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There has been a recent upsurge in research aimed at synthesizing inherently chiral molecules devoid of point, axial, planar and helical chiralities. We present herein our design and enantioselective synthesis of a series of inherently chiral macrocycles. These compounds, termed nor-heteracalixaromatics, feature a biaryl bond that replaces one of the aryl-heteroatom-aryl linkages found in classic heteracalix[4]aromatics. Macrocyclization of linear achiral substrates via an intramolecular Suzuki-Miyaura cross-coupling reaction affords the 15-membered cyclophane without any chiral elements in high yields and enantioselectivities. Notably, the formation of the aryl-aryl bond does not induce axial chirality at the biaryl linkage. Instead, it restricts the free rotation of an aromatic ring located four bonds away, leading to the inherent chirality of the macrocycle. The intriguing chiroptical properties of these compounds made them promising platform for the development of CPL emitters.
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Functional traits are indicators of the responses and adaptation of organisms to environmental changes and cascade to a series of ecosystem functions. The functional traits of soil animals are sensitive to environmental factors and may characterize and predict the changes of ecosystem functions. Multiple dimensions of biodiversity that combing species, phylogenetic, and functional diversity improves the understanding of distribution patterns, community assembly mechanisms and ecosystem functions of soil animals. In this review, we listed the categories of soil animal functional traits and their ecological significance, and summarized current researches on the responses of soil animal communities to environmental changes and the community assembly processes based on trait-based approaches. We proposed to strengthen the study on the impacts of eco-evolution processes of biotic interactions to soil animal functional traits, establish the database of soil animal functional traits, and apply trait-based approaches in the ecological restoration in the future, which would benefit soil biodiversity conservation and sustainability of soil ecosystems.
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Biodiversidade , Ecossistema , Solo , Animais , Conservação dos Recursos Naturais , Ecologia , Distribuição AnimalRESUMO
Mild whole-body hyperthermia has been shown to have anti-tumor effects through an immune-modulating mechanism. Before it is widely applied in the clinic, tremendous mechanistic research in animals is necessary to adhere to evidence-based principles. The radio frequency electromagnetic field (RF-EMF) based heating facility could be a good choice for hyperthermia treatment, but the heating characteristics of a facility, including structure design, electromagnetic and thermal dosimetry, and the biologic effects of hyperthermia, need to be well elucidated. Here, we reported the heating characteristic study on a resonant chamber (RC) excited by a 1800 MHz solid source. The EMF in the RC was stirred by 24 static reflectors, which resulted in the standard deviation of electric field intensity being below 3 dB in the EM homogeneity evaluation. For the exposure scenario, six free-moving mice were loaded into separate cases and exposed simultaneously in the RC. The EMF energy absorption and distribution in exposed mice were calculated with the 12-plane-waves method of numerical simulation. Different levels of core body temperature increment in exposed mice were achieved through regulation of the source output power. Overexpression of heat shock proteins (HSPs) was detected in the liver, lung and muscle, but not in the brain of the exposed mice. The levels of representative inflammatory cytokines in the serum, TNF-α and IL-10 increased post RC exposure. Based on the heating characteristic study and validation, the applied RC would be a qualified heating system for mild whole-body hyperthermia effect research in mice.
Mild whole-body hyperthermia has potential anti-tumor effects by modulating the immune system. A radio frequency electromagnetic field (RF-EMF)-based heating facility emerges as a suitable option for hyperthermia treatment. However, a qualified heating facility for scientific research must elucidate its heating characteristics and validate the biological effects associated with hyperthermia. In this study, we report the characteristics of a rodent heating chamber using EMF energy. The special structure of the chamber not only achieved efficient EMF usage but also ensured the homogeneity in EMF spatial distribution, animal EM absorption, and EMF-caused biological effects. Our work may offer insights for designing a low-cost yet reliable heating facility for scientific research.
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Campos Eletromagnéticos , Ondas de Rádio , Animais , Camundongos , Hipertermia/terapia , Hipertermia Induzida/métodos , Hipertermia Induzida/instrumentação , Calefação , MasculinoRESUMO
The order Agaricales was divided into eight suborders. However, the phylogenetic relationships among some suborders are largely unresolved, and the phylogenetic positions and delimitations of some taxa, such as Sarcomyxaceae and Tricholomopsis, remain unsettled. In this study, sequence data of 38 genomes were generated through genome skimming on an Illumina sequencing system. To anchor the systematic position of Sarcomyxaceae and Tricholomopsis, a phylogenetic analysis based on 555 single-copy orthologous genes from the aforementioned genomes and 126 publicly accessible genomes was performed. The results fully supported the clustering of Tricholomopsis with Phyllotopsis and Pleurocybella within Phyllotopsidaceae, which formed a divergent monophyletic major lineage together with Pterulaceae, Radulomycetaceae, and Macrotyphula in Agaricales. The analysis also revealed that Sarcomyxaceae formed a unique major clade. Therefore, two new suborders, Phyllotopsidineae and Sarcomyxineae, are proposed for the two major lineages. Analyses of 450 single-copy orthologous genes and four loci suggested that Tricholomopsis consisted of at least four clades. Tricholomopsis is subsequently subdivided into four distinct sections. Seventeen Tricholomopsis species in China, including six new species, are reported. Conoloma is established to accommodate T. mucronata. The substrate preference of Tricholomopsis species and the transitions of the pileate ornamentations among the species within the genus are discussed.
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We report herein the synthesis of highly enantiopure inherently chiral N3,O-calix[2]arene[2]triazines from enantioselective macrocyclization enabled by chiral phosphoric acid-catalyzed intramolecular nucleophilic aromatic substitution reaction. In contrast to documented examples, the inherent chirality of the acquired compounds arises from one heteroatom difference in the linking positions of heteracalix[4](het)arenes.
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It was reported that the Wnt/ß-catenin pathway is involved in the regulation of aerobic glycolysis and that brain glycolytic dysfunction results in the development of Alzheimer's disease (AD). Icariin (ICA), an active component extracted from Epimedii Folium, has been reported to produce neuroprotective effects in multiple models of AD, but its underlying mechanism remains to be fully described. We aimed to investigate the protective effects of ICA on animal and cell models of AD and confirm whether the Wnt/ß-catenin pathway has functions in the neuroprotective function of ICA. The 3 × Tg-AD mice were treated with ICA. HT22 cells, the Aß25-35 peptide and Dickkopf-1 (DKK1) agent (a specific inhibitor of the Wnt/ß-catenin pathway) were used to further explore the underlying mechanism of ICA that produces anti-AD effects. Behavioral examination, western blotting assay, staining analysis, biochemical test, and lactate dehydrogenase (LDH) assays were applied. We first demonstrated that ICA significantly improved cognitive function and autonomous behavior, reduced neuronal damage, and reversed the protein levels and activities of glycolytic key enzymes, and expression of protein molecules of the canonical Wnt signaling pathway, in 3 × Tg-AD mice back to wild-type levels. Next, we further found that ICA increased cell viability and effectively improved the dysfunctional glycolysis in HT22 cells injured by Aß25-35. However, when canonical Wnt signaling was inhibited by DKK1, the above effects of ICA on glycolysis were abolished. In summary, ICA exerts neuroprotective effects in 3 × Tg-AD animals and AD cellular models by enhancing the function of glycolysis through activation of the Wnt/ß-catenin pathway.
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Doença de Alzheimer , Flavonoides , Glicólise , Camundongos Transgênicos , Via de Sinalização Wnt , Animais , Masculino , Camundongos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , beta Catenina/metabolismo , beta Catenina/genética , Modelos Animais de Doenças , Flavonoides/farmacologia , Glicólise/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/metabolismo , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
BACKGROUND: Previous studies have shown an association between gut microbiota and cardiovascular diseases (CVDs). However, the underlying causal relationship remains unclear. This study aims to elucidate the causal relationship between gut microbiota and CVDs and to explore the pathogenic role of gut microbiota in CVDs. METHODS: In this two-sample Mendelian randomization study, we used genetic instruments from publicly available genome-wide association studies, including single-nucleotide polymorphisms (SNPs) associated with gut microbiota (n = 14,306) and CVDs (n = 2,207,591). We employed multiple statistical analysis methods, including inverse variance weighting, MR Egger, weighted median, MR pleiotropic residuals and outliers, and the leave-one-out method, to estimate the causal relationship between gut microbiota and CVDs. Additionally, we conducted multiple analyses to assess horizontal pleiotropy and heterogeneity. RESULTS: GWAS summary data were available from a pooled sample of 2,221,897 adult and adolescent participants. Our findings indicated that specific gut microbiota had either protective or detrimental effects on CVDs. Notably, Howardella (OR = 0.955, 95% CI: 0.913-0.999, P = .05), Intestinibacter (OR = 0.908, 95% CI:0.831-0.993, P = .03), Lachnospiraceae (NK4A136 group) (OR = 0.904, 95% CI:0.841-0.973, P = .007), Turicibacter (OR = 0.904, 95% CI: 0.838-0.976, P = .01), Holdemania (OR, 0.898; 95% CI: 0.810-0.995, P = .04) and Odoribacter (OR, 0.835; 95% CI: 0.710-0.993, P = .04) exhibited a protective causal effect on atrial fibrillation, while other microbiota had adverse causal effects. Similar effects were observed with respect to coronary artery disease, myocardial infarction, ischemic stroke, and hypertension. Furthermore, reversed Mendelian randomization analyses revealed that atrial fibrillation and ischemic stroke had causal effects on certain gut microbiotas. CONCLUSION: Our study underscored the importance of gut microbiota in the context of CVDs and lent support to the hypothesis that increasing the abundance of probiotics or decreasing the abundance of harmful bacterial populations may offer protection against specific CVDs. Nevertheless, further research is essential to translate these findings into clinical practice.
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In the entire world, hepatocellular carcinoma (HCC) is one of the most frequent cancers that lead to death. Experiments on the function of long non-coding RNAs in the emergence of malignancies, including HCC, are ongoing. As a crucial RNA monitoring mechanism in eucaryotic cells, nonsense-mediated mRNA decay (NMD) can recognize and destroy mRNAs, which has an premature termination codons (PTC) in the open reading frame to prevent harmful buildup of truncated protein products in the cells. Nonsense transcript regulator 1 (Up-frameshift suppressor 1, UPF1), as a highly conserved RNA helicase and ATPase, plays a key role in NMD. Our laboratory screened out the highly expressed lncRNA LINC02561 in HCC from the TCGA database. Further research found that LINC02561 enhanced the invasion and transition abilities of liver cancer cells by regulating the protein N-Myc downstream regulated 1 (NDRG1). Hypoxia inducible factor-1 (HIF-1α) can bonded to LINC02561 promoters under hypoxic conditions, thereby promoting the upregulation of LINC02561 expression in liver cancer cells. LINC02561 competes with NDRG1 mRNA to bind UPF1, thereby preventing the degradation of NDRG1 mRNA to facilitate NDRG1 protein level. Taken together, the HIF1α-LINC02561-UPF1-NDRG1 regulatory axis could be an entirely novel target of liver cancer-related treatment.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Transativadores/genética , Neoplasias Hepáticas/genética , RNA Helicases/genética , RNA Helicases/metabolismo , Degradação do RNAm Mediada por Códon sem Sentido , Códon sem SentidoRESUMO
Objectives. Studies have shown that fasting blood glucose (FBG) is closely associated with poor prognosis in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI), but its association with in-stent restenosis (ISR) is still unclear. Therefore, this study was to explore the association between FBG with ISR in patients with CHD after PCI. Design. In this cohort study, we included 531 patients with CHD who underwent PCI. Logistic regression, receiver operating characteristic (ROC), subgroup analysis and restricted cubic spline (RCS) were used to assess the association between FBG with ISR. Results. A total of 124 (23.4%) patients had ISR. Patients with higher levels of FBG had higher incidence of ISR compared to those with lower levels of FBG (p = 0.002). In multivariable logistic regression analyses, higher levels of FBG remained strongly associated with higher risk of ISR (as a categorical variable, OR: 1.89, 95% CI: 1.21-2.94, p = 0.005; as a continuous variable, OR: 1.12, 95% CI: 1.03-1.23, p = 0.011). ROC analysis also showed that FBG might be associated with the occurrence of ISR (AUC = 0.577, 95% CI: 0.52-0.64, p = 0.013). Subgroup analyses showed the association of FBG with ISR was also stable in several subgroups (< 60 years or ≥ 60 years, male, with or without smoking, without diabetes and without hypertension). And RCS analysis showed that FBG was linearly and positively associated with the risk of ISR. Conclusions. Higher levels of FBG were closely associated with higher risk of ISR in patients with CHD after PCI.
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Reestenose Coronária , Intervenção Coronária Percutânea , Humanos , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Estudos de Coortes , Glicemia , Reestenose Coronária/etiologia , Constrição Patológica , Jejum , Angiografia Coronária/efeitos adversos , Fatores de Risco , Estudos Retrospectivos , Stents/efeitos adversosRESUMO
Objective: Coronary heart disease is incurable and prone to recurrence, and long-term dependence on medication and good nursing management to improve the prognosis. The effect of clopidogrel in the treatment of coronary heart disease is affected by many factors, so paying more attention to details in the process of patient care is conducive to creating more ideal recovery conditions for patients. The purpose of this study is to conduct detailed intervention for coronary heart disease (CHD) after clopidogrel treatment, and to analyze the clinical efficacy of this intervention mode on CHD patients and the relief of angina pectoris. Methods: A total of 120 patients with coronary heart disease who were diagnosed and treated in our hospital from May 2020 to March 2022 were selected as the research objects and divided into a detail group (n=60) and a routine group (n=60) according to the computer randomization method, All research subjects were given clopidogrel intervention, followed by routine intervention in the routine group, and detailed intervention in the detail group. Detailed intervention includes specific measures such as psychological intervention, life intervention, health education, medical assessments, personalized care. The control of angina pectoris of the subjects was analyzed, and the daily life, motor function, quality of life score, negative emotion score and complications were observed. Results: The dimension score of TS [(83.50±5.14) points vs (77.42±4.35) points], DP [(85.59±5.78) points vs (80.14±5.43) points], PL [(79.62±5.19) points vs (74.18±5.04) points], AS [(90.69±6.35) points vs (85.57±6.12) points], AF[(83.54±5.22) points vs (77.51±5.16) points] in the detail group were higher than those of conventional group (P < .001). The differences in daily life, motor function of the subjects before the intervention were not comparable (P > .05), and the scores of daily life [(86.14±5.52) points vs (65.48±5.17) points] and motor function [(88.97±5.34) points vs (70.58±5.46) points] in the detail group at 4 weeks after intervention were higher than those in the routine group (P < .001). The quality of life in the detail group [mental state of (17.56±2.12) points vs (20.13±2.09) points, mental health of (15.62±2.34) points vs (18.09±2.06) points, social function of (15.86±2.41) points vs (18.11±2.14) points, emotional function of (14.36±3.45) points vs (16.78±3.69) points] were lower than those of the conventional group (P < .001). The negative mood scores [SAS score of (41.70±3.14) points vs (67.14±3.25) points, SDS score of (39.59±4.11) points vs (60.58±4.54) points] in the detail group were lower than those of the conventional group (P < .001). In addition, the total incidence of complications (3.33% vs 13.33%) in the detail group was significantly lower than that in the regular group (P < .001). Conclusions: Detailed intervention after clopidogrel treatment in CHD patients can significantly improve the efficacy of patients, reduce angina pectoris, and at the same time can effectively improve various physical functions and relieve their negative emotions, which is worthy of being widely used in clinical practice. Better control of angina pectoris is beneficial to reduce the frequency of hospital admission and save medical resources. The sample size of this study is small, and the sample size will be further expanded in the future to improve the scientific conclusion.
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OBJECTIVE: To investigate the efficacy and safety of CD19/CD3 bisecific monoclonalantibody (Blinatumomab) in the treatment of adult patients with relapsed / refractory Ph-negative acute B-lymphoblastic leukemia (R/R-B-ALL). METHODS: Ten adult R/R B-ALL patients were all treated with Blinatumomab. Each treatment cycle was administered for 28 days and stopped for 14 days. The dose was 9 µg/day for the first 7 days of cycle 1, and 28 µg/day for days 8-28 if there were no adverse reactions. From the second cycle onwards, the daily dose was 28 µg. The remission, survival time (EFS and OS) and adverse reactions were observed after treatment. RESULTS: Nine patients with curative effect could be evaluated. Four patients achieved CR after one course, and one patient achieved CR after two courses, the overall remission rate was 55.6%(5/9). The median EFS was 4 months (1-12 months), and the median OS was 6 months (2-44 months). Nine of the 10 patients had fever of different degrees. Serum levels of cytokines such as IL-6, IL-10, IL-17 and IFN-γ increased. Two patients resumed medication after 1 week of treatment interruption due to neurotoxicity and CRS, respectively. One patient was discontinued due to grade 3 CRS and died of tropical candidiaemia. CONCLUSION: Blinatumomab has a good response rate in the treatment of relapsed/refractory B-ALL patients, but the duration of remission is shorter. Drug-related adverse reactions are mainly CRS and neurotoxicity. Inflammatory factors IL-6, IL-10, IL-17 and IFN-γ can be used as indicators to monitor CRS. The bisspecificity MAbs provide an opportunity for subsequent allogeneic hematopoietic stem cell transplantation in R/R-B-ALL patients.
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Background: Previous studies have examined symptom clusters in children with acute leukemia, yet a knowledge gap persists regarding central symptom clusters and their influencing factors. By identifying these central clusters and associated factors, healthcare providers can enhance their understanding and effective management of symptoms. Our study seeks to address this gap by identifying symptom clusters, exploring central clusters, and investigating the demographic and health-related factors associated with these clusters in children with acute leukemia undergoing chemotherapy. Methods: A total of 586 children with acute leukemia from January 2021 to April 2023 were recruited from China. They were investigated using Memorial Symptom Assessment Scale 10-18 during chemotherapy. The principal component analysis was used to identify the symptom clusters. An association network was conducted to describe the relationships among symptoms and clusters. A multiple linear model was used to investigate the associated factors for the severity of overall symptoms and each symptom cluster. Results: Five clusters were identified, including oral and skin cluster, somatic cluster, self-image disorder cluster, gastrointestinal cluster and psychological cluster. Gastrointestinal cluster was the most central symptom cluster. Age, sex, clinical classification, number of having chemotherapy and education degree and marital status of the primary caregiver are associated with the severity of these five symptom clusters. Conclusion: Our study highlights the importance of evaluating symptom clusters in children with acute leukemia during chemotherapy. Specifically, addressing gastrointestinal symptoms is crucial for effective symptom management and overall care.
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PURPOSE: Children with acute leukemia have suffered from a considerable symptom burden during chemotherapy. However, few studies have focused on exploring the mechanisms among symptoms in children with acute leukemia. Our study aims to explore core symptoms and describe the interrelationships among symptoms in children with acute leukemia during chemotherapy. METHODS: From January 2021 to March 2023, 469 children with acute leukemia were recruited from 20 Chinese cities. The Memorial Symptom Assessment Scale 10-18 (MSAS 10-18) was used to evaluate the prevalence and severity of symptoms during chemotherapy. A network analysis was performed by the R software based on 31 symptoms. Centrality indices and density were used to explore core symptoms and describe interrelationships among symptoms in the network during chemotherapy. RESULTS: Worrying and feeling irritable were the central symptoms across the three centrality indices, including strength, closeness, and betweenness. Lack of energy was the most prevalent symptom; however, it was less central than other symptoms. The density of the "induction and remission" network significantly differed from other cycles' counterparts (p < 0.001). Global strength was greater in the " ≥ 8 years group " network than the " < 8 years group " network (p = 0.023). CONCLUSION: Network analysis provides a novel approach to identifying the core symptoms and understanding the interrelationships among symptoms. Our study indicates the need to assess emotional symptoms in children with acute leukemia during chemotherapy, especially during the induction and remission phases, as well as in older children. Future research is imperative to construct trajectories of dynamic symptom networks and centrality indices in longitudinal data to investigate the causal relationships among symptoms.
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Antineoplásicos , Leucemia , Criança , Humanos , Povo Asiático , Emoções , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/epidemiologia , Software , Antineoplásicos/uso terapêutico , Leucemia/diagnóstico , Leucemia/tratamento farmacológico , Leucemia/psicologia , Doença Aguda , ChinaRESUMO
Objective: To investigate the mechanism of RNA-binding protein hnRNP A1 in mouse hippocampal neurons (HT22) on glycolysis. Methods: RIP and CLIP-qPCR were performed by HT22 in vitro to observe the mechanism of hnRNP A1 regulating the expression of key proteins in glycolysis. The RNA binding domain of hnRNP A1 protein in HT22 was inhibited by VPC-80051, and the effect of hnRNP A1 on glycolysis of HT22 was observed. Lentivirus overexpression of hnRNP A1 was used to observe the effect of overexpression of hnRNP A1 on glycolysis of Aß25-35-injured HT22. The expression of hnRNP A1 in brain tissues of wild-type mice and triple-transgenic (APP/PS1/Tau) AD mice at different ages was studied by Western blot assay. Results: The results of RIP experiment showed that hnRNP A1 and HK1 mRNA were significantly bound. The results of CLIP-qPCR showed that hnRNP A1 directly bound to the 2605-2821 region of HK1 mRNA. hnRNP A1 inhibitor can down-regulate the expression of HK1 mRNA and HK1 protein in HT22 cells. Overexpression of hnRNP A1 can significantly reduce the toxic effect of Aß25-35 on neurons via the hnRNP A1/HK1/ pyruvate pathway. In addition, inhibition of hnRNP A1 binding to amyloid precursor protein (APP) RNA was found to increase Aß expression, while Aß25-35 also down-regulated hnRNP A1 expression by enhancing phosphorylation of p38 MAPK in HT22. They interact to form bidirectional regulation, further down-regulating the expression of hnRNP A1, and ultimately aggravating glycolytic dysfunction. Protein immunoblotting showed that hnRNP A1 decreased with age in mouse brain tissue, and the decrease was greater in AD mice, suggesting that the decrease of hnRNP A1 may be a predisposed factor in the pathogenesis of AD.
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In contrast to a plethora of macrocyclic and cage compounds, spirophanes have remained largely unexplored. We report herein the construction, structure and properties of unprecedented tetrahomo corona[4]arene-based ditopic and tritopic macrocycles of spiro structures. Synthesis was conveniently achieved by means of an efficient SNAr reaction from simple and commercially available starting materials. Racemic samples were resolved into enantiopure chiral tetrahomo i-corona[4]arenes, spirophanes and bispirophanes which show interesting chiroptical properties. The acquired electron-deficient macrocyclic compounds were found to adopt unique conformational structures and to form distinct complexes with TTF in the solid state. Our study provides a new opportunity to develop multitopic macrocycles of different topologies which have potential applications in supramolecular chemistry.
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Previous studies have shown that Vibrio splendidus infection causes mitochondrial damage in Apostichopus japonicus coelomocytes, leading to the production of excessive reactive oxygen species (ROS) and irreversible apoptotic cell death. Emerging evidence suggests that mitochondrial autophagy (mitophagy) is the most effective method for eliminating damaged mitochondria and ROS, with choline dehydrogenase (CHDH) identified as a novel mitophagy receptor that can recognize non-ubiquitin damage signals and microtubule-associated protein 1 light chain 3 (LC3) in vertebrates. However, the functional role of CHDH in invertebrates is largely unknown. In this study, we observed a significant increase in the mRNA and protein expression levels of A. japonicus CHDH (AjCHDH) in response to V. splendidus infection and lipopolysaccharide (LPS) challenge, consistent with changes in mitophagy under the same conditions. Notably, AjCHDH was localized to the mitochondria rather than the cytosol following V. splendidus infection. Moreover, AjCHDH knockdown using siRNA transfection significantly reduced mitophagy levels, as observed through transmission electron microscopy and confocal microscopy. Further investigation into the molecular mechanisms underlying CHDH-regulated mitophagy showed that AjCHDH lacked an LC3-interacting region (LIR) for direct binding to LC3 but possessed a FB1 structural domain that binds to SQSTM1. The interaction between AjCHDH and SQSTM1 was further confirmed by immunoprecipitation analysis. Furthermore, laser confocal microscopy indicated that SQSTM1 and LC3 were recruited by AjCHDH in coelomocytes and HEK293T cells. In contrast, AjCHDH interference hindered SQSTM1 and LC3 recruitment to the mitochondria, a critical step in damaged mitochondrial degradation. Thus, AjCHDH interference led to a significant increase in both mitochondrial and intracellular ROS, followed by increased apoptosis and decreased coelomocyte survival. Collectively, these findings indicate that AjCHDH-mediated mitophagy plays a crucial role in coelomocyte survival in A. japonicus following V. splendidus infection.
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Stichopus , Vibrioses , Animais , Colina Desidrogenase/metabolismo , Células HEK293 , Mitofagia/genética , Espécies Reativas de Oxigênio/metabolismo , Proteína Sequestossoma-1/metabolismo , Stichopus/metabolismo , Vibrioses/veterináriaRESUMO
OBJECTIVE: To detect the gene mutations in patients with myeloid malignancies by high-throughput sequencing and explore the correlation between gene mutations and prognosis. METHODS: A retrospective analysis was performed on 56 patients with myeloid malignancies who were hospitalized in the department of hematology, Peking University International Hospital from January 2020 to May 2021. The genetic mutations of the patients were detected by next-generation sequencing technology, and the correlation between the genetic mutations and prognosis of myeloid malignancies was analyzed. RESULTS: In 56 patients, the number of mutated genes detected in a single patient is 0-9, with a median of 3. Sequencing results showed that the most common mutated genes were RUNX1(21.4%), TET2(17.9%), DNMT3A(17.9%), TP53(14.3%) and ASXL1(14.3%), among which the most common mutations occurred in the signaling pathway-related genes (23.3%) and the transcription factor genes (18.3%). 84% of the patients carried multiple mutated genes (≥2), and correlation analysis showed there were obvious co-occurring mutations between WT1 and FLT3, NPM1 and FLT3-ITD, and MYC and FLT3. TP53 mutation was more common in MDS patients.The overall survival time of patients with NRAS mutation was significantly shortened (P =0.049). The prognosis of patients with TP53 mutation was poor compared with those without TP53 mutation, but the difference wasn't statistically significant (P =0.08). CONCLUSION: The application of next-generation sequencing technology is of great significance in myeloid malignancies, which is helpful to better understand the pathogenesis of the disease, to judge the prognosis and to find possible therapeutic targets.
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Leucemia Mieloide Aguda , Transtornos Mieloproliferativos , Humanos , Leucemia Mieloide Aguda/genética , Nucleofosmina , Prognóstico , Estudos Retrospectivos , Sequenciamento de Nucleotídeos em Larga Escala , MutaçãoRESUMO
BACKGROUND: Insect pheromones are highly effective and environmentally friendly, and are widely used in the monitoring and trapping of pests. However, many researchers have found that various factors such as ultraviolet light and temperature in the field environment can accelerate the volatilization of pheromones, thus affecting the actual control effect. In recent years, electrospinning technology has demonstrated remarkable potential in the preparation of sustained carriers. Moreover, the utilization of biodegradable materials in electrospinning presents a promising avenue for the advancement of eco-friendly carriers. RESULTS: In this study, homogeneous and defect-free pheromone carriers were obtained by electrospinning using fully biodegradable polyhydroxybutyrate materials and pheromones of Spodoptera litura. The electrospun fibers with porous structure could continuously release pheromone (the longest can be ≤80 days). They also had low light transmission, hydrophobic protection. More importantly, the pheromone-loaded electrospun fiber carriers showed stable release and good trapping effect in the field. They could trap pests for at least 7 weeks in the field environment without other light stabilizers added. CONCLUSION: Sustained-release carriers constructed by electrospinning and green materials could improve the efficacy of pheromones and ensure environmental friendliness, and provided a tool for the management of S. litura and other pests and sustainable development of agricultural. © 2023 Society of Chemical Industry.
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Mariposas , Feromônios , Animais , Spodoptera , Feromônios/farmacologia , Preparações de Ação Retardada/farmacologia , InsetosRESUMO
Although adequate intake of manganese (Mn) is essential to humans, Mn in excess is neurotoxic. Exposure to extremely high doses of Mn results in "manganism", a condition that exhibits Parkinson-like symptoms. However, the mechanisms underlying its neurotoxic effects in Mn-induced parkinsonism pathogenesis are unclear. In this study, 8-week-old male C57BL/6 J mice were injected intraperitoneally with saline and 50 mg/kg MnCl2 respectively once daily for 14 days to produce an acute Mn neurotoxicity model. Accumulation of Mn in the midbrain, motor dysfunction and loss of dopaminergic neurons in the substantia nigra evidenced Mn neurotoxicity. Untargeted lipidomic analysis demonstrated that Mn overexposure altered lipidome profiles. A significant modulation of 12 lipid subclasses belonging to 5 different categories were found in the midbrain and among the most abundant lipids were sphingolipids, glycerophospholipids, and glycerides. The levels of sphingomyelin (SM) were significantly decreased after Mn treatment. The expression of SM biosynthesis genes was decreased dramatically while sphingomyelinase was up-regulated. In addition, we observed oxidative stress in both the midbrain of mice and MN9D cells, indicated by the increase of MDA level, the decrease of reduced GSH level and the inhibition of SOD and GPx enzyme activities. There was a correlation between these changes and motor dysfunctions. Overall, our study is the first to use lipidomics techniques to explore the pathogenesis of Mn-induced parkinsonism in C57BL/6 J mice. Mn induced molecular events in the midbrain, such as lipid metabolism disorders, oxidative stress and dopaminergic neurons injury, may mechanistically play important roles in the pathogenesis of Parkinson-like symptoms. Moreover, these findings emphasize the necessity for reducing the health risk of environmental neurotoxic pollutants in relation to parkinsonism.
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Doença de Parkinson , Transtornos Parkinsonianos , Masculino , Humanos , Animais , Camundongos , Manganês/toxicidade , Camundongos Endogâmicos C57BL , Estresse Oxidativo , Transtornos Parkinsonianos/induzido quimicamente , LipídeosRESUMO
Despite their interesting stereochemistry and potential applications in (supramolecular) chemistry and chiroptical materials, inherently chiral macrocyclic compounds remain rare and are largely unexplored. We report herein a fragment coupling method to construct ABAC- and ABCD-type inherently chiral heteracalix[4]aromatics. The synthesis involves SNAr CuI-catalyzed Ullmann coupling and aliphatic nucleophilic substitution reactions as key steps using readily available starting materials. Postmacrocyclization functionalization reactions enabled the production of amino-substituted and (benzo[d])imidazole-2-(thi)one-bearing heteracalix[4]aromatics. Enantiopure ABCD-type macrocycles were obtained from resolution.