômago , RNA Ribossômico 16S/genética , Ácidos Graxos/química , Humanos , DNA Bacteriano/genética , Estômago/microbiologia , Hibridização de Ácido Nucleico , Ubiquinona , Fosfolipídeos/química
19.
J Am Chem Soc ; 146(19): 13226-13235, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38700957

RESUMO

Strained carbon nanohoops exhibit attractive photophysical properties due to their unique π-conjugated structure. However, incorporation of such nanohoops into the pincer ligand of metal complexes has rarely been explored. Herein, a new family of highly strained cyclometalated platinum(II) nanohoops has been synthesized and characterized. Strain-promoted C-H bond activation has been observed during the metal coordination process, and Hückel-Möbius topology and random-columnar packing in the solid state are found. Transient absorption spectroscopy revealed the size-dependent excited state properties of the nanohoops. Moreover, the nanohoops have been successfully employed as active materials in the fabrication of solution-processable resistive memory devices, including the use of the smallest platinum(II) nanohoop for the fabrication of a binary memory, with low switching threshold voltages of ca. 1.5 V, high ON/OFF current ratios, and good stability. These results demonstrate that strain incorporation into the structure can be an effective strategy to fundamentally fine-tune the reactivity, optoelectronic, and resistive memory properties.

20.
Int J Biol Macromol ; 269(Pt 1): 131761, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38663705

RESUMO

Lepidium meyenii Walp., also known as the "Peruvian national treasure", is a popular functional food in the daily lives of Peruvian people due to its bioactive with main polysaccharides. However, studies on polysaccharides isolated from Lepidium meyenii were few. Two new highly heterogeneous polysaccharides, MCP-1a and MCP-2b, were isolated and purified from the tuber of Lepidium meyenii. The structure characterization revealed that MCP-1a primarily consisted of D-Glc and had a molecular weight of 6.6 kDa. Its backbone was composed of 1,4,6-α-D-Glc, while branches feature T-α-L-Ara, 1,5-α-L-Ara, and T-α-D-Glc attached to the O-6 positions. MCP-2b was a rare arabinogalactan with a molecular weight of 49.4 kDa. Interestingly, the backbone of MCP-2b was composed of 1,6-ß-D-Gal, 1,3,6-ß-D-Gal with a few 1,3-ß-D-GlcpA-4-OMe units inserted. Side chains of MCP-2b were mainly composed of 1,3-ß-D-Gal, T-ß-D-Gal, T-α-L-Ara, 1,5-α-L-Ara, with trace amounts of 1,4-ß-D-Glc and T-ß-D-Glc. The bioactivity assay results revealed that MCP-1a and MCP-2b increased the release of NO, IL-1ß, TNF-α, and IL-6 from RAW 264.7 cells at concentrations ranging from 50 µg/mL to 400 µg/mL. Furthermore, MCP-1a and MCP-2b could promote the expression of key transcription factors (IκB-α, p-IκB-α, p65, and p-p65) in the NF-κB pathway, indicating that MCP-1a and MCP-2b had potential immunomodulatory activities.


Assuntos
Lepidium , NF-kappa B , Polissacarídeos , Transdução de Sinais , Lepidium/química , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Camundongos , NF-kappa B/metabolismo , Animais , Transdução de Sinais/efeitos dos fármacos , Células RAW 264.7 , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Peso Molecular , Citocinas/metabolismo
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